Vol 17  •  Issue 9  •  September 2015

NEW! Volume 17  •  Issue 9  •  September 2015  • ISSN 1098-612x

Journal of Feline

Journal of Feline Medicine and Surgery

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 2015 American Association of
Feline Practitioners
presents

3rd World Feline Veterinary Conference

WEIGHT + FLUTD
Distinguished Speakers
Livia Benigni, DVM, MRCVS, CertVDI, PGCertAP, DECVDI
Elizabeth Colleran, DVM, MS, DABVP (Feline)
Let’s address Sue Ettinger, DVM, DACVIM (Oncology)
William Folger, DVM, MS, DABVP (Feline)

them together
S. Dru Forrester, DVM, MS, DACVIM
Lorrie Gaschen, PhD, DVM, Dr.med.vet, DECVDI
Erika Krick, VMD, DACVIM (Oncology)
Michael Lappin, DVM, PhD, DACVIM
Zoe Lenard, BVSc (Hons) FANZCVS (Radiology)
Susan Little, DVM, DABVP (Feline)
CLINICALLY PROVEN NUTRITION: Erica Mattox, CVT, VTS (ECC)
Brook Niemiec, DVM, DAVDC
Greg Ogilvie, DVM, DACVIM (IntMed, Oncology)
REDUCES BODY WEIGHT1 Michael Petty, DVM, CVPP, CVA, CCRT, DAAPM
Jane Robertson, DVM, DACVIM
Ilona Rodan, DVM, DABVP (Feline)

DISSOLVES STRUVITE STONES

Margie Scherk, DVM, DABVP (Feline)
Annette Smith, DVM, MS, DACVIM (IntMed, Oncology)
IN AS LITTLE AS 7 DAYS2
Conference Features
■ Feline-specific material presented by expert
speakers.
■ Sessions for veterinarians who see cats at all
levels of their career.
■ Two Veterinary Tracks and one
Para-professional Track.
■ Labs – two Hands-on Dental Radiography Labs
will be offered. Attendance is limited.
■ Lunch & Learns – additional CE is offered through
lunch with speakers. Attendance is limited.
■ Networking and social activities with colleagues.
■ Meals and coffee breaks in our interactive
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Kick-off Sessions – topics such as Pain Management Updates
and Compelling & Clinically Relevant JFMS Updates.
Diagnostic Imaging – topics such as Thoracic Radiographs/
Ultrasound; Interpretation of the Feline Abdomen; Ultrasound
of GI, Hepatic and Pancreatic Diseases; Imaging: Urinary Tract
Disease; Do Cats Have 9 Lives?- Feline Trauma Imaging;
Radiographic Pulmonary Patterns & Heart Disease; Choosing
& Using Equipment; MRI & CT; and Dental Radiography.
Oncology – topics such as Managing Feline Cancer, Oral Tumors,
Lymphoma, Neoplastic Effusions, Improving Quality of Life,
Chemo Drugs, Less Common Cancers, Diagnostic Secrets,
Soft Tissue Sarcomas, Kitty Emergencies, Lumps & Bumps
Awareness, and Polyunsaturated Fatty Acids.

For more information, talk to your Hill’s Territory Manager.

1
Data on file. Hill’s Pet Nutrition, Inc.
www.catvets.com/education October 1- 4, 2015
Lulich JP, Kruger JM, MacLeay JM, et al. Efficacy of two commercially available, low-magnesium,
Manchester Grand Hyatt
2

urine acidifying dry foods for the dissolution of struvite uroliths in cats. J Am Vet Med Assoc.
2013;243:1147-1153. Average 27 days in vivo study in urolith forming cats. Partnering with the
FLUTD stands for Feline Lower Urinary Tract Disease
™Trademarks owned by Hill’s Pet Nutrition, Inc. ©2015 HillsVet.co.uk / HillsVet.ie
International Society of Feline Medicine San Diego, California USA
737_Contents.qxp_FAB 10/08/2015 12:48 Page 737

Journal of Feline Medicine and Surgery Volume 17 Number 9 September 2015

CONTENTS

Editorial
Non-surgical fertility control: current and future options
for cat health and welfare 740
J Briggs

CLINICAL Reviews
Progestins to control feline reproduction
Historical abuse of high doses and potentially safe use of low doses 743
s Romagnoli

Alternative methods for feline fertility control

Use of melatonin to suppress reproduction 753
M A Kutzler

Vaccines for feline contraception

GonaCon GnRH–hemocyanin conjugate immunocontraceptive 758
v A w Benka and J K Levy

Long-term contraception in a small implant

A review of Suprelorin (deslorelin) studies in cats 766
C Fontaine

Intratesticular and intraepididymal injections to sterilize male cats

From calcium chloride to zinc gluconate and beyond 772
M A Kutzler

No surgery required: the future of feline sterilization

An overview of the Michelson Prize & Grants in Reproductive Biology 777
s Johnston and L Rhodes

Put a label (claim) on it

Getting non-surgical contraceptives approved for use in cats and dogs 783
L Rhodes

Methods of fertility control in cats

Owner, breeder and veterinarian behavior and attitudes 790
J K Murray, J R Mosteller, J M Loberg, M Andersson and v A w Benka

Better trap–neuter–return for free-roaming cats

Using models and monitoring to improve population management 800
J D Boone

Ear tips to ear tags

Marking and identifying cats treated with non-surgical fertility control 808
v A w Benka

Clinical/research abstracts accepted for presentation

at ISFM Congress 2015 816

Feline Focus 829

AAFP Position Statement: Declawing 829

 Editorial Board

J Archer A Estrada B Jones A F B Petite

Cambridge, UK Gainesville, FL, USA Katikati, New Zealand Kings Hill, Kent, UK
V R Barrs M Forster-van Hijfte B Kohn A Poli
Sydney, NSW, Australia Bletchingley, UK Berlin, Germany Pisa, Italy
J Bartges S F Foster H S Kooistra B Pypendop
Stamford, CT, USA Perth, WA, Australia Utrecht, Netherlands Davis, CA, USA
J Beatty P Galloway S Langley-Hobbs A Radford
Sydney, NSW, Australia Lower Hutt, New Zealand Bristol, UK Liverpool, UK
D Bennett L Garosi M Lappin N Reed
Glasgow, UK Higham Gobion, Fort Collins, CO, USA Fife, UK
J P Billet Bedfordshire, UK B D X Lascelles M Rishniw
Nantes, France A C German Raleigh, NC, USA Cornell, USA
J D Bonagura Liverpool, UK S Lester J V Robertson
Columbus, OH, USA A J German Lake Stephens, Davis, CA, USA
D D Bowman Liverpool, UK WA, USA S Robertson
Ithaca, NY, USA U Giger S Little East Lansing, MI, USA
S A Brown Philadelphia, PA, USA Ottawa, ON, Canada E Rudloff
Athens, GA, USA D J Gould H Lutz Glendale, WI, USA
S M A Caney Higham Gobion, Zurich, Switzerland K Smith
Edinburgh, UK Bedfordshire, UK L A Lyons Hatfied, Hertfordshire, UK
M Cannon D Gunn-Moore Davis, CA, USA P Steagall
Oxford, UK Roslin, UK D J Maggs Saint-Hyacinthe (Québec),
M Chandler K Halling Davis, CA, USA Canada
Edinburgh, UK Oakville, ON, Canada R Malik P M Taylor
G B Cherubini A Harvey Sydney, NSW, Australia Cambridge, UK
Six Mile Bottom, Sydney, NSW, Australia F Mancianti S Taylor
Cambridgeshire, UK J Hauptman Pisa, Italy Bristol, UK
G Child Michigan, USA X Manteca L Trepanier
North Ryde, NSW, C Heinrich Barcelona, Spain Madison, WI, USA
Australia Solihull, UK G E Mauldin H von Euler
S Corr A Hibbert Calgary, AB, Canada Uppsala, Sweden
Sutton Bonington, Bristol, UK K E Michel C B Webb
Leicestershire, UK M Hoenig Philadelphia, PA, USA Fort Collins, CO, USA
J Davies Urbana, IL, USA A S Moore K Wildermuth
Calgary, AB, Canada J O Jarrett Wauchope, NSW, Australia Wiesbaden, Germany
J Debraekeleer Glasgow, UK K Overall M D Willard
Tienen, Belgium R Jerram Philadelphia, PA, USA College Station, TX, USA
L De Risio Mt Albert, Auckland, M Papich J Williams
Newmarket, Suffolk, UK New Zealand Raleigh, NC, USA Chester, Cheshire, UK
S L H Ellis L Johnson M E Peterson S Wills
Lincoln, UK Davis, CA, USA New York, NY, USA Amport, Hampshire, UK

Editors Editorial Team

A H Sparkes C Bessant (Executive Editor)
International Society of Feline Medicine, M Melling (Managing Editor)
Veterinary Division of International Cat Care, A Tansley (Assistant Editor)
High Street, Tisbury, Wiltshire SP3 6LD, UK International Society of Feline Medicine,
Email: andy@icatcare.org Veterinary Division of International Cat Care,
High Street, Tisbury, Wiltshire SP3 6LD, UK
M Scherk Email: jfms@icatcare.org; jfmsclinicalpractice@icatcare.org
catsINK, 4381 Gladstone Street,
Vancouver,
BC, Canada V5N 4Z4
Email: hypurr@sagepub.co.uk

00_JFM_17_9_TOC.indd 650 11/08/2015 4:27:06 PM

 ONLY BUPRENORPHINE

FDA
APPROVED
FOR CATS

Once-daily* 24-hour surgical pain control

*Administered subcutaneously for up to 3 days.

The first and only buprenorphine FDA approved for cats

Demonstrated safety and efficacy in more than 200 cats treated with SIMBADOL

Up to 3 once-daily subcutaneous doses for a total of 72 hours of pain control

INDICATION: SIMBADOL is indicated for the control of postoperative pain associated with surgical procedures in cats.
IMPORTANT SAFETY INFORMATION
WARNINGS, PRECAUTIONS and CONTRAINDICATIONS: Due to serious human safety and abuse
concerns, including physical or psychological dependence, life-threatening respiratory depression
and additive CNS depressant effects, read the full prescribing information before using this drug,
including the complete Boxed Warning. Not for use in humans. Hospital staff should be trained in
the handling of potent opioids and should avoid accidental exposure. For subcutaneous (SQ) injectable
use in cats. Opioid excitation has been observed up to 8 hours after anesthetic recovery. Use with caution in
cats with impaired hepatic function. SIMBADOL has not been evaluated in breeding, pregnant, or lactating
cats, in cats younger than 4 months of age or moribund cats. Do not use in cats with known hypersensitivity to
buprenorphine hydrochloride or any of the components of SIMBADOL, or known intolerance to opioids.
See attached full Prescribing Information, including the complete Boxed Warning for human safety
and adverse reactions.
All trademarks are the property of Zoetis Inc., its affiliates and/or its licensors.
©2015 Zoetis Inc. All rights reserved. April 2015. SIM-00014
 PRECAUTIONS: Hyperactivity (opioid excitation) has been observed up to
8 hours after anesthetic recovery (see ADVERSE REACTIONS). Safety has
not been evaluated in moribund cats. Use in such cases should be based on
the risk-benefit assessment of the veterinarian. Use with caution in cats with
1.8 mg/mL impaired hepatic function. The use of SIMBADOL has not been evaluated in
breeding, pregnant, or lactating cats, or in cats younger than 4 months of age.
For subcutaneous use in cats
ADVERSE REACTIONS: In two controlled field studies, the following
BRIEF SUMMARY: Before using SIMBADOL, please consult the full adverse reactions were reported.
prescribing information, a summary of which follows.
CAUTION: Federal law restricts this drug to use by or on the order of a Adverse Reactions in Two Field Studies
licensed veterinarian. SIMBADOL (N = 224) Control (N = 226)
Adverse During After During After
HUMAN SAFETY WARNING Reactiona Surgeryb Surgery Surgeryb Surgery

Abuse Potential Hypotensionc 68 (30.4%) 51 (22.8%) 60 (26.5%) 40 (17.7%)

SIMBADOL contains buprenorphine (1.8 mg/mL), an opioid Tachycardiad 55 (24.6%) 73 (32.6%) 30 (13.3%) 44 (19.5%)
agonist and Schedule III controlled substance with an abuse
potential similar to other Schedule III opioids. Buprenorphine has Hypothermia (≤98.0°F) 38 (17.0%) 1 (0.4%) 47 (20.8%) 0
certain opioid properties that in humans may lead to dependence Hyperthermia (≥103.0°F) 1 (0.4%) 91 (40.6%) 0 33 (14.6%)
of the morphine type. Abuse of buprenorphine may lead to physical
Hypertensione 10 (4.5%) 40 (17.9%) 17 (7.5%) 18 (8.0%)
dependence or psychological dependence. The risk of abuse by
humans should be considered when storing, administering and Anorexia 0 40 (17.9%) 0 35 (15.5%)
disposing of SIMBADOL. Persons at increased risk for opioid Hyperactivity 0 26 (11.6%) 0 11 (4.9%)
abuse include those with a personal or family history of substance
abuse (including drug or alcohol abuse or addiction) or mental Reduced SpO2
illness (suicidal depression). (≤90%) 8 (3.6%) 1 (0.4%) 11 (4.9%) 0

Life-Threatening Respiratory Depression Bradycardia

Respiratory depression, including fatal cases, may occur with (≤90 beats/min) 5 (2.2%) 1 (0.4%) 4 (1.8%) 1 (0.4%)
abuse of SIMBADOL. Tachypnea
Additive CNS Depressant Effects (≥72 breaths/min) 0 5 (2.2%) 1 (0.4%) 6 (2.7%)
SIMBADOL has additive CNS depressant effects when used with Arrhythmia 1 (0.4%) 1 (0.4%) 2 (0.9%) 0
alcohol, other opioids, or illicit drugs that cause central nervous
system depression. Blindness 0 2 (0.9%) 0 1 (0.4%)

Accidental Exposure Apnea/Death 1 (0.4%) 1 (0.4%) 0 0

Because of the potential for adverse reactions associated with
accidental injection, SIMBADOL should only be administered by
veterinarians or veterinary technicians who are trained in the
handling of potent opioids.
See Human Safety for detailed information.
INDICATION: SIMBADOL is indicated for the control of postoperative pain
associated with surgical procedures in cats.
DOSAGE AND ADMINISTRATION: The dosage of SIMBADOL is
0.24 mg/kg (0.11 mg/lb) administered subcutaneously once daily, for up
to 3 days. Administer the first dose approximately 1 hour prior to surgery.
Do not dispense SIMBADOL for administration at home by the pet owner
(see Human Safety).
CONTRAINDICATIONS: SIMBADOL is contraindicated in cats with known
hypersensitivity to buprenorphine hydrochloride or any of the components
of SIMBADOL, or known intolerance to opioids.
WARNINGS: For subcutaneous (SQ) injectable use in cats.
Human Safety: Not for use in humans. Keep out of reach of children.
Because of the potential for adverse reactions, hospital staff should avoid
accidental exposure and contact with skin, eyes, oral or other mucous
membrane during administration. SIMBADOL contains buprenorphine,
a mu opioid partial agonist and Schedule III controlled substance with an
abuse potential similar to other Schedule III opioids. SIMBADOL can be
abused and is subject to misuse, abuse, addiction and criminal diversion.
SIMBADOL should be handled appropriately to minimize the risk of
diversion, including restriction of access, the use of accounting procedures,
and proper disposal methods, as appropriate to the clinical setting and as
required by law. Abuse of SIMBADOL poses a hazard of overdose and
death. This risk is increased with concurrent abuse of alcohol and other
substances including other opioids and benzodiazepines. Buprenorphine
has been diverted for non-medical use into illicit channels of distribution.
All people handling opioids require careful monitoring for signs of abuse.
Drug abuse is the intentional non-therapeutic use of a prescription drug for
its rewarding psychological or physiological effects. Abuse of opioids can
occur in the absence of true addiction. Naloxone may not be effective in
reversing respiratory depression produced by buprenorphine. The onset
of naloxone effect may be delayed by 30 minutes or more. Doxapram
hydrochloride has also been used as a respiratory stimulant.
Ataxia 0 1 (0.4%) 0 0
Hyperesthesia 0 1 (0.4%) 0 0
a. Cats may have experienced more than one type or occurrence of an adverse reaction.
Cats experiencing the same reaction both during and after surgery are presented in both
time periods.
b. During surgery is the time from the administration of the anesthetic induction agent until
discontinuation of the gas anesthetic.
c. Hypotension is defined as a mean blood pressure of ≤60 mmHg during surgery and
≤90 mmHg after surgery.
d. Tachycardia is defined as a heart rate of ≥180 beats per minute during surgery and
≥200 beats per minute after surgery.
e. Hypertension is defined as a mean blood pressure of ≥120 mmHg during surgery and
≥160 mmHg after surgery.
To report suspected adverse events, contact Abbott Animal Health
at 1-888-299-7416, FDA at 1-888-FDA-VETS or FDA online at
http://www.fda.gov/AnimalVeterinary/SafetyHealth.
EFFECTIVENESS: The effectiveness of SIMBADOL was demonstrated
in two randomized, masked, placebo-controlled, multi-site field studies
involving client-owned cats of various breeds. A descriptive, interactive pain
assessment system was used by the trained assessor over the 72-hour
post-operative period to determine pain control, and treatment success was
defined as a cat that completed the 72-hour post-operative period without
rescue analgesia. A statistically significant difference (P ≤ 0.005) in the
number of successes in the treatment group over the placebo control
group was observed. The results of two field studies demonstrate that
SIMBADOL is effective and has an acceptable safety margin for the control
of postoperative pain in cats.
HOW SUPPLIED: SIMBADOL (buprenorphine injection) is supplied in a
carton containing one 10 mL amber glass vial. Each multidose vial contains
1.8 mg/mL of buprenorphine.
NADA 141-434, Approved by FDA
SIMBADOL is a trademark of Abbott Laboratories.
Manufactured for: Abbott Laboratories, North Chicago, IL 60064 USA
Product of United Kingdom
 Aims and Scope
The Journal of Feline Medicine and Surgery is an international journal, and the official journal of both the International Society
of Feline Medicine (veterinary division of International Cat Care – icatcare.org/vets) and the American Association of Feline
Practitioners (catvets.com). It is published monthly in two formats. The ‘classic’ editions (published in February, April, June,
August, October and December) contain high quality original papers on all aspects of feline medicine and surgery,
including relevant basic research. Manuscripts can be submitted as full papers, short communications, case series or letters to
the editor. The ‘clinical practice’ editions (published in January, March, May, July, September and November) primarily contain
commissioned opinionated review articles of direct relevance to feline clinical work, along with other relevant articles such as
consensus guidelines. Offers of reviews and topics for consideration should be directed to the editors, via the editorial office,
jfmsclinicalpractice@icatcare.org, for initial editorial approval. All submissions are subject to peer review by the editors and
selected referees. A society news section provides information about ISFM and AAFP activities.
An online, open access sister journal, Journal of Feline Medicine and Surgery Open Reports, publishes high quality case
reports and short case series presenting novel information, as well as short communications reporting valuable regional preva-
lence data or other relevant data related to well-recognised diseases of domestic cats. Further information at jfmsopenreports.com.

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00_JFM_17_9_TOC.indd 651 11/08/2015 4:28:11 PM

740_741_Editorial .qxp_FAB 10/08/2015 12:58 Page 740
Journal of Feline Medicine and Surgery (2015) 17, 740–741
EDITORIAL
Non-surgical fertility control: current and
future options for cat health and welfare
Fertility control One of the earliest Egyptian
goddesses, Bast (later Bastet),
is likely the is associated with both fertility
and childbirth. Bast is usually
greatest aid
depicted as a beautiful woman
in managing with the head of a domestic cat.
That symbolism is no surprise.
the health and Cats are known for their ability to
welfare of the reproduce in their first year of life
and to produce multiple litters
world’s pet a year. Like rabbits, they are one
of a limited number of species
cats, as well whose ovulation is typically
as feral cats. induced by mating, giving
them quite an advantage for
conception. Add their current
popularity as pets, and the
kind-heartedness of people who
feed homeless cats, and feline
population numbers can easily Bast, generally thought of as
careen out of control. the cat goddess, personified
the playfulness, grace,
For the individual cat, and at affection and cunning
the population level, fertility of a cat. Courtesy of Penn
control is likely the greatest aid in Museum, image 152022
managing the health and welfare
of the world’s pet cats, as well as feral cats
that live in a wilder, more independent state.
Currently, surgical sterilization is essentially
the sole tool in the fertility control toolbox
to achieve long-term (lifelong) control of
breeding. While it is a vital tool, it is also one
that, we believe, is unable to reach as widely
as needed to keep up with the fecund feline.
Furthermore, in many parts of the world
where population control is needed there
may not be trained veterinarians or resources
to be able to undertake surgical sterilization.
As a result, the non-profit Alliance for
Contraception in Cats & Dogs (ACC&D)
serves to advance methods of non-surgical
reproduction control to save the lives of more
cats, expand options for pet owners, and
improve the wellbeing of animals and
communities worldwide. Part of our role is
to increase awareness of and dialogue about
current initiatives, and help pave a pathway
to future products that meet the needs of
veterinary practitioners and the clients, both
human and feline, that they serve.
Given that, we are thrilled to partner
with the Journal of Feline Medicine and Surgery
740 JFMS CLINICAL PRACTICE
on this Special Issue. It is fitting
that this first-ever full issue of a
veterinary journal on this topic
should be the collaborative
publication of AAFP and ISFM,
the leading veterinary advocate
organizations for cats across the
world. We are most grateful to
Andy Sparkes, Claire Bessant and
Margaret Melling for their vision
and mentorship on this project.
The 10 articles in this issue are
authored by experts in the field
and are, for the most part, review
articles. Five cover specific
contraceptives used to date for
cats, or the limited array of
sterilants and contraceptives
being researched or used off-
label in cats in the past decade.
The emergence in 2008 of a
USD$25 million prize and up
to $50 million in grant funds
has spurred more research than
ever before, and in a number of
novel areas. A glimpse into that new work is
shared by the Director of Scientific Research
for the Found Animals Foundation, the
parent organization for this initiative: the
Michelson Prize & Grants in Reproductive
Biology.
The requirements involved for a drug or
vaccine affecting fertility to get regulatory
approval in the US or EU is the focus of
another article. It is an area that often
comes up in the discussion about ‘how long
will this take?’
Other articles in this Special Issue look at
the context for a future in which a simple
syringe could stand in for surgical tools
to prevent unwanted litters. Attitudes of
veterinarians, cat owners and breeders all
influence the ability of new research to
translate into tools for your practice.
Researchers from the UK, Sweden and
the USA collaborated to review studies of
attitudes toward sterilization surgery and
limited research on non-surgical options,
along with some new primary research on the
topic, and translate this into implications for
future products.
DOI: 10.1177/1098612X15594986
© The Author(s) 2015
740_741_Editorial .qxp_FAB 10/08/2015 12:58 Page 741

International Society of Feline Medicine (ISFM) is the veterinary
division of the charity International Cat Care, which
has been working to improve the health and welfare of cats
since 1958.
International Cat Care works for the benefit of cats in three
main ways:
< Through its veterinary activities
< Through its education and resources for cat owners
and cat carers
< By working to improve the lives of unowned cats
When it comes to working with unowned cats, International
Cat Care is active in a number of spheres, but dealing with the
problem of overpopulation of cats and unwanted cats is a major
global issue. Because cats are so efficient at
reproducing, unowned populations can
expand rapidly and this can bring with it
considerable problems, both in terms of
nuisance to humans and also welfare issues
for the cats if food and other resources
become restricted.
Wo r k i n g f o r t h e b e n e f i t o f c a t s
Controlling unowned cat populations is a major international
welfare challenge. International Cat Care has been active in
promoting and providing training resources for TNR
(trap–neuter–return) programmes, but in many parts of the
world this approach is inadequate or unachievable.
This is the reason why International Cat Care is passionate
about our partnership with the Alliance for Contraception in Cats
& Dogs. We support and promote the ACC&D’s aims of finding
long-term or permanent non-surgical approaches to controlling
feline reproduction as we recognise that this will be a vital means
of controlling feline reproduction in the future and will have an
enormous welfare impact. This Special Issue of JFMS, following
on from our joint pre-congress day in Porto, provides a state-of-
the-art overview of where we are, and a glimpse of where we may
get to in the (hopefully not too distant) future. These are exciting
times, and as we make significant advances
in this area it is ultimately cats that will
benefit.
Andy Sparkes, BVetMed PhD DipECVIM
MANZCVS MRCVS
Veterinary Director, iCatCare/ISFM

This Special A population biologist shares perspectives
on how computer modeling and ways to
Issue looks better ‘count cats’ can aid projects to control
the fertility of free-roaming cat populations.
at a future in In another article, an initiative to create new
which a simple visible methods to identify free-roaming cats
takes us on a journey to prepare for a time
syringe could when unowned, free-roaming and feral cats
can be treated in the field without the full
stand in for anesthesia necessary to tip the ear as a sign
surgical tools of sterility.
Practicing veterinarians are the respected
to prevent authority on issues related to cat health, and
unwanted can be leaders in tomorrow’s methods to
advance it. We hope that this Special Issue
litters. will provide you with a strong resource to
counsel your clients on today’s possibilities
for non-surgical fertility control, as well as to
play a leadership role as an early adopter of
upcoming technologies in this emerging field.
I’d like to thank the editorial committee
that worked hard on this issue: Valerie Benka,
MS MPP; Amy Fischer, PhD; Cynthia Mills,
DVM MPH; and Steve Zawistowski, PhD
CAAB; the 12 authors or co-authors, and the
20 expert reviewers. Their passion for this
topic and for feline health and welfare shows
in this publication and beyond.
We are pleased to have partnered with
ISFM on this very topic for a full day session
at the 2015 ISFM European Congress in Porto,
Portugal. Most authors in this Special Issue
also presented at the Congress. Access
the links to their recorded sessions at
http://icatcare.org/vets/videos to learn
more from the presenters at this ground-
breaking event.
Joyce Briggs, MS
President, ACC&D

Available online at jfms.com

Reprints and permission: sagepub.co.uk/journalsPermissions.nav
JFMS CLINICAL PRACTICE 741
JFMS-recordings-ad5.qxp_Layout 1 10/08/2015 11:44 Page 1

2015
European Congress

Feline fertility and population control

pre-congress day recordings
in collaboration with

Recordings of sessions
at the ground-breaking
pre-congress day on
feline fertility and
population control are
now freely available
to view at:

www.icatcare.org/vets/videos
743_752_Progestins_Romagnoli_with Fig 1.qxp_FAB 10/08/2015 13:01 Page 743

Journal of Feline Medicine and Surgery (2015) 17, 743–752

CLINICAL review

progestins to control
feline reproduction
Historical abuse of high doses and
potentially safe use of low doses
Stefano Romagnoli

Relevance: The high fertility rate of

Introduction
cats means that methods to control
feline reproduction are a requirement
The high fertility rate of cats, and the presence of large free-roaming cat
for cat breeders and pet owners,
populations in many countries, have made control of feline reproduc-
as well as for those involved in the
tion an object of debate in the Western world for the past several
management of feral cat populations.
decades. According to The American Society for the Prevention of
Progestins continue to be used to
Cruelty to Animals, an estimated 1.4 million cats are euthanized annu-
prevent queens from cycling, and also as
ally in US animal shelters alone.1 Surgery is currently the preferred
an adjunct or alternative to surgical sterilization
approach to small animal sterilization. Trap–neuter–return (TNR) pro-
within trap–neuter–return (TNR) programs.
grams have been effective at reducing the feline population size in many
Evidence base: A considerable body of
countries,2 particularly in select areas or island-type communities. An
information exists on megestrol acetate (MA) and
example is Venice, italy, where a TNR program was started in the early
medroxyprogesterone acetate (MPA), thanks to
1980s as a joint effort between the neighboring municipalities of Venice,
the many studies and case reports published
Cavallino-Treporti, Marcon and Quarto d’Altino. Since 2005, no further
in the scientific literature over the past 50 years
neutering has been done within Venice’s city limits, while cat neutering
documenting their clinical use in cats.
continues in the adjacent municipalities (C Guadagno, 2015, personal
Comparatively less is known about the use in cats
communication).
of more recent progestins such as levonorgestrel,
Where TNR programs are unsuccessful in urban areas, this may be
proligestone, delmadinone, chlormadinone and
due to the fact that cats are abandoned or spontaneously migrate
altrenogest.
into areas where TNR
Dosing, safety and efficacy: Based on a
is being performed,
Progestins are the only type of drug thereby reducing its
combination of dose, frequency and duration of
treatment, MA can be categorized into low (0.625
approved for temporary or reversible effects;3 in some
mg/kg/week for up to 30 weeks), medium (0.625
situations, these new
control of reproduction in cats. animals constitute up
mg/kg q24h for 1 week or q48h for up to 2 weeks)
and high (0.625 mg/kg q24h or q48h for several
to 21% of the popula-
weeks, or weekly for months or years) dosages.
tion.3 Furthermore,
Studies suggest that low dosages can be used
issues such as veteri-
relatively safely in cats, while higher dosages
nary infrastructure costs, availability of trained staff and volunteers,
increase the risk and severity of adverse reactions.
and high levels of stress that cats may experience during the trapping
Early work showing that an oral MPA dosage of
process have raised concerns and reduced the effectiveness of some
0.01 mg/kg administered q24h for 12 months
For these reasons, programs dedicated to funding research on non-
TNR programs.3,4
suppresses oestrus in queens effectively and safely
surgical approaches to feline contraception and sterilization have been
has not been considered, and much higher MPA
developed. Through such programs several interesting new sterilants
dosages (>6.25 mg/kg q24h) have been used in
based on mechanisms such as gene silencing, immunocontraception
cats over the past 40 years.
and targeted delivery of cytotoxins are being researched (see accompa-
Recommendations: Progestins should always
nying article in this Special Issue).5
be used with caution. Using the lowest possible
dosages, MA and MPA may, however, continue
to be used safely in pet queens as well as (in
conjunction with TNR programs) for the control of
feral cat colonies. More recent progestins appear to
Stefano Romagnoli
DVM MS PhD Dipl ECAR be effective and safe, albeit their efficacy and safety
Professor, Department of Animal need to be further investigated.
Medicine, Production and Health,
University of Padova, Italy

Email: stefano.romagnoli@unipd.it

doi: 10.1177/1098612X15594987
© The Author(s) 2015 JFMS CLINICAL PRACTICE 743
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R E V I E W / Progestins for fertility control in cats

widely used in cats over the past four decades

and for which a wealth of information exists
on pharmacology, safety, effective dosages and
Alliance for Contraception in Cats & Dogs

risk of side effects. Indeed, for these two drugs,

This article is part of a Special Issue of the Journal of Feline Medicine and

it appears that initial work demonstrating

Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline

their relative safety has been overlooked while

fertility control’ and coordinated by the Alliance for Contraception in Cats

a great deal of attention has focused on case

& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of

reports documenting side effects that were, in

non-surgical fertility control to save the lives of cats and dogs, expand

fact, caused by improper use.

options for pet owners, and improve animal welfare. Serving as a trusted

As a result, many feline veterinarians are

resource for scientific and educational

reluctant to (or never) use progestins in their

information, the ACC&D brings together key

female patients,6 which is unfortunate as prog-

stakeholders to advance humane sterilization

estins are the only type of drug approved for

options that are faster, easier and more

temporary or reversible control of reproduc-

accessible than surgery.

tion in cats. If their use is discouraged and

queens cannot be prevented from cycling,
More information is available at www.acc-d.org

many more pharmacological abortions or

While waiting for the perfect, single-shot
sterilant, medical contraceptive methods using
progestins (progestogens) may serve as an
important adjunct or alternative to surgical
sterilization through TNR programs.
Furthermore, progestins can be the appropriate
(and only) answer for some types of reproduc-
tive presenting complaints in domestic queens.
From a breeder’s perspective, achieving a
short-term, reversible block of a queen’s fertility
can be of the utmost importance. Most
kitten euthanasias will be performed, which
clearly is not in the interest of cat welfare. The
following discussion reviews the literature on
dosages of all progestins marketed as veteri-
nary drugs to control feline reproduction, with
a particular focus on MA and MPA. It docu-
ments historical use of these drugs and makes
the case that, at appropriate doses, they can be
considered relatively safe for use in cats.
Clinical use of progestins in cats

European cat fancy clubs do not allow more

than a certain number of litters in a defined
Progestins are synthetic derivatives of proges-

period of time (normally no more than three

terone that bind to the progesterone receptor

litters in 2 years). Therefore, a breeder needs to

on target organs, producing the same biologi-

avoid any risk of their breeding queens becom-

cal effect as endogenous progesterone but

ing pregnant for at least 6–9 months every 2

with a much higher potency. These com-

years. While this should not be a problem for

pounds are commonly used to control the

breeding catteries that do not house tom cats,

reproductive cycle of female domestic animals

this does not necessarily negate the require-

and achieve their main contraceptive effect by

ment for reproduction control. Queens normal-

suppressing clinical manifestations of oestrus

ly vocalize continuously and eat less when in

as well as preventing ovulation. in bitches,

season, and as a result lose condition and devel-

progestins effectively suppress the ovulatory

op a rough coat, compromising their chance of

process by altering ovarian secretion of

success in the judging ring at cat shows. For

oestradiol, inhibin and/or activin, resulting in

such reasons veterinarians are frequently asked

insufficient stimulation of the pituitary and no

to administer reproduction control drugs to

preovulatory peak of follicle-stimulating hor-

breeding queens.
mone and luteinizing hormone.7,8 Although

Progestins such as megestrol acetate (MA)

not as well defined in cats, the similarity of

and medroxyprogesterone acetate (MPA) have

clinical outcome in queens treated with prog-

long been used in cats to control reproduction,

estins strongly indicates that the mechanism

while less clinical information is available for All progestins administered to queens clear-
of action in cats is the same as in bitches.

other, more recent compounds such as levon -
orgestrel, proligestone, delmadinone, chlor-
madinone or altrenogest. In ‘the field’ these
compounds generally suffer a widespread rep-
utation of posing risks and serious side effects
from a reproductive as well as a general health
standpoint. However, such a reputation is
unjustified as all side effects appear to have
been associated with excessively high dosing
or inappropriate patient selection for treat-
ment. This is particularly true for MA and
MPA, the two drugs that have been more
ly suppress oestrus signs. The effect is short-
lived in the case of MA9,10 and of variable
duration for all other progestins tested in cats,
including MPA, proligestone, chlormadinone
acetate, delmadinone acetate, levonorgestrel
and altrenogest.11–14
Progestins produce the same biological
effect as endogenous progesterone,
but have a much higher potency.

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R E V I E W / Progestins for fertility control in cats

Megestrol acetate (FdA) approved veterinary drug for female

MA (6-methyl-6-dehydro-17α-acetoxyproges-
terone) is a potent progestin with an activity
estimated to be several times greater than that
of endogenous progesterone,15 and with a 75%
and 37% affinity for the androgen and gluco-
corticoid receptors, respectively.16 With a half-
life of a few hours, MA is the shortest acting
progestin available on the veterinary market
and, in fact, the only product that can justifi-
ably be labelled as ‘short acting’. it is currently
commercially available as an oral formulation
(pills or syrup) in many European countries
including the UK, the Netherlands, Belgium,
France, Switzerland and italy.
dogs (ovaban; intervet Schering-Plough); off-
label use in cats was common.17 An extralabel
formulation of MA (FeralStat) was also devel-
oped in North America for use in cats and pri-
vately marketed from 2008 by a veterinarian
(dr John Caltabiano) outside of regulatory
oversight.4 FeralStat was popular with some
American cat colony managers, although no
scientific data exist on this particular prod-
uct’s efficacy and safety in cats. By 2011, after
the passing of dr Caltabiano, FeralStat orders
were no longer being fulfilled. Since then,
compounding pharmacies have been selling
MA to feral cat colony managers with a veteri-

MA dosages can be categorized into low,

Launched in 1975 and continuing for sever- nary prescription.

medium and high (see box), based on a

al decades, MA was commercially available in
the USA as a Food and drug Administration

Dosing of MA
Low dosage Intermediate dosage
Despite its short half-life, MA has proven to be quite helpful When a >0.625 mg/kg dosage is administered q24h for 1 week or
for controlling reproduction in queens, both for oestrus q48h for up to 2 weeks, short-term reversible side effects such
suppression as well as for temporary or prolonged oestrus as adrenocortical suppression20,21 and temporary impairment of
postponement. glucose metabolism leading to diabetes mellitus22–26 have been
Early work reported the efficacy of MA for prolonged oestrus reported in cats. Such a dosage could be defined as ‘intermedi-
postponement in cats using ‘low’ doses of 2.5 mg/week ate’. Intermediate dosage regimens (0.625 mg/kg q24h for
(approximately 0.625 mg/kg/week for a 4 kg cat) for up to 30 1 week or q48h for up to 2 weeks) have been used with relative
weeks.10 Side effects in the 244 queens of this study were: safety in the past for non-reproductive (dermatological or behav-
one case of pyometra and mammary adenocarcinoma in a ioral) indications.27–31 Not all cats develop diabetic and/or
queen that had received MA for a total duration of 3 years adrenocortical side effects; and, even when such effects occur,
(and with a 5.0 mg/week dose for the first 2 years); increased they normally disappear once treatment is discontinued due to
appetite in 33.6% of queens; and increased body weight in the short action of MA. Use of MA for these non-reproductive
13% of queens.10 In a separate study, a dosage conditions has become less common recently
of 5.0 mg q24h for 3 days was used to suppress due to availability of other, superior classes of
heat and then followed by a prolonged (10
Research strongly drugs for these (particularly dermatological)
weeks) postponement with the 2.5 mg weekly suggests that indications.
dosage in 126 queens.9 Short-lived side effects
were observed in a total of 18 queens and higher dosages of High dosage
included weight gain (n = 5 cats), diarrhea Intermediate dosage regimens administered for
(n = 2), listlessness (n = 3), urine odor (n = 3),
MA increase the prolonged periods of time (q24h or q48h for
temperament change (n = 2), mammary enlarge- risk and severity several weeks, or weekly for months or years)
ment (n = 2) and hair color change (n = 1).9 can lead to the development of mammary gland
A contraceptive effect of MA in cats has also of adverse lesions (hyperplasia, benign and malignant nod-
been reported in a study in which queens in ules) in queens and tom cats,32–39 and uterine
reactions.
oestrus were treated over 15 cycles with 2.0 or lesions (cystic endometrial hyperplasia, pyo-
3.0 mg/kg MA on the second day of heat, then metra, adenomyosis),40–49 as well as more severe
18
were mated on the third day; none of them conceived. Similar and longer lasting endocrine (diabetes and adrenocortical
results were reported by Jöchle and Jöchle using a single dose suppression) side effects.50–52 Cutaneous xanthomatosis and
of 5.0 mg MA 24 h after mating.19 Given these contraceptive blindness due to hyperlipidemia causing opacity of the anterior
properties of MA, it is probably unnecessary to use a 5.0 mg chamber have also been reported.53,54 MA-induced diabetic con-
q24h dosage for a few days prior to starting a queen on a ditions may be characterized by retinopathy and retinal detach-
2.5 mg/week protocol. ment.51 All published cases of side effects due to MA in cats were
The 2.5 mg weekly protocol of MA9 can be considered associated with use of high dosages (0.625–1.25 mg/kg q24h or
relatively safe for cats. In fact, the product insert for MA-based 2.5–5.0 mg/kg weekly for 1 or more years). Such high doses
formulations marketed in most European countries lists 2.5 should definitely be avoided, as endocrine, uterine and mammary
mg/week for a maximum of 30 weeks as a suggested dosage side effects appear more rapidly, develop to a greater severity
regimen (www.virbac.co.uk). and may be irreversible.

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R E V I E W / Progestins for fertility control in cats
Further studies are required to establish
the efficacy and safety of prolonged use of
very low doses of MA in cats.
combination of the dose given in a single
treatment, the frequency and the duration of
treatment. Research strongly suggests that
higher dosages increase the risk and severity
of adverse reactions.
Treatment protocols using dosages of MA
lower than the ‘low’ dosage of 0.625
mg/kg/week may be effective in controlling
oestrus activity and ovulation in cats. The
dosage of FeralStat was 0.1–0.2 mg/kg/week,4
corresponding to a dosage of 0.014–0.028
mg/kg q24h. Another non-FDA-approved oral
formulation of MA anecdotally reported as
being effective for reproductive control in
feral cat colonies has a suggested dosage of
5.0 mg/week for groups of five to seven cats,
which corresponds (for groups of 4 kg cats)
to 0.7–1.0 mg/cat/week or 0.18–0.25 mg/kg/
week or 0.025–0.035 mg/kg q24h (www.birth-
controlforcats). An Italian oral formulation of
MA (Estropill; MSD) is administered to cats
at a dosage of 0.011 mg/kg q24h and has
recently been used by the author successfully
to control oestrus in queens (unpublished
data).
Further studies are required to establish the
efficacy and safety of very low (0.01–0.03
mg/kg q24h) doses of MA administered to
cats for prolonged periods of time.
Medroxyprogesterone acetate
MPA (17α-hydroxy-6α-methylprogesterone
acetate) is a synthetic derivative of proges-
terone that is also more potent than proges-
terone.55 MPA also acts as an agonist of the
androgen and glucocorticoid receptors,
although its affinity for the androgen and
glucocorticoid receptors is much lower than
that of MA.56 its half-life is 12–17 h following
an oral dose and 40–50 days following an
intramuscular (iM) dose. it has long been
available as a veterinary drug in Europe with
an indication for use in cats, and it is still
available in several countries including
Austria, Germany, the Netherlands, Belgium,
Luxembourg, Sweden, Norway, Spain,
In one of the first scientific studies on the
Portugal and italy.
use of MPA in cats, oestrus was suppressed
using oral doses of 0.05 and 0.01 mg/kg
administered q24h for 12 months to two
groups of six queens, respectively.57 Only one
case of breakthrough heat occurred after
7 months of treatment in the 0.01 mg/kg
746 JFMS CLINICAL PRACTICE
group, while the 0.05 mg/kg dose showed
100% efficacy, with no oestrus reported in
treated queens. All queens from the latter
group were in good health throughout the
study, came back in heat at the end of the
study and queened 83–184 days following
discontinuation of the treatment. According to
the authors, ‘… many of the kittens of these
first litters were stillborn or small and weak;
however, succeeding litters were normal.’57
The results of this study point to a negative
effect of prolonged treatment with a 0.05
mg/kg q24h dosage of MPA on fertility at the
first post-treatment heat in queens. However,
long-term fertility of treated queens was not
altered. Also, although general and mammary
health, as well as haematology and biochem-
istry, were not assessed, one could speculate
that MPA did not cause major health prob-
lems in these queens based on the fact that,
firstly, they all queened normal litters later on
and, secondly, negative effects of MPA on the
uterus, mammary glands, glucose tolerance
and general health have only been reported
using dosages >100 times higher than those
used in this study.57
Unfortunately, there is almost no trace of
this publication in the subsequent MPA-relat-
ed scientific literature. In 1965, a study by
Colton58 investigating either an oral dosage of
5.0 mg/cat q24h (12.5 mg/kg q24h for a 4 kg
cat) for 3–5 days or a single subcutaneous
injection of 25–100 mg (equivalent to 6.25–25
mg/kg in a 4 kg cat) suggested both as being
effective treatments to achieve oestrus
suppression of at least 2–4 months.58 Two
subsequent case reports described the occur-
rence of mammary hyperplasia in a queen
treated with a single 50 mg MPA injection59
and mammary tumors in five queens treated
with 25–50 mg/cat every 3–4 months for sever-
al years.60
Despite these two case reports pointing to
an evident risk of high doses of MPA, all
authors of reviews and book chapters pub-
lished over the following 20 years continued
to advise prolonged oestrus suppression in
queens with MPA using a single parenteral
injection of 25–100 mg to be repeated every
4–6 months, sometimes even preceded by a
5 day course of 5.0 mg/day if the queen was in
heat at the beginning of the treatment.61–64
The same high-dosage protocols (25–100 mg
parenteral injections every 4–6 months, some-
times with an initial 5 day oral treatment) are
reported in later reviews during the 1990s,65–67
as well as in more recent publications.68–72
Admittedly, side effects of MPA in cats are
always carefully described; however, no dis-
cussion on MPA dosages can be found, some-
times dosages are generically reported (if at
all) and readers are simply warned about the
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R E V I E W / Progestins for fertility control in cats

Extrapolation from the many side effects of
high doses of MA has led some authors to state
that MPA is not recommended for use in cats.
However, if used judiciously, MPA may be
helpful in feline practice.
Other progestins
Although MA and MPA have been used most
widely in cats, other progestins tested with
some degree of success for reproductive
control in cats include levonorgestrel, chlor-
madinone acetate, delmadinone acetate,
proligestone and altrenogest.
< Levonorgestrel (LEV) is frequently used
as a component of combined hormonal
contraceptives in humans. When administered

risk of side effects, with no mention of a dis-

for 12 months as a 16–36 mg subdermal slow

tinction between a high risk of side effects

release implant in queens, LEV suppressed

with high dosing and low or no risk with low

reproductive activity without any relevant side

dosing.
effects on the mammary glands, body weight,

Interestingly, the aforementioned two case

and glucose or adrenocortical metabo-

reports on MPA side effects in queens59,60 are

lism.13,78,79 Cessation of ovarian activity is quite

almost never cited in the subsequent litera-

rapid following placement of the implant,

ture, which means that the MPA side effects in

although there is often no effect on the oestrous

cats referred to in publications until the early

cycle that starts before treatment.79 one study

2000s were either assumed to be similar to

demonstrated normal fertility following

those caused by another progestin, MA (again

cessation of treatment in the majority of treated

used at much higher doses than normal), or

queens (3/4 queens exhibited estrus and

assumed to be similar to the side effects of

conceived within 54 days following implant

MPA in the bitch. One might speculate that

removal), although endometrial hyperplasia

mammary, uterine and endocrine side effects

was observed and fluid accumulation occurred

in cats may be similar for all progestins,

in one case, suggesting the development of

and/or that side effects may be similar across

pyometra.13
< Chlormadinone acetate (CMA) adminis-
the canine and feline species. However, unlike
MA, there is a lack of reports on diabetogenic
tered for 1 year either in oral weekly doses of

side effects in cats treated with even very high

2.0–12.5 mg in 28 queens,12 or as 2.5, 5.0 or 20

doses of MPA. This may be due to the lower

mg/kg implants in 13 queens,80,81 suppressed

affinity of MPA for the glucocorticoid receptor

oestrus signs for the duration with only an

when compared with MA,56 and it shows that

increase in body weight for the oral treatment12

extrapolating between drugs and across

or endometrial hyperplasia with mild uterine

species is not always appropriate.

fluid accumulation with the 20 mg/kg

Extrapolation has led some authors to state

implant.81 When the 2.0 mg CMA dose was

that MPA is not recommended for use in

administered weekly for several years, there

cats,73 based on the many side effects of high

were no clinical signs of abnormality for 4.6

doses of MA in cats. Such unsubstantiated

years in 24 queens except for the increase in

claims have been subsequently cited,69,72 con-

body weight.81 in a longitudinal study involving

tributing to the negative reputation of MPA

24 queens, 19, 16 and four cats were treated for

among feline practitioners.

6, 8 and 10 years, respectively.82 Mammary

As with many other drugs, MPA should be

nodules and vaginal discharge or pyometra

used with caution and only in healthy

were recorded in 11% of cats treated for 6 years,

animals. However, if used judiciously, it

38% of cats treated for 8 years, and 25% of cats

may be helpful in feline practice. Case reports

treated for 10 years.82
< Delmadinone acetate (DMA) administered
documenting side effects of MPA in cats due
to overdosing clearly indicate that the mam-
as a single oral dose (2.5 mg) is reportedly

mary gland is the first target organ to suf-

effective as a contraceptive when given once

fer,59,60,74–77 while glucose or mineralocorticoid

24 h after the onset of heat.19 The same study

metabolism derangements have never been

found a single dose of 5.0 mg CMA likewise to

reported in cats following the use of high

be effective.
< Proligestone (PRG) has been marketed since
MPA dosages. Thus, MPA and MA seem to be
characterized by a different range of side
the 1990s in many European countries as a

effects, and this might be important when

veterinary drug with an indication for use in

deciding upon a treatment. Provision of com-

cats, at a dosage of 100 mg/cat (or 25–30

plete and accurate information on the safety

mg/kg) to be repeated every 5 months. in

of MPA could allow veterinarians to imple-

comparison with other progestins, PRG is

ment appropriate control of reproduction in

claimed to be as effective for the control of

queens in countries in which MPA is the only

oestrus (ie, on the hypothalamic–pituitary–

available progestin.
gonadal axis) but less active on the reproductive
system (uterus and mammary glands) in

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R E V I E W / Progestins for fertility control in cats

queens.11 in a study comparing the efficacy of

30 mg/kg PRG with 25 mg/cat MA in two
Queens to be treated with progestins
groups of 15 queens, a duration of efficacy of should be healthy and in post-estrus or anestrus
approximately 8 months was reported for PRG
vs 3–5 months for MA.83 No mammary or (not oestrus or diestrus).
uterine side effects were observed in the queens
in the PRG group, while no mammary disease
but two cases of pyometra were observed in Considerations for safe use
the queens in the MA group.83 However, the of progestins in cats
treatment protocol included for both drugs the
induction of ovulation with gonadotropin- Several factors must be taken into account to
releasing hormone (GnRH) when queens were optimize the likelihood of safe use of prog-
in heat. Although induction of ovulation should estins in queens, as reviewed below.
not be performed prior to administration of a

Queens to be treated with progestins should

progestin (as the occurrence of diestrus will Client-owned cats

be healthy and in post-estrus or anestrus (not

cause overdosing), these results suggest that

oestrus or diestrus). This requires a careful

PRG may stimulate the feline mammary gland

When compared with MA in an acute evaluation.

to a lower degree than MA.

toxicity study, PRG had fewer effects on

adrenocorticotropic hormone (ACTH) and
blood glycaemia, and no effect on insulin
Evaluation of queens prior to progestin treatment
levels.84 In a single-cat case report, a 7-month-
< Collect a detailed history
old Maine Coon queen weighing 4.2 kg devel-
< Perform a careful clinical examination
oped benign mammary hyperplasia 2 months
< Take a vaginal smear (to rule out oestrus)
after being treated with a fairly low dose of
< Palpate the mammary glands (to rule out presence of masses)
0.75 ml (17.8 mg/kg) PRG.85 Also, a case of
< Palpate the abdomen (to rule out abnormal uterine size)
calcinosis circumscripta has been reported in
another single-cat case report describing a
Ideally, evaluation would also include performing a uterine ultrasound

9-month-old Burmese queen treated with

examination (to confirm normality of uterine size and echotexture)

100 mg PRG to suppress oestrus 4 months

and assaying serum progesterone (P4) to rule out diestrus (as adding

previously.86 Calcinosis circumscripta has

exogenous to endogenous P4 would be equivalent to administering

been reported in the bitch following the use of

a high dosage).

MPA.87,88
Although the above studies and case reports
point to a similarity in the range of side effects
between PRG and other progestins, currently
available information on uterine and endocrine
side effects of PRG in cats could indicate a
lower affinity of PRG for the uterus and for
glucose and adrenal metabolism in cats.
< Altrenogest (ALG) has been used at an oral
dose of 0.044, 0.088 and 0.352 mg/kg for
Sadly, the package insert of several prog-
estin drugs marketed in Europe for small
animal use, including queens, still reports
diestrus as being one of the reproductive cycle
stages in which progestin treatment may be
initiated. Assaying P4 is costly and involves
drawing a blood sample. Consequently, a P4
assay is often not advised prior to administer-
ing progestins on the assumption that queens
cannot be in diestrus if not bred. However,

research has found that 35–87% of queens

38 days in groups of five, five and six queens,

may ovulate spontaneously.79,89,90 Therefore,

respectively.14 All three doses investigated in

when considering progestin treatment the

this study were effective in suppressing and

possibility of a queen being in diestrus should

controlling heat, although queens with

not be underestimated.
elevated estrogen concentrations at the

Use of progestins in male cats is not advised

beginning of treatment completed their heat

for the following reasons:

before entering a drug-induced anestrus.14

< Lack of efficacy for reproductive

Post-treatment follicular activity resumed

indications (post-castration urine marking

soon after the end of the study, and in a

or aggressiveness can only be solved

fairly synchronous way (within 10–16 days)

temporarily with progestins and should be

for the 0.088 mg/kg treatment. There were

addressed from a behavioral perspective);

no side effects in treated queens.14 Beyond

< Lack of efficacy for dermatological

this single study, little is known about the

presentations;91
safety of ALG use in queens, although the

< Risk of mammary hypertrophy;33,37,39

compound seems effective for the control of

Further studies are necessary to assess the < Males are at a significantly higher risk
reproduction.

safety and efficacy of prolonged use of LEV, of developing a diabetic condition when
CMA, DMA, PRG and ALG in queens. treated with MA compared with females.92

748 JFMS CLINICAL PRACTICE

743_752_Progestins_Romagnoli_with Fig 1.qxp_FAB 10/08/2015 13:02 Page 749

R E V I E W / Progestins for fertility control in cats

Feral cat colonies

While the above precautions can and should
be adopted when treating client-owned
animals, a ‘population level’ or ‘herd health’
approach may be warranted when using a
progestin in colonies of feral cats (Figure 1).
When the history of a patient is not avail-
able, or when clinical examination or any fur-
ther testing cannot be performed for practical
or financial reasons, clinicians must be guided
by the ethical principle of doing the least harm
to each individual cat while ensuring the
maximum possible level of health for the
entire colony. on this basis, a low dose treat-
ment of MA or MPA may have potential to be
employed in feral cat colonies in conjunction
with a TNR program to prevent pregnancies
Practical use of progestins
Both MA and MPA can probably
be used safely in cats provided that
the lowest possible dosage is
employed. Research to date sug-
gests that MA at 0.02 mg/kg q24h
and MPA at 0.05 mg/kg q24h seem
to be appropriate dosages to be
administered orally, both in feral cat
colonies (in conjunction with a TNR
program) as well as in pet cats. MA
has the advantage of a short half-life
and is supported by a much greater
body of information on efficacy and
side effects in cats, making it an
appropriate drug for this use in cats,
(perhaps <5 months), although this
should be offset by a higher degree
of safety in treated queens.
Doses >2.5 mg/kg MPA should be
avoided in breeding cats, and cer-
tainly injectable doses in the range
of 3.0–10 mg/kg or higher may
pose serious health risks for all
cats59,60,74–77 and should definitely
not be used. There is no scientific
information on what is a safe length
of progestin treatment using low
doses of MPA. The choice probably
depends on health conditions: a
healthy young adult queen can prob-

The use of reproductive control drugs in

in animals waiting to be spayed. although further investigations are ably be treated safely with a low

feral cat colonies remains highly controver-

warranted. While not enough infor- dose of MPA for longer than 1 year,

sial. Issues such as environmental fate (inges-

mation is available on long-term use while an adult female is more likely

tion of baits by non-target species, including

of injectable formulations of MPA in to have undergone age-related

humans), human safety (progestins are

queens, dosages of 2.0–2.5 mg/kg changes of the uterus and/or mam-

absorbed through intact skin), stability (shelf-

IM every 5 months95–97 or as low as mary gland and therefore should

life in the intended packaging before and after

3.0 mg/cat (equivalent to 0.75 mg/kg probably not be treated for longer

being opened), food interaction, dose accura-

in a 4 kg cat)98 are effective and like- than 1 year. Also, it should be kept in

cy and use as a prescription-only medication

ly to be devoid of any long-term mind that (high doses of) progestins

(a bait-based drug may have to be prescribed

health risks, although it is possible in cats significantly increase the risk

by a veterinarian who would not themselves

that lower doses could be effective of mammary carcinoma and benign

be administering it) raise more concern than

as well. It should be kept in mind tumors if given regularly, but there is

target animal safety (which could actually be

that a lower dose might be associat- evidence of no such increase in risk

acceptable when using ‘very low’ doses of MA

ed with an earlier return to oestrus if the use is not regular.99

or MPA).
Nonetheless, when using a bait system there
is the potential for overdosing as well as inad-
vertent treatment of prepubertal or mature
males, and prepubertal or pregnant females,
which may cause side effects (ie, mammary
hyperplasia in male and female cats).
However, in queens, mammary hyperplasia
occurs (sporadically) only at the first luteal
Figure 1 Potentially, low-
same queen. Thus, when mammary hypertro-
phy occurs in a young queen following use of
a progestin, one might argue that it would
have occurred anyway in that individual
queen at her first ovulation. The specific risks
with regard to tom cats have been discussed

phase; there are no case reports of this above. However, it is worth noting that the
dose progestins may be a

condition occurring more than once in the risks for diabetes and mammary hypertrophy
useful adjunct to TNR in the
control of free-roaming or

in males have been reported following use of

feral cats, by preventing

high dosages; therefore, from a feral cat per-

pregnancies in animals
waiting to be spayed.

spective, the use of progestins (particularly

Courtesy of Valerie Benka/

MA) at very low dosages is probably less

ACC&D

dangerous.
In countries of the European Union a pre-
prepared progestin-based bait for use in feral
cats would represent an entirely new product,
even if the active pharmaceutical agent was a
well known one. Because of all the above con-
cerns there is no guarantee that a competent
authority would accept the risk/benefit analy-
sis that is necessary for the registration
dossier, particularly on the grounds of
environmental93 and human94 safety. For these
reasons, interest among drug companies to
invest in a reproductive control bait-type drug
for feral cats in Europe is realistically likely to
be minimal at this time.

JFMS CLINICAL PRACTICE 749

743_752_Progestins_Romagnoli_with Fig 1.qxp_FAB 10/08/2015 13:02 Page 750

R E V I E W / Progestins for fertility control in cats

KEY points
< Further studies are needed to establish the longest possible treatment with progestins
(MA or MPA) that is free of side effects, incorporating information on haematobiochemical
as well as uterine ultrasonographic changes in queens on long-term progestin treatment.
< Most importantly, there is a need to change our approach to the use of progestins
in queens (and bitches alike) and clarify best protocols when using a progestin.
< Too many queens have been treated with excessively high doses of progestins,
and many more are at risk because of inaccurate or incomplete information
on their use that persists around the world.

Adenohypophysial function in bitches treated with

ISFM CONGRESS RECORDING
A recording of Stefano Romagnoli’s session
on progestins for feline fertility control,
presented at the 2015 ISFM Congress in Porto,
is available at:
http://icatcare.org/vets/videos
It is also included as
Supplementary material at: jfms.com
DOI: 10.1177/1098612X15594987
Funding
The author received no specific grant from any funding agency in
the public, commercial or not-for-profit sectors for the prepara-
tion of this article.
Conflict of interest
The author has no conflict of interest to declare.
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98 Sarchahi AA, Emadi M and Azarpeykan S. Effects of three
steroidal compounds on oestrus suppression in queens.
Iran J Vet Res 2008; 9: 144–149.
99 Misdorp W, Romijn A and Hart AAM. Feline mammary
tumors: a case-control study of hormonal factors. Anticancer
Res 1991; 11: 1793–1797.
Reprints and permission: sagepub.co.uk/journalsPermissions.nav
Title photograph on page 743 ©iStockphoto.com/toxawww
For reuse of Figure 1, contact the author
753_757_Melatonin_Kutzler.qxp_FAB 10/08/2015 13:08 Page 753
Journal of Feline Medicine and Surgery (2015) 17, 753–757
AlternAtive methods for
feline fertility control
Use of melatonin to suppress
reproduction
Michelle A Kutzler
Melatonin – the rationale
Reversible contraceptives are highly desired by purebred cat breeders for
managing estrous cycles and by scientists managing assisted reproduc-
tion programs. Artificial insemination (Ai) has significant potential for
improving the ex situ management and conservation of wild felid popu-
lations.1 Suppressing endogenous ovarian activity before Ai or in vitro
fertilization/embryo transfer improves pregnancy rates in the domestic
cat.2 Short-term pharmacologic control of the feline estrous cycle is most
commonly accomplished using progestins despite potential undesirable
side effects associated with high doses of these compounds (eg, cystic
endometrial hyperplasia–pyometra complex, mammary fibroadeno-
matosis, mammary neoplasia, hyperglycemia–glucosuria syndrome due
to insulin resistance).3 As the interestrus interval in unmated cycling
queens is 9.0 ± 7.6
As the interestrus interval in unmated days during the breed-
ing season,4,5 adminis-
cycling queens is 9.0 ± 7.6 days during tration of exogenous
melatonin to suppress
the breeding season, administration of ovarian activity is an
exogenous melatonin to suppress attractive option.
Melatonin (5-
ovarian activity is an attractive option. methoxy-N-acetyl-
tryptamine) is a Challenges: The therapeutic use of melatonin is
tryptophan-derived
neurohormone pro-
duced by the pineal gland in a circadian rhythm of secretion, with
greater concentrations during darkness.6 The pineal gland is a neural
organ with multifunctional significance in modulating endocrine control
and synchronizing physiologic functions with internal and external con-
ditions.7 Melatonin exerts its action through two membrane-associated
(high affinity G-protein coupled) receptors (MT1 and MT2),8 which are
present in neuronal and non-neuronal tissues.9 Within the brain, MT1
and MT2 receptors are located in the suprachiasmatic nucleus (the
‘central clock’), which is responsible for the effect of melatonin on circa-
dian rhythms.10–12 in the cat, rhythms for both arginine vasopressin and
melatonin are endogenously generated within the suprachiasmatic
nucleus and entrained by the light–dark cycle.13
Michelle A Kutzler
DVM PhD DACT
Associate Professor of Companion Animal Industries,
Department of Animal and Rangeland Sciences,
Oregon State University,
Corvallis, Oregon, USA
Email: Michelle.Kutzler@oregonstate.edu
doi: 10.1177/1098612X15594988
© The Author(s) 2015
CLINICAL review
Practical relevance: Reversible
contraceptives are highly desired by
purebred cat breeders for managing
estrous cycles and by scientists
managing assisted reproduction
programs. A variety of alternative
medicine approaches have been explored
as methods to control feline fertility.
Scope: In the field of veterinary homeopathy,
wild carrot seed and papaya have been used
for centuries. Both appear to be safe, but their
efficacy as feline contraceptives remains anecdotal.
In contrast, the use of melatonin in cats has been
investigated in a number of studies, findings from
which are reviewed in this article.
Rationale: Cats are seasonally polyestrous (they
cycle several times during their breeding season)
and are described as long-day breeders because
endogenous melatonin negatively regulates estrous
cyclicity. Exogenous melatonin administered
parenterally also suppresses ovarian activity in cats,
and long-term oral or subcutaneous melatonin
administration is safe.
limited by its short biological half-life (15–20 mins),
its poor oral bioavailability and its central effects
in reducing wakefulness. Research is required to
determine whether higher doses, longer-release
formulations, repeated administration or combination
implants might overcome these limitations.
ISFM CONGRESS RECORDING
A recording of Michelle Kutzler’s session on
intratesticular sterilants and alternative
methods for feline fertility control, presented at
the 2015 ISFM Congress in Porto, is available at:
http://icatcare.org/vets/videos
It is also included as
Supplementary material at: jfms.com
DOI: 10.1177/1098612X15594988
JFMS CLINICAL PRACTICE 753
753_757_Melatonin_Kutzler.qxp_FAB 10/08/2015 13:08 Page 754

R E V I E W / Use of melatonin to suppress feline reproduction

Cats cease estrous cyclicity immediately when
the photoperiod is reduced from 14 h to 8 h.
The role of the pineal gland and melatonin
in mammalian physiology has been previous-
ly reviewed.14 While the effects of melatonin
in other species are beyond the scope of this
current review, melatonin has been extensive-
ly studied in other seasonal species for estrous
cycle control.15
The domestic cat is a seasonal long-day
breeder, meaning that reproductive activity is
influenced by photoperiod. in the northern
hemisphere, ovarian activity typically ceases
in october under decreasing photoperiod and
resumes in January with increasing photo-
period.16 Reducing the photoperiod to 8 h of
light inhibits folliculogenesis in queens.17 Cats
cease estrous cyclicity immediately when the
photoperiod is reduced from 14 h to 8 h, and
estrous cycles resume in 12–26 days (15.6 ± 0.5
days) after the photoperiod is increased from
8 h to 14 h.17,18 The immediate suppressive
effects of melatonin on follicular growth may
be mediated through a cytoplasmic receptor,19
which could directly interfere with estrogen
Melatonin – the evidence base
decreasing photoperiod is related to high
endogenous melatonin concentrations, which
are then followed by decreased sexual activity.
Exogenous melatonin can be used to mimic
this situation. Either oral or parenteral admin-
istration of exogenous melatonin or melatonin
receptor agonists will suppress feline repro-
ductive function. The dose, frequency and
route of administration as well as the repro-
ductive outcome determined by melatonin
research in cats are summarized in Table 1.
Pharmacokinetics and pharmacodynamics
< Exogenous melatonin administered parenterally suppresses
ovarian activity in the domestic cat maintained under a 24 h light
photoperiod.20
< Following a single intravenous injection of 1 mg melatonin, the half-life
is <5 mins.20
< Serum melatonin concentrations peak approximately 1 h after a
single oral dose of 30 mg melatonin and remain elevated above
endogenous daytime concentrations for >8 h.2
< Mean ± SEM circulating half-life and elimination rate of oral melatonin
are 45.4 ± 3.5 mins and 55.2 ± 4.2 mins, respectively.2

Oral melatonin treatment (30 mg q24h for 30

synthesis. Melatonin has also been shown in Oral treatment

days) prior to an estrus induction protocol for

one study to decrease the amount of luteiniz-

AI only marginally reduced ancillary follicle

ing hormone (LH) released in response to

development.2 The authors speculated that a

mating.20 However, 67% of cats followed in
the study ovulated despite changes in LH.20

Table 1 Dose, frequency and route of administration of exogenous melatonin administered to female and
male cats and associated reproductive outcomes
Dose and route Cycle stage at
Sample size (n) of administration initiation of treatment Outcome Reference
16 females 5 mg q48h SC Not stated Suppressed ovarian activity even under a 24 h light 20
photoperiod for 60 days
6 females 30 mg q24h PO 3 h before Not stated Returned to estrus 33 ± 2.8 days (range 21–40 days) 2
lights off for 35 days after treatment ended
4 females 60 mg (five 12 mg Not stated Suppressed estrus in 75% (duration of estrus suppression 21
implants) not given)
9 females 18 mg (single implant) During interestrus Within 3–9 days of implant insertion, 33% had superficial 22
cells present on their vaginal cytology and estrous behavior
for 2 days followed by estrus suppression for 4 months
9 females 18 mg (single implant) During estrus Within 9–11 days of implant insertion, 78% had superficial 22
cells present on vaginal cytology and estrous behavior for
2–3 days followed by estrus suppression for 2 months
12 females 4 mg/cat q24h PO until During interestrus Prolonged interestrus (interval between onset of treatment 23
onset of estrus and first estrous cycle was 50 ± 6.1 days)
17 females 18 mg (single implant) During interestrus Prolonged interestrus (interval between onset of treatment 23
and first estrous cycle was 51 ± 4.7 days)
4 males 18 mg (single implant) Not applicable 100% significantly decreased their sperm quality until 24
120 ± 15 days after implant insertion
12 females 18 mg (single implant) Prepubertally Did not delay puberty 23
10 females 4 mg/cat q24h PO until Prepubertally Did not delay puberty 23
onset of estrus
SC = subcutaneous, PO = oral

754 JFMS CLINICAL PRACTICE

753_757_Melatonin_Kutzler.qxp_FAB 10/08/2015 13:08 Page 755

R E V I E W / Use of melatonin to suppress feline reproduction

longer duration of melatonin treatment may

provide greater inhibition of ovarian activity.2
It is important to note that this treatment had
Alliance for Contraception in Cats & Dogs

no significant effect on the quantity or quality

This article is part of a Special Issue of the Journal of Feline Medicine and

of embryos produced by AI, thus demonstrat-

Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline

ing its safety for this application.2 With the

fertility control’ and coordinated by the Alliance for Contraception in Cats

exception of one case report of cystic endome-

& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of

trial hyperplasia following administration of a

non-surgical fertility control to save the lives of cats and dogs, expand

melatonin implant,21 no other side effects have

options for pet owners, and improve animal welfare. Serving as a trusted

been reported.4,22 Although the uterus has not

resource for scientific and educational

been specifically evaluated in melatonin-

information, the ACC&D brings together key

treated cats, some treated females have been

stakeholders to advance humane sterilization

bred following treatment and have become

options that are faster, easier and more

pregnant, demonstrating the likelihood of

accessible than surgery.

normal uterine integrity and future fertility.23

In addition, when administered prepubertal-
More information is available at www.acc-d.org

ly, melatonin does not affect growth.

However, oral melatonin treatment is
unlikely to reliably suppress fertility unless it
Either oral effect,17,21 while other studies report a 5–30 day

is administered at a set time of the day

delay prior to estrus suppression.2,20,22
or parenteral
(around 2 h before darkness). Such a treat-
delayed estrus suppression using mela-

ment may not be realistic in field conditions

administration tonin may be an artefact of a lack of detailed

because cats dislike oral administration and

estrous cycle monitoring before the implant
of exogenous
compliance with treatment delivered at a set
was administered, as administration of mela-

time of the day may be limited. The advice to

tonin during estrus results in a rapid return to
melatonin or
practitioners, therefore, is not to contemplate
estrus.22,23 High estrogen concentrations have

this option.
melatonin previously been shown to interfere with
responses to both endogenous and exogenous
receptor melatonin.26 High serum estradiol concentra-

Prolonged-release subcutaneous formulations

Subcutaneous implants agonists will tions decrease expression of melatonin ovarian

of melatonin have been tested in cats as a more

receptors via downregulation in rats27,28 and

practical option than oral administration.21–23

suppress feline humans.29–31 it is not known whether queens

The interscapular space is commonly used as

have ovarian melatonin receptors; if they do,
reproductive
an implant insertion site, and the implant can
this could explain the shorter interestrus inter-

be administered in an unsedated patient with

function. val observed when melatonin implants are

local infiltration of anesthetics. Melatonin

administered during estrus.22 Having said this,

implants (18 mg, Melovine; Ceva Santé

the primary action of melatonin in suppress-

Animale) are commercially available for vet-

ing reproductive activity in the cat is centrally

erinary use in several countries, whereas mela-

mediated.

tonin tablets are readily available over the

counter in pharmacies and health food stores
worldwide. In sheep, subcutaneous melatonin
Melatonin in tom cats
implants maintain constant serum melatonin
Tom cats produce semen throughout the year with moderate annual varia-

concentrations, unlike oral melatonin admin-

tions, improving their semen quality during the breeding season.32–34 A

istration.25 Data demonstrating constant

single subcutaneous melatonin implant (18 mg; Syntex) effectively and

melatonin concentrations following implant

reversibly reduced sperm production and quality in eight male domestic

placement in cats are lacking, but the effect is

cats without clinically detectable adverse effects.24 At 91 ± 7 days after

presumed to be similar to that seen in sheep.

Results concerning efficacy (rapid and pro-
longed estrous cycle suppression) with mela-
tonin implants have not been consistent
among reports, possibly due to the variability
in the timing of implant administration rela-
tive to the onset of estrus or time of year. For
example, estrus suppression for about 2–4
months following administration of melatonin
implants ranged from 100% (9/9 cats, 18 mg
implants)22 to 50% (2/4 cats, 12 mg implants).23
Although the sample sizes are small, these
data suggest that ovarian responses to mela-
tonin implants are dose-related.23 in addition,
some studies demonstrate an immediate
implant insertion, the following average decreases were recorded com-
pared with pre-implant values: sperm motility 38.5%, velocity 26.5%, total
sperm count 82%, acrosome integrity 22%, plasma membrane integrity
30%, and normal sperm morphology 32%.24 These effects were present
until 120 ± 15 days after implant insertion.24 During the period of melatonin
suppression, feline sperm parameters were similar to those previously
reported during the non-breeding season35 and during the photorefractory
period.36 After 120 days, semen parameters started to increase and reached
pre-implant values at approximately 140 ± 7 days after implant insertion.24
Conversely, ejaculate volume (0.15 ± 0.02 ml) and serum testosterone
concentrations (1.1 ± 0.1 ng/ml) did not differ between melatonin-treated
and control tom cats.24 Given that treated cats conserved the capacity to
ejaculate sperm, a fertility trial is needed to determine if a queen can
became pregnant when mated with a tom cat that has melatonin-induced
oligospermia.24

JFMS CLINICAL PRACTICE 755

753_757_Melatonin_Kutzler.qxp_FAB 10/08/2015 13:08 Page 756
R E V I E W / Use of melatonin to suppress feline reproduction
Melatonin receptor agonists
Several melatonin receptor agonist com-
pounds are available but only a few have been
investigated in cats. The oral administration
of compound 4d (0.1 mg/kg) results in a
sleep-promoting action in cats, but reproduc-
tive activity was not reported.37 Ramelteon is
an MT1/MT2 receptor agonist for the treat-
ment of insomnia and circadian rhythm dis-
orders in humans. oral administration of
ramelteon (0.001, 0.01 and 0.1 mg/kg) has
also been investigated in cats.9 Ramelteon
decreased wakefulness for up to 6 h, whereas
exogenous melatonin (1.0 mg/kg Po) only
reduced wakefulness for 2 h.9 Although both
male and female cats were evaluated in this
study, there was no information provided
about reproductive effects.
Melatonin – the challenges
The therapeutic use of melatonin is limited by
its short biological half-life (15–20 mins), its
poor oral bioavailability and its ubiquitous
action. indeed, the chronobiotic effects of
melatonin have led to many therapeutic tar-
gets in humans such as sleep disorders,38
neurodegenerative diseases,39,40 cancer41,42
and stroke.43 in the cat, melatonin can be a
useful tool for the treatment of uveitis.44
The cat has proven to be a very useful
model for studying the sleep-promoting
action of melatonin and its receptor agonists.9
doses of exogenous melatonin in excess of
1 mg/kg affect wakefulness.9 However, the
mechanisms behind the sleep-promoting
effects of melatonin are still unknown.9
GABA-A receptors are widely distributed in
the suprachiasmatic nucleus and may serve
both presynaptic and postsynaptic roles in
controlling mammalian circadian rhythms.45,46
These effects can be reversed by GABA-A
receptor antagonists.47 Thus, the sleep-
promoting action of melatonin might be
derived from responses of the GABAergic
system in the suprachiasmatic nucleus.9
What to conclude?
Long-term melatonin administration is safe,
but this treatment only results in short-term
estrus suppression in postpubertal cats; it has
not been effective in prepubertal cats.23 Some
view the short estrous cycle suppression in
cats induced by melatonin as insufficient,23
leaving opportunities for researchers to inves-
tigate ovarian effects from higher melatonin
doses, a longer-release formulation or repeat-
ed administrations. As prolactin release is also
higher during darkness in the female cat,48
and both melatonin and prolactin secretion
are very responsive to changes in photoperiod
756 JFMS CLINICAL PRACTICE
KEY points
< Exogenous melatonin administered parenterally has short-term
effects of suppressing ovarian activity in cats.
< Therapeutic use of melatonin is limited by its short biological
half-life (15–20 mins), its poor oral bioavailability and its
central effects in reducing wakefulness.
< Long-term subcutaneous melatonin administration
is safe in cats and repeated administration of
melatonin implants may extend contraceptive efficacy.
in the cat,49 it is likely that the two hormones
are involved in modulating the responsive-
ness of the hypothalamus to the negative
feedback effects of estrogen.49 implants
containing a combination of melatonin and
prolactin may provide superior estrous cycle
suppression compared with melatonin alone.
Funding
The author received no specific grant from any funding agency in the public,
commercial or not-for-profit sectors for the preparation of this article.
Conflict of interest
The author has no conflict of interest to declare.
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758_765_GonaconLH_Benka and Levy.qxp_FAB 10/08/2015 13:15 Page 758
CLINICAL REVIEW
Vaccines for feline
contraception
GonaCon GnRH–hemocyanin
conjugate immunocontraceptive
Valerie A W Benka and Julie K Levy
Vaccine: GonaCon™ is the trade
name of a GnRH–hemocyanin
conjugate immunocontraceptive
vaccine formulation shown to
prevent reproduction and inhibit
production of sex hormones in
numerous mammalian species for
extended durations. GonaCon is currently
registered with the US Environmental Protection
Agency (EPA) for contraception of female
white-tailed deer, and GonaCon™-Equine
for female wild horses and burros. Multiple
formulations of this GnRH-hemocyanin conjugate
immunocontraceptive vaccine have been
developed at the National Wildlife Research
Center in the United States.
Evidence base: Three studies employing an
early generation vaccine formulation indicated
its potential for multi-year contraception of female
cats (median duration of effect in excess of
39.7 months). The contraceptive effect for male
cats was less predictable and of shorter duration
(median duration of effect 14 months). Since these
initial feline studies there have been formulation
composition changes, and further investigation
of the safety, efficacy and duration of this
contraceptive vaccine for cats is warranted.
Future prospects: Individual country regulations
will determine if GonaCon could be registered for
unowned, free-roaming and/or pet cats.
758 JFMS CLINICAL PRACTICE
Journal of Feline Medicine and Surgery (2015) 17, 758–765
Introduction
At present, communities tend to employ one of two intervention
strategies to reduce populations of unowned, free-roaming cats:
removal (often through trapping and euthanizing) and trap–
neuter–return (TNR). The former is controversial on grounds of animal
welfare, ethics, efficacy and cost. The latter, which can trace its begin-
nings to England in the 1950s before making its way to the United
States some four decades later,1 has a passionate following that crosses
national boundaries. However, it too is controversial. TNR also pres-
ents economic and logistical constraints, plus the challenge of steriliz-
ing sufficient numbers of animals to see a sustained population
decline. A ‘third option’, trap–
contracept–return (TCR), may The option of
now be on the horizon.
trap–contracept–return
Non-surgical, long-term (3 years
or more) contraception could offer may now be on the horizon
unique value for feral or ‘commu-
nity’ cat population management. as an intervention strategy
Important characteristics of a
to reduce populations of
product for this feline cohort
include safety for both target ani- free-roaming cats.
mals and the environment, single-
dose long-term (ideally perma-
nent) contraception in both sexes
and across age groups, rapid onset, stability and ease of use under field
conditions, inhibition of sex hormones, and affordability.2 GonaCon™, a
gonadotropin-releasing hormone (GnRH) immunocontraceptive vac-
cine, has the potential to fulfill many of these requirements. An early
generation GonaCon formulation yielded a median contraceptive effect
of over 3 years in female cats. While cats may require sedation to ensure
proper injection, the vaccination process does not require anesthesia
and thus does not necessitate holding animals overnight to ensure a
safe release. For that reason it warrants further evaluation as an addi-
tional tool for managing unowned, free-roaming cats, particularly with
regard to its practical applications and long-term contraceptive impact.
Valerie A W Benka
MS MPP*
Project Manager, Alliance for Contraception in Cats & Dogs,
Portland, Oregon, USA
Julie K Levy
DVM PhD
Maddie’s Shelter Medicine Program,
College of Veterinary Medicine,
University of Florida, USA
*Corresponding author: valerie@acc-d.org
doI: 10.1177/1098612X15594989
© The Author(s) 2015
758_765_GonaconLH_Benka and Levy.qxp_FAB 10/08/2015 13:16 Page 759

R E V I E W / Vaccines for feline contraception

GonaCon and GonaCon™-Equine immuno-

contraceptive vaccines are registered with
the US Environmental Protection Agency
(EPA) for use in female white-tailed deer, and
wild and feral horses and burros, respectively
(Figure 1), per the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA).3
This creates precedent for registration for
additional wildlife species and ‘feral’ animals,
including unowned, free-roaming cats.4
Country- and region-specific regulatory
processes determine registration pathways for
each product, species and type of animal. The Figure 1 GonaCon and GonaCon-Equine immunocontraceptive vaccines are registered with
European Medicines Agency (EMA), for the US Environmental Protection Agency for use in female white-tailed deer, and female wild
and feral horses and burros, respectively
example, regulates all veterinary medicinal
products in the European Union (EU).4

Physiological feasibility formulation with either protein. AdjuVac™

adjuvant, used in current GonaCon formula-
The past two decades have seen multiple tions, contains a purified fraction of inactivated
studies on the effect of GnRH-based immuno- Mycobacterium avium in oil.14,17 The quantity of
contraceptive vaccines on feline fertility.5–9 M avium used has varied as NWRC scientists
Research into this fertility control approach have sought to reduce injection-site reactions
continues today.10,11 GonaCon is one such without compromising vaccine efficacy.
GnRH immunocontraceptive vaccine. Studied The NWRC’s objective is for GonaCon to
in multiple species using both intramuscular offer multi-year infertility with a single injec-
and subcutaneous routes of administration, tion. The EPA registration label for deer states
GonaCon is designed to trigger development that a single vaccination will have a minimum
of antibodies that inactivate the GnRH pro- 1 year contraceptive effect, and both deer and
duced by the hypothalamus. Without GnRH equine labels note that the contraceptive effect
stimulation, the release of gonadal hormones may be longer.18,19 For both species, re-immu-
in both males and females and across mam- nization can extend infertility. For white-tailed
malian species remains negligible, and deer and wild and feral equids, as well as sev-
gametes do not mature.12–14 eral species for which GonaCon does not have
GonaCon was developed at the National regulatory approval (including cats), there is
Wildlife Research Center (NWRC), the evidence of multi-year effect in some animals
research arm of the United States department with a single injection. Beyond preventing
of Agriculture (USdA)-Animal and Plant reproduction, GonaCon should eliminate
Health Inspection Service (APHIS) Wildlife estrous cycles in females so long as sufficient
Services program. The EPA approved GnRH antibodies are present. It should also
GonaCon for contraception of adult female suppress behaviors and health effects associat-
white-tailed deer in 2009 (EPA Registration ed with male and female sex hormones.2,20
Number 56228-40) and GonaCon-Equine for
adult female wild and feral horses/burros in
Multiple generations of GonaCon formulations
2013 (EPA Registration Number 56228-41).15
The NWRC has produced multiple formulations of a GnRH–hemocyanin
Although registration is currently limited to
conjugate immunocontraceptive vaccine, and the name ‘GonaCon’ has
these aforementioned species and to females,
been used loosely in the literature and been attributed to these multiple
multiple generations of GonaCon formula-
generations of NWRC-developed product. Although there are certain unifying
tions developed by the NWRC have been
features, different formulations also have distinguishing features, including
shown to have a contraceptive effect in both
the conjugate protein used, quantity of M avium in the AdjuVac adjuvant,
sexes of multiple mammalian species.
additives, type of mineral oil, and conditions in which the vaccines are
The GnRH peptide is a small self-antigen
produced.
that cannot independently produce an immune
In this article, ‘GonaCon’ refers to the EPA-registered formulation for
response and must be coupled with a carrier
white-tailed deer, and ‘GonaCon-Equine’ refers to the EPA-registered
protein to make it more antigenic. The
formulation for wild horses and burros. The authors have made every
GnRH–carrier protein conjugate is, in turn,
effort to distinguish earlier generations of GonaCon formulations (includ-
combined with an adjuvant to enhance the
ing but not limited to those used in three feline studies) from the
immune response.13,14,16,17 GonaCon formula-
EPA-approved formulations.
tions have used both keyhole limpet hemo-
It is important to note that the variations in formulations, mineral oil and
cyanin (KLH) and Concholepas concholepas
production process may or may not have an impact on vaccine efficacy
hemocyanin (‘blue protein’) to create conjugate
and duration of fertility suppression, as well as on adverse side effects.
antigens. EPA regulatory approval allows

JFMS CLINICAL PRACTICE 759

758_765_GonaconLH_Benka and Levy.qxp_FAB 10/08/2015 13:16 Page 760
R E V I E W / Vaccines for feline contraception
Evidence base
To date, three feline laboratory studies using
an early generation GonaCon formulation
have been conducted at the University of
Florida College of Veterinary Medicine.2,12,20,21
The studies, each of which used a single intra-
muscular injection, measured vaccine efficacy
based on GnRH antibody levels and serum
hormone levels (for males and females), sperm
quality and quantity (for males), and breeding
trials (for males and females). A longitudinal
feline study using the GonaCon formulation
registered with the EPA for deer and equids
began in August 2015 (see box on page 761).
The three University of Florida studies found
individual variation among both females and
males. They also suggest that female cats over-
all have more predictable antibody develop-
ment following vaccination than males. The
GnRH antibody titer required to block fertility
in females was lower than in males, and the
duration of response to a single vaccine longer.2
This has also been observed in other species,
possibly related to greater difficulty in blocking
continuously secreted GnRH in males com-
pared with episodic secretion in females.2,22
In a long-term study with 20 female cats aged
8–14 months, all 15 cats receiving the early
containing 400 µg/ml GnRH–KLH conjugate
generation GonaCon vaccine (0.5 ml
and 170 µg/ml M avium) had delayed pregnan-
cies, compared with none of the five that
received a sham vaccine. of the 15 vaccinated
cats, 93% were infertile for at least 1 year, 73%
for 2 years, 53% for 3 years and 40% for 4 years;
27% were still infertile at the conclusion of the
5 year study.12 (one treated cat was bred in
three successive periods of estrus between days
129–164 and became pregnant on day 164.)12
The vaccinated cats had a longer time to concep-
tion (median ⩾39.7 months) compared with the
control group (4.4 months). Response to vacci-
nation was accompanied by cessation of estrous
cyclicity and weight gain, similar to effects seen
in cats undergoing surgical sterilization.2,12
Two studies in male cats have evaluated both
short- and long-term response to multiple early
generation GonaCon formulations.20,21 The first
study included 12 male cats aged 9–12 months;
taining 50, 200 or 400 µg GnRH–KLH conjugate
three groups of three cats received 0.5 ml con-
(100, 400 or 800 µg/ml) and 85 µg M avium (170
µg/ml); three cats served as controls.2,20 All nine
cats that received the vaccine developed GnRH
antibodies after 1 month, which persisted
throughout the 6 month study. However,
antibody levels varied among individuals.
Six of nine treated cats were identified as
‘responders’, and three of nine as ‘non-respon-
ders’. Responders had undetectable serum
testosterone by 3 months post-treatment, plus
760 JFMS CLINICAL PRACTICE
Alliance for Contraception in Cats & Dogs
This article is part of a Special Issue of the Journal of Feline Medicine and
Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline
fertility control’ and coordinated by the Alliance for Contraception in Cats
& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of
non-surgical fertility control to save the lives of cats and dogs, expand
options for pet owners, and improve animal welfare. Serving as a trusted
resource for scientific and educational
information, the ACC&D brings together key
stakeholders to advance humane sterilization
options that are faster, easier and more
accessible than surgery.
More information is available at www.acc-d.org
marked testicular atrophy and no viable sperm.
Non-responders had lower GnRH antibody
titers and intermediate serum testosterone
concentrations, testicular atrophy and reduced
sperm counts compared with responders and
control cats receiving a placebo vaccine.2,20,21
In a second longitudinal study, a single
containing 400 µg/ml GnRH–KLH conjugate
early generation GonaCon injection (0.5 ml
and 170 µg/ml M avium) led nine of 12
vaccinated male cats to develop high GnRH
antibody titers (‘responder’ cats).21 Long-term
immune response varied. Among the respon-
ders, the median time for testosterone to
become undetectable was 2 months (range
1–12 months), and testosterone production
remained undetectable for a median of 14
months (range 5–33 months). Azoospermia
(absence of viable sperm) was generally
observed 1–2 months after loss of detectable
testosterone, and normal sperm counts
returned 2 months after testosterone levels
recovered. one cat had an unexplained
In three feline delayed response to the vaccine; the GnRH
laboratory antibody titer did not begin to increase until
6 months after vaccination, and the cat did not
studies experience suppression of testosterone and
performed azoospermia until 12 months and 14 months
after vaccination, respectively.2,21
to date, The breeding trial with males in the longitu-
dinal study showed that the mean time to suc-
GonaCon has cessful breeding was 12 months for respon-
resulted in ders, 5 months for the ‘non-responder’ cats
that did not develop high antibody levels, and
female cats 3 months for 12 sham-treated cats. Median
litter size sired by cats was not significantly
ceasing to different between groups. All but one cat
come into recovered fertility by 3 years post-treatment.2
GonaCon – both the current EPA-approved
estrus and earlier generation formulations – sup-
presses production of sex hormones, and thus
and male cats should suppress reproductive functions (eg,
losing their estrus) and behaviors associated with these
hormones. The studies described above
libido. resulted in female cats ceasing to come into
758_765_GonaconLH_Benka and Levy.qxp_FAB 10/08/2015 13:16 Page 761
Due to GonaCon’s potential to complement surgical sterilization for unowned, free-roaming cats,
the ACC&D is sponsoring two studies to advance knowledge about vaccine efficacy and duration
in a free-roaming population.
Short-term safety study
The first study was a short-term safety study
conducted in partnership with the Center for
Conservation and Research of Endangered
Wildlife (CREW) at the Cincinnati Zoo & Botanical
Garden (Cincinnati, Ohio, USA).
In November 2014, three female cats received
the EPA-registered GonaCon vaccine to confirm
that it would not cause unacceptable acute injec-
tion-site reactions; three control cats received a
The ACC&D sham vaccination of saline. Due to promising find-
is sponsoring ings during the 2 months post-treatment, a second
phase began in January 2015. The three cats
two studies vaccinated in November 2014 received a GonaCon
vaccination to determine if a ‘booster’ may cause
to advance a reaction not produced by a single injection. The
knowledge three original control cats received a single dose
of GonaCon to increase the sample size for the
about vaccine single-dose safety profile.
Injection-site reactions (small masses) were
efficacy and
noted in four of the six cats during the second
duration in a phase of the study. Two of these cats had received
a single GonaCon injection; the other two had
free-roaming received two GonaCon injections 60 days apart,
and reactions developed only after the second
population
injection. An adverse event matrix (a tool for
of cats. recording observations) was developed by the
study investigators prior to beginning the study.
At each evaluation cats were assigned a number to
reflect heat, swelling and pain (1 = lowest, 4 =
highest, based on signs defined in advance of the
trial). All reactions remained in the lowest score (1).
No cat demonstrated adverse effects on ambula-
tion or behavior. Two cats’ masses completely
resolved by the end of the 120 day study; the other
two cats’ masses were still palpable, but had
estrus12 and male cats losing their libido (JK
Levy, unpublished data).
To date, no pregnant cats have been vacci-
nated with any GonaCon formulation.
However, Levy et al found that upon concep-
tion (median duration ⩾39.7 months follow-
ing vaccination), cats treated with the early
generation GonaCon formulation averaged
smaller litter sizes than sham-treated cats.12
There was no difference in the number of still-
born kittens.12 Product labels for deer and
wild equid GonaCon vaccines specify that
treatment should not affect an existing preg-
nancy; instead, it should cause infertility in
the vaccinated animal for, at a minimum, the
subsequent year.18,19 A study of an early gen-
R E V I E W / Vaccines for feline contraception
ACC&D-sponsored studies
reduced in size and were following a similar pat-
tern of resolution as the first cats’ masses.
In addition, blood was drawn monthly for a
6 month period to assess anti-GnRH antibody
titers. Samples were titrated to a maximum of
1:128,000, and beginning 1 month following vacci-
nation all cats appear to have responded strongly
enough to reach and maintain titers of at least
1:128,000. In the previous study at the University
of Florida,12 titers ⩾1:128,000 were sufficient to
prevent pregnancy in most cats. They are a prom-
ising initial indication of the vaccine’s ability to
elicit a humoral immune response.
All cats participating in the study were adopted
into permanent homes. They are currently enjoying
life with a study advisor, a veterinarian, and both a
sibling and a close friend of a co-investigator.
Field study
Overall, the acute injection-site reactions observed
in the small safety study were minimal, and the new
formulation was deemed safe enough to proceed
with the proposed field study. This second study,
which began in August 2015, will evaluate the abil-
ity of GonaCon to suppress fertility among female
cats in a semi-controlled environment that offers
an indoor space combined with a one-third acre
enclosed outdoor wooded area, and thus more
closely approximates the living environment of
free-roaming cats. Veterinary care, food, water and
enrichment will be provided, however, to ensure a
high quality of life. The primary endpoint for this
study will be pregnancy during a 5 year continuous
breeding trial. At the end of the study period all cats
will be surgically sterilized and adopted or kept at a
closely managed colony setting.
eration GonaCon formulation in dogs found
that two bitches that received the vaccine
while pregnant delivered healthy puppies.23
A study is under way to evaluate the safety
in cats of a ‘booster’ vaccine, using the EPA-
approved GonaCon formulation (see box
above). This will be the first of its kind – to date,
no study has evaluated the safety or titer effects
of a booster contraceptive vaccine in cats.
However, booster vaccines have been studied
in white-tailed deer,24,25 and GonaCon labels for
female white-tailed deer and wild horses report
that a second vaccine may be given 30–60 days
or 30+ days after the first injection, respectively,
or ‘during the following year’ to achieve a
longer contraceptive effect.18,19
JFMS CLINICAL PRACTICE 761
758_765_GonaconLH_Benka and Levy.qxp_FAB 10/08/2015 13:16 Page 762
R E V I E W / Vaccines for feline contraception
Considerations for using
GonaCon
Multiple factors, discussed below, warrant
consideration when determining both optimal
and feasible contexts for using GonaCon for
feline contraception.
Individual variability
Completed feline studies found that individ-
ual animals of the same sex, breed and age
had variable responses to an early generation
GonaCon formulation in terms of GnRH anti-
body production and both the onset and dura-
tion of contraceptive effect.2,12,20,21 The studies
demonstrate that, overall, a higher proportion
of queens than toms were ‘responders’ to
the vaccine, as measured by fertility status.
Queens also remained infertile for a longer
duration than toms. Levy et al noted that the
variable response in cats is not believed to be
related to vaccine dose and proposed that, in
some cats, the immune response was diverted
to certain components of the vaccine (the car-
rier protein, mycobacterial adjuvant or other
vaccine components) rather than the intended
GnRH.20 As with all vaccines, it is likely that
duration of effect (infertility) will vary among
individuals; GonaCon must be used with this
understanding and expectation.
Injection-site reactions
Two features of GonaCon, both EPA-
approved and early generation formulations,
facilitate long-term contraception with a sin-
gle injection. First, the inactivated M avium in
the AdjuVac adjuvant stimulates the immune
system to react against the target antigen by
inducing a local inflammatory response.
Secondly, the use of a water-in-oil emulsion
slows release of the vaccine and protects the
antigen from rapidly degrading, thus extend-
ing vaccine duration.17,26 The components that
extend vaccine duration are also believed
to contribute to injection-site reactions.12,17,26,27
The timing, type and severity of these reac-
tions vary significantly among species, and
have also been shown to vary among individ-
uals of a particular species.
during the 6 month study with 12 male cats
400 or 800 µg/ml GnRH–KLH conjugate,
(that received 0.5 ml vaccine containing 100,
µg/ml M avium), no injection-site or systemic
adjuvanted with AdjuVac containing 170
reactions (eg, inflammation or tenderness)
were detected.2,20 Late-onset (2 years post-
treatment) granulomatous injection-site mass-
es developed in five of 15 treated female cats
in the aforementioned long-term study.12 In
one cat, the mass grew to 4 cm x 5 cm in size;
the other four cats developed single or
multiple masses under 1 cm in diameter. The
762 JFMS CLINICAL PRACTICE
As with all vaccines, it is likely that duration
of effect (infertility) will vary among individuals;
GonaCon must be used with this understanding
and expectation.
masses were persistent and waxed and waned
for the duration of the study, but did not drain
or appear painful.12 A biopsy of the largest
mass revealed granulomatous inflammation
with interlesional acid-fast bacteria and pro-
duced negative aerobic, anaerobic and
mycobacterial cultures.12
Although the masses in all cats appeared
benign, they nonetheless prompt some con-
cern given indications that cats may be at an
increased risk for developing malignant
sarcomas at the site of vaccine-induced
inflammation. of potential relevance, several
cats receiving adjuvant containing mycobacte-
ria in oil (Freund’s adjuvant) in a study of
zona pellucida immunocontraception (a
different vaccine from GonaCon, and with a
different adjuvant) developed systemic gran-
ulomatous disease accompanied by hypercal-
cemia, and one cat developed an injection-site
sarcoma.27
Effect of laboratory vs ‘field’ conditions
To date, feline studies with early generation
GonaCon formulations have taken place
exclusively in a laboratory setting. Males and
females were specific pathogen-free domestic
shorthair cats, acquired from the same commer-
cial vendor.12,20 Each study housed cats in
climate-controlled indoor spaces with con-
trolled light cycles; water and food were avail-
able ad libitum.12,20 This is in contrast to
research on GonaCon formulations in other
species, dogs included, which have relied heav-
ily – sometimes exclusively – on field studies.
At this time, it is not known if factors such as
greater or lesser genetic heterogeneity, parasite
load, age or variable light duration could
potentially impact cats’ response to the vaccine.
Variable formulations
The GonaCon formulations that the NWRC
has developed warrant attention with respect
to future feline use. Although the agency
began by using KLH to create a GnRH conju-
gate antigen, and KLH was used in the studies
conducted at the University of Florida, the
NWRC now uses C concholepas hemocyanin.
KLH became cost-prohibitive once it became
attractive for human cancer vaccines (K
Fagerstone, 2014, personal communication).
The NWRC has also trialed the immunocon-
traceptive vaccine with different concentra-
tions of GnRH–KLH conjugate and adjuvant.
758_765_GonaconLH_Benka and Levy.qxp_FAB 10/08/2015 13:16 Page 763
As discussed above, University of Florida
studies in male cats used three concentrations
µg/ml).2,20 The formulation used in the female
of GnRH–KLH conjugate (100, 400, 800
study contained 400 µg/ml GnRH-KLH conju-
gate.12 Currently GonaCon and GonaCon-
of GnRH conjugate antigen (1000 µg/ml) and
Equine formulations use a higher concentration
C concholepas hemocyanin, although EPA regis-
tration permits either C concholepas or KLH.
Regulatory considerations
Regulatory processes specific to individual
countries or to the EU would determine regis-
tration pathways for different feline ‘cohorts’. < Rapid onset
The EMA, for example, regulates all medicines
for veterinary use in the EU.4 In the United
States, veterinary pharmaceuticals may be
regulated by the FdA Center for Veterinary
Medicine, the USdA Center for Veterinary
Biologics or the EPA (see accompanying arti-
cle in this Special Issue for further details4).
The EPA regulates use of pesticides for ‘pest’
species management under FIFRA.
GonaCon is registered as a pesticide with
the EPA for adult female white-tailed deer,
and GonaCon-Equine is registered with the
EPA for reproductively mature female wild or
feral horses and burros. These registrations
may create precedent for the EPA registration
of GonaCon to be used in additional wildlife
species and ‘feral’ animals, including
unowned, free-roaming cats. This might
entail, in this limited context, defining such
cats as wildlife or ‘pests’. It would likely also
restrict use to unowned ‘feral’ cats, rather
than pet cats with owners seeking a non-
surgical fertility control option.
Certainly a company or group could pursue
regulatory approval of GonaCon with the FdA,
or in the EU with the EMA, which would per-
mit use for owned and unowned, socialized
and feral cats alike under the supervision of a
veterinarian. However, FdA and EMA regula-
tory approval would likely be challenging due
to the high cost of conducting all the studies
required, including the complexity of achiev-
ing a manufacturing process that would satis-
fy the good manufacturing practice (GMP)
requirements of these agencies. The manufac-
turing process is complex, and includes a
bacterial component (AdjuVac), presenting
significant challenges to meeting requirements
(L Rhodes, 2014, personal communication).
Free-roaming cats have a relatively short average
lifespan and high kitten mortality rate. This
potentially makes a multi-year contraceptive a
valuable tool for population control and stability.
R E V I E W / Vaccines for feline contraception
Conclusions and
recommendations
GonaCon has the potential to meet many of
the requirements of a non-surgical ‘tool’ to
control fertility
in unowned,
Desirable features of a non-surgical sterilant free-roaming cat
for free-roaming cats populations (see
< Safety for animals, the environment and box). Although
administrators further studies
< Ability to induce long-term (ideally permanent) are needed
infertility with a single dose in both sexes and using the current
across age groups E PA - re g i s t e re d
GonaCon formu-
< Stability, ease of use and effectiveness in the lation and under
field field conditions,
< Ability to inhibit or suppress sex hormones and the results of stud-
hormone-related ‘nuisance’ behaviors ies to date are rea-
< Cost-effectiveness son for optimism.
The risks and ben-
efits of registering
GonaCon for free-roaming cats must also
be balanced against the welfare implications
of no intervention, uncontrolled breeding,
euthanasia and/or inhumane culling in com-
munities where surgical sterilization is not
available at the rate required to have a signifi-
cant impact on population size.
Permanent sterilization and efficacy in 100%
of vaccinated animals would be optimal for
population control; this is particularly true for
animals without the more consistent monitor-
ing and veterinary care enjoyed by many pet
cats. However, free-roaming cats have been
found to have a relatively short average lifespan
and high kitten mortality rate;28–32 this potential-
ly makes a multi-year contraceptive a valuable
tool for population control and stability. This is
particularly true if GonaCon proves to contra-
cept female free-roaming cats for approximately
3 years, and if permanent sterilization cannot be
performed on the scale needed to achieve pop-
ulation management goals. GonaCon might be
used in conjunction with sterilization, allowing
TNR programs more time to catch and trans-
port animals for surgery. GonaCon also does
not necessitate anesthesia and the associated
recovery time; while some cats may require
sedation to ensure proper injection, the proce-
dure is such that animals would not need to be
held overnight to ensure a safe release.
Computer modeling shows promise for the
effect of multi-year contraception on popula-
tion reduction (as discussed in an accompany-
ing article in this Special Issue,33 and else-
where34). Although the model suggests that
more cats must be contracepted than sterilized
in order to see a reduction in population, it is
possible that GonaCon’s financial savings and
technical ease of administration could offset the
higher numbers of animals requiring treatment.
JFMS CLINICAL PRACTICE 763
758_765_GonaconLH_Benka and Levy.qxp_FAB 10/08/2015 13:16 Page 764
R E V I E W / Vaccines for feline contraception
KEY points
< GonaCon and GonaCon-Equine are the trade names of a
GnRH–hemocyanin conjugate immunocontraceptive vaccine
formulation developed by the National Wildlife Research Center
and registered with the US Environmental Protection Agency (EPA)
for a minimum 1 year contraception of female white-tailed deer,
wild horses and wild burros with a single vaccine injection.
< GonaCon is designed to trigger creation of antibodies that
inactivate the GnRH produced by the hypothalamus. Without
GnRH stimulation, the release of gonadal hormones in both males
and females and across mammalian species is suppressed, and
gametes do not mature.
< Three studies of male and female cats used an earlier generation
of the GnRH–hemocyanin conjugate immunocontraceptive
vaccine, the composition of which varied moderately from the
EPA-registered formulation. The median duration of effect was
⩾39.7 months for female cats, indicating potential application
for long-term contraception. Testosterone production in male
cats remained undetectable for a median of 14 months.
The EPA-registered GonaCon formulation is currently being
studied in cats to confirm safety and production of
GnRH antibody titers. A field study using the
EPA-approved formulation began in August 2015.
ISFM CONGRESS RECORDING
A recording of Julie Levy’s session on a
multi-year GnRH-based immunocontraceptive
vaccine for feline fertility control, presented at
the 2015 ISFM Congress in Porto, is available at:
http://icatcare.org/vets/videos
It is also included as
Supplementary material at: jfms.com
DOI: 10.1177/1098612X15594989
Funding
The authors received no specific grant from any
funding agency in the public, commercial or not-
for-profit sectors for the preparation of this article.
Conflict of interest
The authors have no conflict of interest to declare.
References
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Bethesda, Md: Alley Cat Allies, 2004.
2 Levy JK. Contraceptive vaccines for the
humane control of community cat popula-
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3 Fagerstone K and Eisemann J. Feral cats: new
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4 Rhodes L. Put a label (claim) on it: getting non-
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5 Alliance for Contraception in Cats & dogs (ACC&d).
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6 Baker HJ, Griffen B, Smith BF, et al.
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adjuvantation. Proceedings of the 2nd
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Methods for Pet Population Control; 2004
June 24–27; Breckenridge, Co, USA.
7 Robbins SC. Active immunization of pre-
pubertal cats against gonadotropin-releasing
hormone and its effects on gonadal hormone
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8 Enright WJ and Swift PJ. GnRH immunization
of peripubertal male cats: dose titration of a
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J Reprod Fertil Abstr Ser 1995; 15: 15.
9 Ladd A, Tsong YY, Walfield AM, et al.
Development of an antifertility vaccine for
pets based on active immunization against
luteinizing hormone-releasing hormone. Biol
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10 Munks MW, Montoya A, Talmage G, et al.
Development of attenuated feline herpes-
virus-1 as a cat contraceptive vaccine vector.
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on Non-Surgical Contraceptive Methods of Pet
Population Control; 2013 June 20–22; Portland,
oR, USA. http://www.acc-d.org/resource-
library/ symposia/5th-symposium.
11 Samoylova TI, Samoylov AM, Chochran AM, et al.
Filamentous phage as a platform for develop-
ment of contraceptive vaccines for animals.
Proceedings of the 5th International Symposium
on Non-Surgical Contraceptive Methods of
Pet Population Control; 2013 June 20–22;
Portland, oR, USA. http://www.acc-d.org/
resource-library/symposia/5th-symposium.
12 Levy JK, Friary JA, Miller LA, et al. Long-term
fertility control in female cats with
GonaCon™, a GnRH immunocontraceptive.
Theriogenology 2011; 76: 1517–1525.
13 Miller LA, Rhyan J and Killian G. GonaCon™, a
versatile GnRH contraceptive for a large variety
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of pest animal problems. Proceedings of the 21st
Vertebrate Pest Conference; 2004 March
1–4; Visalia, CA, USA. davis: University of
California, davis, pp 269–273.
14 Munks MW. Progress in development of
immunocontraceptive vaccines for permanent
non-surgical sterilization of cats and dogs.
Reprod Dom Anim 2012; 47 Suppl 4: 223–227.
15 Eisemann J. Recent advances in the develop-
ment of GonaCon™ immunocontraceptive
vaccine. Proceedings of the 5th International
Symposium on Non-Surgical Contraceptive
Methods of Pet Population Control; 2013 June
20–22; Portland, oR, USA. http://www.acc-d.org/
resource-library/symposia/5th-symposium.
16 Kutzler M and Wood A. Non-surgical
methods of contraception and sterilization.
Theriogenology 2006; 66: 514–525.
17 Miller L, Fagerstone K, Kemp J, et al. Immune
mechanisms and characterization of injection
site reactions involved in the multi-year
contraceptive effect of the GonaCon™ vac-
cine. Proceedings of the 23rd Vertebrate Pest
Conference; 2008 March 17–20; San diego, CA,
USA. davis: University of California, davis,
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18 Anonymous. GonaCon immunocontraceptive
vaccine for use on female white-tailed deer.
US department of Agriculture, Animal and Plant
Health Inspection Service, Pesticide Product label,
US. Environmental Protection Agency Registration
Number 56228-40, 2009.
19 Anonymous. GonaCon Equine. US department
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Environmental Protection Agency Registration
Number 56228-41, 2013.
20 Levy JK, Miller LA, Crawford C, et al. GnRH
immunocontraception of male cats.
Theriogenology 2004; 62: 1116–1130.
21 Levy JK. Multi-year study of single-dose
GnRH immunocontraceptive in cats.
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on Non-Surgical Contraceptive Methods for Pet
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Alexandria, VA, USA. http://www.acc-d.org/
resource-library/symposia/3rd-symposium.
22 Bender SC, Bergman dL, Wenning KM, et al.
No adverse effects of simultaneous vacci-
nation with the immunocontraceptive
GonaCon™ and a commercial rabies vaccine
on rabies virus neutralizing antibody produc-
tion in dogs. Vaccine 2009; 27: 7210–7213.
23 Vargas-Pino F, Gutiérrez-Cedillo V, Canales-Vargas
Available online at jfms.com
Reprints and permission: sagepub.co.uk/journalsPermissions.nav
For reuse of the photograph on page 758 of the semen analysis station, contact the corresponding author
Figure 1 ©iStockphoto.com/Christine_Bariana (white-tailed deer) and ©iStockphoto.com/Gary Alvis (wild horses)
R E V I E W / Vaccines for feline contraception
EJ, et al. Concomitant administration of
GonaCon™ and rabies vaccine in female dogs
(Canis familiaris) in Mexico. Vaccine 2013; 31:
4442–4447.
24 Miller LA and Killian GJ. Seven years of white-
tailed deer immunocontraceptive research at
Penn State University: a comparison of two
vaccines. The Ninth Wildlife damage Management
Conference Proceedings; 2000 oct 5–8; State
College, PA, USA, pp 60–69.
25 Miller LA, Johns BE and Killian GJ.
Immunocontraception of white-tailed deer
with GnRH Vaccine. Am J Reprod Immunol 2000;
44: 266–274.
26 Perry KR, Miller LA and Taylor J. Mycobacterium
avium: is it an essential ingredient for a single-
injection immunocontraceptive vaccine?
Proceedings of the 23rd Vertebrate Pest
Conference; 2008 March 17–20; San diego, CA.
davis: University of California, davis,
pp 253–256.
27 Munson L, Harrenstien LA, Acton AE, et al.
Immunologic responses and adverse reactions
to Freund’s-adjuvanted porcine zona pelluci-
da immuno-contraceptives in domestic cats.
Vaccine 2005; 23: 5646–5654.
28 Gunther I, Finkler H and Terkel J. Demographic
differences between urban feeding groups of
neutered and sexually intact free-roaming cats
following a trap–neuter–return procedure.
J Am Vet Med Assoc 2011; 238: 1134–1140.
29 Horn JA, Mateus-Pinilla N, Warner RE, et al.
Home range, habitat use, and activity patterns
of free-roaming domestic cats. J Wildl Manage
2011; 75: 1177–1185.
30 Schmidt PM, Lopez RL and Collier BA. Survival,
fecundity, and movements of free-roaming
cats. J Wildl Manage 2007; 71: 915–919.
31 Nutter FB, Levine JF and Stoskopf MK.
Reproductive capacity of free-roaming domes-
tic cats and kitten survival rate. J Am Vet Med
Assoc 2004; 225: 1399–1402.
32 Warner RE. Demography and movements of
free-ranging domestic cats in rural Illinois.
J Wildl Manage 1985; 49: 340–346.
33 Boone J. Better trap–neuter–return for free-
roaming cats. Using models and monitoring to
improve population management. J Feline Med
Surg 2015; 17: 800–807.
34 Miller PS, Boone Jd, Briggs JR, et al. Simulating
free-roaming cat population management
options in open demographic environments.
PLoS ONE 2014; 9: e113553. doI:10.1371/
journal.pone.0113553.
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Journal of Feline Medicine and Surgery (2015) 17, 766–771

CLINICAL REVIEW

Long-term contraception
in a smaLL impLant
A review of Suprelorin (deslorelin)
studies in cats
Christelle Fontaine

Rationale: Deslorelin (Suprelorin®; Introduction to deslorelin

Virbac) is a gonadotropin-releasing
hormone (GnRH) agonist licensed
in select countries for the long-term
suppression of fertility in adult male
dogs and male ferrets. This article
summarizes studies investigating the use
of deslorelin implants for the long-term suppression
of fertility in male and female domestic cats.
Deslorelin (the active ingredient in Suprelorin® 4.7 mg and Suprelorin®
9.4 mg; Virbac) is a synthetic gonadotropin-releasing hormone (GnRH)
agonist that is seven times more potent than GnRH.1 Prolonged
stimulation of GnRH receptors by deslorelin leads to desensitization of
these receptors.2 This results in a lack of synthesis and/or lack of
release of the gonadotropins luteinizing hormone (LH) and follicle-
stimulating hormone (FSH), inducing temporary infertility in treated

The 4.7 mg deslorelin implant is registered under the brand name

Evidence base: Slow-release deslorelin implants individuals.3

Suprelorin in the European Union (EU), Australia and New Zealand

have been shown to generate effective, safe and

for the long-term suppres-

reversible long-term contraception in male and

sion of fertility in adult

female cats. In pubertal cats, a 4.7 mg deslorelin

male dogs. The EU and

implant suppressed steroid sex hormones for an
Ease of administration, efficacy,
Australia have further reg- safety and reversibility explain why
average of approximately 20 months (range 15–25

istered the 9.4 mg implant

months) in males and an average of approximately

for chemical castration of

24 months (range 16–37 months) in females.
deslorelin implants are perceived
adult male dogs and adult
Reversibility has been demonstrated by fertile

male ferrets; Australia has

matings approximately 2 years post-treatment in
as a promising method for
additionally approved the
both male and female adult cats. In prepubertal
controlling reproduction in male
implant to manage hyper-
female cats of approximately 4 months of age,

adrenocorticism in ferrets.
puberty was postponed to an average of
and female cats.
(Suprelorin F, a 4.7 mg
approximately 10 months of age (range 6–15

deslorelin implant, is
months) by a 4.7 mg deslorelin implant. ®

available in the United States as a Food and Drug Administration

Challenges: The large variability in the duration of

Indexed Product to manage adrenal disease in sterilized and sexually

suppression of gonadal activity makes the definition

intact male and female ferrets.) Suprelorin 9.4 mg contains a double

of the optimal time for reimplantation quite

dose of deslorelin and a matrix without the excipient sodium acetate

challenging. In addition, the temporary stimulation

anhydrous to allow for a longer duration of infertility.

phase occurring in the weeks following deslorelin

As the GnRH amino acid sequence is highly conserved and as desen-

implantation can induce in adult female cats a fertile

sitization always occurs following continuous exposure to GnRH

estrus that needs to be managed to avoid unwanted

agonists (such as deslorelin), several research teams have investigated

pregnancy. Longer duration and larger scale

the potential of deslorelin to control reproduction and/or to prevent or

controlled field studies implementing blinding,

suppress sex hormone-related behavior and disease in male and

a negative control group and a carefully controlled

female cats.4
randomization to each group are needed.
Furthermore, the effects of repeated treatment need
to be investigated. Finally, the effect of treatment on
growth and bone quality of prepubertal cats needs
to be assessed. However, the ease of use,
long-lasting effects and reversibility of deslorelin
implants are strong positive points supporting their
use for controlling feline reproduction.
Christelle Fontaine
DVM
Medical Manager – Companion Animal
Medical Department, Virbac, France

Email: christelle.fontaine@virbac.com

766 JFMS CLINICAL PRACTICE

Doi: 10.1177/1098612X15594990
© The Author(s) 2015
766_771_Suprelorin_Fontaine.qxp_FAB 10/08/2015 13:23 Page 767
Alliance for Contraception in Cats & Dogs
This article is part of a Special Issue of the Journal of Feline Medicine and
Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline
fertility control’ and coordinated by the Alliance for Contraception in Cats
& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of
non-surgical fertility control to save the lives of cats and dogs, expand
options for pet owners, and improve animal welfare. Serving as a trusted
resource for scientific and educational
information, the ACC&D brings together key
stakeholders to advance humane sterilization
options that are faster, easier and more
accessible than surgery.
More information is available at www.acc-d.org
Physiological feasibility
The ease of administration, efficacy, safety
and reversibility of deslorelin implants
explain why they are perceived as a promis-
ing method for controlling male and female
domestic cat reproduction; in particular by the
owners of cats temporarily not intended for
breeding, but also by veterinary practitioners
for cats at increased anesthetic risk and by
organizations in areas without easy access to a
In most feline studies published in the
surgical facility.
scientific literature, deslorelin implants are
inserted subcutaneously through a needle
between5–12 or in the region of the shoulder
blades.13,14 If easy removal of the implant is
desired (eg, in an attempt to shorten the dura-
tion of action), the implant may also be insert-
ed into the umbilical area.15,16 Anesthesia or
sedation are not required.4,5,11
The aim of this review is to critically
appraise the available data on the off-label use
of Suprelorin 4.7 mg and Suprelorin 9.4 mg
for the control of reproduction in male and
female domestic cats, including both adult
and prepubertal populations. Pivotal informa-
tion used in this review has been obtained
from scientific papers in peer-reviewed jour-
nals,5,10–14,17–20 while supportive information
has been sourced from meeting summaries
and posters.6,7,9,15,16,21
Suprelorin dosing in studies
Most of the available data related to off-
label use of deslorelin implants in cats has
been obtained with Suprelorin 4.7 mg. This
review is, therefore, focused on data using
this drug dose. Where this is not the case,
the use of Suprelorin 9.4 mg is specified.
R E V I E W / Suprelorin (deslorelin) for fertility control in cats
Evidence base
Pharmacodynamics of deslorelin implants
in cats
in cats, neither the deslorelin release profile
nor the LH/FSH patterns after treatment
have been characterized. The efficacy of
Suprelorin in cats is therefore documented
through the use of indirect markers including
testosterone, progesterone or estradiol
The response to deslorelin, as observed with
concentrations.5,11,17,22
other GnRH agonists, is biphasic with an
initial stimulation period lasting a few days/
weeks followed by a long-lasting suppression
period.23 Following the stimulation phase
post-deslorelin implant insertion, during
which increases in progesterone and/or estra-
diol have been observed in female cats,11 all
The response
studies have demonstrated an extended peri-
od of reproductive suppression in both adult
to deslorelin
is biphasic, male cats (n = 10, 1–6 years of age)5 and adult
female cats (n = 20, 2–5 years of age).11 During
the suppression period, steroid concentrations
with an initial
below 1 ng/ml for progesterone and 10 pg/ml
stimulation
for estradiol have been observed in females;11
in male cats, plasma testosterone concentra-
period lasting
tion has remained at basal levels (<0.1 ng/ml).5
The time interval between Suprelorin inser-
a few
tion and the drop in steroid concentrations to
days/weeks
basal levels is defined in this review as the
‘time to downregulation’. In a study involving
followed by a
10 adult male cats (1–6 years old), the curve
describing time to downregulation, presented
long-lasting
suppression in Figure 1, demonstrates that downregulation
was reached in 90% (n = 9/10) of the cats after
3 months.5 Desensitization was achieved in
period.
half of the cats within 20 days of treatment, but
other cats needed more time. Reasons for this
large variability are not yet understood.
Figure 1 Probability of downregulation (testosterone plasma concentration <0.1 ng/ml)
in 10 sexually mature male cats according to the time after treatment with Suprelorin 4.7 mg.
Data extracted from Goericke-Pesch et al5
JFMS CLINICAL PRACTICE 767
766_771_Suprelorin_Fontaine.qxp_FAB 10/08/2015 13:23 Page 768
R E V I E W / Suprelorin (deslorelin) for fertility control in cats
The ‘duration of action’ of Suprelorin can be
defined as the interval between desensitiza-
tion and recurrence of ovarian or testicular
function. In female cats, the time to return to
continuous seasonal cycling,11 as assessed by
recurrence of a new estrous period including
typical sexual behavior, was 680.4 ± 62.0 days
(mean ± SD, n = 19/20), ranging from 483 days
(approximately 16 months) to 1025 days
(approximately 37 months).11 In one female
cat, the implant was still active at the end of
the study, with a duration of action of more
than 1102 days (>37 months).11 Noteworthy is
the large variability in the duration of action
of Suprelorin.
In a study involving seven adult male cats
(1–6 years of age), and using plasma testos-
terone concentration exceeding 0.5 ng/ml as
the threshold for resumption of gonadal func-
tion, duration of action was 78.8 ± 12.9 weeks
(mean ± SD) and ranged from 61.7 weeks
(approximately 15 months) to 100.7 weeks
(approximately 25 months).17
Overall, studies demonstrate a similar dura-
tion of efficacy in female and male cats, and
also very large individual variability in this
parameter in the two sexes. Factors involved
in this variability have not been clarified in
cats. Some authors suggest an individual sus-
ceptibility to deslorelin,11,13,17 while the impact
of vascularization at the insertion site, of drug
metabolism in the individual animal and of
individual variation in the desensitization
mechanism has not been explored.
Clinical effects of slow-release deslorelin
implants in male cats
Pivotal studies focused on sexually mature
male cats assessed the clinical effects of
Suprelorin both in experimental conditions,
with animals 1–6 years old (n = 10 and n =
7),5,17 and in field conditions with privately
owned indoor cats 1–4 years old (n = 22 and
n = 12).13,14 in one additional experimental
study of five adult male cats, the age of the
A significant increase in sexual behavior
animals was not reported.22
(libido, mounting and mating) was observed
in 8/10 adult male cats5 from the time of
Suprelorin administration until day 16 after
treatment, likely owing to the stimulation
phase of the treatment. After stimulation,
disappearance of penile spikes5 and signifi-
cant decreases in testicular volume5 and in
sexual behavior5 were observed in 10/10 treat-
ed male cats.
In two studies, complete disappearance of
penile spikes was recorded 9.4 ± 1.0 weeks
(mean ± SD, n = 10)5 and 5.8 ± 1.1 weeks (range
4–7 weeks) (mean ± SD, n = 5)22 after treatment.
In one of these studies, involving 10 cats,5
testicular volume (mean volume of right and
768 JFMS CLINICAL PRACTICE
All use of deslorelin implants in cats
is currently off-label.
left testes), relative to pretreatment values, was
significantly decreased by approximately 25%
at week 4, by about 60% at week 12 (approxi-
mately 3 months) and by 73.5% at week 36
(approximately 9 months).5 Similar results
were observed in another study run in field
conditions, with a significant decrease in tes-
ticular volume of 29.8% after 1 month (n = 22),
48% at 2 months (n = 18), 54% at 3 months
(n = 15) and 60.6% at 4 months (n = 12) post-
treatment.13
Sexual behavior (libido, mounting and
mating) was also assessed in a study involv-
ing 10 experimental cats kept in the presence
of a female in estrus.5 No interest in an estrous
female cat was observed commencing from
weeks 11 (n = 3), 12 (n = 5) and 16 (n = 2),
and this continued until the end of the
observation period at 36 weeks (approximate-
ly 9 months).5
Studies have assessed the impact of
Suprelorin on semen quality. Novotny et al
showed that sperm counts were significantly
decreased compared with pretreatment val-
ues, with a median of 0.001 x 106 spermatozoa
per ejaculate (range 0.000 x 106 to 18.000 x 106)
at week 16 (n = 12).13 Another study observed
complete azoospermia in all assessed cats
(4/4), but not until 6 months after treatment,14
indicating that there is a significant delay
between the initial changes in sperm produc-
tion and the onset of infertility. This is to be
expected given that the sperm production
cycle in tom cats lasts 46.8 days.24
Cats treated with deslorelin demonstrated
multiple behaviors commonly observed in
male cats following surgical castration. Urine
marking disappeared in all cats (n = 10) within
10 weeks of treatment.5 Furthermore, a small
supportive study involving six cats demon-
strated a gradual cessation of aggression
towards the owner (scratching, biting), and
reduction of vocalization and the strong intact
male cat smell within 18.7 ± 3.5 days (range
10–35 days).7 This lasted for at least 6–8
months, until the end of the observation peri-
od.7 Finally, in their study involving 10 cats,5
Goericke-Pesch et al observed a significant
increase in appetite 7.5 months following
treatment,5 similar to that commonly seen
after surgical castration.
Duration and reversibility of long-term
deslorelin effects in male cats were assessed in
a single study involving seven experimental
cats.17 Pretreatment testicular volumes were
reached 6.9 ± 3.4 weeks (range 5–11 weeks)17
766_771_Suprelorin_Fontaine.qxp_FAB 10/08/2015 13:23 Page 769
(mean ± SD, n = 7) after the last basal testos-
terone concentration was recorded, on aver-
age approximately 21 months after implant
administration.17 Time of reappearance of
penile spikes was idiosyncratic. They
reappeared in 2/7 cats while testosterone was
still at basal levels; while, in the other cats,
normal-size spikes were observed 10.8 ± 2.3
weeks (mean ± SD, n = 5/7) after the last basal
testosterone concentration was recorded.17
Normal penile spikes were observed in these
five cats on average approximately 21 months
after treatment.17
Return to fertility was assessed in four cats
allowed to mate estrous female cats until they
became pregnant.17 Libido first resumed
around 22 months after treatment, and 1–3
additional months were needed for normal
mating behavior to occur.17 Fertile matings
shown a similar
were achieved between 7 and 42 weeks
(approximately 10 months) after the last basal
testosterone concentration was recorded.17
The resulting litter size was 4.0 ± 0.0 kittens.17
Although obtained on a very small sample,
these results suggest high variability in the
time to return to full fertility after long-term
downregulation induced by Suprelorin.
Following treatment with a 4.7 mg deslore-
lin implant, no local reaction (eg, swelling or
scratching) was observed.5,13 There was no
change in the cats’ health status based on clin-
ical examinations, and blood counts and
serum biochemistry throughout Suprelorin
treatment remained in the normal inter-
val.5,7,9,15,21
Clinical effects of slow-release deslorelin
implants in female cats
Three pivotal studies have addressed the clin-
ical effects of Suprelorin in sexually mature
female cats.10–12 All trials were performed
under experimental conditions. Two evaluat-
ed Suprelorin 4.7 mg in 10 and 20 adult female
cats, respectively.10,11 The third study was a
controlled trial in which 28 adult female cats
were allocated to three groups that received:
one Suprelorin 9.4 mg implant alone (n = 14);
one Suprelorin 9.4 mg implant together with
concomitant megestrol actetate treatment
During the stimulation period, the increase
(n = 7); or a placebo implant (n = 7).12
in steroid concentrations was associated with
a behavioral estrus in 2/2011 and 4/1010 female
cats after treatment with a Suprelorin 4.7 mg
implant. Typical estrous behavior started by
3.8 ± 2.2 days (mean ± SD) post-treatment10
and lasted for 3.5 ± 3.1 days10 (n = 4/10).
Following the 9.4 mg deslorelin treatment,
estrous behavior was observed 2 days after
treatment in 2/14 female cats belonging to the
Suprelorin-only group.12
Despite estrus-like fecal estradiol concentra-
R E V I E W / Suprelorin (deslorelin) for fertility control in cats
tions, no estrous behavior was observed dur-
ing the stimulation period in 7/7 female cats
treated with 5 mg oral megestrol acetate at
14 days before, 12 h before and 14 days
after administration of a 9.4 mg deslorelin
implant.12 These results are encouraging, but
the small study size precludes any firm con-
clusion as to whether megestrol acetate
administration prior to Suprelorin treatment
is an efficient strategy to prevent induced
estrus.
The time to return to continuous seasonal
cycling was assessed in a single study involv-
ing 20 female cats that received Suprelorin
4.7 mg.11 The first post-treatment estrous peri-
od appeared in 680.4 ± 62.0 days (mean ± SD,
Studies have n = 19/20) (range 483 days [approximately 16
months] to 1025 days [approximately 37
months]).11 The high variability in this param-
Resumption of full fertility was assessed in
duration of eter mirrors that observed in male cats.
efficacy of eight female cats mated after the end of effica-
cy of Suprelorin 4.7 mg.11 Seven female cats
became pregnant immediately. All eight
Suprelorin
females delivered naturally and spontaneous-
ly. Litter size was 3.3 ± 1.5 kittens (mean ± SD),
in male and
female cats. ranging from one to five kittens.11
Both Suprelorin implants (4.7 mg and 9.4
mg) were well tolerated by adult female cats
The two sexes
in the aforementioned pivotal studies.10–12
Occasionally, slight and temporary adverse
also show a
similarly wide reactions at implant sites in the subcutaneous
interscapular area were observed, including
swelling of the skin (n = 1/20),11 pyodermatitis
individual
variation in (n = 1/10),10 edema (n = 3/21)12 and an erosive
laceration due to scratching (n = 1/21).12
In a single case report, a female cat
duration of
unintentionally treated with Suprelorin 4.7 mg
8–9 days after mismating delivered four
efficacy.
healthy kittens 66 days after the mismating,
but showed no interest in the kittens and milk
production was inadequate.20 Reproductive
behavior and parameters were reportedly
normal at the subsequent pregnancy.20
To assess the ability of Suprelorin to post-
pone puberty, one pivotal trial involved 30
prepubertal female cats treated when 114.4 ±
12.7 (mean ± SEM) days (approximately 4
months) old and weighing 1.5 ± 0.1 kg (mean
± SEM).19 Fourteen of the 15 treated kittens
reached puberty (diagnosed by estrous behav-
ior and vaginal cytology) when 281.2 ± 21.6
days old (mean ± SEM) (range 180–428
days).19 This was significantly later than the 15
queens of the control group, which displayed
puberty when 177.8 ± 10.8 days old (mean ±
SEM) (134–286 days).19 Body weight at puber-
ty was not different between the treated and
the control groups.19 However, one treated
queen showed induced estrus and another
showed clinical signs of pyometra 13 and 92
days, respectively, after treatment.19
JFMS CLINICAL PRACTICE 769
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R E V I E W / Suprelorin (deslorelin) for fertility control in cats

KEY points
< Deslorelin implants have been shown to effectively, safely and reversibly postpone puberty
or suppress reproductive function and related behaviors in male and female cats.
< In sexually mature cats, the duration of efficacy of a 4.7 mg deslorelin implant has been
shown to be approximately 20 months (range 15–25 months) in males and approximately
24 months (range 16–37 months) in females.
< The effects of deslorelin are reversible, as demonstrated by fertile matings approximately
2 years post-treatment in both male and female adult cats.
< However, the high variability in the onset of downregulation, duration of efficacy and
return to full fertility are potential challenges for practitioners and owners.
< Deslorelin implants are registered and sold in select countries under the brand name
of Suprelorin for long-term contraception in adult male dogs and ferrets.
< The market need for a long-term contraceptive method for cats, combined with the
encouraging preliminary results obtained with deslorelin, should encourage the
development of a new cat indication for Suprelorin implants once these initial results
have been confirmed in large clinical studies.

Challenges

Despite the fact that prevention of gonadal

function and fertility by deslorelin implants
has been shown to be safe, reversible and ISFM CONGRESS RECORDING
effective at managing undesirable sexual A recording of Christelle Fontaine’s session
behavior, this GnRH agonist is currently not on Suprelorin (deslorelin) studies in cats,
approved by any regulatory agencies for use presented at the 2015 ISFM Congress in Porto,

There are two main challenges that need to

is available at:
in cats. Hence all use in cats is off-label.
http://icatcare.org/vets/videos

be addressed before Suprelorin may be suc-

It is also included as

cessfully used in cats. Firstly, owing to the

Supplementary material at: jfms.com

large variability in the duration of efficacy, it is

DOI: 10.1177/1098612X15594990

very difficult to define the duration of effect

for the label claim – and, therefore, the time
for retreatment if an owner wishes to continue
contraception. Secondly, the stimulation
phase during the first weeks after implant
Funding

administration is associated in some female

cats with a fertile estrus that needs to be care-
The author received no specific grant from any

fully managed to avoid unwanted pregnan-

funding agency in the public, commercial or not-

cies. The efficacy of the two possible methods

for-profit sectors for the preparation of this article.

for reducing the occurrence of induced heats

(progestogens and treatment of prepubertal
Conflict of interest

queens) needs to be carefully evaluated.

Additionally, studies addressing the impact
The author is an employee of Virbac.

of deslorelin on growth (in particular on the

time of epiphyseal closure), and on the pheno-
References

type of treated prepubertal cats, are lacking. 1 Padula AM. GnRH analogues – agonists and
antagonists. Anim Reprod Sci 2005; 88: 115–126.
Conclusion 2 Navarro C and Schober P. Pharmacodynamics and
pharmacokinetics of a sustained-release implant
it is concluded that, although off-label, of deslorelin in companion animals. Proceedings
Suprelorin appears to be a safe, convenient of the 7th international Symposium on Canine and
and efficient reversible contraceptive for male Feline Reproduction. Whistler, BC, Canada; 2012
and female cats. July 26–29; pp 177–178.

770 JFMS CLINICAL PRACTICE

766_771_Suprelorin_Fontaine.qxp_FAB 10/08/2015 13:23 Page 771
R E V I E W / Suprelorin (deslorelin) for fertility control in cats
3 Junaidi AA, Williamson PEA, Martin GBB, et al.
Pituitary and testicular endocrine responses to
exogenous gonadotrophin-releasing hormone
(GnRH) and luteinising hormone in male dogs
treated with GnRH agonist implants. Reprod Fertil
Dev 2007; 19: 891–898.
4 Johnson JG. Therapeutic review: deslorelin
acetate subcutaneous implant. J Exot Pet Med
2013; 22: 82–84.
5 Goericke-Pesch S, Georgiev P, Antonov A, et al.
Clinical efficacy of a GnRH-agonist implant
containing 4.7 mg deslorelin, Suprelorin, regard-
ing suppression of reproductive function in tom-
cats. Theriogenology 2011; 75: 803–810.
6 Romagnoli S, Pisu M, Geretto N, et al. Duration
of control of reproductive function following
administration of a single 4.7 mg deslorelin
implant in tomcats and effect on testicular
histology. Proceedings of the 14th EVSSAR
Congress: Advances in Feline Reproduction; 2011
March 11; p 47.
7 Gültiken N, Ay S, Schäfer-Somi S, et al. The use
of the GnRH agonist deslorelin for contraception
in tom cats. Proceedings of the 14th EVSSAR
Congress: Advances in Feline Reproduction; 2011
March 11; p 46.
8 Ackermann C, Trevisol E, Destro F, et al. Effect of
deslorelin acetate (Suprelorin) in domestic cat
testicular morphology. Proceedings of the 7th
international Symposium on Canine and Feline
Reproduction. Whistler, BC, Canada; 2012 July
26–29; p 5.
9 Ackermann C, Trevisol E, Destro FC, et al.
Deslorelin acetate (Suprelorin) effects in semen
quality of domestic cats. Proceedings of the 7th
international Symposium on Canine and Feline
Reproduction. Whistler, BC, Canada; 2012 July
26–29; pp 3–4.
10 Ackermann CL, Volpato R, Destro FC, et al.
Ovarian activity reversibility after the use of
deslorelin acetate as a short-term contraceptive
in domestic queens. Theriogenology 2012; 78:
817–822.
11 Goericke-Pesch S, Georgiev P, Atanasov A, et al.
Treatment of queens in estrus and after estrus
with a GnRH-agonist implant containing 4.7 mg
deslorelin; hormonal response, duration of effi-
cacy, and reversibility. Theriogenology 2013; 79:
640–646.
12 Toydemir TSF, Kılıçarslan MR and olgaç V. Effects
of the GnRH analogue deslorelin implants
on reproduction in female domestic cats.
Theriogenology 2012; 77: 662–674.
13 Novotny R, Cizek P, Vitasek R, et al. Reversible
Available online at jfms.com
Reprints and permission: sagepub.co.uk/journalsPermissions.nav
Title photograph on page 766 courtesy of Kathy Milani/The Humane Society of the United States
For reuse of Figure 1, contact the author
suppression of sexual activity in tomcats with
deslorelin implant. Theriogenology 2012; 78:
848–857.
14 Novotny R, Vitasek R, Bartoskova A, et al.
Azoospermia with variable testicular histology
after 7 months of treatment with a deslorelin
implant in toms. Theriogenology 2015; 83:
1188–1193.
15 Gogny A and Tropie E. Normal fertility and kit-
tening after injection and removal of a deslorelin
implant in a breeding queen. Proceedings of the
17th EVSSAR Congress: Reproduction and
Pediatrics in Dogs, Cats and Exotics. Wroclaw,
Poland; 2014 Sept 26; p 181.
16 Romagnoli S, Mollo A, Scenna L, et al. Effect of a
9.4 mg deslorelin implant on reproduction in
male cats: a preliminary report. Proceedings of
the 17th EVSSAR Congress: Reproduction and
Pediatrics in Dogs, Cats and Exotics. Wroclaw,
Poland; 2014 Sept 26; p 155.
17 Goericke-Pesch S, Georgiev P, Antonov A, et al.
Reversibility of germinative and endocrine tes-
ticular function after long-term contraception
with a GnRH-agonist implant in the tom – a
follow-up study. Theriogenology 2014; 81: 941–946.
18 Goericke-Pesch S, Wehrend A and Georgiev P.
Suppression of fertility in adult cats. Reprod
Domest Anim 2014; 49 Suppl 2: 33–40.
19 Risso A, Corrada Y, Barbeito C, et al. Long-term-
release GnRH agonists postpone puberty in
domestic cats. Reprod Domest Anim 2012; 47: 936–938.
20 Goericke-Pesch S, Georgiev P, Atanasov A, et al.
Treatment with Suprelorin in a pregnant cat.
J Feline Med Surg 2013; 15: 357–360.
21 Novotny R, Vitasek R, Bartoskova A, et al. The
influence of initial stimulatory effect of deslore-
lin implant on semen quality in tomcats. in:
Proceedings of the 17th EVSSAR Congress:
Reproduction and Pediatrics in Dogs, Cats and
Exotics. Wroclaw, Poland; 2014 Sept 26; p 200.
22 Goericke-Pesch S, Georgiev P, Fasulkov i, et al.
Basal testosterone concentrations after the appli-
cation of a slow-release GnRH agonist implant
are associated with a loss of response to busere-
lin, a short-term GnRH agonist, in the tom cat.
Theriogenology 2013; 80: 65–69.
23 Rubion S and Driancourt MA. Controlled delivery
of a GnRH agonist by a silastic implant (Gonazon)
results in long-term contraception in queens.
Reprod Domest Anim 2009; 44 Suppl 2: 79–82.
24 França LR and Godinho CL. Testis morphometry,
seminiferous epithelium cycle length, and daily
sperm production in domestic cats (Felis catus).
Biol Reprod 2003; 68: 1554–1561.
JFMS CLINICAL PRACTICE 771
772_776_IntratesticularLH_Kutzler.qxp_FAB 10/08/2015 14:19 Page 772
CLINICAL REVIEW
intratesticular and intraepididymal
injections to sterilize male cats
From calcium chloride to
zinc gluconate and beyond
Michelle A Kutzler
Aim and rationale: The aim of
intratesticular and intraepididymal
injections is to provide an inexpensive
non-surgical method for sterilizing
tom cats. Intratesticular and
intraepididymal injections have been
studied for decades and warrant
continued investigation. While both methods result
in azoospermia, intratesticular injection of sclerosing
agents induces orchitis, resulting in decreased
spermatogenesis, whereas intraepididymal injection
blocks sperm transport but does not alter
spermatogenesis.
Evidence base: Sclerosing agents that have
been used effectively for intratesticular injections
in cats include calcium chloride dihydrate and
zinc gluconate. For sclerosis by intraepididymal
injections, chlorhexidine digluconate has been used
successfully in cats. The volume, formulation and
concentration of sclerosing agents for intratesticular
and intraepididymal injections in cats have not been
standardized.
Challenges: Neither intratesticular nor
intraepididymal injections entirely eliminate gonadal
testosterone production, which may be undesirable
for pet cats and therefore may restrict the application
of this method of sterilization to feral cats with limited
human contact. In addition, both methods may
require sedation or general anesthesia, leading some
to support routine castration over these non-surgical
methods. Lastly, even if the technique is successful
in inducing permanent
sterility, normal fertility
may persist in treated
males for 1–2
months after
ISFM CONGRESS RECORDING treatment
A recording of Michelle Kutzler’s session on because of
intratesticular sterilants and alternative methods sperm present
for feline fertility control, presented at the 2015 within the
ISFM Congress in Porto, is available at:
epididymis and
http://icatcare.org/vets/videos
vas deferens.
It is also included as
Supplementary material at: jfms.com
DOI: 10.1177/1098612X15594991
772 JFMS CLINICAL PRACTICE
Journal of Feline Medicine and Surgery (2015) 17, 772–776
Intratesticular injections
Intratesticular injections have been investigated as a method of male
contraception for more than six decades.1 Improvements in the injec-
tion technique and refinements in the solutions injected have greatly
reduced the incidence and severity of adverse reactions. In search of an
ideal non-surgical sterilant for intratesticular injection, a broad range
of agents has been tested in a wide range of species. For the purposes
of this review, only those substances used for intratesticular injection in
The goal of intratesticular injection is to induce aspermatogenic
cats will be discussed.
orchitis, resulting in permanent azoospermia. According to current
research, intratesticular injections in cats induce prolonged (and theo-
retically permanent) azoospermia (or teratospermia or necrospermia)
following a 4–6 week delay.2,3 This treatment efficacy delay is most
likely attributable to sperm reserves present in the epididymis.4
Depending on the agent injected, there may also be a reduction in
androgen concentrations. However, complete elimination of gonadal
sources of testosterone is unlikely, irrespective of treatment.
Rationale
The technique of intratesticular injection is precise but not technically
challenging, and it is inexpensive compared with surgical castration.
However, the various agents used for feline intratesticular injection are
still under research and
development, and cur-
rently not yet suitable Injection technique
for large-scale steriliza- The scrotal skin should be disinfected to
tion programs in cats. minimize iatrogenic infections. The procedure for
With respect to intratesticular injection involves inserting a
restraint, recommenda- 27 gauge, 12 mm (0.5 inch) needle into one pole
tions vary from general of the testis and gently pushing it towards the
anesthesia3,5,6 to ‘stan- other pole, depositing the solution homo-
dard humane manual geneously through the testis while extracting the
restraint’.7 The scrotal needle. The needle is inserted into the cranial or
hair may need to be caudal pole, depending on the chemical being
clipped to allow for injected (see later, under ‘Evidence base’). A
proper injection tech- separate needle should be used for each testis.
nique.
Michelle A Kutzler
DVM PhD DACT
Associate Professor of Companion Animal Industries,
Department of Animal and Rangeland Sciences,
Oregon State University,
Corvallis, Oregon, USA
Email: Michelle.Kutzler@oregonstate.edu
doI: 10.1177/1098612X15594991
© The Author(s) 2015
772_776_IntratesticularLH_Kutzler.qxp_FAB 10/08/2015 13:26 Page 773
The goal is to inject enough chemical to
cause necrosis in the majority of the testicular
tissue without injecting excess solution that
can leak out and result in skin necrosis or
adversely affect adjacent tissues.
Studies using this method for male steriliza-
tion in cats report no or minimal signs of
discomfort following injection, which can be
explained by the fact that afferent nerve end-
ings associated with pain sensation are locat-
ed only on the scrotal skin and in the testicular
capsule rather than within the testicular
parenchyma.8 Within 24 h following the injec-
tion, a transient increase in testicular diameter
may occur, resulting in pain secondary to
swelling of the testicular capsule. None of the
systemic reactions reported after intratesticu-
lar injections in dogs (neutrophilia, vomiting,
anorexia and lethargy)9 have been reported
in cats.
Evidence base
Calcium chloride dihydrate (CaCl2)
Intratesticular injection of a CaCl2 solution
induces sterilization via two mecha-
nisms:
< Intratesticular edema following
the injection leads to necrosis and
fibrosis, which causes degeneration of
seminiferous tubules (and germ cells)
and the interstitial (Leydig) cells;
< Free radicals produced within
testicular tissue following the
injection lead to lipid peroxidation
and destruction of other cellular
structures, which also directly
CaCl2 intratesticular injections
impairs spermatogenesis.2
should be performed using a sterile
27 gauge needle directed from the
ventral aspect of each testis approxi-
mately 0.5 cm from the epididymal
tail towards the cranial aspect of that
testis (Figure 1). The CaCl2 should be
carefully deposited along the entire
route by linear infiltration while with-
drawing the needle from the proximal
to distal end.
Although there has been consider-
able research in other species (includ-
ing dogs) using CaCl2 intratesticular
injections for sterilization, there have
only been two studies in cats. First,
Baran and colleagues injected a vol-
ume of 0.2 ml per testis of 0% (n = 1
cat), 5% (n = 1 cat), 10% (n = 1 cat) or
20% (n = 1 cat) CaCl2 and found that
the 5% and 10% treated cats were
oligospermic (<20 million sperm/ml in ejacu-
late), whereas the 0% treated cat had a normal
Figure 1 Injection of
calcium chloride dihydrate
ejaculate (>20 million sperm/ml).10 The 20%
(CaCl2) solution into the right
treated cat did not ejaculate any sperm, and
and left testis of a male cat.
Reproduced from Baran et al,10
with permission
R E V I E W / Intratesticular and intraepididymal injections for non-surgical sterilization
histologic evaluation showed degeneration
and calcification of the seminiferous tubules
and interstitial cells along with significant
fibrosis at 60 days post-treatment.10
In a similar study, Jana and Samanta inject-
ed a volume of 0.25 ml per testis of 0% (n = 6
cats), 5% (n = 6 cats), 10% (n = 6 cats) or 20%
(n = 6 cats) CaCl2 in saline with 1% lidocaine.7
The intratesticular injection of 5% CaCl2
induced dissolution of germ cells associated
with atrophy of the seminiferous tubules.7
However, the effects were uneven and
inconsistent throughout the testes.7 The intra-
The
intratesticular testicular injection of 10% CaCl2 induced
coagulative necrosis in the seminiferous
epithelium and interstitial spaces.7
injection
Degenerated and coagulated germ cells were
present in combination with fibrous tissue in
technique is
precise but not tubular and interstitial spaces.7 Intratesticular
injection of 20% CaCl2 solution resulted in
complete testicular necrosis of the entire
technically
germinal epithelium, with only fibrous and
hyaline tissue remaining.7 At 60 days post-
challenging.
treatment, serum testosterone concentrations
were an average of 2.15 ng/ml in the
20% CaCl2 group compared with 7.82
ng/ml in the 0% CaCl2 group. Anecdotal
reports also note a reduction in sex-
linked behaviors following treatment.
Intratesticular CaCl2 injection is
reported to be well tolerated.10 Mild
discomfort can be observed 1–5 mins
after injection.7 Testicular swelling is
evident by 24 h, peaking 2–4 days
following injection and then
decreasing over a period of 3–4 weeks.7
Care should be taken to prevent seep-
age of CaCl2 solution from the injection
site because, if the solution remains on
or under the scrotal skin, tissue necrosis
occurs.7 If the solution is immediately
wiped away, then complications may
be avoided.7 Scrotal skin necrosis can
also develop if an excessive volume is
injected or leakage occurs outside of the
tunic.11 Although sample sizes are
small, no serious adverse effects have
been reported.
Ingredients to prepare the CaCl2
solution for intratesticular injection
(eg, sterile analytical grade CaCl2) are
readily available in many countries
where commercially manufactured
products for canine intratesticular
injection are not available or are too
expensive.12 However, the formulation,
concentration and volume of the CaCl2
solution for intratesticular injection in
cats are not yet standardized. Studies to date
suggest that alcohol or lidocaine are superior
to saline or water as a vehicle.12
Effectiveness of the CaCl2 solution appears
JFMS CLINICAL PRACTICE 773
772_776_IntratesticularLH_Kutzler.qxp_FAB 10/08/2015 13:26 Page 774
R E V I E W / Intratesticular and intraepididymal injections for non-surgical sterilization
to vary from no change to complete destruc-
tion of sperm production depending on vol-
ume, vehicle and CaCl2 concentration.12 The
final volume (0.2–0.25 ml/testis) administered
depends upon testicular mass. The injection
volume of 0.25 ml was selected by standardi-
zation with a concentration-dependent
study;7 in that study, this volume of a high-
concentration CaCl2 solution caused necrosis
of the entire testicular parenchyma without
any leakage.7 At the highest concentrations,
sterility appears to be permanent based on the
type of testicular destruction seen, but few
studies have allowed these chemically steril-
ized toms to mate or have followed the
histopathological results past 3 months.
Zinc gluconate
Ark Sciences (New York, USA) manufactures
a proprietary zinc gluconate solution for
intratesticular injection. This product contains
0.2 M zinc gluconate (13.1 mg zinc/ml), which
is neutralized to pH 7.0 with 0.2 M L-arginine.
Zeuterin™ (approved by the US Food and
drug Administration [FdA] for use in male
dogs 3–10 months of age) and EsterilSol™
(the formulation name marketed in select
Latin American countries) have been used
off-label in cats and in older dogs. BioRelease
Technologies (Birmingham, Alabama, USA)
also manufactures a proprietary zinc glu-
conate solution for intratesticular injection
(Testoblock®). This product contains 0.2 M
zinc gluconate (13.1 mg zinc/ml), which is
pH-neutralized with arginine in a physiologic
Irrespective of the product, the procedure
proprietary vehicle.13
for intratesticular injection of zinc gluconate
involves inserting a 27 gauge needle connected
to a 0.5 ml U100 insulin syringe into one pole
of the testis and gently pushing it towards the
other pole. The solution is deposited homoge-
neously throughout the testis as the needle is
withdrawn. Similar to CaCl2, the needle for
zinc gluconate should be inserted parallel to
the long axis of the testis. However, unlike
CaCl2, the needle for zinc gluconate should be
inserted into the dorsal-cranial area of each
testis, lateral to the caput epididymis (close to
the rete testis and efferent ducts). No explana-
tion is provided by investigators using either
CaCl2 or zinc gluconate for the difference in
direction of needle insertion.
More extensive research with zinc glu-
conate has taken place in dogs than in cats;
the incidence of side effects using the Ark
Sciences product to sterilize male dogs is
lower than reported for surgical castration
(incidence of injection-site reactions reported
in 270 dogs was 1.1%).12 Levy reported that
115 cats were treated with a dose of 0.3–0.4
ml/testis of EsterilSol at 6 months of age, with
774 JFMS CLINICAL PRACTICE
Alliance for Contraception in Cats & Dogs
This article is part of a Special Issue of the Journal of Feline Medicine and
Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline
fertility control’ and coordinated by the Alliance for Contraception in Cats
& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of
non-surgical fertility control to save the lives of cats and dogs, expand
options for pet owners, and improve animal welfare. Serving as a trusted
resource for scientific and educational
information, the ACC&D brings together key
stakeholders to advance humane sterilization
options that are faster, easier and more
accessible than surgery.
More information is available at www.acc-d.org
no injection-site reactions developing during
12 months of monitoring. Treatment resulted
in reduced serum testosterone concentrations,
testicular atrophy and absence of sperm.14
Using Testoblock in cats, no biting or licking
of the scrotum or testes following intratesticu-
lar injection have been reported, but a tran-
sient testicular swelling 1 day after injection
does occur.3 No apparent scrotal or testicular
pain or tenderness was noted with Testoblock,
except for one treated cat that displayed
reduced activity and feed intake for 2–3 h
post-injection.3
Oliveira and coworkers injected 0.44–0.51
ml/testis of Testoblock on the basis of testis
width (measured with calipers). The zinc glu-
conate solution was administered at a rate of
1 ml for every 27 mm of testis width.3 The
dose of zinc gluconate for intratesticular injec-
tion is non-linear. According to the authors,
this dose was adapted from research in dogs
using 0.3 ml of zinc gluconate solution for a
testis 12–14 mm wide.15 The testicular width
No explanation
is provided by of zinc gluconate-treated cats decreased over
120 days, and testosterone-dependent penile
spines were absent in 36% (4/11) and
investigators
decreased in 54% (6/11) of treated cats. One
cat still had well-developed penile spines.3 On
using either
CaCl2 or zinc day 60, 91% (10/11) of treated cats were
azoospermic, and the remaining cat had
reductions in both sperm count and sperm
gluconate for
motility.3 However, on day 120, only 73%
(8/11) of treated cats were azoospermic.3 One
the difference
in direction treated cat had necrospermia and two had
asthenospermia.3 Plasma testosterone concen-
trations were not significantly different
of needle
between controls and cats treated with zinc
gluconate3 and remained within the normal
insertion into
the testis. reference interval for domestic cats.16 Despite
normal testosterone levels on days 60 and 120,
owners reported that treated cats showed
reduced aggression, roaming, mounting and
urine marking (spraying), whereas these
activities persisted in control cats.3
772_776_IntratesticularLH_Kutzler.qxp_FAB 10/08/2015 13:26 Page 775
The testes from the treated cats in the
Oliveira and coworkers’ study were evaluated
histopathologically by Fagundes and col-
leagues.5 Cats treated with zinc gluconate had
few or no germ cells present in the basal and
adluminal compartments of the seminiferous
epithelium and most of the seminiferous
tubules were atrophied.5 Conversely, some
tubules had increased in size owing to an
expanded lumen, but these tubules also had
fewer germ cells and incompletely formed
spermatids.5 Sertoli cells displayed intra-
cytoplasmic vacuolation and most of the
seminiferous tubules had a thicker basement
membrane.5 Hyalinized formations were
present within the intertubular tissue along
with clusters of Leydig cells surrounded by
collagen, fibroblasts and inflammatory cells.5
Challenges
To date, less research has taken place on
intratesticular injection in cats than in dogs.
Large scale (eg, 100–1000 cats) field experi-
ments with a methodology that will allow for
determination of the appropriate dose (and
formulation with respect to CaCl2), as well as
long-term (eg, 2–3 years) follow-up on fertility
outcomes (eg, sperm counts, testicular histol-
None of the intratesticular injection products
ogy), are needed.
described herein entirely eliminates gonadal
testosterone production. The minimum thresh-
old for circulating testosterone concentration
for behavior change on a par with castration is
not known, and additional behavioral studies
following intratesticular injections in cats are
warranted. Elimination of gonadal testosterone
production would be preferential for indoor
cats, as even low levels of circulating testos-
terone may be associated with characteristic
tom cat behaviors (eg, urine marking/spraying,
inter-cat aggression). For pet cats (either
owned or in shelters available for adoption)
and unowned, free-roaming/feral cats close to
human habitation, this behavior would be
unacceptable. A reduction in male reproduc-
tive behaviors has, however, been anecdotally
reported with intratesticular injections, which
warrants additional research in this area.
Intraepididymal injections
The use of a broad range of sclerosing agents
to chemically vasectomize and induce perma-
nent sterility has also been investigated in a
wide range of species. For the purposes of
this review, only research on intraepididymal
injection in cats will be discussed.
Rationale
The site of injection is important to the
mechanism of action: intraepididymal injec-
R E V I E W / Intratesticular and intraepididymal injections for non-surgical sterilization
Intraepididymal injection blocks sperm transport,
whereas intratesticular injection decreases
spermatogenesis and results in azoospermia.
tion blocks sperm transport, whereas intra-
testicular injection decreases spermatogenesis
and results in azoospermia.17 Unlike the dog,18
the tail of the epididymis in cats is very small
and may be more difficult to locate. For this
procedure, a 30 gauge needle should be used.6
Evidence base
Pineda and dooley administered intra-
epididymal injections of 4.5% chlorhexidine
digluconate to mature tom cats and collected
weekly semen samples for 36 weeks.6 There
was considerable variation in the response
to treatment among cats, both within and
between treatment groups (0.05 ml vs 0.10
ml), including inconsistent and transient
severe oligospermia or azoospermia.6 At vari-
ous time points following the intraepididymal
injection, three of the four (75%) cats in the
0.05 ml treatment group became azoospermic
compared with only one of the four (25%)
given 0.10 ml of the sclerosing agent.6 A tran-
sient scrotal swelling was reported within the
first 2 weeks following injection.6 during this
same period, cats demonstrated a withdrawal
reaction when pressure was applied to the
epididymal area of the scrotum.6 However,
open wounds and other undesirable clinical
signs were not observed and the intraepididy-
mal injections did not impair ambulation or
alter the general behavior of the cats.6
At the conclusion of the study, toms were cas-
trated and the testes and epididymides were
histologically evaluated. Cats given intraepi-
didymal injections of chlorhexidine diglu-
conate had normal germinal epithelium and
active spermatogenesis.6 Microscopic sperm
granulomas were found bilaterally in the epi-
didymides of the treated cats irrespective of
whether or not they became azoospermic.6
Challenges
Intraepididymal injections for sterilizing male
cats have demonstrated both successes and
failures. Intraepididymal injections do not
reduce gonadal testosterone production. This
may be advantageous for feral cat trap–
neuter–return (TNR) programs because domi-
nant, high libido, sterilized males will mate
with queens and induce pseudopregnancy,
possibly limiting opportunities for queens to
actually become pregnant by non-sterilized
toms. By contrast, this behavior would be
unacceptable for pet cats and unowned, free-
roaming/feral cats close to human habitation.
JFMS CLINICAL PRACTICE 775
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R E V I E W / Intratesticular and intraepididymal injections for non-surgical sterilization

KEY points
< Intratesticular and intraepididymal injections are inexpensive compared with surgical sterilization. Once optimized
for success with additional research, intratesticular injection may be suitable for large-scale sterilization programs.
< Although both methods may require sedation or general anesthesia, the technique of intratesticular injection is not
technically challenging; intraepididymal injection is more difficult owing to the relatively smaller size of the tail of the
epididymis compared with the testis.
< Normal fertility may persist in treated males for 1–2 months after either intratesticular or intraepididymal treatment
because of sperm present within the epididymis and vas deferens.
< Intraepididymal injections do not affect testosterone production, which is undesirable for pet cats and feral cats
close to human habitation. Although intratesticular injections do not entirely eliminate testosterone production,
a reduction in male reproductive behaviors has been anecdotally reported, which warrants additional research.

Funding
The author received no specific grant from any funding agency in
the public, commercial or not-for-profit sectors for the prepara-
tion of this article.
Conflict of interest
The author has no conflict of interest to declare.
References
1 Freund J, Lipton MM and Thompson GE. Aspermatogenesis
in the guinea pig induced by the testicular tissue and adju-
vants. J Exp Med 1953; 97: 711–726.
2 Jana K, Samanta PK and Ghosh d. Evaluation of single
intratesticular injection of calcium chloride for nonsurgical
sterilization of male Black Bengal goats (Capra hircus): a
dose-dependent study. Anim Reprod Sci 2005; 86: 89–108.
3 oliveira EC, Fagundes AK, Melo CC, et al. Intratesticular
injection of a zinc-based solution for contraception of
domestic cats: a randomized clinical trial of efficacy and
safety. Vet J 2013; 197: 307–310.
4 Axnér E. Sperm maturation in the domestic cat.
Theriogenology 2006; 66: 14–24.
5 Fagundes AK, oliveira EC, Tenorio BM, et al. Injection of a
chemical castration agent, zinc gluconate, into the testes of
cats results in the impairment of spermatogenesis: a poten-
tially irreversible contraceptive approach for this species?
Theriogenology 2014; 81: 230–236.
6 Pineda MH and dooley MP. Surgical and chemical vasecto-
my in the cat. Am J Vet Res 1984; 45: 291–300.
7 Jana K and Samanta PK. Clinical evaluation of non-surgical
sterilization of male cats with single intra-testicular injec-
tion of calcium chloride. BMC Vet Res 2011; 7: 39.
8 Schummer A, Nickel R and Sak Wo. The viscera of domestic
animals. In: Schummer A, Nickel R and Sak Wo (eds).
Urogenital system: male genital organs of the carnivores.
2nd ed. New York: Springer-Verlag, 1979, pp 324–328.
9 Zeuterin package insert. http://www.arksciences.
com/images/pdf/ZeuterinCMCPackageInsertFinal.pdf
(accessed october 7, 2014).
10 Baran A, ozdas A, Gulcubuk A, et al. Pilot study: intratestic-
ular injection induces sterility in male cats. Proceedings of
the 4th International Symposium on Non-Surgical Methods of
Pet Population Control; 2010 April 8–10; dallas, TX, USA.
Alliance for Contraception in Cats & dogs [abstract], 2010.
http://www.acc-d.org/resource-library/symposia/4th-
symposium.
11 Koger LM. Calcium chloride castration. Mod Vet Pract 1978;
119–121.
12 Golden T. Calcium chloride as a non-surgical sterilant for
male dogs and cats: a history and summary of research.
http://www.acc-d.org/docs/default-source/Research-and-
Innovation/accd_cacl2review-nov2014.pdf?sfvrsn=2
(accessed october 7, 2014).
13 oliveira EC, Moura MR, de Sá MJ, et al. Permanent contra-
ception of dogs induced with intratesticular injection of
a zinc gluconate-based solution. Theriogenology 2012; 77:
1056–1063.
14 Levy J. Current contraceptive approaches for feral cats.
Proceedings of the 4th International Symposium on Non-
Surgical Methods of Pet Population Control; 2010 April 8–10;
dallas, TX, USA. Alliance for Contraception in Cats & dogs,
[PowerPoint slides]. http://www.acc-d.org/docs/default-
source/4th-symosium/levy_cats_ppt.pdf?sfvrsn=2 (2010,
accessed october 7, 2014).
15 Wang M. Neutersol: intratesticular injection induces sterili-
ty in dogs. Proceedings of the 1st International Symposium
on Non-Surgical Methods for Pet Population Control;
Alliance for Contraception in Cats & dogs; April 2002, Pine
Mountain, GA, USA. pp 62–65.
16 Kirkpatrick JF. Seasonal testosterone levels, testosterone
clearance, and testicular weights in male domestic cats.
Can J Zool 1985; 63: 1285–1287.
17 Bloomberg MS. Surgical neutering and nonsurgical alterna-
tives. J Am Vet Med Assoc 1996; 208: 517–519.
18 Pineda MH, Reimers TJ, Faulkner LC, et al. Azoospermia in
dogs induced by injection of sclerosing agents into the
caudae of the epididymides. Am J Vet Res 1977; 38: 831–838.

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777_782_MPG_Johnston and Rhodes.qxp_FAB 10/08/2015 13:32 Page 777

Journal of Feline Medicine and Surgery (2015) 17, 777–782

CLINICAL review

No surgery required: the

future of feliNe sterilizatioN
An overview of the Michelson Prize
& Grants in Reproductive Biology
Shirley Johnston and Linda Rhodes

Introduction Overview: For many years, researchers

For over 30 years, researchers have investigated non-surgical technolo-
gies that might be used to suppress fertility in cats and dogs. When
women began using oral contraceptives composed of progestogens
and/or estrogens, various similar oral drugs for dogs were tried briefly,
but were found to have deleterious side effects. in cats, progestational
drugs suppress male and female reproduction but also lead to type 2
diabetes, mammary nodules and, in females, increased risk of pyome-
tra. These sex steroid therapeutic approaches cannot provide permanent
sterility without repeated dosing, and so cannot be considered a true
have been studying reproduction of cats
and dogs, including approaches to
non-surgical sterilization, but scant
funding has been available for this work.
Recognizing the need to fund research and
to attract researchers from the biomedical
community to apply their expertise to this area,
the Michelson Prize & Grants (MPG) in Reproductive
Biology program was founded. Since 2009, it has
funded 34 research projects in seven countries

Immunocontraception has been tested in cats and dogs using vac-

alternative to castration for males and ovariohysterectomy for females. toward discovery of a safe single-administration

cines against zona pellucida proteins and gonadotropin-releasing hor-

lifetime non-surgical sterilant in male and female

mone (GnRH). These methods showed some promise, but they require
cats and dogs.

multiple boosters. Hormone implants with the GnRH agonist deslore-

Goal: The goal of the MPG program is the

lin (Suprelorin®; Virbac) became available about 6 years ago in Europe.

reduction or elimination of the approximately

However, they also have the limitation of only lasting a year and being
2.7 million deaths of healthy shelter cats and dogs

labeled for use only in male dogs. All of these approaches are short-
in the US every year. The successful product is

term solutions and particularly unsuited to use for feral or shelter cats
expected to be a single-dose injectable product

and dogs, where permanent sterility is the goal.

approved by the US Food and Drug Administration

Surgical ovariohysterectomy (or ovariectomy) and castration remain

as a veterinary prescription item. The most

the gold standard for inducing permanent sterility in cats and dogs.
optimistic prediction is that such a product will

Surgical sterilization not only prevents generation of offspring, it also

reach the hands of practicing veterinarians within

prevents undesirable behav-

the next decade.

iors associated with estrogen

Areas of research: Active research is in progress

secretion in the female and

using approaches such as immunocontraception

testosterone secretion in the

Surgical sterilization has had a with a single-administration vaccine against

male that can be barriers to

gonadotropin releasing hormone (GnRH). Long-term
significant impact in reducing the
successful pet ownership.
therapy with GnRH agonists such as deslorelin

Although surgical steriliza-

numbers of animals euthanized in administered in controlled-release devices is also

tion is associated with

being studied. Other scientists are targeting cells
shelters, but requires expensive
undesirable sequelae in
in the brain or gonads with cytotoxins, such as are

some pets (obesity, urinary

used in cancer chemotherapy. Gene therapy
infrastructure and substantial
incontinence, joint disease
expressing proteins that suppress reproduction and

and some cancers), it also

community commitment. gene silencing of peptides essential to reproduction
are further avenues of research. Findings are
available at www.michelsonprizeandgrants.org/
michelson-grants/research-findings.
Shirley Johnston
DVM PhD DACT
Director of Scientific Research, Found Animals Foundation,
Los Angeles, California, USA
Email: s.johnston@foundanimals.org

Linda Rhodes
VMD PhD
Board of Directors, Alliance for Contraception
in Cats & Dogs (ACC&D), Portland, Oregon, USA
Email: ladycowvet@gmail.com

doi: 10.1177/1098612X15594992
© The Author(s) 2015 JFMS CLINICAL PRACTICE 777
777_782_MPG_Johnston and Rhodes.qxp_FAB 10/08/2015 13:32 Page 778

R E V I E W / Michelson Prize & Grants in Reproductive Biology

prevents significant undesirable outcomes that tions from around the world and from
occur in intact pets. These include a high disciplines such as reproductive biology, gene
incidence of mammary and testicular cancer, therapy, neuroendocrinology, immunology,
prostatic hypertrophy, undesired mating and oncology, bioengineering, medicinal chem-
pregnancy, pyometra and pregnancy disorders istry and many more.
such as dystocia. Applications for Michelson grant funding
An estimated 2.7 million healthy dogs and are accepted after approval of a two-page
cats are euthanized in US shelters alone every Letter of Intent, and they are reviewed by
year.1 While surgical sterilization has had a a 20-member Scientific Advisory Board
significant impact in reducing the numbers of (www.michelsonprizeandgrants.org/about/
shelter animal deaths, it requires substantial scientific-advisory-board) that meets three
and expensive infrastructure and community times per year to review and recommend
commitment. There are not enough veterinary approval of applications.
surgeons or adequate financial resources to
make surgery available to all homeless pets.
(For a comprehensive review of the various
Research in progress

methods of cat and dog non-surgical contra-

ception used over the years, see the Alliance
Found Animals Foundation has received 338

for Contraception in Cats & Dogs’ 2013

Both the prize Letters of intent and 124 full applications for

report.)2
research funding since 2008, of which 34 pro-
and grants posals have been funded. Proposals funded to
date encumber approximately $14.2 million of
are directed
Research in projects funded has fallen into
The Michelson Prize & Grants the $50 million available.

four broad approaches:

program toward
Prior to 2008, very little competitive research discovery of <  immunocontraception;
funding from federal or foundation sources <  High-dose/long-term GnRH agonists;
<  Targeted delivery of cytotoxins; and
was available to the scientific community
a safe low-cost
to investigate technologies for safe and effec- single-dose <  Gene silencing/gene therapy.
tive contraception in cats and dogs. in 2008,
the Los Angeles billionaire orthopedic non-surgical Immunocontraception
surgeon, Gary Michelson, Md, established sterilant for immunocontraception uses the immune
Found Animals Foundation to reduce or response of the animal to block reproduction.
eliminate shelter euthanasia of cats and dogs male and it works by vaccinating cats or dogs with an
in the United States. He funded a $25 million antigen that is important in maintaining nor-
Michelson Prize in Reproductive Biology and female cats mal reproduction, such as GnRH. Because this
committed $50 million for Research Grants in and dogs that antigen is a ‘self’ antigen, various ingredients
Reproductive Biology (www.michelsonprize- are added to the vaccine to help make the

Both the prize and grants are directed

andgrants.org). lasts for their antigen more immunogenic. Vaccines to

toward discovery of a safe low-cost single-

GnRH and zona pellucida proteins (porcine
10–20 year
dose non-surgical sterilant for male and
origin, PZP) have been developed successful-

female cats and dogs that lasts for their 10–20

lifespan. ly for use in wild deer and wild horses3

year lifespan. The sterilant also must ablate

(GonaCon™, ZonaStat-H™), but both require

the presence or action of sex steroids (thereby

boosters to remain effective. GnRH vaccines

preventing sexual behaviors as well as

have proven to be successful for long-term

mating), have a pathway to US Food and

suppression of fertility in cats and dogs.

Drug Administration (FDA) regulatory

approval as a veterinary prescription product,
and be amenable to delivery in a field setting;
Alliance for Contraception in Cats & Dogs
an injectable product (SC, IM or IV) is pre-
This article is part of a Special Issue of the Journal of Feline Medicine and

ferred. While the Foundation’s mission is

Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline

directed toward reducing euthanasia of shel-

fertility control’ and coordinated by the Alliance for Contraception in Cats

ter pets, it anticipates that a successful prod-

& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of

uct also will be made available domestically

non-surgical fertility control to save the lives of cats and dogs, expand

and internationally to groups managing feral

options for pet owners, and improve animal welfare. Serving as a trusted

and community-owned populations of cats

resource for scientific and educational

and dogs.
information, the ACC&D brings together key

The influx of resources for research with the

stakeholders to advance humane sterilization

goal of better understanding reproductive

options that are faster, easier and more

control in cats and dogs has attracted wide

accessible than surgery.

interest from scientists in the global biomed-

ical research community, with grant applica-
More information is available at www.acc-d.org

778 JFMS CLINICAL PRACTICE

777_782_MPG_Johnston and Rhodes.qxp_FAB 10/08/2015 13:32 Page 779
GnRH is a promising target for immunocon-
traception, as this decapeptide is the same in
male and female dogs and cats, and is at the
top of the reproductive cascade from the brain
to the gonads that regulates reproduction.
Vaccines against GnRH have been reported to
suppress reproduction safely in cats4 and dogs,5
but a drawback is that booster vaccinations are
necessary at intervals to maintain suppression.
New research areas in immunocontracep-
tion involve the use of different antigens and
different ways to present those antigens to the
immune system. Antigens being tested in vac-
cines, not before investigated, include unique
antigens on sperm, GnRH receptor proteins,
GnRH DNA or specific recombinant zona pel-
lucida proteins. Various methods for presen-
tation or delivery of familiar antigens, such as
GnRH, include some type of delivery vehicle
or matrix that will allow for longer-term expo-
sure. Some of these approaches use viral vec-
tors or ‘smart’ delivery devices that can
expose dogs or cats to antigen over a lifetime,
without booster injections.6
High-dose/long-term GnRH agonists
GnRH agonists act by binding to the GnRH
receptors on gonadotroph cells of the anterior
pituitary, causing an initial stimulation of these
cells (to secrete luteinizing hormone [LH] and
follicle-stimulating hormone [FSH]); in males
this produces an increase in testosterone, and
in females it may elicit an estrous cycle. Native
GnRH delivery in normal reproduction is
episodic and pulsatile; constant delivery is
hypothesized to suppress reproduction by
eliminating the pulsatility of effect. After about
10 days, the GnRH receptors in the gonado-
trophs are downregulated, and this results in a
complete shutdown of the reproductive system
in both males and females (called ‘medical
For many years, GnRH agonist drugs have
castration’ in human medicine).
been used in humans to suppress secretion of
reproductive hormones. GnRH agonists (eg,
leuprolide) are used to treat such human
conditions as precocious puberty and are
formulated as subcutaneous implants that can
release the drug for as long as 1 year.
Similarly, in the past 10 years, a GnRH agonist
called deslorelin has been formulated in
implants that release the drug over 6 or 12
months (Suprelorin) and have been approved
in Australia, New Zealand and Europe for
suppression of fertility in male dogs.
Several grantees are exploring how GnRH
agonists might be used for induction of steril-
ity in cats and dogs. For example, if the length
of time an implant could deliver a drug could
be increased to over 5 years, it may be that
this is long enough in some populations,
perhaps feral cats, to essentially cause lifetime
R E V I E W / Michelson Prize & Grants in Reproductive Biology
sterility. This type of delivery might be
achieved using some kind of novel implant
formulation, or perhaps a medical device that
could hold sufficient drug for lifetime
administration (Microchips Biotech,
www.mchips.com, is a company developing
such a device for human contraception).
Although it sounds far-fetched that a device
might deliver a drug for the lifetime of an ani-
mal, because only very low levels of GnRH
agonists are needed to maintain reproduction
suppression, this might be possible.
Another approach being investigated is the
possibility that giving high doses of GnRH
agonists early in life might significantly delay
or even prevent puberty. One grantee demon-
strated a significant delay in the onset of
puberty (to 42–91 weeks of age) in male and
female kittens given a 1.6 mg deslorelin
acetate implant within 24 h of birth; control
kittens demonstrated onset of puberty at
15.5 ± 1.7 weeks.7
Proposals
funded to date
encumber Targeted delivery of cytotoxins
instead of surgically removing reproductive
approximately organs such as the uterus, ovaries or testes,
some scientists are exploring whether it might
$14.2 million of be possible to specifically target and kill cells
the $50 million that are vital to maintain reproduction. Would
it be possible to create a drug that, when inject-
available for ed, could go directly to a specific subset of
research cells, such as the GnRH neurons in the brain or
primordial follicle cells in the ovary, and kill
In order for this approach to work, three
funding. those cells without damaging other tissues?
things are required: a method for targeting a
particular subtype of cell; a potent toxin that
can kill cells when delivered by the targeting
mechanism; and, finally, a way to get the
drug–toxin conjugate to the specific cells. This
approach is used to kill cancer cells in human
medicine. For example, a prostate cancer ther-
apy has been developed that uses antibodies
to a protein specific to many prostate cancer
cells and conjugates this antibody to a potent
toxin. Once the antibody has bound to the
prostate cancer cell surface, the toxin is deliv-
ered and kills only the cancer cells.8
A number of grants using this type of
approach have been funded by the MPG pro-
gram. Researchers are targeting neurons in the
brain that secrete GnRH with the understand-
ing that, if these neurons are killed, the entire
reproductive cascade is shut down in both male
and female cats and dogs. The challenge with
this approach is getting treatments through the
blood–brain barrier. Despite this obstacle, these
neurons are an appealing target. Another brain
target is the population of gonadotrophs in the
anterior pituitary. Gonadotrophs are located
outside of the blood–brain barrier, but the chal-
lenge here is that stem cells of the pituitary may
JFMS CLINICAL PRACTICE 779
777_782_MPG_Johnston and Rhodes.qxp_FAB 10/08/2015 13:32 Page 780
R E V I E W / Michelson Prize & Grants in Reproductive Biology
be able to replenish gonadotroph populations
killed with toxins.9
Another exciting target are the stem cells in
the gonads – the cells that differentiate into
ovarian follicles and sperm. If those cells
could be specifically destroyed, then cats or
dogs could be made sterile. This may be easier
in females born with a finite population of fol-
licles than in male animals that continuously
make sperm. Targeting of the exact cell popu-
lation to be killed is important to this
approach as well; male and female gonadal
cells will likely need different methods.
Several grants have been awarded to study
these approaches. Grantees are targeting
GnRH neurons with IV administration of the
peptide kisspeptin conjugated to the toxin
saporin; kisspeptin binds to receptors on
GnRH neurons. Others are linking GnRH
analogs with toxins that are expected to bind
to, and kill, gonadotrophs. Scientists targeting
gonadal stem cells are searching for homing
peptides that can specifically deliver an agent
to those cells, and seeking agents that can be
internalized into cells and destroy them.
Gene silencing/gene therapy
Some of the most cutting-edge technologies in
biomedical sciences are gene therapy and gene
silencing. it has been known for many years
that it is possible to genetically engineer virus-
es to be vectors to deliver genes to cells. Early
days of gene therapy focused on developing
therapies for genetic diseases, where a child
might be born with, for example, hemophilia
because they lacked the gene for a specific clot-
ting factor. Gene therapies were designed to
deliver these genes to the child’s cells, so the
cells could actually produce the clotting fac-
tors – in essence, providing the gene that the
child lacked. Such an approach sounds simple,
but it took many years for these therapies to be
developed and made safe enough for clinical
use. Gene therapy for hemophilia in dogs has
resulted in dogs with genetic clotting defects
having normal clotting function restored for
How could this approach work for fertility
8 or more years.10
suppression? Suppose we could identify a
specific protein that could suppress reproduc-
tion and then deliver that protein for a life-
time using a viral vector? Instead of the gene
restoring function, it could potentially inter-
Emphasis is placed on developing methods
for lifetime sterilization that accurately
target reproduction while avoiding side effects
on other organ systems.
780 JFMS CLINICAL PRACTICE
fere with function. In order to make this
approach possible, we need to identify a
protein or toxin that suppresses reproduction,
make a viral vector that carries the gene for
that substance into cells in a cat or dog, and
get that protein expressed, either systemically
or locally, such as within the ovaries or testes.
Some progress has been made exploring
this approach to suppressing reproduction.
Scientists are studying the feasibility of insert-
ing genes that cause over-expression of anti-
bodies to GnRH. They are also studying the
feasibility of inserting genes that cause over-
expression of gonadotropin-inhibitory hor-
mone (GnIH) or Mullerian inhibiting substance
(which regulates primordial follicle recruit-
ment in adult females and testosterone produc-
tion in adult males) in both cats and dogs.
In human medicine, a number of companies
are using the technology of gene silencing to
‘turn off’ specific genes to regulate various
physiological functions. Gene silencing is a
biological phenomenon that has fairly recent-
ly been discovered and involves the realiza-
tion that small RNA fragments are used by
cells to regulate gene expression. If synthetic
small interfering RNA (siRNA) can be
synthesized and delivered to the body as a
drug, it could theoretically be designed to
specifically shut off expression of certain
genes. Companies such as Alnylam
(www.alnylam.com) are developing small
molecule drugs for amyloidosis and por-
phyria using this mechanism of action. But
can this approach be used for suppression of
reproductive genes?
For induction of sterility in cats and dogs,
use of siRNA drugs is not practical, since they
would need to be given daily and likely by
injection. If, however, these molecules could
be delivered to cells using viral vectors, where
the vector would incorporate into cells and
deliver the gene-interfering siRNA over long
periods of time, it is possible to imagine that
this would be an elegant system for the induc-
tion of long-term and possibly permanent
sterility.
Three steps are required of such a system in
order for it to be effective: a gene to turn off
needs to be defined; a viral vector to deliver
the siRNA required to suppress that gene
needs to be identified; and, finally, that viral
vector needs to get to the cells that express
the gene to be turned off. One approach that is
under investigation is construction of a viral
vector that targets kisspeptin, a regulatory
protein that is required to elicit GnRH secre-
tion.11,12 This viral vector must be tailored to
deliver the siRNA to the brain – a tall order,
since penetrating the blood–brain barrier is
difficult. However, if the appropriate hypo-
thalamic neurons could be reached by a
777_782_MPG_Johnston and Rhodes.qxp_FAB 10/08/2015 13:32 Page 781
vector, that viral vector could cause the cell to
produce a lifetime of siRNA to shut down
As part of the MPG program, significant new
reproduction. If this could be achieved, a sin-
gle product could theoretically work in both
findings are becoming available to the research
male and female cats and dogs for a lifetime of community that help shed light on basic
fertility suppression.
Targeting GnRH neurons in the brain makes
reproductive mechanisms in domestic cats.
sense as these cells are the master regulators
of reproduction, but it may be easier to target
specific cells in the gonads to avoid the
difficulties of getting a therapy across the
blood–brain barrier. Another interesting
approach is to use microRNA technology to
inhibit androgen receptor expression in the
testes, as androgen stimulation is required for
normal testicular function including sperm
production. Androgen receptor gene silencing
constructs could be delivered with viral
vectors to ‘turn off’ male reproduction.
Another fascinating approach is to target
the small RNA molecules that have been iden-
tified as vital for ova and sperm to undergo
maturation. Interfering with these small RNA
molecules, which appear to be unique to
gametes, might be an interesting target.13,14
Once the right cat and dog small RNAs that
regulate, for example, spermatogenesis have
been identified, then antagonists to those
RNAs can be designed and potentially deliv-
ered using viral vectors.
Safety and animal welfare
The goal of the supported research is to dis-
cover an effective method to sterilize male
and female cats and dogs for a lifetime. in
pursuing this goal, the Foundation committed
to making sure that any product that might be
developed using the various approaches out-
lined above is not only effective, but is also
safe for the treated animals. Emphasis is
placed on developing methods that accurately
target reproduction while avoiding side
In addition, the Foundation and MPG
effects on other organ systems.
program are committed to the welfare of all
research animals used in the grant-supported
Predicted timeline for a non-surgical sterilant
Many in the animal welfare community, as well as many veteri-
narians, are impatient for that new tool that will transform
spay/neuter clinics into a thing of the past and enable steriliza-
tion of many more cats and dogs with less invasive and more
cost-effective treatments. When will this investment of time and
resources, both human and financial, lead us to a technology
that can be moved into full drug development, regulatory
approval and commercialization?
Since this is research, the answer is ‘we just don’t know.’
The most optimistic prediction is within the next 10 years.
R E V I E W / Michelson Prize & Grants in Reproductive Biology
research. Grantees are required to review
the Foundation and MPG program’s ‘Policy
for Animals Involved in Research’ (www.
michelsonprizeandgrants.org/resources/
animal-welfare-policy), are required to rigor-
ously justify numbers of animals (usually
mice and rats, occasionally cats and dogs)
used in projects, and must, prior to approval
of any project, demonstrate that behavioral
enrichment will be provided to research ani-
mals. In addition, grant applicants must pro-
vide a plan for placing research cats and dogs
in adoptive homes at the end of the study
where they can enjoy living as a pet.
Targeted research
one of the interesting things learned as grants
have been submitted and reviewed is how
very little is known about control of normal
reproduction in cats and dogs. Agencies that
fund biomedical research do not provide
support for this work, and entities such as the
United States department of Agriculture
(USdA) and pharmaceutical companies have,
for the most part, stopped funding reproduc-
As part of the MPG program, significant
tive research in animals.
new findings are becoming available to the
research community that help shed light on
basic reproductive mechanisms in domestic
cats and dogs. As these findings are shared via
publication in peer-reviewed journals, other
researchers benefit and the knowledge of
reproductive biology is spread. This, in turn,
should encourage new approaches and col-
laborations, something we are already seeing
happen among the grantees.
Regulatory approval in itself is a very long process (see accom-
panying article in this Special Issue15), particularly for a long-
acting therapy. But breakthroughs happen in science, and in
drug development as well. Given that 10 years ago there were
no new therapies, very little basic research in cat and dog repro-
duction, and no grants available, it is clear that we are jump-
starting this field. We are hopeful that bringing together the best
minds, the best technologies and significant financial resources
will give us the best ‘shot’ at creating one or more solutions that
can reach veterinarians’ hands within the next decade.
JFMS CLINICAL PRACTICE 781
777_782_MPG_Johnston and Rhodes.qxp_FAB 10/08/2015 13:32 Page 782
R E V I E W / Michelson Prize & Grants in Reproductive Biology
KEY poiNts
< The Michelson Prize & Grants (MPG) in Reproductive Biology
program supports the scientific community to advance
non-surgical sterilization research for cats and dogs. The MPG
Program has allocated $50 million grant funding for promising
research; since 2009, it has funded over 30 projects in seven
countries. A $25 million prize is available to the first entity to
develop a product meeting established criteria.
< The MPG program has the goal of developing a safe low-cost
single-dose lifelong non-surgical sterilant for cats and dogs of
both sexes. In addition, in order to win the Prize, the solution must
ablate the presence or action of sex steroids, have a pathway to
US FDA regulatory approval as a veterinary prescription product,
and be amenable to delivery in a field setting.
< MPG-funded grantees are investigating a wide range
of approaches. Current research falls into four broad
categories: immunocontraception, high-dose
and/or long-term GnRH agonists, targeted delivery
of cytotoxins, and gene silencing/gene therapy.
ISFM CONGRESS RECORDING
A recording of Linda Rhodes’ session on
current research on non-surgical fertility
control, presented at the 2015 ISFM Congress
in Porto, is available at:
http://icatcare.org/vets/videos
It is also included as
Supplementary material at: jfms.com
DOI: 10.1177/1098612X15594992
Funding
The authors received no specific grant from any
funding agency in the public, commercial or not-
for-profit sectors for the preparation of this article.
Conflict of interest
The authors have no conflict of interest to declare.
References
1 American Society for the Prevention of Cruelty
to Animals (ASPCA). Pet statistics. ASPCA fre-
quently asked questions. https://www.aspca.
org/about-us/faq/pet-statistics (2014, accessed
october 22, 2014).
Available online at jfms.com
Reprints and permission: sagepub.co.uk/journalsPermissions.nav
Title photograph on page 777 ©iStockphoto.com/pyotr021
782 JFMS CLINICAL PRACTICE
2 Alliance for Contraception in Cats & dogs
(ACC&d). Contraception and fertility control in
dogs and cats: a report of the Alliance for
Contraception in Cats & Dogs (ACC&D).
http://www.acc-d.org/resource-library/e-book
(2013, accessed october 22, 2014).
3 Journal of Zoo and Wildlife Medicine: Special
issue on Wildlife Contraception, 2013; 44 (4s).
4 Enright WJ and Swift PJ. GnRH immunization of
peripubertal male cats: dose titration of a GnRH-
gly-cys-ovalbumin (GnRHOVAL) conjugate on
immune and testicular responses [abstract].
J Reprod Fertil Abstr Ser 1995; 15: 15.
5 Jung MJ, Moon YC, Cho iH, et al. Induction of
castration by immunization of male dogs with
recombinant gonadotropin releasing hormone
(GnRH)–canine distemper virus (CDV) T helper
cell epitope p35. J Vet Sci 2005; 6: 21–24.
6 Munks MW. Progress in development of
immunocontraceptive vaccines for permanent
non-surgical sterilization of cats and dogs.
Reprod Dom Anim 2012; 47 Suppl 4: 223–227.
7 Carranza A, de la Sota P, diaz Jd, et al. Effects
of prepubertal GnRH agonist administration in
domestic cats: preliminary results [abstract].
Proceedings of the 1st international Conference on
dog Population Management; 2012 Sept 4–8; York,
UK.
8 olson WC and israel RJ. Antibody–drug conju-
gates targeting prostate-specific membrane
antigen. Front Biosci 2014; 19: 12–33.
9 Struthers RS. Gonadotropin-releasing hormone
targeting for gonadotroph ablation: an approach
to non-surgical sterilization. Reprod Dom Anim
2012; 47 Suppl 4: 233–238.
10 Herzog RW, Mount Jd, Arruda VR, et al. Muscle
directed gene transfer and transient immune sup-
pression result in sustained partial correction of
canine hemophilia B caused by a null mutation.
Mol Ther 2001; 4: 192–200.
11 Albers-Wolthers KHJ, de Gier K, Kooistra HS, et al.
Identification of a novel kisspeptin with high
gonadotrophin stimulatory activity in the dog.
Neuroendocrinology 2014; 99: 178–189.
12 dissen GA, Lomniczi A, Boudreau RL, et al.
Targeted gene silencing to induce permanent
sterility. Reprod Dom Anim 2012; 47 Suppl 4:
228–232.
13 He A, Kokkinaki M, Gallicano Gi, et al. Small
RNA molecules in the regulation of spermato -
genesis. Reproduction 2009; 137: 901–911.
14 Fu Q and Wang PJ. Mammalian piRNAs: bio-
genesis, function and mysteries. Spermatogenesis
2014; 4: 1e27889.
15 Rhodes L. Put a label (claim) on it. Getting
non-surgical contraceptives approved for use
in cats and dogs. J Feline Med Surg 2015; 17:
783–789.
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Journal of Feline Medicine and Surgery (2015) 17, 783–789

CLINICAL Review

Put a label (claim) on it

Getting non-surgical contraceptives
approved for use in cats and dogs
Linda Rhodes

Introduction Relevance: Non-surgical contraceptives

or sterilants need regulatory approval
Veterinarians use drugs every day and are skilled at reading labels and to be sold for that use. This approval
understanding nuances of how various common drugs affect their process gives veterinarians the
patients. drug labels and package inserts contain information to help information required to assess the
guide veterinarians about how to use drugs safely to have the desired benefits and risks of each product, and to
effect in their patients. But what does it take for a manufacturer to get provide comprehensive information on the
regulatory approval – be it from the US Food and drug Administration required dose, method and duration of use, safety
(FdA), Environmental Protection Agency (EPA) or European and effectiveness.
Medicines Agency (EMA) – and generate the information that is Aim: This article reviews the information that must

The label is usually the result of 5–10 years of intense research and
included with each drug? be developed and provided to regulatory agencies

development. For drugs for cats and dogs, the cost of getting an
worldwide, with a focus on the European Union and

approval can range from approximately USD $8–12 million. Why so

the United States, in order to achieve regulatory

long and so much? The basic reason is that each drug needs to be
approval.

rigorously tested to assure that it is

Processes: The main components of developing

The label is usually the result safe and effective for the indication,
a drug include developing extensive information

and that each time a veterinarian

on the safety and effectiveness of the product, and

dispenses the drug, it is exactly

also the safety to the environment and to humans

what it is supposed to be – essential-

of 5–10 years of intense handling and administering the drug. Most

ly the same concentration, potency

importantly, a robust method of manufacturing both
research and development.
and bioavailability in every pill or
the drug itself and the formulated drug product

liquid dose.
(pill, liquid implant or injection) must be developed

Regulatory requirements for approval of contraceptives for cats and

to assure quality and consistency in each batch.

dogs differ depending on the mechanism of action of the contraceptive

This information is then compiled and submitted

approach, as well as the country in which approval is sought. The pur-

to regulatory agencies; in the United States, this

pose of this article is not to serve as a detailed guide for regulatory

includes the Food and Drug Administration, the

approval of specific products, but instead to give an overview of the

United States Department of Agriculture and the

regulatory processes and issues.

Environmental Protection Agency, and, in Europe,

Regulatory requirements worldwide generally fall into three major

the European Medicines Agency.

categories for companion animal products:

Challenges: Because of the unique nature of
non-surgical contraceptives for use in cats and
< Effectiveness; dogs, particularly the desire to have these products
< Safety; last over multiple years, there are special challenges
< Manufacturing (also called chemistry, manufacturing and controls, to their regulatory approval that are discussed in

In addition, products are evaluated for their possible environmental

or ‘CMC’). this review.

impact and the safety of humans handling the product. (Note that
there are additional requirements for products intended for animals
used for food – meat and milk – and discussion of these requirements
is beyond the scope of this article.)

Linda Rhodes
VMD PhD
Board of Directors, Alliance for Contraception
in Cats & Dogs (ACC&D), Portland, Oregon, USA

Email: ladycowvet@gmail.com

doi: 10.1177/1098612X15594993
© The Author(s) 2015 JFMS CLINICAL PRACTICE 783
783_789_Label_Rhodes.qxp_FAB 10/08/2015 13:44 Page 784

R E V I E W / Regulatory approval process for non-surgical contraceptives

For both cats and dogs, it is important for a

Europe is an attractive market for non-surgical developer of a contraceptive product to make
sure that the clinical trials are conducted in
the widest possible population in order to
contraceptive products due to a historical and
achieve the broadest claim. For example, cats
of various ages and breeds should be used for
general reluctance to surgically alter cats and dogs.
the clinical work, as some veterinarians
The company developing the product (the might want to use a contraceptive in adult
‘sponsor’) is responsible for submitting all cats, while others will be interested in treating
information required for review by regulatory kittens, should owners not want their female
authorities prior to approval. In addition, cats to exhibit even one estrus.
most regulatory bodies require payment of Duration and potential reversibility of effect
significant fees (hundreds of thousands of need to be measured in clinical trials. If the
dollars) as part of their review process. label claim is intended to be ‘effective contra-
This article specifically considers the regula- ception for a year’, studies of at least a year’s
tory process for products for companion length will be necessary. How will effective-
animal species (cats and dogs). However, non- ness be proven if the label claim is permanent
surgical fertility control products have been sterilization? Multi-year trials over the life-
approved for wildlife as well (see Table 1, time of a pet are not practical, and so it is
page 788); when appropriate, examples from unlikely that such a label claim would be real-
other species are presented. istic unless the product produced actual tissue
destruction of the testicles or ovaries. One
strategy that companies developing these
types of products might adopt is to initiate
Effectiveness

launch of the product with a label defining

duration as 12 months, and then continue the
For a contraceptive, the sponsor must prove

studies, filing label extensions to increase the

that the drug will suppress fertility in a partic-

duration claim, if possible, or to demonstrate

ular species for a specific length of time. This

that repeat treatment extends the duration of

is called a ‘claim’ or ‘label indication’. What

effect.
claims might the label of a contraceptive prod-

What about products that may have a vari-

uct contain? The claims are based on the effec-

able onset of and decline in effectiveness, such

tiveness of the product and are backed up

as a gonadotropin-releasing hormone (GnRH)

by clinical data in the relevant species, collect-

vaccine or porcine zona pellucida vaccine that

ed from both laboratory and field studies.

may provide 6 months of contraception in one

Regulatory agencies use the proposed claim to

animal and 2 years in another? Even in the

determine what type of data will be needed to

best of cases, individual animals in a clinical

support approval of the product. design of

trial will probably have to be followed for at

the effectiveness claims and clinical trials to

least a year, making clinical efficacy trials

prove them must be coordinated with a clear

long, labor intensive and expensive. If claims

strategy so that, at the end of the development

for continued effects based on booster immu-

process, the market is defined and communi-

For contraceptives and fertility control nizations are desired, multi-year trials may be
cation with veterinarians can be effective.

drugs, claims must include the species in needed.

which the product will be used (eg, cat or dog) One of the major reasons pet owners spay or
and might include: castrate their cats is because the animals are
< definition of the population for which the
product is useful (eg, for male and female
cats over 6 months of age);
< How quickly the product will show its
Alliance for Contraception in Cats & Dogs
This article is part of a Special Issue of the Journal of Feline Medicine and
effect (eg, for vaccines, how long is it from
Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline
the initial injection and any follow-up
fertility control’ and coordinated by the Alliance for Contraception in Cats
boosters to full contraceptive effect?);
< The length of time for which the product
& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of
non-surgical fertility control to save the lives of cats and dogs, expand
is proven to work (duration of effect);
< The potential reversibility of the treatment
options for pet owners, and improve animal welfare. Serving as a trusted
resource for scientific and educational
(eg, will cats regain their ability to breed
information, the ACC&D brings together key
when treatment is discontinued? if so,
stakeholders to advance humane sterilization
in how long a time?);
< How the product is used (injections, oral
options that are faster, easier and more
accessible than surgery.
dosing, implants);
< Schedule of use (eg, once every 6 months);
< dose (if applicable).
More information is available at www.acc-d.org

784 JFMS CLINICAL PRACTICE

783_789_Label_Rhodes.qxp_FAB 10/08/2015 13:44 Page 785
exhibiting unwanted sexual behaviors; for
example, estrous behavior in females and ter-
ritorial marking/spraying, roaming, inter-cat
aggression and yowling in male cats. To
include label claims on their contraceptive
products such as ‘use of this product will
reduce sexual behavior’, sponsoring compa-
nies may have to conduct behavioral evalua-
tions. Even if it can be demonstrated that the
proposed contraceptive suppresses serum sex
steroids (eg, testosterone in male cats), it is
unlikely that regulatory authorities will allow
the use of this surrogate endpoint to make
behavior claims. It is interesting to note that
the package insert for Zeuterin™ (Ark
Sciences), an injectable sterilant for male dogs
approved by the FDA without behavior
studies being required, includes the following
statement: ‘As with surgical sterilization,
secondary male characteristics (roaming,
marking, aggression, or mounting) may be
displayed.’1
Safety
Target animal safety
Contraceptive products should be demonstrat-
ed to be safe for the treated animals, but what
exactly does ‘safe’ mean? For regulatory
approval, safety is proven by conducting a
study in the ‘target’ animal (ie, the species in
which the product will be used). ideally the
resulting study shows that the normal dose
and higher doses, sometimes given multiple
times, cause limited or no adverse effects.
The study must include a reasonable number
of animals of appropriate ages. A regulatory
guideline has been developed that is used
in several countries as the standard for design-
ing these safety studies. The Veterinary
international Cooperation on Harmonization
(ViCH) guidelines for target animal safety
suggest using laboratory cats and dogs, which
can be observed closely during the study.2 The
guideline requires the use of four males and
four females per group and suggests inclusion
of 0, 1, 3 and 5 x groups; that is, cats or dogs in
the study should be treated with a placebo, the
intended dose, or 3 x or 5 x that dose, which
The guidelines say that safety studies
can help define a safety margin.
should be conducted for three times the dura-
tion of the proposed use. For example, if an
antibiotic is prescribed to be used for 10 days,
the safety study should be conducted for 30
days. For potential cat contraceptives that are
designed for multi-year effectiveness, if this
guideline were strictly followed, studies
would be required to run for many years,
which is impractical. Sponsors will need to
work with the regulators to help design a safe-
ty study that adequately addresses long-term
R E V I E W / Regulatory approval process for non-surgical contraceptives
safety without requiring studies that are so
long as to be impossible. Regulatory authori-
ties are likely to work with sponsors to find a
way to adequately assess long-term safety of
potential contraceptive drugs.
During the safety study, animals are
observed for any behavioral changes, and
injection or implant sites are monitored for
any signs of irritation, pain or inflammation.
Clinical pathology parameters such as hema-
tology, urinalysis and serum chemistry are
monitored, and at the end of the target animal
safety study, animals are euthanized and full
necropsies performed. Gross pathology and
histopathology are required, along with other,
more specialized measurements depending
on the product. All procedures must be done
under good laboratory practice (GLP) regula-
tions. Conduct of this study can take a year
and up to USD $500,000 or more, depending
on the species and duration of the experiment.
Many agencies also require ‘field safety’ to
be evaluated in a wider population of breeds
and ages in a ‘real world’ situation. To satisfy
this requirement, safety information (adverse
events) is required to be documented and
reported to regulatory authorities. Finally,
after a product is approved, the FDA, EMA
and other regulatory bodies worldwide
Probably the
require post-approval monitoring for safety
most important
(‘pharmacovigilance’). This means that the
sponsor is required to establish a way to col-
step in bringing
lect reports of problems or side effects seen in
animals treated with the product, and these
a product
adverse events must be reported regularly to
through
regulatory agencies to monitor safety in the
actual population of cats and dogs being treat-
commercial
ed with the product.
development is
developing a Human safety
formulation. in all cases, the safety of the person handling
drugs or immunocontraceptives is a concern.
if a vaccine or other injectable contraceptive
has a long-lasting or permanent effect, the
people administering the product will be at
risk for self-injection and compromise of their
own fertility, and the labeling will have to
reflect these issues. it is likely that some types
of products could be restricted to use by
veterinarians or trained personnel only. For
example, the label for Gonacon™ (regulated
by the EPA for use in adult female white-
tailed deer, wild horses and wild burros)
states: ‘Restricted use pesticide: due to non-
target injection hazard. For the use by USdA-
APHiS wildlife services or state wildlife
management agency personnel or persons
Exposure to toxic substances such as
working under their authority.’3
chemotherapeutic agents, and worries about
HIV and other infectious agents in human
blood, have prompted a number of companies
JFMS CLINICAL PRACTICE 785
783_789_Label_Rhodes.qxp_FAB 10/08/2015 13:44 Page 786
R E V I E W / Regulatory approval process for non-surgical contraceptives
to develop injection technology that protects
the person giving the treatment. It should be
possible for some type of device to be devel-
oped for veterinary contraceptive injections
that would similarly protect the veterinarian
or technician giving the injections to animals.
This could become an issue in the develop-
ment of immunocontraceptives that may be
entering clinical trials. Veterinary clinics could
be reluctant to participate in a trial in which
their staff members may be exposed to an
experimental contraceptive. Certainly it
would decrease the risk of non-participation if
the experimental immunocontraceptive were
to be delivered via a device that minimized
the possibility of human exposure.
Environmental assessment
Particularly for the US EPA, but also for
other regulatory agencies, the environmental
impact of contraceptives must be evaluated,
and the scope of this assessment will depend
Regulatory agencies
United States agencies
The regulatory landscape for dog and cat contraceptives in the
US is complicated. Contraceptives can be divided into two
broad categories: drugs and vaccines (immunocontraceptives).
Drugs to be used for contraception are regulated by the FDA
Center for Veterinary Medicine (CVM). Although vaccines for
animals are usually approved by the USDA Center for Veterinary
Biologics (CVB), the FDA has in the past indicated that it will
regulate vaccines used for immunocontraception in pet cats
and dogs (and, indeed, in all species).
One example of a challenging regulatory landscape is how
immunocontraceptives for ‘feral’ cats (which may include,
depending on definition, unowned, free-roaming or community
cats) might be regulated. A murky regulatory area that may have
implications for feral cats is the regulation of immunocontracep-
tive vaccines for fertility suppression in wildlife. A regulatory
decision was made in 2006 to clarify the role of the FDA, USDA
and EPA in regulating contraceptives for use in wildlife and free-
roaming animals. A draft Memorandum of Understanding (MOU)
between the FDA and the EPA was developed (but not signed),
in which the EPA agreed to register contraceptives and immuno-
contraceptive vaccines for wildlife and feral animals (eg, white-
tailed deer, wild horses). In particular, the EPA agreed to regulate
GonaCon™, the GnRH vaccine labeled as an ‘immunocontra-
ceptive vaccine for use in white-tailed deer’, and the label, as
approved by the EPA, further defines the product as a ‘restricted
use pesticide’.4
In 2006, at the ACC&D’s 3rd International Symposium on
Non-Surgical Contraceptive Methods of Pet Population Control,
representatives of the National Wildlife Research Center
(NWRC), a governmental agency within USDA Wildlife Services
that developed GonaCon, announced that in addition to
agreeing to review the application for GonaCon for white-tailed
786 JFMS CLINICAL PRACTICE
on the specific product and may include data
on field use. oral, implanted or injected drugs
that are given to individual pets, and therefore
have limited effects on the environment gen-
erally, will receive a waiver from conducting
an extensive environmental assessment.
However, in the case of a product used for
unowned, free-roaming or feral animals, field
Over the years, various research approaches
use data may be needed.
to contraception for wildlife and feral animals
have included attempts at designing baits
to place in the area where feral animals live.
Baited contraceptives for cats and dogs are
very unlikely to be approved, since the
probability of ‘off-target’ animals or humans,
including children, being exposed is high.
Development efforts are under way to achieve
a species-specific product in which only the
target species will respond to or be able to
access the bait, but species specificity is a
significant obstacle.
deer, the EPA might consider being the regulatory agency for
fertility control products targeted at feral cats, based on an
EPA/FDA MOU.4
The FDA at that time agreed to retain authority over drug-
based contraceptive and immunocontraceptive vaccines for
use in captive and pet animals, including livestock, companion
animals (cats and dogs) and zoo animals (K Fagerstone, person-
al communication, 2012). The NWRC indicated that it is interest-
ed in seeking EPA registration of GonaCon for use in feral
and loosely owned dogs on Native American tribal lands.
Additionally, approval by the EPA may be a step towards a
new fertility control tool for free-roaming dogs internationally,
where the dog rabies problem is far greater than in the US,
because international regulatory agencies will often accept
approval by US regulatory agencies as a basis for approval in
their countries.
The NWRC received a letter from the EPA, dated December
2012, stating: ‘We have reviewed your request for a determina-
tion of whether EPA would have regulatory oversight for a new
proposed use of Gonacon™ for use in wild and feral free-roam-
ing dogs. This proposed use of Gonacon™ will be targeted for
wild and feral free-roaming dogs on tribal lands. We discussed
this proposed use internally and with the Food and Drug
Administration. It was decided that this is a pesticidal use that
EPA will have regulatory jurisdiction over’ (K Fagerstone,
personal communication, 2012). THe NWRC requested an
Experimental Use Permit from the EPA to conduct a large-scale
efficacy study on US Native American reservations to collect
the necessary field effectiveness data for a registration
(K Fagerstone, personal communication, 2012). For the purpos-
es of labeling and regulatory jurisdiction, this would mean that
these dogs would be classified as ‘pests’.
Continued on page 787
783_789_Label_Rhodes.qxp_FAB 10/08/2015 14:27 Page 787
Manufacturing
Selecting the right manufacturing process and
In the case of drugs registered by the FDA,
manufacturer can make or break a product
EMA and EPA, manufacture of the active
pharmaceutical ingredient and the formulated and its ability to meet regulatory requirements.
product must be conducted under good
manufacturing practice (GMP) regulations.
For immunocontraceptives, regulated by the
FDA or EPA (eg, ZonaStat-H™ for feral hors-
es), similar quality standards apply. This is to
demonstrate to the veterinarian and the pub-
lic that strict quality standards are used in the
manufacturing of the product, which assures
its safety and effectiveness will be essentially
the same as that demonstrated during the
Probably the least appreciated, but most
drug development process.
important step in bringing a product through
commercial development successfully is
developing a formulation – that is, the active
ingredient in combination with excipients
that help keep the product stable, in solution,
buffered appropriately, etc. In terms of stabil-
ity, the active drug or antigen has to remain
Continued from page 786
There are some interesting issues for cats here. How would
‘feral cat’ be defined? Might it cause a problem if feral cats
are defined as ‘pests’ as a condition for a feral cat contra-
ceptive to be approved by the EPA? The worry is that
defining feral cats as pests would then allow eradication
programs and might affect trap–neuter–return (TNR) pro-
grams. This concern was raised in considering EPA regis-
tration for the wild horse contraceptive ZonaStat-H, and
ultimately it was concluded that EPA registration offered
benefits that outweighed the concerns (H Hazard, personal
communication, 2012). Another interesting question: how
will it work if the EPA regulates immunocontraceptives for
feral cats and the FDA regulates the same product used in
pet cats? The same product could end up with different
labels, indications and regulations for use. Clearly, careful
thought is required to develop a common-sense regulatory
pathway for immunocontraceptives for feral cats.
If the EPA is the regulatory review body for a new product
and classifies an immunocontraceptive as a pesticide under the
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA),
data requirements might be abbreviated based upon proposed
labeling and the method of application (eg, an injection or
implant). Data requirements for pesticides are determined by use
and likelihood of exposure to humans, domestic animals and the
environment. A strategy for conducting studies for any pesticide
is based on a thorough understanding of how the product would
be used. For example, for the subject product to sterilize feral
cats, consideration should be given to the following:
< How the product will be packaged;
< Draft labeling;
< Where the product will be used (eg, states, locations,
rural/urban areas);
R E V I E W / Regulatory approval process for non-surgical contraceptives
intact over a reasonable shelf-life. It must be
determined if the product needs special
storage requirements (such as refrigeration),
which may impact practical use in the field.
The formulation must be non-irritating to
tissue when injected or implanted, especially
if multiple applications are required (eg,
boosters or repeat implants).
Product sterilization methods must be
developed that are effective and do not
degrade the antigen or drug. If an implant is
being developed, release rates of the active
ingredient need to be demonstrated under a
variety of conditions, and if the product is to
be an injectable, syringeability must be good –
that is, it must not be too thick to pass through
a needle small enough to inject a cat or dog.
< Opportunities that may exist for human exposure and potential
effects, and whether restricted use would be appropriate
to minimize likelihood of such exposure and effects;
< How long the contraceptive/sterilant effect lasts in cats;
< Opportunities that may exist for environmental exposure;
< Effective measures of package disposal; indicate return to
manufacturer if appropriate;
< Identifying and analyzing potential effects in humans should
exposure occur; developing methods of treatment for any
human exposure; include a telephone emergency response
number.
European agency
Europe in particular is an attractive market for non-surgical con-
traceptive products for pets due to what is characterized as a
historical and general reluctance to surgically alter cats and
dogs. The EMA regulates ‘veterinary medical products’ for the
EU, and this includes all types of products regardless of mode
of action or target species. There is a centralized procedure for
the approval of innovative new drugs so that a sponsor can sub-
mit one set of required documents (dossier) to achieve approval
in all EU member countries. (Individual country applications can
also be made should the sponsor so choose.) Note that
Suprelorin® 6 and 12 month implants have been approved by the
EMA in the EU for fertility control in male dogs; the product is
marketed by the animal health company Virbac. There are no
EU-wide approved products for use in cats.
Rest of the world
Review of all international regulatory considerations and proce-
dures is beyond the scope of this article. In general, each country
has its own procedures for meeting requirements, and it cannot
be assumed that registration (ie, regulatory approval) is assured
in other markets once EMA, FDA or EPA requirements are met.
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R E V I E W / Regulatory approval process for non-surgical contraceptives

Once a few possible formulations have been
defined that meet the aforementioned criteria,
one ‘lead’ formulation is selected. For this for-
mulation, effectiveness must be confirmed in
a reasonable number of animals. For a contra-
ceptive product, these tests can take 6 months
to a year, assuming the product claim is for
that length of time. Depending on the prod-
uct, the process of defining a final formulation
can take several years and cost several million
dollars. Separate formulations may be needed
for cats and dogs, especially for immuno-
contraceptives requiring adjuvants in order to
be effective.
For manufacturing the final product, many
requirements need to be fulfilled. For example,
packaging, sterility, reproducibility from lot-to-
lot, stability under a variety of handling condi-
tions, cleaning requirements and labeling need
to be worked out. The impact of manufacturing
on the environment must be defined.
Manufacturing must be scaled up to meet
demand once the product is launched.
Selecting the right manufacturing process and
toll manufacturer (contract manufacturers
used if a company does not manufacture its
own products) can make or break a product
and its ability to meet regulatory requirements.
The costs and timing of meeting the require-
ments and getting successfully through the
Since 2003, we have seen only three prod-
ucts (Suprelorin, Gonazon™, Zeuterin™)
achieve regulatory approval for contraception
or permanent sterilization in dogs, and no
products have been approved for cats.
Gonazon was approved for use in female dogs
in the EU and not commercialized. Suprelorin
is approved for use in Australia, New Zealand
and the EU, but only for male dogs. Zeuterin,
which was originally approved by the FDA
under the brand name Neutersol™, is on the
market in the US for male dogs; the product
was also approved in several Latin American
countries under the brand name EsterilSol,
and it has been re-launched and is on the mar-
ket in the US as Zeuterin.
Since 2003, only Suprelorin, Gonazon
and Zeuterin have achieved regulatory approval for
contraception or permanent sterilization in dogs.
No products have been approved for cats.
the
Table 1 Animal contraceptives approved in the US (by the FDA
or EPA) and EU (by the EMA) between 2003 and 2013
Species EPA FDA EMA

approval process with the FDA, EPA, EMA

Dogs – Zinc gluconate Deslorelin acetate implant

and other regulatory agencies worldwide

neutralized with (Suprelorin; Virbac) for males

vary depending on the complexity of the

arginine (Zeuterin;

product. Experienced companies know that

Ark Sciences) for Azagly-nafarelin acetate
males (also known implant (Gonazon; Merck)

assembling the necessary documentation for

as Neutersol) for females*

manufacturing can take a minimum of 2–3 Cats – – –

years and carries a multi-million dollar price

tag. In some cases, a factory needs to be built,
White-tailed GnRH–hemocyanin – –

requiring large capital investment.

deer protein conjugate
(Gonacon; National
Wildlife Research
Center, USDA-
Time frame for regulatory APHIS Wildlife
Services Program)
approval for females
Wild horses GnRH–hemocyanin – –
How quickly regulatory approval can follow protein conjugate
after submission of all required documenta- (Gonacon; National
tion varies widely depending on the country, Wildlife Research
Center, USDA-
the product and the quality of the submission. APHIS Wildlife
Working closely with a given regulatory body Services Program)
during the development of a drug or for females
immunocontraceptive can speed up the
Porcine zona
process in some cases, but it would not be pellucida vaccine
unusual for the entire approval process, (ZonaStat-H;
including required studies and regulatory The Science and
Conservation
review, to take up to 5–10 years; the process Center) for females
could be longer for long-acting products.
Canada Nicarbazin – –
Nonetheless, products for domestic species geese, wild (OvoControl;
(dogs) and wildlife have been approved, as pigeons and Innolytics)
shown in Table 1, which lists products that ducks
received regulatory approval between 2003 EPA = Environmental Protection Agency; FDA = Food and Drug Administration;
and 2013. The list does not include older EMA = European Medicines Agency; USDA-APHIS = United States Department of
products based on progesterone or related Agriculture’s Animal and Plant Health Inspection Service
*Gonazon (developed by Intervet and acquired by Merck) is no longer on the market
compounds.

788 JFMS CLINICAL PRACTICE

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R E V I E W / Regulatory approval process for non-surgical contraceptives

Compounding
Veterinarians in some countries can legally use drugs ‘off-label’ cies are not required to conduct the rigorous safety, effectiveness
for their patients, either by prescribing them through pharmacies and manufacturing testing that is required of drugs that have
or having drugs compounded specifically for their individual achieved regulatory approval. For compounded drugs, there may
patients at compounding pharmacies. For example, megestrol only be anecdotal evidence of safety and effectiveness, and no
acetate is a progestational compound that has been used to information regarding, for example, the drug’s stability or purity
suppress estrus in female cats when fed under conditions of use. Compounded drugs
orally on a regular basis; it is available in bulk, Using do not carry labeling to guide the veterinarian
and can be purchased through compounding on appropriate use, what side effects to be
pharmacies. compounded aware of that might be relevant for their patients,
When a veterinarian decides to use com- drugs is a ‘buyer or any mechanism to report adverse events.
pounded drugs, she or he must carefully weigh Using compounded drugs is, therefore, a ‘buyer
the risks and benefits. Compounding pharma- beware’ situation. beware’ situation.

Conclusions Conflict of interest

There is a long road from demonstrating that The author has no conflict of interest to declare.
a certain contraceptive approach can suppress
fertility in a cat or a dog and achieving regula- References
tory approval for a product that can be
marketed. For each potential prod- 1 Package insert for Zeuterin. https://www.
uct, the regulatory path is unique. zeuterin.com/images/pdf/ZeuterinCMCPackage
The scarcity of cat and dog con- insertFinal.pdf
traceptives approved for use 2 Veterinary international Cooperation on
reflects both the lack of ISFM CONGRESS RECORDING Harmonization of Technical Requirements for
research into new approaches A recording of Linda Rhodes’ session on Registration of Veterinary Medicinal Products.
by pharmaceutical companies getting non-surgical fertility control products Guidance for industry (ViCH GL43). Target animal
approved for use in cats, presented at the 2015
and how difficult the ISFM Congress in Porto, is available at:
safety for veterinary pharmaceutical products. 2009.
regulatory hurdles can be. http://icatcare.org/vets/videos 3 GonaCon immunocontraceptive Vaccine for use
one can hope that these few It is also included as on Female White-tailed deer. US department of
approved products have pio- Supplementary material at: jfms.com Agriculture, Animal and Plant Health inspection
DOI: 10.1177/1098612X15594993
neered the way for future break- Service, Pesticide Product label, US Environmental
throughs for feline and canine Protection Agency Registration Number 56228-40,
contraception. 2009.
4 Fagerstone K and Eisemann J. Feral cats: new regu-
Funding latory pathway, new approaches. Proceedings of
the 3rd international Symposium on Non-Surgical
The author received no specific grant from any Methods of Pet Population Control; 2006 November
funding agency in the public, commercial or not- 9–12; Alexandria, VA, USA. Alliance for Contra-
for-profit sectors for the preparation of this ception in Cats & dogs. http://www.acc-d.org/
article. resource-library/symposia/3rd-symposium.

KEY Points
< Worldwide regulatory requirements for companion animal products fall into three major categories: effectiveness,
safety and manufacturing. In addition, products are evaluated for possible environmental impact and safety for
humans handling the product.
< The European Medicines Agency (EMA) regulates pharmaceutical products for animals in the European Union.
In the US, the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) regulate
depending on the nature of the product. Due to the high standards for safety, effectiveness and manufacturing,
it may take 5–10 years and USD $8–12 million to achieve regulatory approval.
< Veterinarians in some countries can legally prescribe or use drugs ‘off-label’, including having the drug
compounded. Compounding pharmacies are not required to assure safety, effectiveness or quality
of drugs they dispense.

Available online at jfms.com

Reprints and permission: sagepub.co.uk/journalsPermissions.nav
JFMS CLINICAL PRACTICE 789
Title photograph on page 783 ©iStockphoto.com/iguasu
790_799_Attitudes_Murray.qxp_FAB 10/08/2015 13:47 Page 790
CLINICAL REVIEW
METHODS OF FERTILITY
CONTROL IN CATS
Owner, breeder and veterinarian
behavior and attitudes
Jane K Murray, Jill R Mosteller, Jenny M Loberg, Maria Andersson
and Valerie A W Benka
Overview: Fertility control is
important for population
management of owned and unowned
cats, provides health benefits at
the individual level and can reduce
unwanted sexually dimorphic behaviors
such as roaming, aggression, spraying and calling.
This article reviews the available evidence regarding
European and American veterinarian, owner and
pedigree cat breeder attitudes toward both surgical
sterilization and non-surgical fertility control.
It additionally presents new data on veterinarians’
and pedigree cat breeders’ use of, and attitudes
toward, alternative modalities of fertility control.
Proportion of cats that are neutered: Within the
United States and Europe, the proportion of cats
reported to be sterilized varies widely. Published
estimates range from 27–93% for owned cats and
2–5% for cats trapped as part of a trap–neuter–return
(TNR) program. In some regions and populations
of cats, non-surgical fertility control is also used.
Social context, cultural norms, individual
preferences, economic considerations, legislation
and professional organizations may all influence
fertility control decisions for cats.
Non-surgical methods of fertility control:
Particularly in Europe, a limited number of
non-surgical temporary contraceptives are available
for cats; these include products with regulatory
approval for cats as well as some used ‘off label’.
Non-surgical methods remove the risk of
complications related to surgery and offer potential
to treat more animals in less time and at lower cost;
they may also appeal to pedigree cat breeders
seeking temporary contraception. However,
concerns over efficacy, delivery methods, target
species safety, duration and side effects exist with
current non-surgical options. Research is under way
to develop new methods to control fertility in cats
without surgery. US and European veterinarians
place high value on three perceived benefits of
surgical sterilization: permanence, behavioral
benefits and health benefits. Non-surgical options
will likely need to share these benefits to be widely
accepted by the veterinary community.
790 JFMS CLINICAL PRACTICE
Journal of Feline Medicine and Surgery (2015) 17, 790–799
Introduction
Fertility control is widely acknowledged as necessary to prevent repro-
duction in individual cats and to manage populations. Surgical sterili-
zation is a well established and permanent method of fertility control.
Most commonly, it entails castration of toms and ovariohysterectomy
of queens, but it can also include vasectomy and ovariectomy, respec-
tively. Non-surgical fertility control approaches are used in a much
smaller proportion of cats, with notable geographic variation and,
overall, greater use in Europe than in the United States.
Fertility control of cats depends on a range of factors that include the atti-
tudes and behavior of owners/caretakers/feeders/shelter staff, plus the
interactions these individuals have with veterinary professionals. Cultural
norms, social influences, individual attitudes and economic considerations
may all influence fertility control decisions.
Understanding the behaviors, attitudes and circumstances of different
communities, regions and stakeholders is important for advancing
fertility control options that
effectively meet the needs of Cultural norms, social influences,
cats and their caretakers. This
article is divided into three
individual attitudes and economic
sections. The first reviews considerations may all influence
published research on surgical
sterilization rates in the US fertility control decisions.
and Europe, and the second
reviews existing literature on factors that influence surgical sterilization
decision-making and outcomes for cats. The third section discusses
previously unpublished results of surveys from multiple stakeholder
groups (European and US general practice veterinarians, US shelter-
focused veterinarians, and pedigree cat breeders) on attitudes toward
non-surgical ‘tools’ that exist today or that may be future options.
Jane K Murray
BScEcon (Jt Hons) MSc PhD*
University of Bristol, UK
Jill R Mosteller
BS MA PhD
Colorado State University, USA
Jenny M Loberg
MSc PhD
Swedish University of Agricultural Sciences, Sweden
Maria Andersson
MSc PhD
Swedish University of Agricultural Sciences, Sweden
Valerie A W Benka
MS MPP
Alliance for Contraception in Cats & Dogs, USA
*Corresponding author: Jane.Murray@bristol.ac.uk
doi: 10.1177/1098612X15594994
© The Author(s) 2015
790_799_Attitudes_Murray.qxp_FAB 10/08/2015 13:47 Page 791
Terminology
< Sterilization is used throughout this review to describe permanent
(irreversible) methods of fertility control, also referred to as ‘neutering’
or ‘surgical spay/neuter’
< Contraception is used to refer to methods of fertility control designed
to be temporary (reversible)
Where are we now? Sterilization
rates by country and region
The proportions of surgically neutered cats in
different countries provide a measure of neu-
tering behavior within these populations. in
the United Kingdom, recent national esti-
mates of the percentage of neutered adult cats
have varied from 67–93%.1–3 Elsewhere in
Europe, the percentage of pet cats reported as
sterilized has ranged from 43% in a study
carried out in Teramo, italy, to 61% for cats
attending a vaccination clinic in France and
76% for cats belonging to households in
ireland.4–6 While data on sterilization num-
bers are not published, in Sweden, Norway,
denmark, Finland and Germany dogs are not
routinely neutered; owners are responsible for
maintaining good control of animals and
preventing uncontrolled breeding.7 Published
research is not available on cat sterilization
rates and owner responsibility in these afore-
Meanwhile, recent national estimates of pet
mentioned European countries.
cats sterilized in the United States range from
77–91%.8–11 However, research has found
is an important
notable regional and community variations in
feline sterilization rates.11 A Massachusetts
study estimated that 94% of owned cats were
sterilized,12 and a survey in a Florida commu-
nity found a 91% cat sterilization rate.13 By
sterilize, beliefs
contrast, a 27% feline sterilization rate was
reported for a community on the Texas–
and knowledge
Mexico border.14
differences in survey findings, particularly
those carried out within the same country,
might be attributable to differences in cat-
related (eg, breed) or owner-related (eg, afflu-
ence) characteristics. There is evidence that
older and purebred cats are more likely to be
sterilized than their younger and mixed-breed
counterparts.2,11 in two US studies, male pet
cats were slightly more likely to be sterilized
than females,10,11 whereas a study in ireland
found the opposite.6 Studies of cats recruited
through veterinary practices are likely to
report higher sterilization rates than studies
of cats with little or no veterinary contact.2,15
Sterilization rates may also be associated with
the geographical (eg, urban vs rural) location
of study samples.16
Estimating numbers of sterilized unowned
R E V I E W / Fertility control methods and stakeholder attitudes
(feral/community/street/stray) cats is con-
siderably more challenging than estimating
proportions of sterilized owned (pet) cats. in
addition to challenges with observation and
counting methodology, there is potential to
incorrectly ‘categorize’ an individual animal –
for example, cats that roam freely can
be owned, semi-owned or unowned.17 These
challenges notwithstanding, two large US
studies estimated that 2–5% of cats trapped
during trap–neuter–return (TNR) programs
had been previously sterilized.18,19
Factors influencing attitudes
and behaviors toward surgically
sterilizing cats
Studies in countries across the globe have
explored factors that influence owners’ and
caretakers’ attitudes and behaviors toward
sterilizing cats and dogs. Several of these
studies have focused on dogs, or on the
species combined. Recognizing that owner
attitudes and behaviors are often species- and
location-specific, this review is limited to
Studies of US, research that distinguishes cats and dogs,
and that took place within a US or European
UK and other context. Studies implemented within these
European parameters suggest that a variety of factors
are associated with cat sterilization attitudes
residents and behaviors at individual, community and
suggest that, national levels.
although cost Owner beliefs, knowledge and awareness
Studies of US, UK and other European
residents suggest that, although cost is an
factor in the important factor in the decision to sterilize
(discussed below), beliefs and knowledge can
decision to strongly influence decision-making.
A 2007 cross-sectional telephone (landline)
survey of US households revealed that the
most common explanations for not sterilizing
cats were the belief that their female should
can strongly have one litter first (41%), the procedure cost-
ing too much (39%) and the plan to breed the
influence cat (20%).9 A second national study found
decision- three times as many unplanned litters of kit-
tens as puppies born in US households.20 Cost
making. was most often reported in that study as the
reason for not sterilizing a queen, followed by
the procedure being inconvenient, not know-
ing the cat was in heat, thinking the cat was
too young, not believing in neutering animals,
and ‘other’ reasons (eg, the owner adopted a
pregnant stray cat, the owner wanted
kittens).20
A 2013 UK study found that the most com-
mon reason owners gave for not neutering
their cat was that they ‘don’t believe in it’,
cited by 16% of respondents, with nearly as
many (15%) saying they ‘haven’t thought
about it’.3 A cross-sectional telephone
JFMS CLINICAL PRACTICE 791
790_799_Attitudes_Murray.qxp_FAB 10/08/2015 13:47 Page 792
R E V I E W / Fertility control methods and stakeholder attitudes
(landline) study of UK cat-owning house-
holds revealed frequent misinformation about
feline reproduction: 26% of cat owners
believed that female cats could not conceive
before 1 year of age; 23% believed that they
should have a litter before being neutered;
while a further 26% were uncertain if they
should have a litter prior to neutering.21
A focus group with irish cat and dog own-
ers, all recruited through private veterinary
clinics, cited three primary reasons for not
neutering. The first was financial cost. The
second was the belief that owners had enough
control over their pets to prevent accidental
reproduction; however, this belief differed
according to species, as cats were perceived as
more difficult to control than dogs. The third
was perceived negative health and welfare
effects of neutering.22
These data indicate that certain beliefs and
knowledge levels, including the preferred
time to sterilize (discussed below), may con-
tribute significantly to feline reproductive
outcomes.
Owner demographics
Although multiple studies have looked at the
demographics of cat owners, a relatively
limited number have explored how owner
characteristics such as ethnicity, sex and reli-
gion are associated with decisions to sterilize
one’s cat. Understanding variability in owner
demographics and characteristics is very
important, particularly when considering
targeted strategies for increasing sterilization
rates or pet-owner populations who might
respond more or less positively to non-surgi-
cal fertility control options.
Research on owner ethnicity and relation-
ships with companion animals is limited, and
the most extensive work on this topic has
focused on US residents self-identifying as
having Hispanic, Spanish or Latino ori-
gins.14,23–25 These studies have found that per-
sons of Hispanic, Spanish or Latino origin are
less likely to report ownership of sterilized
cats compared with cat owners of non-
Hispanic background.14,23–25 (They are also
less likely than other groups to own cats and
more likely to say that they get a sense of
A study of Romanian pet owners found a
personal safety from their pet.)14,23–25
significant difference between male and
female owners’ attitudes toward neutering
male cats and dogs, with men being more
resistant. In contrast, the owner’s sex did
not influence attitudes toward sterilizing
females.26 There was no significant association
between level of attachment to pets and atti-
tudes toward sterilization in this26 or another,
US-based study,27 suggesting that other factors
may be mediating or moderating the decision.
792 JFMS CLINICAL PRACTICE
Alliance for Contraception in Cats & Dogs
This article is part of a Special Issue of the Journal of Feline Medicine and
Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline
fertility control’ and coordinated by the Alliance for Contraception in Cats
& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of
non-surgical fertility control to save the lives of cats and dogs, expand
options for pet owners, and improve animal welfare. Serving as a trusted
resource for scientific and educational
information, the ACC&D brings together key
stakeholders to advance humane sterilization
options that are faster, easier and more
accessible than surgery.
More information is available at www.acc-d.org
Albeit a small sample, one Massachusetts
study found that Catholic pet owners were
less likely to sterilize their pets (cats and dogs)
than were owners of other religions.28
These limited studies indicate that
demographic factors can be associated with
attitudes toward and decisions about steriliza-
tion. Further research on this topic is needed.
Cost of sterilization
Although owners report myriad reasons for
not sterilizing their cats, the cost of the proce-
dure is considered an important concern.
Subsidized sterilization is common in the US
and available in multiple European countries
in an effort to make sterilization economically
feasible.7,29 While research has shown the
complicated relationship between cost and
sterilization behavior across pet populations,
US national and regional studies suggest that
cost is more often the limiting factor for steril-
Moreover, studies in the US and UK have
izing cats than it is for dogs.12,20,30,31
found strong correlations between income
levels and sterilization decisions. A US
random-digit-dial phone survey found that
annual family income was the strongest pre-
dictor of whether a pet cat was sterilized.9 The
differences were dramatic: whereas 96% of
cats in households with family incomes of
$75,000 or higher were neutered, the percent-
age dropped to 51% of cats in households
with annual family incomes below $35,000.9 In
Studies in the
another US survey, 53% of respondents stated
USA suggest
that they would choose low-cost veterinary
care if available.27 These owners tended to
that cost is
more often the have an annual household income below
$40,000 (as well as describe a weak owner–pet
or client–vet bond).27 Even with a subsidized
limiting factor
spay/neuter clinic available, a study in one US
community found that 45% of cat owners
for sterilizing
cats than it is were still unable to pay for surgery, indicating
the extent of financial need or priorities
among certain populations.32
for dogs.
790_799_Attitudes_Murray.qxp_FAB 10/08/2015 13:47 Page 793
One UK study found that cat-owning
householders with low annual incomes
(£10,000 or below) were less likely than higher
income counterparts to report that their cats
were neutered by 6 months of age.33
Cat ‘lifestyle’
Higher sterilization rates have been reported
for pets (cats/dogs combined) in urban com-
pared with rural areas, which indirectly may
be related to indoor–outdoor access.16 Studies
in italy and the UK have documented that
free-roaming pet cats not permitted inside
their owner’s home were significantly less
likely to be sterilized than cats with indoor
access.2,4 in turn, decisions on indoor–outdoor
lifestyle vary over time and between coun-
tries. For example, US pet cats kept strictly
indoors have increased (33% in 1993, 49% in
2005); and, compared with the US, a lower
percentage of cats is reported to be kept strict-
ly indoors in italy (30%) and in the UK
A limited number of studies have evaluated
(9%).4,34
the extent to which those who feed unowned
cats (as distinguished from formal colony
caretakers) also take responsibility for neuter-
ing them. Recent research in the US has found
that only 5.5–14% of persons who feed free-
roaming cats at their home or place of work,
in their community or at a local park, also
sterilize them.13,18,35 This suggests a disconnect
between feeders’ commitment to feeding cats
and their perceived responsibilities toward
population control. It is also consistent with
findings that only 2–5% of cats trapped as part
of TNR programs were already spayed or
neutered.18,19
Recommendations about the appropriate
age for sterilization
Age of sterilization is important to population
control, and the appropriate age to spay or
neuter a cat has been the subject of veterinary
attention and research.36 The positions of vet-
erinary and animal welfare organizations on
appropriate sterilization age may affect rec-
ommendations given by veterinarians and
ultimately decisions of cat owners regarding
In an effort to reduce unplanned litters, the
the procedure.
American Veterinary Medical Association
(AVMA) supports ‘the concept of paediatric
spay/neuter in dogs and cats’,37 and the
British Small Animal Veterinary Association
(BSAVA) supports The Cat Group policy that
recommends neutering at 4 months of age.38,39
Despite these recommendations, veterinarian
and owner surveys indicate that the practice
of prepubertal neutering has not become
widespread in the US or UK.33,40,41 However,
recent developments, including but not limit-
R E V I E W / Fertility control methods and stakeholder attitudes
ed to the Cats Protection Early Neutering
Register and publication of spay–neuter pro-
National
gram guidelines by the Association of Shelter
Veterinarians (ASV), suggest that awareness
legislation
influences and the practice of prepubertal neutering is
pet sterilization increasing.42,43
in 2006 and 2007, the then World Society for
outcomes. the Protection of Animals (WSPA) and the
Royal Society for the Prevention of Cruelty to
In Norway, Animals international (RSPCA international)
routine surgical distributed questionnaires to member soci-
eties and associated organizations in Europe.
sterilization The results indicated variable practice of
‘early-age’ sterilization; however, ‘early-age’
is prohibited. was not defined in the questionnaire.
By contrast, Groups in Bulgaria, Croatia, Estonia,
Germany, Hungary, italy, Malta, Serbia and
it is obligatory the Ukraine reported early-age sterilization of
in Belgium cats. Responses suggested that early-age ster-
ilization was not practiced in the majority of
to neuter all countries in 2006–07.7
(except
Influence of professional associations,
breeding) legislation and policies
Beyond influencing the age at which cats are
cats sold. sterilized, professional organizations may
influence countries’ overall sterilization rates.
So, too, may spay/neuter legislation and poli-
Although veterinary associations of some
cies for companion animals.
countries (eg, the AVMA and British Veterinary
Association)44,45 and most veterinarians within
these countries recommend neutering cats not
intended for breeding, limited legislation exists
to support these recommendations. The 1987
European Convention for the Protection of Pet
Animals states that neutering should be pro-
moted to reduce unplanned breeding of stray
cats and dogs, and that there is a need to dis-
courage unplanned breeding.46 However, this
document has been signed by only 23 of 47
European member states.47 In Norway, routine
surgical sterilization is prohibited by the
Animal Welfare Act; in Sweden, Denmark,
Finland and Germany, surgical sterilization is
not prohibited but removal of organs for the
purpose of convenience to humans is discour-
aged.48,49 In contrast, since September 2014 it
has been obligatory to neuter all cats (exclud-
ing breeding cats) that are sold in Belgium.50
This variance suggests mixed sentiments by
the professional organizations and legislative
authorities across Europe, which likely influ-
ence veterinarians’ recommendations and pet
sterilization outcomes.
With regard to unowned, free-roaming cats,
surveys of groups in 31 European countries
found that the majority of countries perform
TNR in conjunction with culling or catch-and-
removal to control populations; only Belgian
and Greek groups reported using TNR
exclusively.7
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R E V I E W / Fertility control methods and stakeholder attitudes
Why search for new forms of sterilization?
Surgical sterilization can be costly for cat owners and time-consuming for
veterinarians, and its irreversibility can be problematic for pedigree cat breeders.51
It requires surgical infrastructure and, for unowned, free-roaming cats, is not being
performed on the scale needed to have a substantial beneficial impact on popu-
lation control.52 It is also not performed at levels needed to eliminate homeless-
ness and euthanasia of pet cats.53 These considerations prompt questions as to
whether new forms of non-surgical fertility control could supplement surgical
sterilization, under what circumstances they would be most valuable, and which
stakeholder groups would be most receptive to using these methods.
Stakeholder attitudes toward
present and future non-surgical
fertility control options
above, research is under way to develop new
For a variety of reasons, as outlined in the box
methods to control feline reproduction,54,55 many
of which are discussed in accompanying articles
in this Special Issue. Already, progestin contra-
ceptives (eg, medroxyprogesterone acetate,
proligestone, hydroxyprogesterone, megestrol
acetate, chlormadinone acetate, levonorgestrel
and altrenogest) and the long-acting gonado-
tropin-releasing hormone (GnRH) agonist
deslorelin are being used in cats (J Miller, unpub-
lished data; J Murray, unpublished data).56 Some,
but not all, progestins have regulatory approval
for cats in certain countries, and surveys reveal
that these contraceptives are more widely used
in Europe than in the US (J Murray, unpublished
data; J Miller, unpublished data).56
Non-surgical ‘tools’ have the potential to ben-
efit individual cats by removing postoperative
Non-surgical
recovery and risks associated with surgical ster-
ilization; they may also be more affordable, eas-
‘tools’ have the
ier and faster. At the same time, non-surgical
potential to
methods present challenges, concerns and ques-
tions. There is no permanent sterilant currently
benefit cats
available; all options require repeated treat-
ments. Any product given orally, particularly to
by removing
unowned, free-roaming cats using a bait system, postoperative
prompts concerns about proper dosing and
safety for non-target species.55 Certain existing
recovery
products, notably progestins used long term
and/or in high doses (see accompanying article
and risks
in this Special Issue),57 have yielded reports of associated with
adverse side effects such as endometrial hyper-
plasia or endometrial cancer, pyometra, glucose
surgery; and
intolerance and diabetes mellitus, adrenocorti- may be more
cal suppression and mammary tumors.55,58,59
To follow are summaries of original research
affordable,
conducted with veterinarians and pedigree cat
breeders to gauge attitudes toward, and use of,
easier and
non-surgical feline fertility control. Some faster. They
questions have inquired about use of products
currently available (often used off label);
also present
others have presented theoretical future phar-
maceuticals to gauge what features are, and
challenges and
are not, attractive to stakeholders. questions.
794 JFMS CLINICAL PRACTICE
Attitudes and awareness among US
general practice and shelter veterinarians
in 2007 and 2008, 200 general/private practice
and 240 ASV member veterinarians were sur-
veyed about attitudes toward and awareness
of non-surgical fertility control for cats and
The overwhelming majority of general prac-
dogs.60,61
tice and ASV member veterinarians (96% and
98%, respectively) agreed ‘strongly’ or ‘some-
what’ that unplanned litters contributed signif-
icantly to numbers of unwanted pets (cats and
dogs) in their community. The cohorts differed,
however, in their beliefs about the potential for
non-surgical options to reduce unwanted pop-
ulations. Sixty percent of ASV members per-
ceived a need for non-surgical sterilization in
their shelter or clinic, while only 32% of gener-
al practitioners believed there was such a need
in their practice. The latter recognized the
value of non-surgical options for pets that can-
not undergo surgery, and for clients who resist
surgery or cannot afford its cost. However, the
majority of private practice veterinarians felt
that surgical sterilization worked well and
offered behavioral and health benefits; 65%
also felt that spay and neuter was important
for attracting new clients to the practice.
Using mean ratings, both veterinary cohorts
perceived that female cats were most in need
of a non-surgical alternative to sterilization,
followed by male cats. in their opinion, the
need for non-surgical options was also greater
for cats than for dogs. However, while 62% of
ASV member veterinarians rated the need for
female cats as 6 or 7 on a 7-point scale (1 = no
need at all and 7 = a very great need), only
22% of general practice veterinarians assigned
Although ASV member veterinarians viewed
a rating of 6 or 7 for female cats.
female cats as the group that would benefit
most from non-surgical options, they did not
strongly support the idea of a multi-year con-
traceptive as a solution. When presented with a
hypothetical single-injection 3-year contracep-
tive for female cats, veterinarians in general
practice were more likely than ASV member
veterinarians to say they would recommend
the product to their clients (52% versus 30%,
respectively). However, even general practice
veterinarians who supported the hypothetical
product were concerned that owners would
fail to repeat the treatment. When asked about
the relative value of a contraceptive for pet ver-
sus feral cats, both veterinary cohorts thought
that such a contraceptive had the potential to
be most useful for the latter population.
Survey findings offer valuable insights on
different veterinary perspectives regarding
non-surgical fertility control. Differences exist
between the contexts in which veterinarians
work and their perceptions of the need for, and
790_799_Attitudes_Murray.qxp_FAB 10/08/2015 13:47 Page 795

R E V I E W / Fertility control methods and stakeholder attitudes

benefit of, non-surgical options. This variability

warrants consideration, particularly for poten-
predominantly small animal veterinary prac-

tial early adopters of new technologies.

tice and/or who engaged in activities related
to feline population control. Respondents
included 115 European veterinarians, 59 of
US and European veterinary perspectives whom practiced in the UK; in total 18
A 2014 survey, distributed via international European countries were represented. Fifty-

The findings, which are summarized in the

Cat Care (iCatCare) and the American four US veterinarians completed the survey.

box below, suggest geographic heterogeneity

Association of Feline Practitioners (AAFP)
listservs, was modelled loosely on the afore-
mentioned surveys60,61 (J Murray, unpub-
lished data). it sought to gauge veterinarian
attitudes toward and use of fertility control,
in veterinarian attitudes toward, and priori-
ties for, non-surgical fertility control. This
variety warrants attention, as it will influence

This survey also indicates the weight that

both surgical and non-surgical, in Europe and receptiveness to new products.

veterinarians place on the health and behav-

the United States. The survey yielded 169
responses from veterinarians who worked in

Geographic heterogeneity in veterinarian attitudes

A 2014 survey, distributed via iCatCare and AAFP listservs (see Respondents were asked to rate the importance of various
text above), has revealed geographic variation in sterilization of factors when evaluating a new sterilant product for owned cats.
client-owned cats 4 months of age or older, consistent with Both US and European veterinarians viewed permanence,
findings from other research. US veterinarians estimated that an reduction in unwanted hormone-related behaviors and protec-
average of 91% of male and 91% of female client-owned cats in tion against reproductive tract and hormone-related diseases as
their practices were sterilized; this proportion mirrors the high most important; each geographic cohort, on average, rated the
end of US national estimates.8 European respondents reported importance of these features at 6.2 or above on a 7-point scale.
88% and 85% sterilization rates for male and female cats in their US veterinarians were especially interested in permanent sterili-
practices, respectively. Within the European cohort, however, UK zation and reducing behaviors associated with sex hormones,
veterinarians reported an average of 92% and 91% sterilized with 91% rating permanence and 85% rating behavioral impacts
male and female cats within their practices, respectively. a 6 or 7 (1 = not at all important, 7 = extremely important). In
European practitioners outside the UK reported that an average comparison, 80% and 74% of European veterinarians rated per-
of 83% male and 79% female cats in their practices were esti- manence and behavioral effectiveness, respectively, a
mated to be sterilized. 6 or 7. It is notable, as well, that a higher percentage of UK vet-
The survey additionally revealed notable geographic variation erinarians (85%) assigned a 6 or 7 to the importance of
in awareness of non-surgical contraceptives. Among European permanence, whereas 75% of European veterinarians outside
veterinarians outside the UK, 80% were aware of feline products the UK gave this rating.
currently in development or on the market; a smaller 34% of UK When asked about the need for permanent non-surgical steri-
practitioners, and 15% of US veterinarians, were aware. lants for unowned (stray, feral, community) and owned cats of
US veterinarians perceived that the greatest value of non- both sexes, both geographic cohorts viewed unowned female
surgical fertility control was its potential to increase the number cats as having the greatest need, followed by unowned males.
of sterilized animals. The mean rating was 6.06 on a 7-point scale Among US veterinarians, 87% and 78% assigned a 6 or 7 to the
(1 = not at all valuable, 7 = extremely valuable), and 82% of need for female and male unowned cats, respectively; 66% and
respondents ranked it a 6 or 7. In contrast, 34% of European 57% of European veterinarians assigned these ratings for female
veterinarians assigned a 6 or 7 to the value of increasing num- and male unowned cats (1 = no need at all, 7 = a very great
bers of sterilized animals; the mean rating for this cohort was need). Both cohorts, on average, viewed the need as greater for
5.14. unowned than for pet cats.
US veterinarians also valued the potential of non-surgical As with the aforementioned study of US veterinarians,60 survey
sterilants to cost less (67% rated a 6 or 7) and appeal to owners respondents were presented with a hypothetical single-injection
who resist surgery (62% rated a 6 or 7), as well as to help 3 year contraceptive for female cats. Respondents were,
shelters to reduce numbers of unwanted cats on average, less enthusiastic about a 3 year contra-
(66% rated a 6 or 7). European veterinarians ceptive than a permanent non-surgical option.
viewed the greatest value of non-surgical Interestingly, European veterinarians as a group
sterilization as being an alternative for clients viewed the potential for pet and unowned cats
resisting surgery for their cats; 56% of differently; 40% would be ‘somewhat likely’
European veterinarians assigned this benefit SUPPLEMENTARY MATERIAL or ‘very likely’ to recommend a 3 year contra-
The survey questions are included as
a 6 or 7 on a 7-point scale. Meanwhile, both ceptive to their cat-owning clients, while only
Supplementary material alongside the
geographic cohorts viewed attracting new online version of this article at: 24% reported being likely to recommend such
clients and profiting from greater sterilization jfms.com a product to charities performing TNR. In con-
efficiency as relatively unimportant; fewer than DOI: 10.1177/1098612X15594994 trast, US veterinarians were equally likely (40%)
30% of veterinarians in both groups ranked these to recommend this product to both stakeholder
6 or 7. groups.

JFMS CLINICAL PRACTICE 795

790_799_Attitudes_Murray.qxp_FAB 10/08/2015 13:47 Page 796

R E V I E W / Fertility control methods and stakeholder attitudes

ioral effects of sterilization and alternative fer-

tility control methods; in this way, it is consis-
Discussion and conclusion

tent with the earlier study of two US veteri-

nary cohorts.60,61 This survey also reflects vet-
Existing research shows that proportions of

erinarians’ strong desire for permanent versus

sterilized pet cats vary considerably across

temporary sterilization methods for pet and

countries and communities. Unfortunately,

unowned, free-roaming cats. It is notable that,

prevalence estimates for many European

relative to other features of non-surgical fertil-

countries are not available in the peer-

ity control, study participants did not place

reviewed literature, potentially reflecting low

great importance on its potential economic

levels of interest in population control aspects

benefits for the veterinary practice.

of neutering, low numbers of unowned or
unwanted cats, a dearth of active research on
this topic or lack of active promotion of

Variations in reported sterilization rates can

Attitudes of pedigree cat breeders toward neutering in these countries.

be attributed, at least in part, to owner atti-

different fertility control methods

tudes, knowledge and demographic variables.

As new in 2013, The Cat Fanciers’ Association (CFA)

Legislation, policies, veterinary training of

distributed a survey to members seeking feed-
technologies
undergraduates and positions adopted by
back on breeder contraception and sterilization

veterinary organizations surely influence

become methods (J Miller, unpublished data). Approx-

veterinarian recommendations and cat owner

imately 700 responses were recorded; the

decisions, and over time they likely contribute

available to majority (81%) of respondents were pedigree

to sterilization ‘norms’.
cat breeders. Although 82% of survey respon-
control feline
Human behavior, practices and attitudes
dents hailed from the US or Canada, 34 coun-

Ninety respondents reported that they had provide important context for addressing
reproduction, tries from across the globe were represented.

controlled heat cycles in their cats; 358 respon-
dents had not (the remaining respondents did
it will continue
to be important not answer the question). Breeders who
controlled heat cycles most often cited use
of progestins megestrol acetate and medroxy-
to gauge
attitudes, progesterone acetate. Of note, breeders
reported using highly varied dosages, even of
the exact same compound. Smaller numbers
perceptions,
of breeders reported using the GnRH agonist
deslorelin or gonadorelin diacetate tetrahy-
and behaviors
of stakeholders drate. Some respondents indicated extended
use of non-surgical fertility control, but most
indicated short-term use to delay breeding a
across
cat. The safety of a contraceptive and ability to
eliminate secondary behavioral issues were
countries,
communities viewed as primary considerations by cat
breeders.
Whereas veterinarians have conveyed con-
and
cern about the failure of cat owners to return
for follow-up treatment with a long-term
demographics.
contraceptive,60 the possibility of postponing
or temporarily preventing reproduction
appealed to pedigree cat breeders. When
asked if they would welcome an ‘FDA
approved and proven safe, and reversible,
contraceptive for female cats’, 90% of respon-
questions about non-surgical fertility control
for cats. Where is the greatest need, and could
non-surgical options address that need?
Which stakeholders are most open to non-
surgical options? What features of non-surgi-
cal fertility control are most valuable to
different groups?
Among pet owners, those wishing to breed
their cat or for their female to have a litter
prior to sterilization are unlikely to choose a
non-surgical sterilant over surgery. Those
who have not sterilized their cat due to
perceived inconvenience are also unlikely to
benefit from non-surgical options.
However, non-surgical fertility control
could be attractive to owners who resist surgi-
cal sterilization for other reasons: perceived
negative health effects, the invasiveness of
surgery, or a cat that cannot safely be anes-
thetized. An injectable contraceptive or steri-
lant might also gain traction among owners
who resist prepubertal sterilization, particu-
larly if it was proven and perceived to be as
safe as vaccines given as early as 6–8 weeks.
There is compelling evidence that although

dents answered ‘yes’. Those answering ‘no’

cost is not the sole factor discouraging owners

cited concerns about long-term safety and the

from sterilizing their cats, it can be a deterrent,

need for extensive testing. Others resisted

particularly for owners with limited economic

interfering with a cat’s normal reproductive

resources. Less expensive non-surgical meth-

cycle, often for fear of long-term health

ods of fertility control could be attractive to

consequences (J Miller, unpublished data).

this group; however, a comparison would

Approximately equal proportions of respon-

need to be made between the desirability of

dents (34% and 35%, respectively) desired

non-surgical treatment and subsidized low-

options that would allow their female to

cost or free surgical neutering. For persons

regain fertility 3 or 6 months following treat-

with limited resources, the ability to bring a

ment; 24% were interested in options with a

non-surgical sterilant to the community (with-

duration of 1 year.
out the need for a mobile surgical unit) could
be significant.

796 JFMS CLINICAL PRACTICE

790_799_Attitudes_Murray.qxp_FAB 10/08/2015 13:47 Page 797
Veterinary professionals will, without question,
influence the success of non-surgical fertility
control in private practice, animal shelters
and TNR programs.
Veterinary professionals will, without ques-
tion, influence the success of non-surgical fer-
tility control in private practice, animal shelters
and TNR programs. US veterinarians, in par-
ticular, believed that non-surgical options
could have value for pets that cannot undergo
surgery, for clients who resist or cannot afford
surgery, and for shelters and communities
seeking to increase sterilization numbers
(J Murray, unpublished data). It remains to be
seen if the veterinary community will support
a product without all the highly desired
features (permanence and behavioral/health
benefits) if such a product could help in these
areas of veterinarian-identified need.
US veterinarians’ overall response to a hypo-
thetical 3 year contraceptive was tepid at best,
and there were some notable differences
between veterinary cohorts. ASV members
were less likely than their private practice col-
leagues to recommend a 3 year contraceptive
to their clients, possibly due to the assumption
that shelters will have only a single opportuni-
ty to treat a cat. Both US veterinary cohorts
thought that a 3 year contraceptive had great-
est potential for feral cat populations.61,62
Although they were not asked to explain their
reasons for having a greater interest in feral cat
applications, potential explanations might
include the required resources and stress to
animals involved in trapping and transporting
feral cats for TNR, as well as indications that,
in comparison with pet cats, many feral and
free-roaming cats have, on average, relatively
short lifespans.15,62–64
In the 2014 online survey of US and
European veterinarians (see box on page 795)
a minority of respondents reported that they
would be likely to recommend a 3 year contra-
ceptive to their cat-owning clients (J Murray,
unpublished data). However, whereas US
veterinarians reported being equally likely to
recommend such a product to clients and to
organizations performing TNR, European
veterinarians indicated being nearly twice as
likely to recommend to cat owners than to
TNR charities (J Murray, unpublished data).
Feedback on a multi-year contraceptive might
be attributed, at least in part, to survey structure;
namely, the contraceptive was presented as an
alternative to permanent sterilization (surgical
or non-surgical), and veterinarians were asked
which option they would recommend for
owned and unowned cohorts of male and
R E V I E W / Fertility control methods and stakeholder attitudes
female cats. Future surveys might explore con-
texts in which veterinarians would entertain
using a 3 year contraceptive to complement
or supplement permanent sterilization, and
whether veterinarians believe there are circum-
stances in which a ‘combination approach’ could
benefit fertility and population control efforts.
Veterinary attitudes toward a multi-year
contraceptive are particularly relevant given
that a GnRH-hemocyanin conjugate immuno-
contraceptive vaccine has shown promising
results in cats (see accompanying article in this
Special Issue).65 The challenges of pharmaceu-
tical development are such that a long-lasting
contraceptive for female cats will almost cer-
tainly become commercially available before a
permanent sterilant. The potential market for
such a product, particularly for the unowned
female cats deemed most in need of new fertil-
ity control options, remains of interest.
As new technologies become available to
control feline reproduction, it will continue to
be important to gauge attitudes, perceptions
and behaviors of diverse stakeholders (eg,
veterinarians, cat owners, pedigree cat breed-
ers and shelter professionals) across countries,
communities and demographics. Humans
arguably are – and will continue to be – the
most important factor influencing feline
veterinary care and fertility control outcomes.
KEY pOINTS
< Different countries and populations report highly varied
sterilization rates for cats. Social context, cultural norms,
individual preferences, economic factors, legislation and
professional organizations may all influence fertility control
decisions. Attitudes and behaviors may also vary among
stakeholder populations (eg, veterinarians, pet owners and
pedigree cat breeders).
< Understanding human behavior, practices and attitudes is important
when attempting to increase the number of sterilized cats.
< When considering development of non-surgical fertility control
options, areas of interest include identifying populations of
greatest need; stakeholders most open to non-surgical options;
and the features of non-surgical fertility control that are most
desired by different groups.
< Veterinary professionals will influence the success of non-surgical
fertility control in private veterinary practices, animal shelters and
trap–neuter–return (TNR) programs. An online survey of US and
European veterinarians found that US veterinarians, in particular,
believe that non-surgical options could have value for pets that
cannot undergo surgery, for clients who resist or cannot afford
surgery, and for shelters and communities seeking to increase
sterilization numbers. Veterinarians were overall
not supportive of a hypothetical multi-year non-surgical
contraceptive, although attitudes varied by country
and the cohort of cats (owned or unowned) receiving
the product.
JFMS CLINICAL PRACTICE 797
790_799_Attitudes_Murray.qxp_FAB 10/08/2015 13:47 Page 798
R E V I E W / Fertility control methods and stakeholder attitudes
ISFM CONGRESS RECORDING
A recording of Jane Murray’s session on
stakeholder behavior and attitudes to fertility
control in cats, presented at the 2015 ISFM
Congress in Porto, is available at:
http://icatcare.org/vets/videos
It is also included as
Supplementary material at: jfms.com
DOI: 10.1177/1098612X15594994
Funding
The authors received no specific grant from any funding agency
in the public, commercial or not-for-profit sectors for the prepara-
tion of this article. Jane Murray’s post is funded by Cats
Protection.
Conflict of interest
The authors have no conflict of interest to declare.
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spay-neuter.aspx (2014, accessed october 6, 2014).
45 British Veterinary Association. Neutering of cats and dogs.
http://www.bva.co.uk/News-campaigns-and-policies/Policies/
Companion-animals/Neutering/ (2014, accessed october 6,
2014).
46 Council of Europe. European Convention for the Protection of
Pet Animals (ETS No. 125). http://conventions.coe.int/
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47 Council of Europe Treaty office. European Convention for the
Protection of Pet Animals CETS No.: 125. http://conventions.
coe.int/Treaty/Commun/ChercheSig.asp?NT=125&CM=&dF=
Available online at jfms.com
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&CL=ENG (2014, accessed october 20, 2014).
48 Farstad K and Axner E. An internet survey of breeders’ and cat
rescue organisations’ opinions about early castration of cats.
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49 Palmer C, Corr S and Sandoe P. Should we routinely neuter com-
panion animals? Anthrozoös 2012; 25: 153–172.
50 Peeters, E. The multiannual cat plan of Belgium. Animal Welfare
Council, Belgium. http://www.vier-pfoten.eu/conferences/
2014-expert-workshop-on-stray-animals-in-europe (2014,
accessed october 16, 2014).
51 Goericke-Pesch S, Wehrend A and Georgiev P. Suppression of
fertility in adult cats. Reprod Domest Anim 2014; 49 Suppl 2:
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52 Robertson SA. A review of feral cat control. J Feline Med Surg
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53 American Society for the Prevention of Cruelty to Animals
(ASPCA). Pet statistics. ASPCA frequently asked questions.
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54 Michelson Prize and Grants. Michelson Grants Research
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http://www.michelsonprizeandgrants.org/michelson-
grants/research-findings (2014, accessed october 22, 2014).
55 Alliance for Contraception in dogs and Cats. Contraception
and fertility control in dogs and cats: a report of the Alliance
for Contraception in Dogs & Cats. http://www.acc-d.org/
resource-library/e-book (2013, accessed october 16, 2014).
56 Sontas BH, Kaysigiz F and Ekici H. Methods of oestrus preven-
tion in dogs and cats: a survey of Turkish veterinarians’
practices and beliefs. Arch Med Vet 2012; 44: 155–166.
57 Romagnoli S. Progestins to control feline reproduction.
Historical abuse of high doses and potentially safe use of low
doses. J Feline Med Surg 2015; 17: 743–752.
58 Greenberg M, Lawler d, Zawistowski S, et al. Low-dose mege-
strol acetate revisited: a viable adjunct to surgical sterilization
in free roaming cats? Vet J 2013; 196: 304–308.
59 Munson L. Contraception in felids. Theriogenology 2006; 66:
126–134.
60 BN Research. Veterinarian attitude and awareness survey:
non-surgical sterilization. http://www.acc-d.org/docs/default-
source/Research-and-innovation/vetreport.pdf?sfvrsn=2 (2007,
accessed october 21, 2014).
61 BN Research. Shelter veterinarian attitude and awareness
survey: non-surgical sterilization. http://www.acc-d.org/docs/
default-source/Research-and-innovation/asvreport.
pdf?sfvrsn=4 (2008, accessed 21 october 2014).
62 Nutter FB. Evaluation of a trap-neuter-return management pro-
gram for feral cat colonies: population dynamics, home ranges,
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800_807_Population models_Boone.qxp_FAB 10/08/2015 13:54 Page 800
CLINICAL REVIEW
Better trap–neuter–return
for free-roaming cats
Using models and monitoring to
improve population management
John D Boone
Overview: Trap–neuter–return (TNR)
for cat management is transitioning
from an enterprise driven mainly by
an urge to ‘help’ into an enterprise
that draws useful guidance and
precedent from the fields of population
biology and wildlife management.
This transition is in its infancy, however. At the
present time many TNR programs do not produce
substantial and persistent reductions in cat
populations, and those that do often fail to
effectively document this achievement or to
publicize their success.
Challenges: As a result, TNR has become
increasingly controversial, with TNR advocates
and wildlife conservationists often staking out
fundamentally incompatible positions. This may
ultimately prove to be an unproductive debate,
since public opinion in developed countries is
unlikely to support a total abandonment of TNR
in favor of widespread cat management using lethal
methods, and since wildlife advocates are unlikely
to support TNR as it is typically practiced.
Advancements: In contrast, improving the
effectiveness of TNR as a population management
tool can benefit both cats and wildlife, potentially
on a broad scale. Making these advancements
requires the diligent promotion, dissemination
and adoption of tools like population modeling,
population monitoring and adaptive management.
By virtue of their training and exposure to the
scientific method, veterinarians are uniquely
well positioned to translate the more technical
aspects of these approaches to TNR practitioners,
and to facilitate their wider use.
Aim: The purpose of this review is to describe
for a veterinary audience how to facilitate more
effective sterilization-based management of
outdoor cats, using a combination of theoretical
knowledge derived from population modeling
and empirical knowledge derived from population
monitoring. Using both of these information sources
synergistically can offer a viable pathway to better
management outcomes.
800 JFMS CLINICAL PRACTICE
Journal of Feline Medicine and Surgery (2015) 17, 800–807
Introduction
In all likelihood, sterilizing an outdoor cat gives that individual a better
quality of life. Additionally, if the cat is a female, the sterilization almost
certainly prevents many kittens from being born. Does that same
sterilization, however, help to reduce the number of outdoor cats? The
intuitive answer to that question is ‘yes, by preventing multiple kittens
from being born, we must be helping to reduce the number of cats’. The
actual answer, however, is far more conditional, and depends on the
processes that govern biological populations in general and outdoor cat
populations in particular. The unfortunate reality is that many steriliza-
tions currently being performed on outdoor cats have no significant
impact on population size, and that consequently trap–neuter–return
(TNR) cat management programs have come under increasing criticism
and scrutiny.1 However,
this does not have to Cat populations are
remain the status quo. Over
recent years, animal welfare inherently resistant to the
organizations have begun
to pay increasing attention
kind of population-level change
to lessons from the fields we hope to effect.
of population biology and
wildlife management, les-
sons that have the potential
to make the reduction of outdoor cat populations via fertility control an
increasingly common – and increasingly well documented – phenom-
enon. In order to realize this potential, these lessons must be widely
Veterinarians play a critical role in TNR programs at the clinical level,
communicated and applied.
and are often involved at the administrative and planning levels as well.
Veterinarians are, of course, well versed in the organismal biology of
cats, sterilization procedures and the effects of these procedures on the
individual animal. Populations (simply defined as a group of interact-
ing, interbreeding individuals), however, are very different entities from
individuals, and they exhibit properties and dynamics that are not pre-
dictable from knowledge of organismal biology (see later). Successfully
achieving population-level goals requires that we understand the biolo-
gy of populations just as we understand the biology of individual ani-
mals. Veterinarians, by virtue of their technical training and exposure to
the scientific method, have the capacity to constructively incorporate the
critical elements of population biology into TNR practice.
John D Boone
PhD
Research Director, Great Basin Bird Observatory,
Reno, NV 89502, USA
Email: boone@gbbo.org
DOI: 10.1177/1098612X15594995
© The Author(s) 2015
800_807_Population models_Boone.qxp_FAB 10/08/2015 13:51 Page 801
Models
Models are simplified representations of a
system of interest that are created to make
that system easier to understand and explore.
They can be mathematical equations, statisti-
cal relationships, or simulations in which the
system is represented virtually in computer
code. Models in biology (especially popula-
tion models) can never capture all of the
complexity and ‘messiness’ present in the real
world, and will therefore provide only
approximations of the scenarios we will
actually encounter. However, insights derived
from well-constructed models can give us a
meaningful understanding of the require-
ments for effective population control, and
offer a valuable short-cut to the decades of
trial and error that would be required to
The following discussion begins by intro-
obtain the same insights empirically.
ducing some of the ‘stark realities’ of popula-
tion biology that population models aspire to
emulate (and TNR practitioners often struggle
to overcome). There then follows a descrip-
tion of how cat-specific modeling has been
used to better understand these complexities
and deliver practical guidance for more effec-
tive management interventions.
Reality #1: the ‘doomed surplus’ and
Population biology – some stark realities
carrying capacity
Students of population biology are inevitably
exposed early on to the paired concepts of ‘K-
selection’ and ‘r-selection’. These terms repre-
sent different ends of a spectrum of evolution-
ary adaptation with regard to reproductive
strategy.
‘K’ vs ‘r’ species
A K-selected species is characterized by producing
relatively few offspring that receive significant
parental care, and (hopefully) survive at a high rate,
while an r-selected species produces many off-
spring, which receive more limited (if any) parental
care, with many or most not surviving to adulthood.
In short, K-selected species reproduce slowly, and
r-selected species reproduce with relative abandon.
Humans, elephants and whales are typical ‘K’
species, while bacteria, house flies and lemmings
are typical ‘r’ species.
The ‘K’ and ‘r’ concepts are most appropri-
ately used in a relative sense and, within the
world of mammals, free-roaming cats (in
contrast to their wild ancestors) exhibit ‘r’
type characteristics, with a healthy female cat
capable of producing several dozen offspring
during her lifespan.2 Each kitten receives only
a relatively short period of parental care, after
R E V I E W / Population models and monitoring for management of free-roaming cats
Alliance for Contraception in Cats & Dogs
This article is part of a Special Issue of the Journal of Feline Medicine and
Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline
fertility control’ and coordinated by the Alliance for Contraception in Cats
& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of
non-surgical fertility control to save the lives of cats and dogs, expand
options for pet owners, and improve animal welfare. Serving as a trusted
resource for scientific and educational
information, the ACC&D brings together key
stakeholders to advance humane sterilization
options that are faster, easier and more
accessible than surgery.
More information is available at www.acc-d.org
which it becomes independent and begins
reproducing at a relatively young age. In an
outdoor setting, most of these kittens do not
survive to adulthood; if they did, the world
would literally be awash with cats. The envi-
ronment simply does not have the capacity to
support all of these kittens, and the ‘doomed
surplus’ die early by various mechanisms in
An
unfortunate an inexorable adherence to these ecological
limits. These limits, which may vary from
place to place and across time, are collectively
reality is
encompassed in the concept of ‘carrying
capacity’, which can be defined as the number
that many
(or density) of individuals that the local envi-
sterilizations
ronment can, on average, support.
The significance of this concept for cat man-
currently
agement is as follows: sterilization efforts in
places where a cat population is at or close to
being
its carrying capacity will initially serve to pre-
performed on
vent the birth of kittens that are fated to be
part of the doomed surplus. Until sterilization
free-roaming
rates reach a threshold level which effectively
cats have no
eliminates these ‘excess’ kittens, population
size reduction is not possible.
significant
Reality #2: lag times
impact on
population Assuming that the births of the doomed sur-
size. plus have been prevented by a sufficiently
high rate of sterilization, we might expect that
additional sterilization efforts should rapidly
reduce population size. Here population
dynamics has another reality in store for us;
namely, that the population-level effects of
high sterilization rates are not manifested
immediately, but only become apparent after
significant lag times. To understand why this
is so, imagine a free-roaming cat population in
which every cat is suddenly sterilized. Upon
being returned to the colony site, population
size will be no different than it was prior to
sterilization. Population decline will only
occur as existing adults die, and then fail to be
replaced by kittens, a process that occurs over
years.
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R E V I E W / Population models and monitoring for management of free-roaming cats

Reality #3: immigration and abandonment

If high sterilization rates have been achieved, Figure 1 Diagram
and we are expecting population decline to of an idealized
metapopulation. Barrier
manifest, the appearance of a few unsterilized Each numbered circle
immigrants or abandoned cats can greatly represents a distinct

delay this expected decline. Steady immigra-

population (or colony), 1 4
with circle size
tion and abandonment, in effect, is constantly proportional to
population size.
diluting the sterilization rate of the overall Most populations
population, and constitutes one of the most are connected by
periodic exchange
significant impediments to reducing popula- of individuals, which
tion size. In most settings, cats exist in the may be unilateral 3
(single-headed arrows)
form of a ‘metapopulation’, which is an array or bilateral (double-
of distinct groups, or populations, that are headed arrows),
and which can occur
connected by periodic movements of individ- frequently (wide
uals from one population to another, as arrows) or infrequently
(narrow arrows).
illustrated in Figure 1. In most places (with Movements between
the exception of islands or other isolated some populations may 2
locations), some degree of cat emigration and be effectively blocked
or limited by physical
immigration must be expected. Compound- barriers, such as rivers
ing this difficulty, as a local population is driv- or major highways

en below its carrying capacity, immigrants

and abandoned cats become progressively
more likely to successfully ‘settle’ within the
vacated resource space; this is one of many
ways in which population dynamics may shift
as the density of cats rises or falls (usually to
the detriment of population control efforts).
For these reasons, successful TNR programs
must be prepared to overcome the effects of
cat movements and abandonment.
Reality #4: the ‘vacuum’ effect
The so-called ‘vacuum effect’ is a process
whereby new cats tend to replace those that
disappear or are removed from a population.
Although it is most often mentioned as a
potential by-product of traditional ‘trap and
euthanize’ animal control practices, it is in
fact just as likely to occur as a by-product of
successful TNR programs. As a population
falls below its carrying capacity, whether
due to lethal removal, TNR or other factors,
resource space becomes available, and that
space is likely to be filled if there are kittens,
immigrating cats or abandoned cats present in
the same area. Assuming that we are attempt-
ing to reduce population size, the only ways
to avoid a potential vacuum effect are to
ensure that there are too few locally born
kittens or immigrants to fill the vacated space
the sterilization rate does not fall appreciably
below the targeted sterilization rate for any
extended period of time. If it does, the popu-
Models allow lation will begin to grow much more rapidly
than it declined.
us to explore
Synthesizing reality in models
many different
Cat populations are inherently resistant to the
management kind of population-level change we hope to
effect, through the mechanisms described
approaches – above. Although these challenges are very
far more than real and substantial, they are not necessarily
intractable. Overcoming them requires us to
could ever be synthesize our knowledge of population
dynamics into a usable framework and, from
practically there, to generate practical guidelines for gain-
tested in a field ing control of populations. Most often, this
process involves constructing models, which
setting – and to can take many forms. For the purposes of this
discussion, we focus on simulation modeling.
identify those A simulation model that adequately mimics
with the most the functioning of a real population offers us
an opportunity to explore different approaches
potential. to population management that are limited
only by our imagination, and to determine the
specific parameters most likely to make the

Recently, a multidisciplinary group organ-

and/or to reduce carrying capacity along with difference between success and failure.

ized by the Alliance for Contraception in Cats

population size.

Reality #5: reversion & Dogs (ACC&D) published a comprehensive

cat population model that captures the
complexities of population function that are
Once achieved, a high sterilization rate must

described above, incorporates realistic age-

be perpetually maintained by active manage-

specific survival and reproduction rates, and

ment in order to produce lasting population

addresses the impact of immigration and

change. Functionally speaking, this means

abandonment.3 Several different management

that a successful TNR program will need to

approaches were compared within this frame-

conduct periodic assessments of current steril-

work (surgical sterilization, non-surgical

ization rate and population size (see later),
and trap and sterilize cats as needed so that

802 JFMS CLINICAL PRACTICE

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R E V I E W / Population models and monitoring for management of free-roaming cats
A thorough treatment of the practical lessons that can be obtained from Miller et al3 and other models of cat population dynamics
is beyond the scope of this article, but is presented in an online guidance document prepared by the ACC&D.4 The most
important findings are presented below.
Threshold sterilization rates
The sterilization rate that is minimally sufficient to invoke popu-
lation decline over time is not an invariable quantity; but, in most
situations, consistently maintaining a 75% sterilization rate will
produce population decline over time. The degree of population
decline that occurs, and the rate at which it manifests, will
increase as the sterilization rate increases. By way of a specific
example, a previously unmanaged population of 200 cats that
experiences dispersal and abandonment is expected to stabilize
at half its original size if a 75% sterilization rate is achieved and
maintained for approximately 6–7 years. At a given sterilization
rate, the new population equilibrium will tend to be proportional-
ly lower for populations that are initially smaller. Eliminating a
population, especially if it is relatively large, by means of sterili-
zation control will require a higher sterilization rate, and may be
very difficult or impossible when there is substantial immigration
and abandonment (see below).
Lag times
Models show that population decline should typically begin to
occur within 1–3 years of achieving a sufficient sterilization rate;
though it may require 5–10 years to fully develop and for a
population to stabilize at its new lower size.
Effect of immigration and abandonment
As immigration and abandonment rates grow, achieving and
contraception and removal) in order to
determine critical sterilization threshold
rates, expected lag times for population
response, and expected degree of population
decline given different treatment intensities.
Interested readers can refer to this publication
directly,3 highlights of which are summarized
in the box above.
Monitoring
Insights derived from modeling or other
analytical exercises will always be somewhat
generalized in nature, and will never
completely account for important local factors
and contingencies. Therefore, any effective
management program needs to undertake
periodic standardized ‘reality checks’ to
determine what is actually happening over
time. These reality checks are referred to as Any effective management program needs to
A well-designed population monitoring
‘population monitoring’. undertake periodic standardized ‘reality checks’
effort allows us to determine whether our
program is on track, and provides ongoing
(monitoring) to determine what is actually
opportunities to adjust our management prac-
Using models for guidance
maintaining a high sterilization rate becomes much more diffi-
cult. When immigration and abandonment are very common,
adequate sterilization levels can only be maintained with fre-
quent, high-intensity trapping efforts. For this reason, choosing
target populations in a way that minimizes the influx of outside
cats can be advantageous. This might, for instance, dictate that
an entire set of closely spaced colonies be covered by a single
management effort, rather than focusing only on some of these
colonies. In the longer term, taking active steps to reduce aban-
donment should be very helpful in obtaining good management
outcomes.
Alternatives to traditional TNR
Non-surgical methods for cat sterilization and contraception are
under active development, and may become more widely
available in coming years. Permanent non-surgical sterilization
is equivalent to surgical sterilization with regard to population
impact, and may have the additional benefits of lower costs and
faster application. Unsurprisingly, Miller et al3 determined that
temporary contraception has less impact on population size
than permanent sterilization on a per-procedure basis. However,
given the potential cost efficiencies of non-surgical methods,
non-surgical contraception could have more impact on popula-
tion size than surgical sterilization on a per-dollar basis. TNR
practitioners should be open to the potential of non-surgical
fertility control as products become available.
tices to produce the desired outcome. It also
supplies the critical objective documentation
of program impact that is now required by
many funding organizations. A full treatment
of monitoring practice is beyond the scope of
this article, but some key characteristics of
effective monitoring programs, and the types
of information that monitoring can provide,
are described in the following sections. The
ACC&D has recently posted detailed online
guidelines for cat population monitoring.5
Interested readers may wish to examine the
online document in conjunction with this
article, or consult more generalized discus-
sions of monitoring design and practice.6
happening over time.
JFMS CLINICAL PRACTICE 803
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R E V I E W / Population models and monitoring for management of free-roaming cats
Characteristics of effective monitoring
Population monitoring is a systematic, struc-
tured process for counting animals and
recording some basic characteristics of each
observed animal. In order to effectively con-
tribute to management goals, a monitoring
program must meet several critical require-
ments. Failure to adhere to these requirements
will fundamentally undermine the validity
and usefulness of monitoring data.
< A monitoring program must be treated as
an intrinsic part of a management program,
not as an afterthought or peripheral activity.
This means that any substantive management
program should develop a monitoring plan
that defines the monitoring protocol, specifies
the monitoring calendar, and identifies the
resources and personnel needed to conduct
periodic monitoring surveys.
< The monitoring protocol must be
standardized. This means that all the critical
elements of the monitoring protocol are clearly
described and adhered to during every
monitoring count, or survey. These critical
elements may include (among others) the
location of survey routes or points, the time of
day during which surveys are conducted, the
time allotted to conducting a survey, and the
degree of proficiency of the surveyor. Failure
to maintain adequate standardization renders
monitoring data suspect and potentially useless.
Information that monitoring can provide
Monitoring can generate several different types of useful information, as described here in relation to TNR efforts. Most of this
information can be derived from a single simple monitoring protocol.
Baseline data
Ideally, the first monitoring survey(s) will occur before a TNR
program is initiated. This survey provides a ‘pre-management’
snapshot against which future progress can be gauged. If the
opportunity to conduct a baseline survey is missed, monitoring
should still be initiated as soon as possible.
Initial indicators of population change
As discussed, declines in cat populations will require some time
to develop. However, indicators of these changes, such as
reduced numbers of kittens or of pregnant/lactating females,
should occur sooner, and can provide reassurance that the TNR
effort is on the right track.
Sterilization rate
One of the most critical functions of a monitoring program is to
periodically determine sterilization rate within the management
area. This of course assumes that sterilized cats are systemati-
cally marked; the current approach is with ear tips or ear notch-
es, both of which are observable for most cats during a typical
804 JFMS CLINICAL PRACTICE
< The monitoring protocol must be very
simple to explain, follow and understand.
This allows a range of survey workers
(including volunteers) to contribute to the
ongoing monitoring effort with a relatively
high assurance that acceptable standardization
will be maintained. It also keeps the logistical
demands of a monitoring program within
reasonable limits. The initial design of a
monitoring program and subsequent data
analysis may require a more technical
approach, but conducting the surveys should
not require technical expertise.
< Surveys must be repeated at regular
intervals. As a minimum, annual surveys are
recommended, but shorter intervals between
surveys, if feasible, can be advantageous and
allow more frequent opportunities for assessing
and adjusting the management program.
Whatever the frequency of surveys, they should
be repeated at the same seasonal time period(s)
within the annual cycle, year after year.
< Data collected during surveys must
actually be analyzed and used to evaluate
program operation in a timely fashion. Data
that ‘gather dust’ for months or years on end
lose most of their potential to assist the
management effort. Data analysis may require
assistance from individuals with appropriate
technical knowledge, but remains the critical
final step in a monitoring effort.
survey, particularly with the aid of binoculars. Keeping a fre-
quent check on sterilization rate is of fundamental importance,
because maintenance of a high rate is the key to achieving
population reduction. If immigration and abandonment rates are
high, the sterilization rate can decline rapidly without frequent
intervention. Even without substantial immigration and aban-
donment, a high sterilization rate will decline over time without
periodic management effort. For these reasons, TNR practition-
ers need to obtain regular updates on sterilization rate, and then
adjust their trapping and sterilization efforts accordingly.
Population change
As surveys are repeated over time, it becomes possible to deter-
mine if the number of cats is changing in a statistically mean-
ingful way. Usually, this change is expressed in relative terms
(ie, ‘there are now 30% fewer cats than when we started the
program’) rather than absolute terms (‘there were 100 cats when
we started the program, and now there are 70’). If the observed
changes are occurring more slowly than expected, an increase
in trapping and sterilization effort may be warranted.
Continued on page 805
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R E V I E W / Population models and monitoring for management of free-roaming cats

Adaptive management
Goals and
Models allow us to explore many different strategies
management approaches – far more than could
ever be practically tested in a field setting – and
to identify those with the greatest practical Models
potential for achieving a specific population
goal. However, relying solely on model-based Baseline
guidance will always leave us with some survey
uncertainty as to how well our local ‘real-
world’ situations will align with our theoretical
expectations. Monitoring provides the mecha- Analysis
nism to adjust our theoretical knowledge to
better align with reality, and serves to formally TNR
document the impact of the management effort.
Monitoring
This synergistic interplay between models and
monitoring is a crucial part of ‘adaptive man-
agement’, a concept that has been shown to Figure 2 Schematic diagram of a simple adaptive management process for
free-roaming cats
have great practical utility in wildlife manage-
ment and other fields. Adaptive management is

along with wildlife conservation concerns –

an iterative process in which we manage a

can be formally incorporated into the process

system as we simultaneously learn about it

of setting goals and formulating strategies.

(Figure 2), and by virtue of that learning steadi-

This might be accomplished by periodic

ly improve our management effectiveness. For

consensus-building meetings among stake-

adaptive management to work, all the elements

holders. It should be noted that management

in Figure 2 must be functional (ie, the boxes,

techniques are not necessarily limited to TNR;

which indicate program activities, as well as the

they may also include parallel initiatives

arrows, which represent the linkages between

It is important to note that although adap- designed to reduce cat abandonment,

these activities).

tive management is presented in this article improve caretaking practices, or engage in

primarily as a scientific undertaking, a variety partnerships with shelters to remove adopt-
of non-scientific values and viewpoints – able cats from an outdoor population.

Continued from page 804

Population size
Determining absolute population size is a more challenging
exercise than determining population change in a relative sense.
This is because we usually cannot directly count all of the cats
present within a targeted area, especially when dealing with a
large population or metapopulation. For TNR programs, obtain-
ing a population size estimate is not necessary to monitor
population change. There are, however, reasons why it may
sometimes be useful or important to generate a population size
estimate, especially for large ambitious programs that need to
make budget projections and develop a project timeline. If we
wish to produce a population size estimate, we must find a way
to determine how many cats we are missing during the basic
survey counts. Multiple techniques exist to make these determi-
nations,5,6 but they may require expertise to implement appro-
priately. As an alternative, knowledgeable caretakers may be
able to make reasonably accurate estimates of population size
based on their knowledge of individual colony cats.
Immigration and abandonment rates
In cases where high rates of immigration and/or abandonment
are suspected, it may be useful to try to obtain more direct
evidence of their frequency. One way to obtain this information
is to provide selected colony caregivers with a simple protocol
to track the presence of individual animals. Over time, the
frequency at which unknown cats appear in a location by
means other than local birth can be calculated and used to
determine the combined immigration/abandonment rate. By
noting the behaviors and socialization status of these individu-
als, it may also be possible to make informed guesses about the
degree to which abandonment of socialized (ie, previously
owned) cats is driving the overall immigration/abandonment
rate.
Other relevant parameters
Within the framework of a basic monitoring program, informa-
tion on the frequency of visually obvious pregnancy among
females and the frequency of kittens can be easily obtained,
as described above. Declines in both of these parameters are
associated with effective fertility control. Other characteristics,
such as the visually apparent body condition of cats, can also
be tracked. For some programs, improvements in these
indicators of ‘life quality’ can serve as evidence of program
success.

JFMS CLINICAL PRACTICE 805

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R E V I E W / Population models and monitoring for management of free-roaming cats
Suggested practices for
TNR programs
For adaptive management to be effective,
certain standards and practices should be
incorporated into the overall TNR program
and strictly adhered to. These include:
< Identifying the target population. The
population to be managed must be carefully
defined in geographical terms (a whole city,
specific colonies, entire zip codes, particular
city blocks, etc) at the beginning of the TNR
program. If possible, the target population
should correspond to a natural grouping of
cats, rather than comprise some artificially
delineated subset of an active metapopulation.
This will help to minimize the complicating
effects of immigration. This population
becomes the sole target of both the TNR effort
and the corresponding monitoring effort
(although sophisticated monitoring programs
may opt to track unmanaged control pop-
ulations as well).
< Baseline survey. An initial baseline survey
should be conducted if possible. This allows us
to establish a formal, quantitative starting point
against which relative population change can
be compared. If a population size estimate is
also generated as part of the baseline survey,
it can provide information that helps to
determine the project’s budget, goals and
timeline.
< Goals. Program goals should be explicitly
formulated. Population-level goals could
include reducing the current population size
by a specified percentage, preventing further
increases in population size, or maintaining
a stable population while preventing ‘excess’
reproduction. Humane goals could include
reducing the number of births, improving the
condition and health of cats, and increasing
cat lifespans. Making goals explicit allows
program successes or shortcoming to be
unambiguously classified, and reduces con-
fusion in evaluating program performance.
< Ongoing monitoring. As discussed,
preparation of a clear monitoring plan should
be a prerequisite to investing significant effort
in TNR.
< Trapping. In its early stages, a trapping
effort will tend to capture the most easily
trapped cats. Reaching progressively higher
sterilization rates may mean finding ways to
capture the more trap-savvy cats within a
target population. On a per cat basis, therefore,
trapping effort will probably rise as we
increasingly target those more difficult and
less numerous individuals. An effective TNR
program must develop techniques and
strategies for catching these challenging
animals, and must be prepared to devote
sufficient effort to these attempts.
806 JFMS CLINICAL PRACTICE
< Integrated management. TNR, by itself,
may not accomplish population size reduction
in some situations. Parallel use of ancillary
techniques, such as the removal of socialized
cats and socializable kittens for adoption, will
complement TNR efforts, and may be critical
in achieving population size reduction.
Additionally, research or experimentation on
the best methods to discourage abandonment,
by legal means or by education, may further
assist the enterprise.
< Caretaking standards. Colony manage -
ment is not the topic of this article, but suffice
to note here that TNR programs that aspire to
success should consider both the potential
positive and potential negative impacts of cat
feeding. Feeding efforts that are tailored to
population size, as it changes, might help to
Veterinarians reduce hunting activity, and discourage cats
involved in TNR from roaming widely. Over-provisioning,
however, may effectively draw other cats into
efforts are well the managed area, or even encourage the
abandonment of cats.
positioned to
help move TNR Conclusions
onto a more The suggestions in this article are not new,
productive but many are not widely practiced in TNR
programs. The impediments to their broad
pathway. adoption are varied, but may include a
reluctance to devote resources to monitoring,
and the absence of an effective mechanism
for disseminating scientifically derived
information to a lay audience. Veterinarians
involved in TNR efforts are well positioned to
help overcome these impediments and move
TNR onto a more productive pathway. The
challenges in accomplishing such a transition
are quite substantial, but if only a modest
portion of the effort currently expended in
TNR programs were more productively chan-
neled, as described above, tangible success
stories would be more common, and certainly
better documented. Maximizing the potential
of TNR in this way would also serve empiri-
cally and unambiguously to identify the limits
This article is based on the premise that a
of its effectiveness.
transition to more effective TNR is possible,
and on the expectation that broadly applied
(as opposed to specifically targeted) lethal
removal methods for managing free-roaming
cats will not gain wide public acceptance,
regardless of potential wildlife benefits. If this
is true, then encouraging the improvement of
TNR practice, along with concomitant efforts
to improve responsible pet stewardship, will
ultimately be of more practical benefit to both
cats and wildlife than the current polarized
and protracted debate between pro-TNR and
anti-TNR constituencies.
Many of the recommendations made in this
800_807_Population models_Boone.qxp_FAB 10/08/2015 13:51 Page 807
R E V I E W / Population models and monitoring for management of free-roaming cats
article require only commitment and diligence
to implement, not technical training. Certain
recommendations, however (particularly
those involving initial monitoring design and
data analysis), may be more feasibly invoked
with some technical assistance. Appropriate
expertise is often available in universities or
municipal departments of public health or
environmental services, and partnerships can
be explored to acquire donated services from
these sources. Where this is not possible, the
author and colleagues from the ACC&D may
be able to provide advice or assistance to TNR
programs that make a serious commitment to
optimizing their management efforts.
Funding
The author received no specific grant from any
funding agency in the public, commercial or not-
for-profit sectors for the preparation of this article.
Conflict of interest
The author has no conflict of interest to declare.
References
1 Longcore T, Rich C and Sullivan LM. Critical
assessment of claims regarding management of
feral cats by trap-neuter-return. Conserv Biol 2009;
23: 887–894.
2 Nutter FB, Levine JF and Stoskopf MK.
Reproductive capacity of free-roaming domestic
cats and kitten survival rates. J Am Vet Med Assoc
2014; 225: 1399–1402.
3 Miller PS, Boone JD, Briggs JR, et al. Simulating
free-roaming cat population management
options in open demographic environments.
PLoS ONE 2014; 9: e113553. DOI: 10.1371/journal.
pone.0113553.
4 Alliance for Contraception in Cats & Dogs.
Guidance document: briefly summarizing
key findings and their practical application
for managing free-roaming cat populations.
www.acc-d.org/docs/default-source/think-
tanks/guidance-doc-revised-nov-2014.
pdf?sfvrsn=0 (2014, accessed June 8, 2015).
5 Alliance for Contraception in Cats & Dogs.
Available online at jfms.com
Reprints and permission: sagepub.co.uk/journalsPermissions.nav
Title photograph on page 800 courtesy of International Cat Care
KEY points
< Trap–neuter–return (TNR) as currently practiced is often not
sufficient to reduce the size of targeted cat populations.
< By incorporating theoretical knowledge from population
models and empirical information from ongoing monitoring,
TNR practitioners can substantially improve the efficiency and
effectiveness of TNR for population control.
< All of the elements of effective TNR should be coordinated under
the framework of ‘adaptive management’, in which monitoring
data are regularly evaluated to improve the management program.
< Improving the effectiveness of TNR could help to mitigate the
ongoing controversy over TNR as a management strategy.
< By virtue of their technical orientation and frequent involvement
in TNR programs, veterinarians are uniquely positioned to
promote the adoption of improved TNR practice.
ISFM CONGRESS RECORDING
A recording of John Boone’s session on use
of population management tools to improve
TNR for free-roaming cats, presented at the
2015 ISFM Congress in Porto, is available at:
http://icatcare.org/vets/videos
It is also included as
Supplementary material at: jfms.com
DOI: 10.1177/1098612X15594995
Counting cats: a generalized population mon -
itoring program to inform the management
of free-roaming cats. www.acc-d.org/docs/
default-source/think-tanks/frc-monitoring-
revised-nov-2014.pdf?sfvrsn=2 (2014, accessed
June 8, 2015).
6 Sutherland WJ (ed). Ecological census techniques:
a handbook. 2nd ed. Cambridge: Cambridge
University Press, 2006.
JFMS CLINICAL PRACTICE 807
808_815_Ear tagsLH_Benka.qxp_FAB 10/08/2015 14:34 Page 808

Journal of Feline Medicine and Surgery (2015) 17, 808–815

CLINICAL REVIEW

Ear Tips To Ear Tags

Marking and identifying
cats treated with non-surgical
fertility control
Valerie A W Benka

Current approaches: Trap–neuter– Introduction

return (TNR) introduced a humane
means of managing free-roaming Trap–neuter–return (TNR), the roots of which extend to 1950s England,
and feral (‘community’) cats; it also introduced a new method to manage unowned, free-roaming or feral
necessitated a method of marking cat populations (hereafter referred to as ‘community cats’) without
and identifying these cats as sterilized. lethal means, one that has since spread to multiple countries around
Although multiple identification methods the globe.1 The advent of TNR created a challenge, however: identify-
have been studied or attempted in the field, ear ing treated animals. Visual identification is needed to avoid repeat
tipping (or, less commonly, ear notching) has proven trapping and surgery; in addition, it ideally protects a cat from being
to be the best option and is used internationally. trapped and euthanized.
However, ear tipping must be performed under It has the potential, as Visual identification is needed
general anesthesia, and it conveys only binary well, to enhance commu-
information: yes, a cat has gone through a TNR nity acceptance of cats to avoid repeat trapping and
program (and is sterilized); or, no, a cat has not through residents’ knowl-
gone through a TNR program (and may or may not
surgery (or euthanasia),
edge that a female will
be sterilized). never deliver a litter of and has the potential to enhance
Future requirements: Future non-surgical feline kittens under the porch,
fertility control options will require an alternative to and her male counterpart community acceptance of cats.
ear tipping for identifying community cats, one that will not share his trade-
does not require anesthesia in order to mark the mark odor with the

Ear tipping (or, less often, notching) followed the introduction of

animal as treated. Long-term contraceptives (vs neighborhood.

TNR to allow permanent identification of a community cat as steril-

permanent sterilants) will also require a marker that

ized.1 Alternative identification methods such as tattooing, ear mark-

can denote the time when a cat was last treated.

ers, collars and microchipping have also been explored. TNR experts
Objectives and progress: To address this need,

note, however, that they all have shortcomings when used in

the Alliance for Contraception in Cats & Dogs is

community cats, related to visibility, safety, likelihood of infection and

working with an interdisciplinary team from Cornell

durability.2
University, USA, to develop an effective, humane

Although ear tipping has become the current standard for identify-
marking method. Their focus is a new generation of

ing animals that have undergone TNR, the protocol is not without
ear tag. The prototype design uses different shapes

difficulties and detractors. A cat missing the top of the ear due to mites,
and materials, and a different application process,

frostbite or infection can be mistaken as a cat with an ear tip, particu-

than tags used to date. The objective is to minimize

larly when viewed from a distance. Some oppose ear tipping due to its
tag weight, application discomfort, and likelihood

aesthetic implications or perceived mutilation;1 this may be particular-

of blood loss and infection, while simultaneously

ly true for cats found as unowned ‘strays’ or sterilized through a sub-

allowing for coding of information, including

sidized TNR program, but which have potential to be adopted into

treatment time period.

homes as pets. As discussed below, ear tipping also precludes a key

added-value aspect of non-surgical fertility control: the ability to treat
animals without using general anesthesia.

Valerie A W Benka
MS MPP
Project Manager,
Alliance for Contraception in Cats & Dogs,
Portland, Oregon, USA

Email: valerie@acc-d.org

doI: 10.1177/1098612X15594996
808 JFMS CLINICAL PRACTICE © The Author(s) 2015
808_815_Ear tagsLH_Benka.qxp_FAB 10/08/2015 13:57 Page 809
‘How do you know that the cat
has been treated?’
This is among the most common questions
asked about non-surgical fertility control.
Whether a permanent sterilant or long-term
contraceptive, non-surgical options present a
new challenge for marking a treated animal,
and particularly a community cat. The features
that make non-surgical options a ‘game chang-
er’ for community cats – no general anesthesia,
field application capabilities, no postoperative
recovery period – essentially preclude ear tip-
ping. Moreover, a tipped ear reveals only
binary information: ‘yes’ or ‘no’ to treatment.
In order to offer optimal value, multi-year con-
traception, along with rabies vaccination and
boosters, requires conveying information
about when and what treatment was per-
formed. A mark with more than binary
information also facilitates a more nuanced
understanding of the population dynamics of
community cats, thereby adding further value
to efforts to humanely reduce their numbers.
Moreover, it is important that this information
can be conveyed from a distance, without
needing to re-trap a cat – as is the case with ear
Recognizing both need and opportunity, the
tipping.
Alliance for Contraception in Cats & Dogs
(ACC&D) spearheaded a ‘flagship initiative’
to develop an alternative means to mark and
identify animals that have undergone non-
surgical fertility control. The ideal mechanism
would need to fulfill multiple requirements,
including (but not limited to) humane appli-
cation, visibility from a reasonable distance,
Pa r a m e t e r s fo r a fe l i n e i d e n t i f i c a t i o n m a r ke r
< Visibility at moderate distances At a
minimum, the marker should be visible at
12–15 feet (3.5–4.5 m) from the cat. Ideally,
it would be visible at 25 feet (7 m). The more
information conveyed without handling the
animal, the more useful the mark.
< Easy-to-retrieve information Basic
information should be retrieved by vision alone,
potentially with binoculars if at a distance.
< Capacity to convey information The marker
must convey information required to avoid
retreating a cat that has undergone non-surgical
sterilization and identify the retreatment timeframe
for a contraceptive. Ideally, it would also convey
vaccination status and information useful to
population dynamics research.
< Humane for the animal The marker must
be humane for the animal at all times, from
application (any discomfort must be brief
and controlled) and through the duration of
wear or use. This means minimizing the risk
R E V I E W / Marking and identification methods for community cats
Alliance for Contraception in Cats & Dogs
This article is part of a Special Issue of the Journal of Feline Medicine and
Surgery (2015, Volume 17, pages 737–834) dedicated to ‘Non-surgical feline
fertility control’ and coordinated by the Alliance for Contraception in Cats
& Dogs (ACC&D). The ACC&D is a catalyst to advance new methods of
non-surgical fertility control to save the lives of cats and dogs, expand
options for pet owners, and improve animal welfare. Serving as a trusted
resource for scientific and educational
information, the ACC&D brings together key
stakeholders to advance humane sterilization
options that are faster, easier and more
accessible than surgery.
More information is available at www.acc-d.org
Non-surgical
lack of interference with normal behavior,
ease of application, and affordability for com-
options present
munities with limited resources (see box
a new
below). Several stages of research and brain-
storming with experts from across disciplines
challenge for
and around the world led the ACC&D to pro-
pose a ‘better’ ear tag. Since the project was
marking a
formally launched in early 2013, it has become
treated animal,
increasingly clear that such a tag could offer
value not just for community cats sterilized
particularly a
without surgery, but also for cats that have
gone through ‘traditional’ TNR programs and
community cat.
for small wildlife species. This initiative, cur-
rently in the design and prototype develop-
ment phase, is a true interdisciplinary effort to
create a tiny object and achieve a big goal. The
process thus far, as well as planned next steps,
are discussed in the following sections.
of infection, irritation and pain. The ACC&D
< Permanence The marker must persist
for 3 years minimum. Ideally, it would last the has
lifetime of a sterilized animal; an alterable marker
spearheaded
may be required for a long-term contraceptive.
< No impact on behavior The marker should a ‘flagship
have no negative impact on eating, hiding, playing
or other normal feline behaviors. initiative’ to
< Simple application process The marker develop an
should require minimal training to apply safely
and effectively. alternative
< Minimal time to administer Ideally, it should
take under 5 secs to apply the marker, increasing
means to
efficiency and minimizing stress to the cat. Any identify animals
marker requiring over 10 mins to apply would not
be feasible. that have
< Low cost The cost of the marker,
application equipment and any information
undergone
retrieval equipment should be affordable to non-surgical
communities and agencies with limited financial
resources. fertility control.
JFMS CLINICAL PRACTICE 809
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R E V I E W / Marking and identification methods for community cats
Current marking and
identification methods
When marking and identification methods
used for companion, wildlife and livestock
species are viewed as a whole (see box on the
right), there are a lot of options! Several
marking methods besides ear tipping have
been used, or at least evaluated, for cats, as
discussed below.
Neck collars
Collars with tags are often recommended for
owned cats to provide visual identification if
an animal becomes lost. Their potential for
community cats is less clear. A collar’s com-
paratively large surface area offers a canvas
for colors or patterns that identify individual
cats or feline cohorts. Adding numbers, bar-
coding or tags can communicate still more
information. While standard cat collars are
inexpensive, radio or global positioning sys-
tem (GPS) collars are also options; the former
have been used to track and monitor cats.3
Precedent for collar use comes from the field
of wildlife biology; radio- and GPS-enabled
collars have been used widely to track and
However, veterinarians and cat owners
monitor wildlife species.
often express concern about collar safety: the
potential for a collar to strangle an animal,
catch on a cat’s forelimb or mouth, or become
embedded if attached too snugly. A small
number of studies have explored whether or
not these fears are corroborated by data.
One study, which compared three types of
adjustable nylon collars on owned cats (plas-
tic buckle, breakaway plastic buckle safety,
and elastic stretch safety) found that 3.3% of
538 participating cats got a collar stuck in
their mouth, caught a forelimb in the collar, or
caught the collar on another object.4 A second
study found that two of 34 cats fitted with
radio tracking collars died soon after applica-
tion due to collar strangulation.3
A third study surveyed veterinarians, cat
owners from the general public, and members
of a cat shelter and welfare organization about
collar incidents, collar injuries requiring
veterinary treatment or collar-related deaths.5
Interviews with 107 veterinarians revealed an
average rate of one collar injury observed
every 2.3 years of veterinary practice. Collar
incidents (defined as snagging a collar or
catching a paw in the collar) were noted by
relatively large numbers of cat owners (63% of
those from the welfare society and 27% of the
general public), but reports of injury requiring
veterinary attention was much less common
(6% and 3% for the two groups, respectively),
and death rarer still (2% and 0%, respectively).
Vehicular accidents and fighting were much
810 JFMS CLINICAL PRACTICE
Permanent and temporary methods of identification
used across species
< Photographic identification
< Collaring
< Leg bands
< Iris and retinal scanning
< Paint
< Beetroot juice (temporary dye)
< Freeze branding
< Hot branding
< DNA profiling
< Microchipping
< Ear tipping
< Ear notching
< Tattoos
< Ear studs
< Ear tags
< Visible implant elastomer (VIE) tags
more commonly reported reasons for veteri-
nary care and cause of death.
Whether the risks of collars outweigh the
benefits is both subjective and debatable.
However, long-term collar retention and
durability have unarguable and significant
implications for community cats. Although
Lord et al found that 72.7% of cats wore
collars for the 6 month study, approximately
one-third lost a collar at some point and
required reapplication by owners.4 This loss
rate could undermine efforts to effectively
identify and monitor community cats.
Further considerations for use of collars on
community cats include:
< Ease of removal or transfer by humans.
Particularly in areas where ‘proof’ of
sterilization and vaccination can be a literal
lifesaver, there are ample reports of people
transferring collars from treated to untreated
animals (K Coladarci, 2013, personal
communication). While it is possible to use a
design and materials to make removal (or loss)
less likely, it is unclear how this could be
accomplished while simultaneously minimiz-
ing the collar’s potential to cause physical
discomfort or harm.
< Material durability. Lord et al found that
36.1% of the 388 owned cats completing the
study had a frayed collar after 6 months.4
The ‘wear and tear’ on collars belonging
to community cats may be substantially
greater.
< Ability to mark growing animals. Juvenile
wildlife are sometimes fitted with collars that
can accommodate growth. It is unclear if this
could be safely done with cats, and if the
degree of growth could be accurately
predicted.
808_815_Ear tagsLH_Benka.qxp_FAB 10/08/2015 13:57 Page 811

R E V I E W / Marking and identification methods for community cats

a larger range with less power than traditional

RFID tags; they can also provide information
Tattoos

about temperature and relative location, which

Tattoos have long been used to identify own-

might be useful in differentiating individuals

ership of cats, as well as dogs and other

when a scanner sends a signal towards a group

species.6 Tattoos on the ear, abdomen or inner

of animals.9,10 There are unfortunately draw-

thigh are often used to denote sterilization

backs to more powerful RFID chips, however,

status of pet animals; ear tattoos were used as

including a larger size and greater cost.

a method of marking cats in danish TNR

There are concerns about the discomfort of

programs as far back as the 1970s.1

tattooing if performed without anesthesia.6

Tattoos also offer limited visibility, especially
Freeze branding

from a distance; observing abdominal or inner

Freeze branding was developed as an alternative

thigh tattoos requires handling the animal

to hot branding to mark and identify livestock

and potentially even shaving the fur. Faded

and horses,6 and it continues to be used primari-

ink reduces visibility still further. Particularly

ly for this purpose. A metal branding iron is

for unsocialized cats, trapping would be

supercooled, often in either liquid nitrogen or a

required to view an ear tattoo.2 Consequently,

dry ice–alcohol combination, and applied to an

it has been recommended that an identifica-

animal’s skin. This alters the cells that produce

tion tattoo must be used in combination with

hair pigment, resulting in the regrowth of white

‘visible’ methods of identification.6

hair that offers stark contrast on dark-haired ani-

Despite these limitations of traditional

mals. Longer application of the iron can perma-

tattooing, there may be potential for a ‘better’

nently destroy hair-producing cells, resulting in

tattoo that could add value to non-surgical

a bald spot that more closely resembles a hot

fertility control. A tattoo pen designed for rab-

brand; this approach can be used for animals

bits or an adapted needle-free jet injector may

with blonder hair or fur.6 Although used prima-

cause less pain and stress. While these alone

rily for large animal species, the technique has

would not address the challenge of visibility,

been used on smaller animals. only one pub-

it remains to be seen if iridescent, fluorescent

lished study reports freeze branding a (dark-

or fade-resistant ink could enhance the ability

haired) cat – doing so successfully, particularly

to identify cats from a distance and over time.

when the brand was held to the skin for 10
secs11 – but there is anecdotal evidence of current

There is evidence in ruminant species that

use to mark the ear or flank of hunting dogs.12,13

freeze branding causes less discomfort than hot

Microchipping and RFID

branding.14 An Italian study comparing freeze

Microchips are radio-frequency identification

branding and ear tagging in free-roaming dogs

(RFId) devices that are commonly used by shel-

observed that animals did not react to freeze

ters and owners to identify the owners of lost

branding of the ear (whereas tag application

cats and dogs. They are ‘passive’, meaning that

did cause some dogs to show signs of discom-

the tag receives power from the tag reader.

fort), and in fact displayed more stress from

There are three microchip frequencies in the

human handling than the procedure itself.15,16

United States; one of these, 134.2 kHz, is the ISo

Even so, the canine study recognized the

(International Standards organization) stan-

potential for freeze branding to cause pain, and

dard and the primary frequency used world-

the American Veterinary Medical Association

wide. In the frequency band of 120–140 kHz, the

For pets and socialized animals, a 10 cm notes that it is believed to be more painful than
range for passive detection is typically 10 cm.7

read range and ‘invisible’ identification can be
extremely valuable. However, microchips are,
on their own and with current read range, not
adequate for community cats.
There are several potential ways to extend
the read range of RFID chips for animal identi-
fication. Placement outside the body would
reduce interference. High frequency (13.56
MHz) and ultra-high frequency (UHF, 900
MHz) passive tags have larger read ranges
(exceeding 1 m); in 2010, the US Department
of Agriculture approved a passive UHF RFID
tag for tracking cattle through the Animal
Identification Number (AIN) system.8 Surface
acoustic wave (SAW) RFID technology tags
work in the microwave range and reflect back
the incoming signal rather than relying on an
integrated circuit. SAW RFID tags can provide
ear notching, ear tagging or tattooing.14
For marking community cats, the short-
comings and limitations of freeze branding
arguably outweigh the benefits. In addition to
welfare concerns, the tanks of coolant needed
for the procedure are relatively impractical for
field use. The time required to perform freeze
branding also makes it impractical for field use,
and especially for marking cats that are not
anesthetized (the Italian canine study reported
that freeze branding required up to 10 mins per
dog).15 Given a cat’s size, it would be difficult to
create a mark conveying more than the fact that
the cat had been treated once (not unlike ear tip-
ping). There are also questions about whether
the permanent and highly visible mark created
by freeze branding could compromise a free-
roaming cat’s chances of being adopted as a pet.

JFMS CLINICAL PRACTICE 811

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R E V I E W / Marking and identification methods for community cats

Ear markers
Ear tags, bands and studs have all been Ear tags, bands and studs have the advantage
considered as ways to identify cats, both com-
munity and pet cats. They have the advantage of being easily visible from a distance,
of being easily visible from a distance, and
they can be customized by shape or color-
and they can be customized by shape or color-
coding to communicate additional informa- coding to communicate additional information.
tion such as year treated or type of treatment
administered.

Tags and bands tion of the stud when the cat scratched its ear.
Ear tags and bands are a common mechanism Studs marketed commercially were engraved
for individual or group identification among with identification and telephone numbers.
livestock, laboratory animals and wildlife They were promoted as a method to identify
species, including prick-eared animals such lost cats that offered greater retention and
as foxes and coyotes. Ear tagging has been reliability than a collar. one Californian
used in canine sterilization and vaccination veterinarian applied these studs to several
programs in Turkey17 and Romania (S Turetta, dozen cats across the spectrum of indoor and
2013, personal communication), as well as in outdoor, long-haired and short-haired indi-
a study in Italy comparing the efficacy and viduals (E Wexler-Mitchell, 2013, personal

< The good news: All cats participating in the

welfare implications of ear tags and freeze communication).

informal study tolerated initial placement

branding.15,16 In the Turkish and Romanian

without problems, and no cat suffered catching

programs, dogs are tagged while anes-

the stud or having it tear the ear. One cat wore

thetized; in Italy, dogs were manually

There is no tag recommended its stud for over 10 years. Cats

restrained.

for cats at this time. One informal that ventured outdoors seemed to
study tried marking cats on the have no greater rate of infection
ear margin using a band. In addi- than indoor-only animals.
tion to including an individual < The bad: An estimated 40%
cat identification and contact of cats developed infections at the
phone number, the band was site of the stud. These problems
color-coded to correspond with were delayed, sometimes by
the color of the rabies tag used months. Infections were attri-
that particular year (J K Levy, buted to a stud that was unable to
2013, personal communication). freely rotate and, as a result,
The tag was appreciated for its crusting developed between the
ability to convey the year in ear and stud or the ear and stud
which a cat was sterilized, and backing. Cleaning by owners
some persons who did not see the cat’s ear tip seemed to offer the best chance of preventing
Figure 1 Feline ear studs

noticed the colored tag. Unfortunately, the problems. Short-haired cats may have had a
developed by Frank

rate of irritation or infection at the site of lower rate of infection, but overall it was
Andrews, then director

the tag was considered too high to continue ‘impossible to predict which cats would not
of Los Angeles County’s
Department of Animal Care

their use, plus a portion did not stay in the ear have problems’ with the studs.
and Control, in 1997. The

(J K Levy, 2013, personal communication). < The conclusion: While the stud was a
right-hand stud design,
which included telephone

Leading organizations familiar with feline ‘great concept’, this particular design
and individual identification

health or sterilization of community animals ‘didn’t work reliably enough to use long
numbers, was briefly
marketed commercially.

cite tags’ ability to fall off or become snagged, term’ (E Wexler-Mitchell, 2013, personal
The studs are 8 mm at the

to tear the ear or cause other injury, and to communication).

widest point. Studs courtesy
of Joan Miller, The Cat

cause infection.2,6,18 Consequently, these

Fanciers’ Association

organizations recommend ear tipping (or

notching) for community animals undergoing
surgical sterilization.

Studs
In 1997, Frank Andrews, then director of Los
Angeles County’s department of Animal Care
and Control, designed a variety of feline ear
studs (Figure 1). The stud was 8 mm at its
widest point and designed as a hexagon with
smooth, rounded corners. This non-circular
design was intended to encourage gentle rota-
Ear markers – hurdles to be overcome
At present, the American Association of Feline Practitioners and Alley Cat
Allies, among others, cite the infection, loss and tearing risks of ear mark-
ers for cats and discourage their use. Based on results of designs to date,
this concern is warranted. And yet, there is no indication that the potential
for any of these ear-marking mechanisms has been fully explored. It may
be that marker geometry, material and placement can profoundly affect
the likelihood of complications and how well the tag serves the purpose
intended.

812 JFMS CLINICAL PRACTICE

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R E V I E W / Marking and identification methods for community cats

What now?
An acrylic prototype ear marker is being
None of the methods described above is, in investigated for its potential for humane
its current form, optimally suited to mark and
identify community cats sterilized or application, communication of information,
contracepted without surgery. In order for
non-surgical fertility control methods to offer ongoing comfort, durability and
optimal value and impact, this needs to minimization of infection.
In early 2013, the ACC&D sponsored an
change!

InnoCentive Brainstorm Challenge to crowd-

source marking and identification ideas from brass, Monel (nickel–copper alloy) and plated
around the world. Participants were present- steel. Participants recommended exploring
ed with the challenge and marking require- new shapes and materials to limit the pressure
ments, and encouraged to submit their ideas. the tag exerts on the ear and maximize reten-
Suggestions streamed in, with 74 individuals tion, while at the same time allowing for cod-
proposing a total of 99 solutions. Ideas fell ing of information and minimizing the risk of
into such categories as electronic marking, infection. Participants also advised on the
collars, tattoos, fur removal and/or alteration, need to consider new methods of applying a
physical banding and ear tagging. Among the marker to the ear that minimizes pain, poten-
more creative (if not eminently practical) tial for blood loss and potential for infection.
ideas were the attachment of a fiber optic In 2014, the Atkinson Center for a
‘hair’, chip-less RFID ‘ink’, needle-free jet Sustainable Future at Cornell University, USA,
injector (as an alternative to traditional tattoo- generously funded a project to carry an ear
ing), facial recognition software, magnetic ear marker from a concept to a prototype. The
markers, olfactory markers, microdermal project is focusing initially on an ear marker
piercing, visible implant fluorescent elas- for free-roaming dogs internationally; the
tomer tags (currently used in aquatic species), second phase will target cats. Faculty and
and an as-yet-untried ear ‘wrap’ design students from Cornell University’s College of
applied with a gel solution offering analgesic, Veterinary Medicine, College of Human
antibiotic and antiseptic properties. Ecology Fiber Science & Apparel Design and
Research on existing identification methods, College of Engineering partnered with the
combined with creative InnoCentive Brain- ACC&D to form an interdisciplinary team
storm Challenge ideas, formed the basis of an equipped to approach the project from key
ACC&D scientific think tank in the spring of perspectives and areas of expertise. Body
2013. This two-day event sought to identify the jewelry company Kaos Softwear (Portland,
most promising near-term and long-term Oregon, USA) is also providing guidance on
methods to mark cats and dogs treated with a materials and applicator optimization.
non-surgical sterilant. Towards this end, the The team evaluated multiple polyester and
Figure 2 Very early
prototype ear markers.

organization convened experts from diverse acrylic fabrics for their texture, weight, flexi-
Markers are 2–3 cm at their

fields, each invited for his or her ability to con- bility, breathability, antibacterial properties,
widest point. Layering of
two colors and shapes

tribute varied and valuable insights on the chal- time to fading in direct sunlight, durability,
would permit coding and

lenge. Experts in wildlife biology, dog and cat resistance to tearing and cost. Solution-dyed
visual identification of

reproductive biology, software and database

additional information,

acrylic fabric (in which color pigments are put

such as timing of both

design, invention and innovation, and animal into a polymer solution before the fiber is
contraceptive and rabies

identification technologies such as radio- created, thus becoming contained within the
vaccines. Colors will be
determined based on a

frequency identification joined individuals fiber’s physical structure) was determined to

project study at Cornell

experienced in vaccination and sterilization offer the greatest potential due to its weight,
University investigating
optimal colors for viewing

initiatives of free-roaming cats and dogs. breathability, color-fastness and durability.

at a distance. Photographs

A new approach to an ear marker rose as The team also evaluated different applica-
courtesy of Eloïse Cucui/
Cornell University College

the top contender. Participants concluded that tion methods with the goal of minimizing
of Veterinary Medicine

none of ear tags, bands or studs has been discomfort associated with application, likeli-
pushed to reach its full potential for humane hood of infection and damage to the ear. A
application, communication of information, price-tagging ‘gun’ has shown most promise
ongoing comfort, durability and minimization on the ears of cadaver cats and dogs donated
of infection. This is particularly true for to Cornell University College of Veterinary
cats (and dogs), but it arguably applies to Medicine. A 14 gauge needle, the size used to
wildlife and livestock species as well. insert a microchip, creates a lesion less than
Although some advances have taken place, 1 mm in diameter through which a fastener is
ear tags available today use a limited selection threaded. Moreover, the needle is replaceable
of materials, including hard plastic, flexible and the applicator is quiet, thus reducing
polyurethane, aluminum, stainless steel, stress to animals. Nylon is traditionally used

JFMS CLINICAL PRACTICE 813

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R E V I E W / Marking and identification methods for community cats

We look forward to a time when a soft colorful

ear tag will be an essential bit of ‘kitty bling’,
marking each individual cat as important,
cared for and protected.

for commercial tagging, although an alterna-

tive polymer could be used to increase the
fastener’s strength and durability. A study on
the use of nylon barbs in guinea pig ears
found minimal damage at the insertion site, as
well as low tag loss rates.19
Very early prototype designs are depicted in
Figure 2.
Figure 3 The ACC&D’s vision of improving animal welfare
by reducing populations of homeless cats and dogs requires
Where next? a new approach to marking and identifying those that have
undergone non-surgical fertility control. Progress is being
made!
Following development of a prototype mark-
er, the team will trial the marker under closely

appeal to wildlife biologists? To those who

monitored conditions, paying particular

raise small, or even large, species of livestock?

attention to any signs of discomfort or irrita-

Could a new market help offset the cost of

tion, any incidents of catching the marker on

developing and producing ear tags for com-

an object or during play, and any interference

munity cats, such that the product could be

with normal behavior. Prototype design feed-

distributed at a nominal cost? These ques-

back from persons with expertise in the field

tions – and more – are currently being consid-

will also be carefully considered. After any

ered and explored.

necessary refinements, we will determine the

In the meantime, we look forward to a time

best way to test the new markers in a field

In addition to marker design and trialing in when a soft colorful ear tag will be an essen-
environment.

the target species, there are questions about a tial bit of ‘kitty bling’, marking each individ-
potential market for a dare-we-say ‘better’ ual cat as important, cared for and protected
ear tag: is it possible that such a marker will (Figure 3).

KEY poinTs
< Ear tipping (or, alternatively and less commonly, ear notching) is currently the predominant
means of marking and identifying cats that have gone through a trap–neuter–return (TNR)
program. Visual identification is needed to avoid repeat trapping and surgery; in addition,
it ideally protects a cat from being trapped and euthanized.
< Alternative approaches have been considered to mark and identify sterilized and
vaccinated community cats, including neck collars, microchipping and RFID, freeze
branding, ear tags and ear studs. Although these approaches have specific strengths
relative to ear tipping, their undesirable consequences have precluded widespread use.
< Future non-surgical fertility control options will require an alternative to ear tipping for
marking and identifying cats. Application should not require anesthesia, and the marker
itself should be capable of conveying the time when the cat was treated.
< The ACC&D is working with an interdisciplinary team from Cornell University to develop
a new ear marker design. The prototype design uses different shapes and materials,
and a different application process, than markers used to date. The objective is to
minimize marker weight, application discomfort, and likelihood of blood loss and
infection, while simultaneously allowing for coding of information,
including date of treatment.

814 JFMS CLINICAL PRACTICE

808_815_Ear tagsLH_Benka.qxp_FAB 10/08/2015 13:58 Page 815
R E V I E W / Marking and identification methods for community cats
ISFM CONGRESS RECORDING
A recording of Valerie Benka’s session on
methods of identifying cats treated with
non-surgical fertility control, presented at the
2015 ISFM Congress in Porto, is available at:
http://icatcare.org/vets/videos
It is also included as
Supplementary material at: jfms.com
DOI: 10.1177/1098612X15594996
Funding
The author received no specific grant from any
funding agency in the public, commercial or not-
for-profit sectors for the preparation of this article.
Conflict of interest
The author has no conflict of interest to declare.
References
1 Berkeley EP. TNR: Past, present and future: a histo-
ry of the trap-neuter-return movement. Bethesda,
Md, USA: Alley Cat Allies, 2004.
2 Alley Cat Allies. Protocols: eartipping. Feral cat
veterinary protocol. http://www.alleycat.org/
Eartip (2012, accessed November 5, 2014).
3 Subacz KB. Impact assessment of a trap–
neuter–return program on selected features of
Auburn, Alabama feral cat colonies. Masters the-
sis. Auburn, AL, USA: Auburn University, 2008.
4 Lord LK, Griffin B, Slater MR, et al. Evaluation of
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5 Calver MC, Adams G, Clark W, et al. Assessing
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tion%20methods%20for%20dogs%20and%20
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nutshell. Texas Instruments Application Report.
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tsp?literatureNumber=swra284&fileType=pdf (2011,
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Title photograph on page 808 courtesy of debbie Brooks
For reuse of Figures 1–3, contact the author
8 Swedberg C. USDA approves first UHF tag for
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RFID tags. In: Turcu C (ed). development and
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Tech, 2009, pp 145–158.
11 Farrell RK, Koger LM and Winward Ld. Freeze-
branding of cattle, dogs, and cats for identifica-
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(accessed November 5, 2014).
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Freeze irons. http://agr.wa.gov/FoodAnimal/
Livestock/docs/Freeze%20Irons.pdf (accessed
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14 American Veterinary Medical Association
(AVMA). Literature review on the welfare
implications of hot-iron branding and
its alternatives. https://www.avma.org/KB/
Resources/LiteratureReviews/documents/
hot-iron_branding_bgnd.pdf (2011, accessed
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15 Leoci R. A comparison of ear-tagging and ear-
whiting as methods of identification in dogs.
Proceedings of the 5th International Symposium
on Non-Surgical Contraceptive Methods of Pet
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oR, USA. http://www.acc-d.org/docs/default-
source/5th-symposium/leoci_PPT.pdf?sfvrsn=6.
16 Leoci R, Aiudi G, Silvestre F, et al. A comparison
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symposium/leoci_marking_abstract.pdf?sfvrsn=4.
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19 Kitagaki M and Shibuya K. Nylon ear tags for
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Top Lab Anim Sci 2004; 43: 16–20.
JFMS CLINICAL PRACTICE 815
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 816
CONGRESS ABSTRACTS
Clinical/research abstracts accepted
for presentation at ISFM Congress 2015
EFFICACY OF EMODEPSIDE/PRAZIQUANTEL
SPOT-ON (PROFENDER; BAYER) AGAINST
ADULT AELUROSTRONGYLUS ABSTRUSUS
NEMATODES IN EXPERIMENTALLY
INFECTED CATS
Claudia Böhm1, Sonja Wolken2, Manuela Schnyder3,
Walter Basso3, Peter Deplazes3, Katrin Deuster1,
Roland Schaper1
1
Bayer Animal Health GmbH, Leverkusen, Germany
2
Wolkenkonzept, Burgdorf, Germany
3
Institute of Parasitology, University of Zurich, Switzerland
ISFM Congress Email: claudia.boehm@bayer.com
poster session
A total of 25 clinical/ The adulticidal efficacy of a topical combination of
research abstracts were emodepside 2.1% (w/v) plus praziquantel 8.6% (w/v)
accepted for presentation
at the poster session held (Profender Spot-on for cats; Bayer) against adult
during the 2015 ISFM Aelurostrongylus abstrusus nematodes was
Congress in Porto, evaluated in two randomised, placebo-controlled
Portugal, July 1–5, 2015. laboratory efficacy studies. Each study involved
16 cats experimentally inoculated with third-stage
larvae (800 and 600 each in study numbers 1 and 2,
respectively) and randomised into two study groups
of eight cats each after onset of patency. While cats
in the treatment group in study 1 received
a single spot-on application at the minimum
therapeutic dose (3 mg/kg emodepside and
12 mg/kg praziquantel), cats in study 2 were treated
twice with an interval of 14 days. The faecal output
of first stage larvae was monitored throughout the
study. Necropsy was conducted 4 or 5 weeks after
the (first) treatment and the worm counts were
used for efficacy calculations.
The control groups showed a geometric mean
total worm count (live and dead worms) of 28.8
(study 1) and 17.6 (study 2). All control animals
were infected. While the single treatment
in study 1 resulted in a reduction of the total worm
burden by 73.0% (P = 0.0070), the treatment
protocol in study 2 was 99.2% effective (P = 0.0035).
Based on live worm counts, the efficacy in study 2
was 100% (P = 0.0030).
It is concluded that two applications of
Profender Spot-on given 2 weeks apart represent
a safe and highly efficacious treatment regimen
against feline aelurostrongylosis.
816 JFMS CLINICAL PRACTICE
Journal of Feline Medicine and Surgery (2015) 17, 816–827
A PILOT, UNCONTROLLED STUDY OF
POSTSURGICAL TREATMENT WITH
AUTOLOGOUS DENDRITIC CELL-BASED
IMMUNOLOGIC THERAPY IN 20 CATS
WITH FIBROSARCOMA
Thomas Grammel, Marina Grammel
Veterinary Hospital Dr Thomas Grammel, Osterode
am Harz, Germany
This research investigated the use of an autologous
dendritic cell (DC)-based cancer treatment in
20 cats suffering from malignant fibrosarcoma in
various localisations. The production of autologous
DCs and the ability to present autologous and
tumour-specific antigens to the immune system
yielded promising clinical results.
Radical excision of the tumour tissue was
used to reduce the tumour burden for all cats.
A fresh whole blood sample from the patient was
processed by gradient centrifugation and an
adherence step to derive a population of patient
monocytes. These monocytes were cultivated
with specific cytokines to derive autologous DCs.
The DCs were then cultured for 6 days and primed
with autologous tumour lysate on day 5. The next
day the antigen-presenting DCs were harvested,
resuspended and injected intradermally and
into the tumour site area of the patient.
Twenty cats were treated using this protocol
and the median survival time was 448 days after
treatment with the DC vaccine. The survival rate
after 330 days was 58% and after 499 days was
32%. In some patients there was a delay between
surgery and receiving the DC-based cancer
vaccine and thus it is possible these results
can be further improved.
Independent of the site of the fibrosarcoma,
the expected longevity of the patients appeared
to increase. In this study, surgical excision followed
by DC-based therapy yielded promising results for
the treatment of fibrosarcoma in cats with no or
mild side effects. However, further results from
controlled studies are now required to investigate
and confirm any potential efficacy of the DC-based
vaccine therapy.
DOI: 10.1177/1098612X15594997
© ISFM AND AAFP 2015
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 817
MYCOPARASITISM OF PYTHIUM
OLIGANDRUM OBSERVED AGAINST
MICROSPORUM CANIS IN AGAR MEDIA
AND ON HAIRS – IN VITRO OBSERVATIONS
1,2 3
Martina Načeradská, Michaela Fridrichová,
Petr Lány,2 Dita Kellnerová4
1 1
Department of Infectious Diseases and Microbiology,
University of Veterinary and Pharmaceutical Sciences
Brno, Czech Republic
2
Private veterinary practice, Krymská 23, Prague 10,
Czech Republic
3
Institute of Geology AS CR, v. v. i., Prague,
Czech Republic
4
Sevaron s.r.o., Diagnostic Laboratory, Brno,
Czech Republic
Email: info@naceradska.com
Dermatophytosis is a significant disease in cat
shelters and can be a difficult disease to treat
and manage. A simple, inexpensive but effective
treatment is desirable.
Pythium oligandrum (PO) is an obligatory
mycoparasite widely used in the treatment of
fungal infections in plants. Several case studies
have been published in the past 15 years on the
use of PO in the treatment of tinea interdigitalis and
onychomycoses in humans. Moreover, a few studies
have referred to the treatment of dermatophytosis
in animals. However, in vitro observation of
mycoparasitism of PO against Microsporum
canis (MC) has not been published to date.
Our in vitro observations were conducted in a
private veterinary surgery with the use of a collection
strain culture of MC and a fur sample obtained from
a healthy, MC-free cat. The fur was incubated with
culture of MC for 10 days. Afterwards, the fur sample
was placed on a slide and the suspension of PO
and a few drops of mineral oil were added. The
reaction was observed under the microscope and
photographed. After 4 h, the hyphae of MC started
to disappear. The most visible reaction was observed
within 4–5 h of the addition of PO to the sample.
Twenty-eight hours after inoculation, no hyphae
of MC were observed. After 59 h, the hyphae of
MC started to reappear. This suggests that repeated
application of PO is necessary in order to eliminate
MC. With the control sample, treated the same way
but without addition of PO, no changes to hyphae
were observed. Microphotographic documentation
of this experiment was performed. In order to
visualise the processes more clearly, classic
microphotography was supplemented with
scanning electron microscopic images.
To confirm the mycoparasitism by PO, two
different preparations of PO were added to the
culture of collection strain of MC. Seven days
after this, agar plates were microphotographed.
The first macroscopical changes were observed
4 days after inoculation of the MC culture. This
in vitro observation suggests that PO could
be useful in the treatment of dermatophytosis.
A B S T R A C T S / ISFM Congress 2015
MULTIDRUG-RESISTANT UROPATHOGENIC
BACTERIA IN CATS: A 13 YEAR
RETROSPECTIVE SNAPSHOT
Cátia S Marques1, Adriana I Belas1, Catarina S Aboim1,
Natacha M Couto1, Luís T da Gama2,
Constança F Pomba1
Laboratory of Antibiotic Resistance, CIISA, FMV, UL,
Lisbon, Portugal
2
CIISA, FMV, UL, Lisbon, Portugal
Email: cpomba@fmv.ulisboa.pt
The current increase in multidrug-resistant (MDR)
bacteria represents a clinical problem in the
selection of an appropriate antibiotic, but mostly
it is of great public health concern. The aim of
this study was to characterise the existence of
multidrug-resistant uropathogenic bacteria
in cats with urinary tract infection (UTI).
Two hundred and thirty-one uropathogenic bacteria
isolated from cats between January 2002 and
December 2014 at the Laboratory of Antibiotic
Resistance, Lisbon University, were screened for
2015
antimicrobial resistance by disk diffusion. Clinical and
applied and extended-spectrum β lactamase (ESBL),
Laboratory Standards Institute breakpoints were
pAmpC, mecA and aac(6’)-Ie-aph(2’’)-Ia genes were
detected by PCR. Fisher’s exact test, with an α value of
0.05, was used to compare the frequency of resistance
between 2002–2007 and 2008–2014 time periods.
Escherichia coli was isolated in 38.53% (89/231)
of positive urocultures. In relation to amoxicillin-
clavulanate, third-generation cephalosporins,
sulfamethoxazole/trimethoprim, fluoroquinolones
and gentamicin, MDR (resistance to three or more
antimicrobials) E coli (22.9%, 19/83, years
2002–2014) was detected throughout the years and
a significant increase in the 2008–2014 time period
was detected (P = 0.0079). Most of these MDR E coli
were found to carry ESBL CTX-M or pAmpC CMY
enzymes. Although Klebsiella species (5.12%, 12/231)
was not frequently isolated from cats with UTIs,
91.7% (11/12) were found to be MDR. Furthermore,
9/12 strains were identified between 2008 and 2014.
CTX-M was the ESBL most frequently detected
in Klebsiella species. The second most isolated
bacteria were Enterococcus species (13.89%,
32/231) and Staphylococcus species (14.29%,
33/231). Ten methicillin-resistant staphylococci
(MRS) were identified since 2002 and half were
considered MDR. Enterococcus faecalis high level
gentamicin resistance was detected in five strains
isolated in 2003, 2006 and 2014. Four were found
to harbour the aac(6’)-Ie-aph(2’’)-Ia gene.
These results showed a significant increase in MDR
E coli frequency in 2008–2014 in comparison with
2002–2007. Surprisingly, almost all Klebsiella species
from cats with UTIs were MDR, raising some public
health concerns regarding their possible role as
reservoirs of resistant strains. Measures aiming to
reduce MDR frequency and an increased awareness
by veterinarians and owners are imperative.
JFMS CLINICAL PRACTICE 817
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 818
A B S T R A C T S / ISFM Congress 2015
UNCONTROLLED PILOT STUDY OF
RALTEGRAVIR (ISENTRESS) TREATMENT
OF 20 FELINE LEUKAEMIA VIRUS-POSITIVE
NATURALLY INFECTED CATS
Juanjo Vega1, Esther Sánchez2, María Perera1,
Manuel López2, Valentina Aybar1
1 1
Hospital Felino Ventas, Madrid, Spain
2
Clínica Veterinaria Coso, Zaragoza, Spain
Email: esther@cvoso.es
Feline leukaemia virus (FeLV) is a gammaretrovirus
with worldwide distribution, affecting domestic
cats and some free-living felids. Cats persistently
infected with FeLV are at risk of dying within
months to years from FeLV-associated diseases,
such as immunosuppression, anaemia or
lymphoma/leukaemia. The integrase inhibitor raltegravir
has been demonstrated to reduce FeLV replication
in vitro and recently it has been shown to be safe
(20–40 mg/kg q12h) and effective in suppressing
FeLV replication in vivo (40–80 mg/kg q12h) in
experimentally infected cats. The aim of the present
study was to evaluate the response to treatment in
20 cats naturally infected with FeLV and with
persistent viraemia and symptomatic progressive
disease. All cats were positive on quantitative ELISA
(twice, at least 12 weeks apart) and diagnosis was
confirmed with PCR-RNA. All had haematopoietic
disorders such as non-regenerative anaemia.
Cats with any type of neoplasia were excluded.
All cats were treated with raltegravir (Isentress
400 mg; MSD) at 40 mg/kg q12h.
The cats were monitored for 63 days and three
samples were collected every 3 weeks and analysed
for haematology and clinical chemistry (see table).
None of the cats exhibited any adverse reactions.
All cats, except one, recovered from their anaemia
and none developed additional clinical signs. One
cat died during the study. Treatment was continued
after the study in all but three cats, and these had a
relapse of their signs 3–4 weeks after the treatment
was stopped. Of 16 cats maintained on treatment,
eight were healthy at 6 months (thereafter lost to
follow-up), and eight remained healthy at 2 years,
although were still FeLV-positive and viraemic.
Haematocrit values (%) during treatment
Case 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Day 1 12 15 20 19 17 13 14 9 9 11 13 12 14 9 8 11 13 12 11 29.5
Day 21 13 19 24 22 19 17 16 21 21 18 13 17 14 21 22 12 18 21 12 35
Day 42 22 23 29 25 22 23 21 20 20 21 18 25 19 22 23 21 23 27 19 34
Day 63 27 29 32 29 29 30 29 27 27 29 31 20 32 27 29 31 29 34 15 35
In this pilot study, treatment with raltegravir
appeared to reduce the signs of progressive
FeLV infection. Raltegravir may offer one
treatment option for this lethal disease
and further randomised controlled studies
of long-term treatment are justified.
818 JFMS CLINICAL PRACTICE
SAFETY OF CONCURRENT APPLICATION
OF AN IMIDACLOPRID/FLUMETHRIN COLLAR
AND AN EMODEPSIDE/PRAZIQUANTEL
SPOT-ON TO CATS
Katrin Deuster1, Heidi L Erasmus2, Josephus J Fourie2,
Bettina Schunack1
Bayer HealthCare AG, Animal Health Division,
Leverkusen, Germany
2
ClinVet International, Universitas, South Africa
Email: bettina.schunack@bayer.com
In the light of comprehensive ecto- and endoparasite
treatment, the question as to whether products can
be safely used concurrently frequently arises.
Efficacy of imidacloprid/flumethrin containing collars
(IMI/FLU) (Seresto; Bayer) against ticks and fleas on
cats has been extensively studied and 7–8 months
of protection have been demonstrated.
The emodepside/praziquantel (EMO/PRZ)
(Profender; Bayer) spot-on formulation effectively
treats nematodes and cestodes in this species.
The objective of this study was to demonstrate that
no safety concerns arise from the simultaneous use
of the collar and spot-on in cats.
Twenty separately housed cats were divided
into two equal groups, one non-treated and the
other fitted with IMI/FLU collars and at the same
time treated with the EMO/PRZ spot-on formulation.
Clinical examinations and collection of blood
specimens for the evaluation of haematological
and clinical chemistry parameters were conducted
on all cats before treatment, on the day of treatment,
and 2 and 4 weeks thereafter. Clinical pre- and post-
administration and local tolerance observations
were conducted on day –3, prior to treatment
on day 0 and approximately hourly for 4 h
thereafter, as well as twice daily on days 1
and 2. The animals were also observed once
daily for general health and their food
consumption was measured.
All cats in the treated group exhibited the usual
localised, temporary, cosmetic hair coat changes
associated with spot-on applications. Except for
a single cat in the treated group, which exhibited
a moist dermatitis and superficial skin lesion on
the dorsal aspect of its neck on day 14, there were
no significant differences between the two groups
of cats for any of the physical, haematological or
blood chemistry variables measured.
Results thus indicate that cats can be safely
treated simultaneously with both products if both
ecto- and endoparasites are present. Although not
tested, re-treatment with the spot-on as per label
should not have adverse effects on cats already
fitted with the collars. Infections with adult cestodes
and various life stages of different nematodes can
therefore be treated at any time during the 8 month
period the collar is worn to protect against ticks
and fleas. This provides a comprehensive and
convenient treatment option to owners and
veterinarians.
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 819
EVOLUTION OF RETROVIRUS INFECTION
RATE IN CATS AT THE VETERINARY
HOSPITAL OF THE UNIVERSITY
OF CHILE (1999–2014)
Fernando G Elías, Loreto Muñoz
Faculty of Veterinary Sciences, University of Chile,
Santiago, Chile
Email: lmunoz@uchile.cl
Feline leukemia virus (FeLV) and feline
immunodeficiency virus (FIV) are among the most
common infectious agents in domestic and wild
felids. The prevalence of retroviral infections
in domestic cats differs depending on the
geographical region and the cat population
evaluated, being affected by population density,
reproductive status, age, sex and environmental
conditions.
This study was conducted to determine
the fluctuation in the prevalence of retroviral
infections, and risk factors, among two populations
of 52 cats that attended the Veterinary Hospital of
the University of Chile in 1999 and in 2014, using
the SNAP Feline Triple Test Kit (IDEXX Laboratories).
Fifty-two cats attending the clinic for the first
time in 1999 and in 2014 were classified according
to age, sex, reproductive status, contact with other
cats, lifestyle (indoor, outdoor) and health status
(healthy and sick).
FeLV infection was most prevalent in mature
castrated male cats that had contact with other
cats. The prevalence of FIV was low and was
found in a wide age range. A Z-test was performed
to evaluate differences in prevalence between
the two study times. This showed that FeLV and
dual FeLV/FIV infection rates were significantly
higher in 1999 (Z = 5.12 and Z = 4.01, respectively),
but for FIV there was no significant difference
The results of a χ2 test (χ2 = 0.699) showed no
(see table).
association between retroviral infection status and
the health status of the cats in the 2014 study.
Retroviral status in 1999 and 2014
Retroviral status 1999 study 2014 study
FeLV+ 30 6 form of FCoV.
FIV+ 4 3
FeLV+/FIV+ 14 0 amino acid substitution in the spike protein may
FeLV–/FIV– 4 43
Total 52 52
FeLV = feline leukemia virus; FIV = feline
immunodeficiency virus
In summary, this small study showed evidence
of a decrease in the FeLV infection rate between
1999 and 2014, but the FIV infection rate remained
similar.
Our acknowledgement to Laboratories Agrovet
Ltd for its support with IDEXX products.
A B S T R A C T S / ISFM Congress 2015
FELINE CORONAVIRUS PATHOGENICITY
FACTORS
Emily L Porter1, Stuart G Siddell2, Christopher R Helps1,
Séverine Tasker1
1
School of Veterinary Sciences, University of Bristol, UK
2
School of Cellular and Molecular Medicine,
University of Bristol, UK
Email: Emily.Porter@bristol.ac.uk
Feline coronavirus (FCoV) infections are endemic
among cats worldwide. The majority of infections
are asymptomatic, but approximately 5% of cases
go on to develop feline infectious peritonitis (FIP) –
a frequent cause of death in young cats.
Complete FCoV genome sequences were
obtained from a pair of FCoV infected siblings, one
of which died of FIP while the other remained
healthy for at least 12 months after sample
collection. Virus-specific oligonucleotide primers
were used to convert and amplify the FCoV RNA
from each sample into complementary DNA
fragments, which then underwent next generation
2015
sequencing. The de novo assembled genomes were
compared and nucleotide differences identified.
Thirty-two nucleotide differences, which may be
related to the development of FIP, were observed.
Recent evidence has suggested that amino acid
changes in the FCoV spike protein may be
associated with the development of FIP; for
example, the substitution of a methionine in faecal
samples from healthy cats for a leucine in
tissue samples from FIP cats, at position 1058.
A large collection of post-mortem tissue
and faecal samples from very well characterised
ill cats with and without FIP was analysed for
the presence of FCoV by reverse-transcriptase
quantitative PCR and, if positive, spike protein
substitutions by sequencing. A predicted
methionine at position 1058, consistent with
the shedding of an enteric form of FCoV, was
identified in 77% of the faecal samples from cats
with FIP, and in 100% of the faecal samples from
cats without FIP. In contrast, 91% of the tissue
samples from cats with FIP and 89% of the tissue
samples from cats without FIP had a predicted
leucine at position 1058, consistent with a systemic
These results suggest that this particular
be associated with FCoV tissue tropism, rather
than virulence. The amino acid change may
be a necessary step in the development of FIP,
but cannot be the sole determinant of whether
FCoV-infected cats develop FIP or not. Therefore,
host factors and/or other viral mutations must
also play an important role in the development
of disease.
< Emily Porter received the 2015 European Advisory
Board on Cat Diseases (ABCD)/Merial Young Scientist
Award for this research (see page 834).
JFMS CLINICAL PRACTICE 819
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 820

A B S T R A C T S / ISFM Congress 2015

ASSESSMENT OF RENAL FUNCTION OCCURRENCE OF TRITRICHOMONAS

DURING 5 MONTHS IN ADULT CATS
FED A HIGH PROTEIN DRY DIET
Isabelle Leriche1, Gwendoline Chaix2, Agnès André3,
Patrick Nguyen3
1
Virbac Nutrition, Vauvert, France
2
Virbac Medical Department, Carros, France
3
Nutrition & Endocrinology Unit, National College
of Veterinary Medicine, Nantes, France
Email: isabelle.leriche@virbac.fr
Despite the absence of evidence of any deleterious
renal effect of high protein diets, there are still
concerns regarding the impact of such diets
on renal safety in healthy cats.
Twenty-four healthy adult European cats were
randomised into three groups. For 5 months, cats
were fed exclusively one of three maintenance dry
diets: a high protein diet (HP: 48% metabolisable
energy [ME]), a moderate protein diet (MP: 31% ME)
and a low protein diet (LP: 27% ME). Phosphorus
content (% dry matter [DM]) and calcium to
phosphorus ratio were 1.4 and 1.1 in the HP diet,
0.6 and 1.0 in the MP diet, and 1.5 and 1.0 in the
LP diet. The daily rations were calculated to
maintain the cats’ body weight (BW). Blood samples
were taken at the initiation of the study and then
once a month, in the fasted state. To assess renal
function, the plasma parameters listed in the table
were measured. Urine samples were taken during
2 weeks at the end of the study in order to
determine the urinary protein to creatinine ratio.
Tukey’s test was performed to compare the different
FOETUS IN BRAZILIAN CATS
Roberta P Duarte, Alex A Nakamura, Milena A Viol,
José Eduardo S Silva, Paulo Ricardo Dell A Rocha,
Marcelo V Meireles, Gisele F Machado
University of Veterinary Medicine, UNESP,
Araçatuba, São Paulo, Brazil
Email: robertapicciuto.medvet@hotmail.com
Investigation of infections with Tritrichomonas
foetus in Brazilian cats has been neglected, and
there is no current information about the occurrence
of this disease. This study was therefore designed
to investigate the occurrence of this parasite in cats
from the region of Araçatuba, São Paulo, Brazil,
using direct examination of feces and PCR. Fecal
samples from 56 cats were collected by rectal
infusion of 0.9% saline solution. A drop of each
sample was analyzed by optical microscopy.
Subsequently, DNA was extracted using a ZR fecal
DNA kit (Zymo Research). The extracted DNA was
stored at –20°C for PCR. The presence of T foetus
DNA was verified by amplification of 347 base pairs
from primers TFR3 and TFR4. The positive control
was commercially purchased (T foetus VetMAX
Controls; Invitrogen) and the negative control was
ultrapure water. Blood samples were also collected
for hematology.
Most cats (n = 54) were of mixed breed and two
were purebred. Ten cats presented with diarrhea at
the time of collecting the samples. Clinical history
was available from seven cats and three of them
had already been treated for Giardia species.

The mean dietary protein intake was 7.2 ± 0.6

foods for each variable, with 5% significance level. Ninety percent of the cats lived in environments

g/kg BW/day, 4.6 ± 0.3 g/kg BW/day and 4.0 ± 0.2

with more than one cat.
T foetus was not observed in any sample
g/kg BW/day with the HP, MP and LP diets, by direct microscopic examination of stools.
respectively. All plasma parameters and urinary Giardia species was observed in one sample.
protein to creatinine ratios (see table) remained in Ancylostoma species, Isospora species,
the reference intervals throughout the study, with Dipylidium caninum and Aelurostrongylus
no significant difference between groups. abstrusus infections were present in four cats,
and one had co-infection with Ancylostoma
Mean plasma values and urinary protein to creatinine ratio species and Isospora species.
in each group In one cat (1.8%) PCR was positive for
T foetus. This cat was a male 8-year-old mixed
HP diet MP diet LP diet Reference interval breed, without diarrhea or a history of diarrhea.
Urea (g/l) 0.22 ± 0.01 0.19 ± 0.01 0.18 ± 0.01 0.1–0.3 It was from a private shelter, but none of the

15.7 ± 0.6 13.5 ± 0.7 16.0 ± 1.4

other cats were positive for T foetus by PCR.
Creatinine (mg/l) 3–21
51.6 ± 1.7 51.8 ± 2.1 49.7 ± 1.9
Co-infection with other intestinal parasites was
Phosphate (mg/l) 34–85
4.0 ± 0.2 4.1 ± 0.2 4.1 ± 0.3
not detected, and a complete blood count
Potassium (mmol/l) 3.7–5.8 examination revealed moderate eosinophilia.
73.3 ± 1.3 68.0 ± 1.6 69.0 ± 1.1
Total protein (g/l) 54–82 This study confirms that infection with T foetus

36.4 ± 0.7 32.5 ± 1.1 36.3 ± 1.0

must be considered in cases of diarrhea in
Albumin (g/l) 22–44
0.11 ± 0.01 0.17 ± 0.04 0.10 ± 0.02
Brazilian cats; however, asymptomatic infections
Urine protein to <0.2 can occur and asymptomatic carriers can be a
creatinine ratio source of infection in shelters. As highlighted in
HP = high protein; MP = moderate protein; LP = low protein other studies, the sensitivity of direct examination
of feces is much lower than the PCR for T foetus
These results confirm that a high protein content diagnosis. This is the first case of T foetus
in a balanced diet has no impact on renal function detection in a cat from the region of Araçatuba,
in the medium term in healthy adult cats. São Paulo.

820 JFMS CLINICAL PRACTICE

816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 821
ANTIMICROBIAL RESISTANCE IN
FELINE URINARY TRACT INFECTIONS
Cátia S Marques1, Filipa S Manteigas2,
Filipa A Santos2, Joana D Valente2, Rita L Delgado2,
Sofia A Barragão2, Tânia L Tomé2,
Constança F Pomba1, Maria J Fonseca2
1
Laboratory of Antibiotic Resistance, CIISA, FMV, UL,
Lisbon, Portugal
2
Hospital do Gato, Lisbon, Portugal
Email: adcatiamarques@fmv.utl.pt
Urinary tract infections (UTIs) are
frequently diagnosed in cats, especially in
the presence of concurrent diseases such
as diabetes and chronic renal failure. Several
studies point to increasing rates of antimicrobial
resistance limiting the therapeutic options.
The aim of this study was to characterise the
antimicrobial resistance found in cats with
UTIs from a veterinary hospital exclusively
devoted to feline medicine.
Urocultures together with available clinical
data were retrospectively gathered from the
Hospital do Gato during the period from
April 2013 to February 2015.
Of 285 urocultures (including follow-up
analyses) conducted, 18.2% (52/285) were
positive. Cats with a UTI included both sexes
(30 females, 22 males) and comprised a wide
age range (7 months to 18 years). Clinical signs
commonly included haematuria and dysuria,
and several cats had concomitant diseases
such as chronic kidney disease and urinary
obstruction. Single infections (94.2%, 49/52)
were more frequent than mixed infections (5.8%,
3/52). Escherichia coli was the most frequently
isolated bacteria (50.9%, 28/55), followed by
Enterococcus species (18.2%, 10/55). E coli
resistance to amoxicillin-clavulanate (AMC), third
generation cephalosporin (3GC), fluoroquinolone
(FLU) and sulfamethoxazole/trimethoprim (SXT)
was 51.9% (14/27), 30.4% (7/23), 48.1% (13/27)
and 22.2% (6/27), respectively. Enterococcus
species had 40.0% (4/10) ampicillin (AMP),
20.0% (2/10) high level gentamicin (CN120) and
60.0% (6/10) FLU resistance. Considering AMC,
3GC, FLU and SXT as antimicrobial categories,
seven E coli were co-resistant to at least three
antimicrobial categories and were thus considered
multidrug resistant (MDR). Similarly, with respect
to AMP, FLU and CN120, one Enterococcus
species was MDR.
In this study we found high frequencies
of resistance to commonly used antimicrobials
among uropathogenic bacteria isolated from
cats diagnosed with UTI. Furthermore, several
MDR strains were detected. This represents not
only an animal health issue but also a significant
public health concern, since companion animals
may act as reservoirs of antimicrobial-resistant
bacteria.
A B S T R A C T S / ISFM Congress 2015
FOOD-ASSOCIATED FACTORS
IN THE AETIOLOGY OF FELINE
HYPERTHYROIDISM: WHERE
IS THE PROOF?
Ingrid van Hoek1, Myriam Hesta2, Yann Queau1
1
Royal Canin Research & Development Center,
Aimargues, France
2
Department of Nutrition, Genetics and Ethology,
Faculty of Veterinary Medicine, Ghent University,
Ghent, Belgium
Email: Ingrid.van.hoek@royalcanin.com
Since the first description of feline hyperthyroidism
(feHT4), several epidemiological studies have
suggested diet as a causal factor of feHT4. The aim
was to critically assess the evidence presented in
epidemiological studies suggesting food-associated
factors in the aetiology of feHT4.
Scientific literature was screened for peer-
reviewed publications investigating food-associated
factors in feHT4 since it was first described in 1979.
Study designs were checked against classical
2015
epidemiology biases. Food-associated factors
showing an increased risk for feHT4 were assessed
for compatibility with the nine Bradford-Hill (B-H)
criteria, which are used to evaluate whether an
association involves a causal component. Evidence
for a causal component is higher when more B-H
criteria are met.
A total of nine publications investigating food-
associated factors in feHT4 were identified, all
involving retrospective studies. Three publications
investigated qualitative factors only (eg, preferred
food flavours) and not quantitative. Feeding canned
food was not found to be a significant risk factor
for feHT4 in one study, while it was found to be
a significant and quantitative risk factor in five
publications. However, there were important
limitations in study design: controls included sick
cats (three studies), cases outnumbered controls
(two studies), cases and controls differed in age
(three studies), or diet information did not reflect
diet fed at the time feHT4 developed (two studies).
Three out of nine B-H criteria were met when
considering canned diet feeding as an increased
risk for feHT4 development.
From the available literature there is
insufficient evidence to conclude that canned
diet is a food-associated factor in the aetiology
of feHT4. Retrospective studies only describe an
association and not a cause-and-effect relationship,
are sensitive to bias from host and environment,
and are less likely to identify aetiologic factors
when prevalence is below 10%, as is the case
in feHT4. Hypotheses linking food-associated
factors to feHT4 (such as bisphenol A,
polybrominated diphenyl ethers, flavonoids
and iodine content) have never been proven to
date, and lifelong prospective studies are required
to investigate food-associated factors in the
aetiology of feHT4.
JFMS CLINICAL PRACTICE 821
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 822
A B S T R A C T S / ISFM Congress 2015
EFFICACY AND SAFETY OF PROZINC
IN DIABETIC CATS PREVIOUSLY WELL
REGULATED ON LANTUS OR LEVEMIR
AND THEN SWITCHED TO PROZINC
Saskia Kley1, Takahiro Sako2, Akihiro Mori2,
Satoko Maruyama3
1
Boehringer Ingelheim Vetmedica GmbH,
Ingelheim, Germany
2
Department of Veterinary Nursing, Nippon Veterinary
and Life Science University, Tokyo, Japan
3
Boehringer Ingelheim Vetmedica Japan Co, Ltd,
Tokyo, Japan
Email: saskia.kley@boehringer-ingelheim.com
Protamine zinc insulins (PZIs; beef or beef/pork)
had been used for the treatment of cats with
diabetes for many years but were discontinued
several years ago. A similar preparation containing
protamine zinc human recombinant insulin, ProZinc
(Boehringer Ingelheim), is available in the US,
Canada and Germany for use in diabetic cats.
Additionally, insulin analogues registered for use in
humans such as glargine (Lantus; Sanofi) or detemir
(Levemir; Novo Nordisk) have been used off-label
for the treatment of diabetic cats. Both PZIs and
human insulin analogues are recommended for
the treatment of feline diabetes mellitus due to their
appropriate and longer durations of action. In this
study the clinical efficacy of ProZinc was evaluated
in 10 client-owned diabetic cats that had been
previously well controlled with either detemir
(Levemir) or glargine (Lantus) insulin, as indicated
by fructosamine concentrations of <400 µmol/l
and stable clinical signs.
The study design was as follows. On study days
0, 7, 14, 30 and 45, the cats underwent a physical
examination, as well as a complete blood count,
serum biochemistry profile and serum fructosamine
analysis (days 0, 14, 30, 45). Urine was collected by
cystocentesis for urinalysis on days 0, 14, 30 and
45. Serum was drawn for thyroxine (T4)
concentrations and feline leukaemia virus/feline
immunodeficiency virus testing on day 0 only.
ProZinc was administered subcutaneously in lieu
of detemir or glargine in all cats q12h from day
0 to day 45. On each of the five examination days,
glucose was monitored for 9 h post-injection
(glucose curve). Owners kept a record of adverse
reactions, insulin dose and changes in clinical
signs. The dosage of ProZinc could be adjusted
where needed according to standard
recommendations. It was hypothesised that there
would be no significant change in the fructosamine
level at day 45 compared with day 0, irrespective
of the dose change. Statistical analysis of the
data was performed using Systat 13.1 software
(Systat). Values with non-normal distribution
were expressed as median and interquartile
values were expressed as mean ± SD,
range (IQR; 25/75%); normally distributed
and the significance was set at P <0.05.
822 JFMS CLINICAL PRACTICE
the study period (day 0: 3.7 ± 0.5; day 45: 3.7 ± 0.5).
There was no change in body weight (kg) over
Clinical signs were stable and no adverse reactions
were noted. Neither the dose of ProZinc nor the
levels of fructosamine changed significantly during
cat/day) was 1.1 ± 0.6 on day 0 and 1.3 ± 0.8 on day
the study period. The average ProZinc dose (IU per
45. Median fructosamine concentrations (μmol/l;
normal range 191–349) were 191 (183–263) on day 0
and 195 (179–249) on day 45. The median area
under the curve for glucose (mg/dl/h) during the
glucose curve was 73 (IQR 65–89) on day 0 and 79
(IQR 65–85) on day 45. None of these parameters
reached statistical significance (P ⩾0.15). Urine
day 0 (265 ± 175) and day 45 (130 ± 160),
glucose (mg/dl) appeared to decrease between
although this did not quite reach statistical
significance (P = 0.053).
Results of the present study demonstrate that
ProZinc, a veterinary registered PZI, can be safely
and effectively used as an alternative treatment for
cats previously treated with glargine or detemir
insulin analogues.
PREVENTION OF LACTOGENIC TOXOCARA
CATI INFECTIONS IN KITTENS BY
APPLICATION OF AN EMODEPSIDE/
PRAZIQUANTEL SPOT-ON (PROFENDER;
BAYER) TO THE PREGNANT QUEEN
Claudia Böhm1, Sonja Wolken2, Gabriele Petry1,
Roland Schaper1
1
Bayer Animal Health GmbH, Leverkusen, Germany
2
Wolkenkonzept, Burgdorf, Germany
Email: claudia.boehm@bayer.com
This study aimed to evaluate the efficacy of an
emodepside 2.1% (w/v)/praziquantel 8.6% (w/v)
topical solution (Profender Spot-on for cats;
Bayer) in the prevention of lactogenic
Toxocara cati infections.
A controlled test was performed with two groups
of eight cats with confirmed pregnancy. All cats
were infected with daily doses of 2000 T cati eggs
for 10 consecutive days starting 50 days post-
conception to produce an acute infection.
Treatment was performed 60 days post-conception.
Queens in the treatment group received the
emodepside/praziquantel solution at the minimum
therapeutic dose (3 mg/kg emodepside and
12 mg/kg praziquantel), while the control group was
treated with a placebo spot-on. Efficacy was
evaluated 56 days postpartum by necropsy of
one randomly selected kitten from each litter and
comparison of the worm burdens between the
study groups. Additionally, the necropsy results
were supported by quantification of worms expelled
with the faeces after deworming of the remaining
kittens and all queens.
The treatment in late pregnancy resulted in
an efficacy of 98.7% (P <0.0001). All necropsied
control kittens were infected (geometric mean 30.6).
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 823
Seven of eight kittens from treated mothers were
free of T cati (geometric mean 0.4). Worm counts
after deworming reflected the results obtained at
necropsy. No side effects of the treatment were
observed.
It is concluded that treatment with an
emodepside/praziquantel spot-on solution during
late pregnancy effectively prevents lactogenic
transmission of T cati to the offspring. The study
design facilitated the generation of reliable data
while at the same time a minimum number of
animals was sacrificed.
DYSCHEZIA SECONDARY TO
OSTEOCHONDRODYSPLASIA
IN A SCOTTISH FOLD CAT
Carmen Pineda, Alba Galan, Beatriz Blanco,
Juan M Dominguez, Escolastico Aguilera-Tejero,
Ignacio Lopez
Department Medicina y Cirugia Animal,
University of Cordoba, Spain
Email: cpimart@hotmail.com
An 8-month-old entire female Scottish Fold cat was
referred to the Veterinary Teaching Hospital of the
University of Cordoba for evaluation of lameness
of the right hindlimb and dyschezia. On examination
the cat showed evidence of an abnormal gait,
plantigrade stance, an arched back and reluctance
to jump. The cat also showed discomfort when
squatting and strained to defecate.
Bilateral hindlimb radiographs demonstrated
changes consistent with osteochondrodysplasia.
The metatarsal bone and phalanges were
apparently normal. Extensive new bone formation
was evident around the tarsus and proximal portion
of the metatarsus. In agreement with clinical signs,
the lesions of the right tarsus were more prominent
than those of the left tarsus. The distal colon and
rectum were filled with faeces. Radiography did
not show any skeletal abnormalities in the pelvis
or associated vertebrae and the dyschezia was
thought to be a consequence of pain elicited by
adopting the posture to defecate. Treatment was
initiated with lactulose and subsequently
chondroprotective agents (glucosamine and
chondroitin sulfate) and a commercial diet
formulated for joint disease (Feline j/d; Hill’s)
was prescribed.
The Scottish Fold is a purebred cat with forward-
folded ears as a result of autosomal-dominant
inherited osteochondrodysplasia and other signs
of generalised defective cartilage formation.
Previous studies have demonstrated that
osteochondrodysplasia is an inherited trait with
an incomplete dominant pattern. Affected cats
show ambulatory difficulties due to progressive
osteoarthritis resulting from defective maturation
and dysfunction of cartilage.
To our knowledge, dyschezia has not previously
been reported as a clinical sign of this disease.
A B S T R A C T S / ISFM Congress 2015
Although the cat’s quality of life improved after
treatment, this case emphasises the importance
of ceasing breeding cats with inherited defects
that compromise their quality of life. Appropriate
analgesic therapy for affected cats is also an
important consideration.
CLINICAL PRESENTATIONS OF
MOLECULAR SUBTYPES IN FELINE
MAMMARY CARCINOMAS
Maria Soares, Jorge J Correia, Sara Madeira,
Fernando Ferreira
CIISA, Faculdade de Medicina Veterinária,
Universidade de Lisboa, Portugal
Email: mariajosoares@gmail.com
Molecular classification of feline mammary
carcinomas (FMC) can have potential applications
for clinical practice and for comparative oncology.
The main goal of this study was to characterise
both the clinical and the pathological features
of the different molecular phenotypes identified
in a population of cats with mammary carcinomas
2015
(n = 102), using the widely accepted
immunohistochemical-based classification
established by St Gallen’s International Expert
Consensus Panel. Two hundred and twenty-nine
mammary tumours were collected from 102 cats
and their molecular subtypes were defined by
the evaluation of five biomarkers using
immunohistochemistry.
The luminal B/HER2 negative was the most
common subtype (29.4%, 30/102), followed by
the luminal B/HER2 positive (19.6%, 20/102), triple
negative basal-like (16.7%, 17/102), luminal A
(14.7%, 15/102), triple negative normal-like (12.7%,
13/102) and HER2-positive (6.9%, 7/102) subtypes.
Luminal A subtype was significantly associated with
smaller (P = 0.024) and well-differentiated tumours
(P <0.001), showing a better outcome and
presenting the greatest survival time (mean overall
survival = 943.6 days), contrasting with the triple
negative basal-like subtype that was associated
with larger (P <0.001) and poorly differentiated
tumours (P <0.001) and with the presence of
necrotic areas in the tumoural lesion (P = 0.003).
Furthermore, triple negative basal-like tumours also
had the lowest survival times (mean overall survival
= 368.9 days). The luminal B/HER2 positive subtype
was associated with poorly differentiated tumours
(grade III; P <0.001), with absence of necrosis
(P = 0.003) and presented a mean survival time
of 568.3 days.
Our study revealed significant differences in the
clinicopathological characteristics of the six FMC
molecular subtypes, which presented similarities
with the human subtype counterparts. Differences
in the overall survival times among tumour subtypes
could have an important and relevant prognostic
value in veterinary medicine, and may support the
search for new targeted therapies.
JFMS CLINICAL PRACTICE 823
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 824
A B S T R A C T S / ISFM Congress 2015
VIRUS EVOLUTION IN THE PROGRESSION
OF NATURAL FELINE IMMUNODEFICIENCY
VIRUS INFECTION
Paweł M Bęczkowski1,2, Joseph Hughes1,
Roman Biek1,3, Nicola Logan1, Elizabeth McMonagle1,
Navapon Techakriengkrai1, Matthew Harris1,
Dominic J Mellor1, Tsang Long Lin4, Julia A Beatty5,
Annette Litster4, Brian J Willett1, Margaret J Hosie1
1 3
MRC University of Glasgow Centre for Virus
Research, University of Glasgow, Glasgow, UK
2
Small Animal Hospital, University of Glasgow,
Glasgow, UK
3
Boyd Orr Centre for Population and Ecosystem
Health & Institute of Biodiversity, Animal Health
& Comparative Medicine, University of Glasgow,
Glasgow, UK
4
Department of Veterinary Clinical Sciences,
Purdue University, West Lafayette, IN 47907, USA
5
Valentine Charlton Cat Centre, University of Sydney,
Sydney, NSW, Australia
Email: pawel.beczkowski@gmail.com
Feline immunodeficiency virus (FIV) is an
important pathogen of domestic cats, which
in some cases can lead to feline AIDS. FIV is
believed to evolve during the course of infection
as a result of the error-prone nature of reverse
transcriptase and recombination between viral
variants, but relatively little is known about this
process in naturally occurring infection. Ultimately,
it is unknown why some infected cats remain
healthy while others progress rapidly to AIDS.
To address this lack of knowledge, we examined
sequential blood samples obtained during the
course of natural FIV infection in a population
of 44 domestic cats.
Employing a Bayesian coalescent framework,
we demonstrated that the FIV env gene is relatively
stable genetically. Although not necessarily a
prerequisite, this is likely to explain why many
naturally infected cats can remain healthy and do
not progress to AIDS. By determining the cell
tropism of isolated viral variants, we demonstrated
that sick cats were more likely to harbour
viruses of the ‘late’ phenotype than healthy
animals, similar to the co-receptor switch
observed during the progression of HIV
infection. By assessing the strength and
breadth of neutralising antibodies (NAbs),
we found that NAbs did not appear to influence
the course of natural FIV infection, arguing
against a role in controlling infection and
disease progression. Following an examination
of samples collected from a group of privately
owned Australian vaccinates, we showed that
the commercial FIV vaccine did not induce
cross-reactive neutralising antibodies.
< Paweł Bęczkowski received the 2015 European
Advisory Board on Cat Diseases (ABCD)/Merial Young
Scientist Award for this research (see page 834).
824 JFMS CLINICAL PRACTICE
PREVALENCE AND RISK FACTORS FOR
FELINE HYPERTHYROIDISM IN 80 CATS
OF THE GREATER LISBON AREA
Rita OR Ferreira1, Maria TCMVV Brito2,
Cátia VBM Sousa3
1
Lisbon, Portugal
2
Faculty of Veterinary Medicine, University of Lisbon,
Portugal
Veterinary Hospital of Restelo, Lisbon, Portugal
Email: rita_reis_ferreira@hotmail.com
Serum total thyroxine (TT4) was measured in 80 cats
aged 6 years and older presented at a veterinary
hospital in Greater Lisbon, either for routine visits
or health-related problems. A questionnaire-based
cross-sectional observational study in patients
that met the inclusion and exclusion criteria was
undertaken. Data collected included information
regarding diet, environmental exposures,
demographic characteristics and lifestyle.
The prevalence of hyperthyroidism (T4 >4 µg/dl)
was 12.5% and there was no significant (P <0.05)
difference in prevalence in sick (13.5%) and healthy
(10.7%) patients. Older cats, those that ate cooked
meat or were exposed to insecticides were more likely
to be diagnosed with hyperthyroidism. A protective
effect was detected associated with the use of
pipette ectoparasiticides, topical deparasitation
and use of plastic containers for food and water.
Risks and protective factors
Variable P Odds ratio
Age 0.023 –
Insecticides 0.041 4.384
Cooked meat 0.041 4.28
Plastic container 0.039 0.181
Topical deparasitation 0.011 0.011
Pipette ectoparasiticides 0.041 0.228
The prevalence of feline hyperthyroidism in the
study group was similar to the reported prevalence in
other parts of the world. Further studies are needed to
assess the risk and protective factors demonstrated
considering this is a multifactorial disease.
DETERMINATION OF THE INSULIN
RESISTANCE STATE IN OVERWEIGHT
OR OBESE CATS
Pía Astudillo, Paola Ledesma, Loreto Muñoz
Faculty of Veterinary Sciences, University of Chile,
Santiago, Chile
email: lmunoz@uchile.cl
Obesity is the most common nutritional disorder of
cats and is a major risk factor for insulin resistance.
This study was performed in 12 cats, patients of
the Veterinary Hospital of the Faculty of Veterinary
Sciences at the University of Chile. The objective
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 825
was to determine insulin resistance in overweight or
obese cats by the intravenous glucose tolerance test
(IVGTT). All patients were clinically healthy with normal
blood counts and biochemical profiles, were greater
than 5 years of age and had overweight or obese body
conditions (evaluated by body weight, body condition
score, body mass index – abdominal perimeter and
long hindlimb – and percentage of body fat).
During the test, each patient received an
intravenous dose of 1 g/kg of 30% glucose;
measurements of blood glucose were made at 0, 15,
30, 60, 90 and 120 mins after the test started, and
these values were used to plot a curve of blood
glucose over time for each cat in the study. In
addition, glucose tolerance indicators were calculated
by linear regression analysis using blood glucose
concentrations between 15 and 90 mins, the rate of
disappearance of glucose (Kglucose) and the half-life
of glucose (T1/2). The results obtained indicated that
the overweight subset achieved glycemic control
at 120 mins, whereas obese cats showed strong
glucose intolerance, failing to achieve glycemic
homeostasis by the end of the test period (120 mins).
In order to investigate the association between
overweight or obese body conditions and insulin
resistance, a Pearson correlation coefficient was
calculated for the variables of body weight,
body condition score, abdominal perimeter and
percentage of body fat in relation to variables
Kglucose and T1/2. Waist circumference (r = –0.61)
and percentage of body fat (r = –0.53) showed
the highest negative correlation with Kglucose and
suggested a direct relationship between waist
circumference and the risk of insulin resistance.
PELVIC FRACTURES IN CATS: TREATMENT
APPROACH AND IMPLICATIONS FOR
NEUROLOGICAL RECOVERY
Diana G Soares1, João F Requicha1,
Sorrel J Langley-Hobbs2, Lisa A Mestrinho3
1
Faculty of Veterinary Medicine, Lusophone University,
Lisbon, Portugal
2
School of Veterinary Sciences, University of Bristol,
Langford, Bristol, UK
3
Faculty of Veterinary Medicine, University of Lisbon,
Lisbon, Portugal
Email: gs.diana@gmail.com
Pelvic fractures represent 22–32% of all fractures
in cats. This trauma leads to lesions in organs and
nerves, influencing the therapeutic decision-making
and outcome.
The aim of this study was to compare surgical
and conservative treatment in cats with pelvic
fractures, relating to the presence of neurological
signs and the expected outcome.
Thirty cats of different breeds, age and
sex with pelvic trauma were included in the
study. All animals underwent radiographic
examination at the time of presentation and after
bone healing. Clinical data were retrospectively
A B S T R A C T S / ISFM Congress 2015
collected, including cause of fracture, presence
of neurological and orthopaedic signs, and
treatment plan chosen. Prognosis variables
included: presence of neurological signs after
treatment, recovery of motor function and
expected outcome classified in a four-grade
scale from poor to excellent.
In this study, 66.7% of the cats presented
with neurological signs before treatment, most
of these affected motor function. Of the cats
studied, 43.3% had surgical management
and 56.7% had conservative treatment. In the
conservative treatment group, a higher number
of cases still showed neurological signs after
treatment when compared with the surgical
treatment group. Seventy percent of all cases
exhibited a recovery of motor function and
most of these cases were surgical patients.
There was an expected outcome of excellent in
53.8% of surgical cases. Of the cases managed
conservatively, 58.5% had a more negative
outcome (fair or poor).
This work contributes to the characterisation
of pelvic fractures in cats. Surgical treatment
2015
appears to be more effective for recovery,
pain relief and in the improvement of
neurological signs.
PROGNOSTIC ASPECTS OF CD4+:CD8+
T LYMPHOCYTE RATIO IN CATS
NATURALLY INFECTED WITH FELINE
IMMUNODEFICIENCY VIRUS
Elisabeth Müller, Cora-Constanze Sommerey,
Stefanie V Knöpfler, Janine Guthardt
LABOKLIN GmbH & Co. KG, Bad Kissingen, Germany
Email: guthardt@laboklin.de
Feline immunodeficiency virus (FIV) is a retrovirus
of cats that primarily targets activated CD4+
T lymphocytes. During the asymptomatic phase
of infection there is a progressive decline in CD4+
T lymphocyte numbers, resulting in an inverted
CD4+:CD8+ T lymphocyte ratio and a functional
immunodeficiency.
The aim of the study was to evaluate the effect
of CD4+:CD8+ T lymphocyte ratio on the outcome
in cats naturally infected with FIV.
Forty-seven FIV-positive and 12 healthy,
FIV-negative cats (control group) were enrolled in
the study. Diagnoses were based on FIV serology,
using a reference laboratory ELISA test. CD4+:CD8+
T lymphocyte ratio was measured by flow
cytometry (BD FACSCalibur).
Thirty-five FIV-infected cats (70%) were male
(castrated: 23; 46%). The median (range) age
of cats was 8.5 (1–16) years.
Presenting clinical signs included anorexia
(47/47), lethargy (37/47), gingivitis/stomatitis
(20/47) and fever (18/47).
Haematology showed anaemia (n = 23),
leukopenia (n = 18), monocytosis (n = 16),
JFMS CLINICAL PRACTICE 825
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:00 Page 826
A B S T R A C T S / ISFM Congress 2015
leukocytosis (n = 15) and lymphopenia (n = 15)
as the most common findings. Lymphocyte
counts were lower in FIV-positive than in
FIV-negative cats (median 1.71 g/l vs 2.69 g/l,
respectively). Using flow cytometry, CD4+:CD8+
T lymphocyte ratio was significantly lower in
FIV-positive cats than in the control group (0.628
vs 2.685; P <0.001).
Four weeks after these screenings, 23 cats
had to be euthanised due to FIV infection and
associated immunodeficiency diseases. Non-
survivors had a significantly lower CD4+:CD8+
T lymphocyte ratio than survivors (0.334 vs 0.908;
P = 0.001).
The results suggest that the CD4+:CD8+
T lymphocyte ratio is a useful prognostic indicator
to predict outcome in naturally FIV-infected cats.
Especially in FIV-cases with a CD4+:CD8+
T lymphocyte ratio <0.5, the prognosis is guarded.
COX-2 IMMUNOEXPRESSION IS
ASSOCIATED WITH THE HISTOLOGICAL
GRADE OF MALIGNANCY IN FELINE
INJECTION-SITE SARCOMAS
Felisbina L Queiroga1,2, Helena Medeiros3, Joana
Costa2, Justina Prada4, João M Luis3, Isabel Pires4
1
Department of Veterinary Sciences, Universidade
de Trás-os-Montes e Alto Douro, Vila Real, Portugal
2
CITAB, Universidade de Trás-os-Montes e Alto
Douro, Vila Real, Portugal
3
ECVA, Departamento de Genética e Biotecnologia,
Universidade de Trás-os-Montes e Alto Douro,
Vila Real, Portugal;
4
CECAV, Universidade de Trás-os-Montes e Alto
Douro, Vila Real, Portugal
Email: fqueirog@utad.pt
In order to evaluate the potential value of non-
steroidal anti-inflammatory drugs (NSAIDs) in the
treatment of feline injection-site sarcoma, expression
of COX-2 was determined by immunohistochemistry
in 32 tumours. Tumours were classified into three
degrees of histological malignancy (HGM), taking into
account their differentiation, presence and extent of
necrosis and mitotic index. Other histological features,
such as the presence of giant cells and lymphoid cell
infiltrate, were also evaluated. Positive COX-2
expression (Clone SP21 at 1:40 dilution; Transduction
Laboratories) was defined when more than 10% of
the tumour cells showed positive staining. The
staining intensity was not scored in this study.
COX-2 positivity was noted in 22 (70%) of
the 32 feline injection-site sarcomas with a diffuse
cytoplasmic reaction and was completely absent
in 10 (30%) cases. COX-2 positive expression was
also noted in granulocytes and macrophages within
the stromal infiltrate. COX-2 immunoexpression
was significantly higher in tumours graded as
HGM III (P = 0.003) and in tumours with necrosis
(P = 0.012). There was no association with the
presence of giant cells or with lymphoid cell infiltrate.
826 JFMS CLINICAL PRACTICE
In conclusion, the present study demonstrated
COX-2 expression in a considerable number of
cases of feline injection-site sarcomas, and
suggests that selective COX-2 inhibitors should be
evaluated as part of multimodal treatment of feline
injection-site sarcomas.
MASTOCYTOSIS ARISING IN
THE ORAL CAVITY OF A CAT
Melanie J Dobromylskyj1, Danielle Naylor2, Annalize Ide1
1
Finn Pathologists, Histopathology Department, Diss, UK
2
Donaldson Vets, Huddersfield, UK
Email: melanie.dobromylskyj@finnpathologists.com
An 11-year-old, male neutered domestic shorthair
cat presented with multiple, 1–2 mm, slightly raised
nodules on the oral mucosa, affecting the gingiva of the
upper arcades, the palate and the palatoglossal arches.
The cat had concurrent periodontal disease and an
indolent ulcer affecting the upper right lip, together
with a history of miliary dermatitis and conjunctivitis.
Histological examination was performed on
biopsies from representative oral lesions. On
haematoyxlin and eosin-stained sections, there
were multiple well-demarcated focal lesions within
the superficial submucosa, composed of moderate
to large numbers of well-differentiated mast cells,
which extended up to the junction with the surface
epithelium. Mitotic figures were not noted. Sections
stained to highlight mast cell granules (Giemsa)
demonstrated large numbers of positive-staining,
metachromatic cytoplasmic granules within these
cells. Immunohistochemical staining of these
sections for KIT (CD117) and mast cell tryptase
also confirmed these as mast cells. The mast cells
demonstrated a somewhat aberrant staining pattern
for KIT, with both strong membranous staining
(normal) and also frequent focal cytoplasmic
staining, typically adjacent to the nucleus.
Surgical extraction of teeth 104 and 307 was
performed at the time of biopsy, and treatment
with cefovecin and meloxicam was continued
postoperatively for 2 weeks, at which point the
oral lesions appeared to be resolving.
In humans, mastocytosis encompasses a group
of clinical entities characterised by abnormal growth
and accumulation of mast cells within one or more
organs, including the oral cavity in rare cases.
In cats, cutaneous mastocytosis occurs in the form
of urticaria pigmentosa, but mastocytosis has not
previously been reported in the oral cavity. The
precise pathogenesis in this case is uncertain;
given the history of miliary dermatitis and concurrent
rodent ulcer, some form of hypersensitivity response
is possible. Concurrent dental disease may have
provoked a localised mast cell hyperplasia, with
extraction of the affected tooth leading to apparent
clinical resolution of the oral lesions. Alternatively,
the aberrant KIT expression pattern may indicate an
underlying mutation in the KIT gene, a feature often
recognised in human adult-onset mastocytosis.
816_827_Porto_ abstracts.qxp_FAB 13/08/2015 16:01 Page 827
SEBACEOUS GLAND DYSPLASIA
IN A PERSIAN KITTEN
Ana Canadas1, Carlos Sousa2, Patrícia Dias-Pereira1
1
Instituto de Ciências Biomédicas Abel Salazar –
Universidade do Porto (ICBAS-UP), Porto, Portugal
2
Hospital Veterinário da Póvoa, Póvoa do Varzim,
Portugal
Email: pdiaspereira@yahoo.com.br
A 10-month-old female Persian cat was presented
for consultation with signs of generalised
hypotrichosis and hyperpigmentation. The animal
had previously been treated with antibiotics,
glucocorticoids, antifungal drugs and an oral fatty
acid supplementation for a few months; however,
the cutaneous lesions did not improve. The cat’s
clinical condition was good.
Multiple skin biopsy samples were obtained.
Histological examination revealed a diffuse atrophy
of sebaceous glands and loss of the characteristic
lobulated morphology. Discrete clusters of
sebocytes (containing variably sized vacuoles)
and a higher number of small reserve cells were
haphazardly arranged around the follicular isthmus.
Shrunken hyperacidophilic sebocytes with pyknotic
nuclei were also observed, representing cellular
apoptosis.
Based on the histological findings and clinical
history, a diagnosis of sebaceous gland dysplasia
was made. Since this condition represents an
abnormal process of sebaceous gland
development, cure was not expected. However,
in order to improve the kitten’s haircoat, topical
olive oil was applied and a weekly bath with
antiseborrheic shampoo was recommended. The
owners reported that mild solar exposure appeared
to slightly ameliorate the cutaneous lesions.
Sebaceous gland dysplasia is a very rare
congenital dermatosis seen in both dogs and cats,
associated with an abnormal sebaceous gland
formation and differentiation. The young age of
onset of the disease suggests a genetic defect.
Abstracts for Courtesy of Renata Apanaviciene
Malta 2016
Research abstracts of relevance to
feline clinical practice are invited for
the 2016 ISFM Congress in Malta. The
deadline for submissions is March 31,
2016. Presenters of accepted
abstracts will qualify for a 50%
discount on member rate registration
for the congress.
Details from www.icatcare.org/isfm-congress
A B S T R A C T S / ISFM Congress 2015
SEROPREVALENCE OF FELINE
IMMUNODEFICIENCY VIRUS AND
FELINE LEUKAEMIA VIRUS AMONG
OWNED CATS IN LISBON, PORTUGAL
Patricia R Pimenta1,2, Ana C Coelho2,
Maria J Fonseca1
1
Hospital do Gato, Lisboa, Portugal
2
Departamento de Ciências Veterinárias, Universidade
de Trás-os-Montes e Alto Douro (UTAD), Vila Real,
Portugal
Email: patriciapimentaf@gmail.com
The impact of retrovirus infection in feline medicine
is well known. Nevertheless, there is no information
available on its current status in Portugal. For the
first time, a large study was conducted in Lisbon.
The aim of this study was to determine the
seroprevalence of feline immunodeficiency virus
(FIV) and feline leukaemia virus (FeLV) infection
among owned cats in the metropolitan area of
Lisbon and to identify possible risk factors for
seropositivity. Age, sex, breeding status, lifestyle
factors and test results for FIV antibody and FeLV
2015
antigen were analysed for 1157 cats presented to
the Veterinary Cat Hospital since it first opened in
July 2012, until March 2015.
Seroprevalence for FIV antibody was 2.7% and
seroprevalence for FeLV antigen was 5.7%. Three
cats were seropositive for both retroviruses (0.3%),
while 0.5% obtained a dubious result for FIV
antibody and 1.0% for FeLV antigen. Age was the
only factor significantly associated with risk of FIV
and FeLV seropositivity. Meanwhile, factors such
as sex and lifestyle were significantly associated
with FIV seropositivity. Additionally, cats less than
3 years old had 22.9 greater odds of being
seropositive for FeLV.
The result suggests that cats in Lisbon are at
risk of retrovirus infection and support international
guidelines that the retrovirus status of all cats
should be known and preventive measures should
be taken.
JFMS CLINICAL PRACTICE 827
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829_834_Feline Focus.qxp_FAB 10/08/2015 14:48 Page 829
AAFP Position Statement
Declawing
The American Association of Feline
Practitioners (AAFP) strongly believes it is
the obligation of veterinarians to provide
cat owners with alternatives to declawing
(onychectomy). Declawing is an elective
procedure that is highly controversial.
If owners are considering declawing, they
must be provided with complete education
about feline declawing, including the
anatomic details of what a declaw entails
Veterinarians should counsel owners to do the following:
< Provide suitable implements
(‘scratchers’) for normal scratching
behavior. Examples are scratching posts or
pads, cardboard boxes, and lumber (timber)
or logs. Scratchers may be vertical or
horizontal. They should be tall or long
enough to allow full stretching and stable
enough so they do not move or fall over.
Scratching materials preferred by cats include
wood, sisal rope, carpet, cardboard and
rough fabric. In one study, carpet-covered
vertical scratchers were preferred.3 Owners
may need to experiment with a variety of
textures and types of scratchers to determine
one or more that their cat prefers.4
Stringent attention must be given to both
location and suitability, otherwise the cat may
choose other areas/objects that are desirable
to them, but not to the owner.5 Because cats
often stretch and scratch upon awakening,
a scratcher should be placed next to where
the cat sleeps. It may also be effective to
place a scratcher near the cat’s preferred,
yet undesirable scratching object (eg, the
corner of a couch). In addition, access to the
‘undesired’ object needs to be temporarily
denied by removing or covering/protecting
it with a material that is aversive to the cat
(eg, double-sided sticky tape, loose fabric,
foil or plastic).3 Kittens and cats can be
trained to use scratchers by enticing the
The surgical alternative of deep
digital flexor tendonectomy can cause
deleterious results due to the overgrowth
of nails, the need for more extensive
claw care required of the owner, and the
development of chronic discomfort in
some patients. Consequently, deep digital
flexor tendonectomy is not recommended.
Onychectomy is not a medically
necessary procedure for the cat in
(ie, amputation of the third phalanx [P3])
and the importance of proper pain
management. In addition, alternatives
to surgery and the risks and benefits
of surgery need to be discussed.
It is important that owners understand
that scratching is a normal feline behavior;
it is both inherited and learned.1 The
primary reason for scratching is to maintain
the necessary claw motion used in hunting
cat to the item with catnip, treats or toys,
and by rewarding behavior near or on the
scratcher. If the cat scratches elsewhere, the
cat should be picked up gently and taken
to the scratcher, and rewarded. Cats should
be positively reinforced and never punished.6
< Provide appropriate claw care by
regularly trimming the claws to prevent
injury or damage to household items.
Proper feline nail trimmers should be used
to prevent splintering of the nails. Nail
trimming frequency depends on the cat’s
lifestyle. Kittens, indoor-only and older cats
will need more regular nail trims, whereas
outdoor cats may naturally wear their nails
and require less frequent trimming. Trim
nails in a calm environment and provide
positive reinforcement for the cat.6
most instances. There are inherent risks
and complications with this surgical
procedure that increase with age.10
These include, but are not limited to,
the following: acute pain, hemorrhage,
swelling, infection and nerve trauma.11
Long-term complications include
lameness, chronic draining tracts,
retained P3 material leading to claw
regrowth, development of palmigrade
FELINE FOCUS
and climbing.2 In addition, it is done to
re-establish claw sharpness via ‘husk’ (or
‘sheath’) removal and to stretch the body.
Finally, it is an important means of visual
and olfactory communication. Scratching
can be directed to areas that owners
consider appropriate. Steps that should
be taken to prevent destructive scratching
and are alternatives to declawing are
described in the box.
< Consider temporary synthetic nail
caps, which are available as an alternative
to onychectomy (or surgical declawing).
These caps are glued over the nails to
help prevent human injury or damage to
property. Nail caps usually need to be
reapplied every 4–6 weeks.7
< Consider using synthetic facial
pheromone sprays and/or diffusers to help
relieve anxiety or stress.8 Application of
synthetic feline interdigital semiochemical
(FIS) on the desired scratcher has been
shown to induce scratching behavior on an
appropriate target.2 At the time of publication,
FIS is available only in Europe; Feliway
(Ceva) can be used instead in countries
such as the US where FIS is not available.
In addition, deterrent materials (eg, double-
sided sticky tape, foil, plastic) may be
placed on the undesired scratching object.
< Provide appropriate feline
environmental enrichment, which must
be implemented for successful behavioral
modification.9 Repetitive or increases in
scratching behavior of indoor cats may
be related to anxiety, stress, attention
seeking, or lack of perceived security
in their environment.2,5 Anxiety can be
exacerbated by owner punishment, thus
driving the cat to increase scratching
behavior in the same or other locations.5
stance, behavioral problems11 and
chronic neuropathic pain. Fewer than
half of veterinary schools in the USA
include a mandatory lecture or
laboratory to teach this surgery.
Lack of formal training in the procedure
could lead to inferior surgical
technique, thereby increasing
the likelihood of both long- and
short-term complications.10
JFMS CLINICAL PRACTICE 829
829_834_Feline Focus.qxp_FAB 10/08/2015 14:48 Page 830
FELINE FOCUS
Regardless of the method used,
onychectomy causes a significant level
of pain. Patients may experience both
adaptive and maladaptive pain. In addition
to inflammatory pain, the cat may develop
long-term neuropathic or central pain
if its pain is inadequately managed during
the perioperative and healing periods.
In human medicine, the reasons for
phalanx amputation include ‘tumors,
malformations that affect function,
infection, severe post-traumatic vascular
damage or gangrene. Removal of the nail
is done for ingrown toenail or paronychia’
(A Hugo, 2014, personal communication).
Similar medical conditions in a cat might
indicate the need for a specific phalanx
to be removed. This would not support
the amputation of normal digits.10,12
While it has been suggested that
onychectomy is acceptable to prevent
spread of zoonotic disease(s) to immune-
compromised people,10 current research
demonstrates the greater value of proper
hygiene and parasite control in the
prevention of most common zoonoses. In
households where cats come into contact
with immune-compromised individuals,
extensive education about zoonotic
disease potential should be discussed
and documented in the medical record.
Of note, the Centers for Disease Control
and Prevention does not advise declawing
cats owned by HIV-infected persons;
rather, these individuals ‘should avoid
rough play with cats and situations in
which scratches are likely.’13
Because property destruction and
human injury occur less commonly from
the claws on the rear feet, four-paw
declaws are not recommended.
There is no current peer-reviewed data
definitively proving that cats with destructive
behavior are more likely to be euthanized,
abandoned or relinquished. The decision
of whether or not to declaw should not be
impacted by these considerations.
If surgical onychectomy is performed,
the appropriate use of safe and effective
anesthetic agents and perioperative
analgesic medications is imperative.
The AAFP believes that a multimodal
pain management strategy of sufficient
dose (potency) and duration is required
for feline onychectomy. Such a protocol
will lead to reduced patient stress, less
pain, and reduced patient morbidity and
mortality.14,15 Because one of their primary
Submitted by:
Nancy Suska DVM, Gerry Beekman DVM, Paula Monroe DVM,
Carlye Rose DVM, DABVP (Feline; Canine & Feline), CVA
830 JFMS CLINICAL PRACTICE
means of defense has been removed,
declawed cats should be housed
indoors and properly supervised
for their protection when outside.
The AAFP reviews scientific data
and supports controlled scientific
studies that provide insight into all
aspects of feline medicine. The AAFP
recognizes that feline onychectomy is
an ethically controversial procedure.
It has been considered for prohibition
in some US states and cities and Canadian
provinces. It is currently prohibited in
the European Union (including the United
Kingdom),16 Australia, Brazil, Israel
and some other countries, as well as
several cities in California.
References
1 Canadian Veterinary Medical Association.
Scratching behaviour is normal in cats.
www.canadianveterinarians.net/documents/
scratching-behaviour-is-normal-in-cats (2012,
accessed June 9, 2015).
2 Cozzi A, Lecuelle CL, Monneret P, et al.
Induction of scratching behaviour in cats:
efficacy of synthetic feline interdigital
semiochemical. J Feline Med Surg 2013; 15:
872–878.
3 Moesta A. Feline scratching of furniture:
impact, owner attempts to prevent it and
attitudes towards declawing – a survey of
cat owners and veterinarians. MSc thesis,
Graduate Faculty, The University of Georgia,
USA, 2012.
4 American Veterinary Medical Association.
Declawing of domestic cats. www.avma.org/
KB/Policies/Pages/Declawing-of-Domestic-
Cats.aspx (accessed June 9, 2015).
5 Mengoli M, Mariti C, Cozzi A, et al.
Scratching behaviour and its features:
a questionnaire-based study in an Italian
sample of domestic cats. J Feline Med Surg
2013; 15: 886–892.
6 Rodan I, Simpson W, Monroe-Aldridge P, et al;
American Association of Feline Practitioners.
Positive reinforcement of cats.
www.catvets.com/guidelines/position-
statements/positive-reinforcement (2012,
accessed June 9, 2015).
7 Soft Paws Brochure, Soft Paws, Inc.
Lafayette, LA, USA, www.softpaws.com.
8 Feliway Brochure, Ceva Animal Health, LLC,
8735 Rosehill Road, Suite 300 Lenexa,
KS 66215, USA, www.feliway.com.
9 Ellis SL, Rodan I, Carney HC, et al. AAFP and
ISFM feline environmental needs guidelines.
J Feline Med Surg 2013; 15: 219–230.
This Position Statement is an update on the AAFP’s earlier
Position Statement on declawing, dated November 2007.
The photograph on page 829 is ©iStockphoto.com/w-ings
From
time to time the
AAFP will respond to
emerging new knowledge or
issues that are of concern to
veterinary professionals caring
for cats. Our position statements,
which represent the views of the
association, are available at:
www.catvets.com/guidelines/
position-statements
10 Lockhart LE, Motsinger-Reif AA, Simpson WM,
et al. Prevalence of onychectomy in cats
presented for veterinary care near Raleigh,
NC and educational attitudes toward the
procedure. Vet Anaesth Analg 2014; 41: 48–53.
11 Curcio K, Bidwell LA, Bohart GV, et al.
Evaluation of signs of postoperative
pain and complications after forelimb
onychectomy in cats receiving
buprenorphine alone or with bupivacaine
administered as a four-point regional nerve
block. J Am Vet Med Assoc 2006; 228: 65–68.
12 American Veterinary Medical Association.
Welfare implications of declawing of
domestic cats. Literature review. April 9,
2009. www.avma.org/KB/Resources/Literature
Reviews/Pages/Welfare-Implications-of-
Declawing-of-Domestic-Cats-Backgrounder.
aspx (2009, accessed June 9, 2015).
13 Panel on Opportunistic Infections in HIV-
Infected Adults and Adolescents. Guidelines
for the prevention and treatment of
opportunistic infections in HIV-infected
adults and adolescents: recommendations
from the Centers for Disease Control and
Prevention, the National Institutes of Health,
and the HIV Medicine Association of the
Infectious Diseases Society of America,
pp J1-J3, aidsinfo.nih.gov/contentfiles/
lvguidelines/adult_oi.pdf (2013, accessed
June 9, 2015).
14 Hellyer P, Rodan I, Brunt J, et al; American
Animal Hospital Association; American
Association of Feline Practitioners;
AAHA/AAFP Pain Management Guidelines
Task Force Members. AAHA/AAFP Pain
Management Guidelines for Dogs and Cats.
J Am Anim Hosp Assoc 2007; 43: 235–248.
15 Epstein ME, Rodan I, Griffenhagen G, et al.
2015 AAHA/AAFP Pain Management
Guidelines for Dogs and Cats. J Feline Med
Surg 2015; 3: 251–272.
16 Federation of Veterinarians of Europe. Surgery
for cosmetic and other non-curative purposes.
European Convention for the Protection of Pet
Animals. www.fve.org/uploads/publications/
docs/fve_00_066_cosmetic_surgery.pdf
(2001, accessed June 9, 2015).
AAFP-CFP JFMSAd_Sept2015issue:Layout 1 8/6/15 10:07 AM Page 1

Make a difference in feline medicine.

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practices with the tools, resources, and
information to improve the treatment,
handling, and overall healthcare of cats.
The CFP program also focuses on reducing
the stress of the veterinary visit for
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829_834_Feline Focus.qxp_FAB 10/08/2015 14:52 Page 832

FELINE FOCUS

2015 ISFM Congress heads to Porto

Nearly 500 attendees from 40 countries gathered in Porto, Portugal,
for the 14th annual ISFM European Congress. The themes for this
year’s event were dermatology and haematology. A pre-congress day
dedicated to non-surgical feline fertility control, held in association with
the ACC&D, was the forerunner to this current Special Issue of JFMS.

Speakers and science

ISFM was privileged to have four accomplished
speakers delivering a programme of lectures covering
feline dermatology and haematology. Karen Moriello
(right), joined by Aiden Foster (far right), together covered
dermatological topics ranging from cost-effective
diagnostics for dermatology cases, to the good, the
bad and the ugly of flea control in the 21st century.
Barbara Kohn (below left) and Harold Tvedten (below
right) delivered the haematology sessions and addressed
topics such as the causes, investigation and management
of anaemia and how to count platelets in cats

(right) The 2015

ISFM/Hill’s Award
for Outstanding
Contributions to Feline
Medicine was presented
during the Congress to
Karen Moriello, who is
pictured with (from left)
Claire Bessant, Chief
Executive of ISFM,
Andy Sparkes, Veterinary
Director of ISFM, and
Juan Carlos Gimenez,
Veterinary Affairs
Manager of Hill’s
(left) The main scientific
programme was
complemented by several
masterclasses. Reproductive D E L E G AT E F E E D B A C K
<
disorders in the queen and
tom were explored by ‘I always come to ISFM because it is good value, friendly
Stefano Romagnoli (right), and very informative. Good networking opportunities and
while masterclasses in usually held in interesting places, which is an added bonus.’
haematology and cytology (UK delegate)
and in dermatophytosis were < ‘I loved every single lecture and the speakers made it really
led by Barbara Kohn and easy to keep focused.’ (Portuguese delegate)
<
Harold Tvedten, and by
Karen Moriello, respectively ‘Very interesting, current issues and very useful in practice.’
(Italian delegate)
< ‘A friendly, social, happy way to indulge in a few days of
cutting-edge CPD in a beautiful European city.’ (UK delegate)

This year’s poster session comprised

a display of 24 posters. Some of the
presenters are pictured above – from
left, Patricia Pimenta (Portugal), Melanie
Dobromylskyj (UK), Thomas Grammel
(Germany), Fernando Elias (Chile),
Loreto Muñoz (Chile), Martina Načeradská
(Czech Republic) and Roberta Duarte Among the delegates were many returning friends of ISFM Congress,
(Brazil). Abstracts of the posters appear as well as over 100 attending a European Congress for the first time.
on pages 816–827 of this issue of JFMS Newly represented countries were Malta, Chile and Turkey

832 JFMS CLINICAL PRACTICE

829_834_Feline Focus.qxp_FAB 10/08/2015 14:56 Page 833

FELINE FOCUS

Feline fertility and population control Congress

partners’ CPD
Integrated into the Congress
programme were symposia
sponsored by (anti-clockwise from
left): Merial (parasitology); Ceva
(compliance in cats); Hill’s (obesity
and lower urinary tract disease);
Boehringer Ingelheim (pain
assessment and CKD); and Bayer
(infectious disease and use of
antimicrobials). A lecture sponsored
The pre-congress day, held in collaboration with the Alliance for Contraception in Cats & by Agria discussed morbidity and
Dogs (ACC&D), provided the opportunity to learn about non-surgical fertility control: the mortality in pet cats (top right)
rationale, products available and under development, regulatory considerations, and
what lies ahead. The event was introduced by Joyce Briggs (top left) and facilitated by
Amy Fischer (bottom left). The day incorporated Q&A discussions, with panels made up
of the sessions’ presenters: (from left) Christelle Fontaine, Julie Levy, Michelle
Kutzler, Stefano Romagnoli, John Boone, Linda Rhodes, Valerie Benka and Jane Murray.
The recorded presentations can be freely accessed via icatcare.org/vets/videos

Social and chat

As ever, this year’s ISFM Congress was a highly sociable
event, with a variety of opportunities to network with other
delegates, speakers and exhibitors. Evening receptions
provided a relaxed environment for attendees to mingle
in the luxury setting of the Sheraton’s grounds. This year’s
evening event was held at Taylor’s – one of Porto’s oldest
port houses. Situated in the heart of the historic Vila Nova
de Gala, delegates were treated to typical Portuguese
cuisine, a variety of different ports and a guided
tour of the cellars

During lunches and coffee

breaks delegates were able
to browse the stands in the
Commercial Exhibition (below)

The newly launched open access

journal, the Journal of Feline Medicine
and Surgery Open Reports, was on
display alongside its sister title, the
Journal of Feline Medicine and Surgery

Representatives of the
Japanese Society of Feline
A collection of
Medicine add their pins to
photographs from the
the Congress delegates’
Congress can be
map (above). While the
viewed on ISFM’s
majority of delegates hailed
Facebook page:
from Europe, the final map
facebook.com/isfmcats
(right) illustrates the truly
international nature of
this ‘European’ congress

Where next?
Courtesy of Renata Apanaviciene The 2016 ISFM European Congress will
be held in Malta from 29 June to 3 July
and will feature the themes of feline
gastrointestinal disease and feline
orthopaedics. Already over 120 delegates
Members of the ISFM Academy of Feline Practitioners have registered their interest for
(those who have successfully achieved the MANZCVS this event. Full details from
qualification) and the Congress speakers met for a www.icatcare.org/isfm-congress
photograph before a meal kindly supported by Agria

JFMS CLINICAL
JFMS CLINICAL PRACTICE
PRACTICE 833
829_834_Feline Focus.qxp_FAB 10/08/2015 14:57 Page 834
FELINE FOCUS
AAFP
New resource: communicating benefits
of routine exams in 30 seconds
Good communication allows us to
practice better medicine by bonding
clients more closely to our practice
and encouraging their adherence to
our recommendations.
JSFM
Numbers soar for second JSFM
annual symposium
The Japanese Society of Feline
Medicine, JSFM, has held its second
annual symposium. The two main
topics were entitled ‘understand
diseases related to emesis’ and
‘how to handle cats without stress’.
Award
ABCD/Merial Young Scientist Awards
The European Advisory Board on
Cat Diseases (ABCD)/Merial Young
Scientist Awards 2015 were presented
during the ISFM European Congress
in Porto in July. The recipients were
Emily Porter (second left) and Paweł
Bęczowski (centre). They are pictured
with Dr Jean-Christophe Thibault of
Merial (left), Karin Möstl, chairwoman
of ABCD (second right), and Claire
Bessant, Chief Executive of iCatCare.
Abstracts of the research that earned
834 JFMS CLINICAL PRACTICE
Have your clients ever asked,
‘Why do I need to bring my cat in
every year?!’ The AAFP has developed
short elevator scripts that you can
use to answer this common question
and convey the importance
of routine feline check-ups.
Watch this ‘elevator pitch’ video
now and start perfecting your
own preventive care pitch:
catvets.com/education/online/videos
Sponsored by Royal Canin, the
symposium took place on 28 June
2015 and was attended by 440
delegates – an impressive increase
on the 250 delegates who attended
last year.
From left: delegates were provided with
the new Cat Friendly Clinic criteria translated
into Japanese; attendees and lecturers enjoyed
a professional photoshoot complete with feline
props; a symposium session in progress
them their awards appear on pages
819 and 824 of this issue of JFMS.
More professionals
embrace the CFP program
The AAFP’s Cat Friendly Practice (CFP)
program has continued to flourish.
As of July 17 this year, 897 practices
have been designated as CFPs.
The AAFP has also recently
launched a new CFP program website
that is more user-friendly. It can be
found in the AAFP Member Center
(catvets.com/mbrdash). Log in
today to start your application,
continue your progress, or view
the new Marketing Toolkit.
iCatCare
Photography competition
winner
This photograph of a feral cat, nicknamed
‘Shy’ during a trap–neuter–return programme,
has been selected as the winning entry
in the 2015 International Cat Care (iCatCare)
photography competition. The photographer
is Hon Wa Yip from Hong Kong. This is the
third photography competition that iCatCare,
in conjunction with Your Cat and Digital
Photographer magazines, has run and this
year the winner was selected from nearly
2000 entries submitted from 40 countries
Keeping Cats Safe
campaign
iCatCare has teamed up
with the Veterinary Poisons
Information Service (VPIS)
and Agria Pet Insurance to
launch a new ‘Keeping Cats
Safe’ campaign. To date, the
campaign has highlighted
the dangers of disinfectants
and the ingestion of
foreign bodies and will
focus on a range of other
dangers on a month-by-
month basis. For each
topic there is advice for
owners covering where the risks are, the
signs of poisoning/injury, what to do, and
how the risks can be minimised; for veterinary
professionals there is in-depth advice on
clinical signs, treatment and prognosis.
There is also the opportunity to share
stories and experiences via the campaign
website, which can be accessed at:
icatcare.org/keeping-cats-safe
 2015 American Association of
Feline Practitioners
presents

3rd World Feline Veterinary Conference

WEIGHT + FLUTD
Distinguished Speakers
Livia Benigni, DVM, MRCVS, CertVDI, PGCertAP, DECVDI
Elizabeth Colleran, DVM, MS, DABVP (Feline)
Let’s address Sue Ettinger, DVM, DACVIM (Oncology)
William Folger, DVM, MS, DABVP (Feline)

them together
S. Dru Forrester, DVM, MS, DACVIM
Lorrie Gaschen, PhD, DVM, Dr.med.vet, DECVDI
Erika Krick, VMD, DACVIM (Oncology)
Michael Lappin, DVM, PhD, DACVIM
Zoe Lenard, BVSc (Hons) FANZCVS (Radiology)
Susan Little, DVM, DABVP (Feline)
CLINICALLY PROVEN NUTRITION: Erica Mattox, CVT, VTS (ECC)
Brook Niemiec, DVM, DAVDC
Greg Ogilvie, DVM, DACVIM (IntMed, Oncology)
REDUCES BODY WEIGHT1 Michael Petty, DVM, CVPP, CVA, CCRT, DAAPM
Jane Robertson, DVM, DACVIM
Ilona Rodan, DVM, DABVP (Feline)

DISSOLVES STRUVITE STONES

Margie Scherk, DVM, DABVP (Feline)
Annette Smith, DVM, MS, DACVIM (IntMed, Oncology)
IN AS LITTLE AS 7 DAYS2
Conference Features
■ Feline-specific material presented by expert
speakers.
■ Sessions for veterinarians who see cats at all
levels of their career.
■ Two Veterinary Tracks and one
Para-professional Track.
■ Labs – two Hands-on Dental Radiography Labs
will be offered. Attendance is limited.
■ Lunch & Learns – additional CE is offered through
lunch with speakers. Attendance is limited.
■ Networking and social activities with colleagues.
■ Meals and coffee breaks in our interactive
exhibit hall.
NEW PRESCRIPTION DIET™
Metabolic+Urinary
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Together we can help your patients at risk.
Diagnostic Imaging and Oncology
Conference Education
Pre-conference – topics such as End of Life Issues, Emerging
Infectious Disease, and Protein in Nutrition.
Kick-off Sessions – topics such as Pain Management Updates
and Compelling & Clinically Relevant JFMS Updates.
Diagnostic Imaging – topics such as Thoracic Radiographs/
Ultrasound; Interpretation of the Feline Abdomen; Ultrasound
of GI, Hepatic and Pancreatic Diseases; Imaging: Urinary Tract
Disease; Do Cats Have 9 Lives?- Feline Trauma Imaging;
Radiographic Pulmonary Patterns & Heart Disease; Choosing
& Using Equipment; MRI & CT; and Dental Radiography.
Oncology – topics such as Managing Feline Cancer, Oral Tumors,
Lymphoma, Neoplastic Effusions, Improving Quality of Life,
Chemo Drugs, Less Common Cancers, Diagnostic Secrets,
Soft Tissue Sarcomas, Kitty Emergencies, Lumps & Bumps
Awareness, and Polyunsaturated Fatty Acids.

For more information, talk to your Hill’s Territory Manager.

1
Data on file. Hill’s Pet Nutrition, Inc.
www.catvets.com/education October 1- 4, 2015
Lulich JP, Kruger JM, MacLeay JM, et al. Efficacy of two commercially available, low-magnesium,
Manchester Grand Hyatt
2

urine acidifying dry foods for the dissolution of struvite uroliths in cats. J Am Vet Med Assoc.
2013;243:1147-1153. Average 27 days in vivo study in urolith forming cats. Partnering with the
FLUTD stands for Feline Lower Urinary Tract Disease
™Trademarks owned by Hill’s Pet Nutrition, Inc. ©2015 HillsVet.co.uk / HillsVet.ie
International Society of Feline Medicine San Diego, California USA
 Vol 17  •  Issue 9  •  September 2015
NEW! Volume 17  •  Issue 9  •  September 2015  • ISSN 1098-612x

Journal of Feline

Journal of Feline Medicine and Surgery

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