Review article

Post Reproductive Health

2015, Vol. 21(1) 16–23
! The Author(s) 2015
Minimising menopausal side effects whilst Reprints and permissions:
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treating endometriosis and fibroids DOI: 10.1177/2053369114568440
prh.sagepub.com

Paul D Simpson1, James S McLaren2, Janice Rymer3 and

Edward P Morris1

Abstract
Medical management of endometriosis and fibroids involves manipulation of the hypothalamic–pituitary–gonadal axis to
alter the balance of sex hormones thereby inhibiting disease progression and ameliorate symptoms. Unfortunately,
resultant menopausal symptoms sometimes limit the tolerability and duration of such treatment. The use of gonado-
trophin-releasing hormone agonists to treat these diseases can result in short-term hypoestrogenic and vasomotor side
effects as well as long-term impacts on bone health and cardiovascular risk. The routine use of add-back hormone
replacement has reduced these risks and increased patient compliance, making this group of drugs more useful as a
medium-term treatment option. The estrogen threshold hypothesis highlights the concept of a ‘therapeutic window’ in
which bone loss is minimal but the primary disease is not aggravated. It explains why add-back therapy is appropriate for
such patients and helps to explain the basis behind new developments in the treatment of hormonally responsive
gynaecological conditions such as gonadotrophin-releasing hormone antagonists and progesterone receptor modulators.

Keywords
Add-back, endometriosis, fibroids, GnRHantagonists, SPRMs

Introduction
The management of endometriosis and leiomyomata is
a balance between conservative treatment, medical
therapies and timely radiological or surgical interven-
tion. These two conditions affect a large number of
women and result in a significant number of visits to
primary care. The basis of most medical interventions is
hormonal manipulation but unfortunately menopausal
side effects and concerns about the long-term impact of
treatment limit their use. This article explores current
UK practice and introduces some of the newer treat-
ments that are in development.
Defining the problem: Symptom relief
versus menopausal side effects
The balance between symptom relief and side effects is
challenging in the medical management of both endo-
metriosis and fibroids, where iatrogenic menopausal
symptoms are experienced and sometimes tolerated by
patients in the hope of minimising their symptoms.
25% of women presenting with gynaecological symp-
toms in UK and USA, with a peak incidence between
30 and 45 years of age.3 It is an estrogen-dependent and
estrogen-driven disease and so hormonal manipulation
and suppression of estrogen production form the basis
of the majority of medical treatment.
Initially, hormonal manipulation is trialled with a
simple contraceptive agent such as the combined oral
contraceptive pill (COCP) or a progestogen only pill,
which inhibits ovulation. Although concerns have been
expressed that estrogen within the COCP could actually
activate the disease by supressing progesterone produc-
tion or opposing its action, this has not been supported
by studies or indeed in clinical practice. This first-line
management can be initiated empirically without a con-
firmed diagnosis, which minimises any delay between
1
Department of Obstetrics and Gynaecology, Norfolk and Norwich
University Hospital, UK
2
Department of Obstetrics and Gynaecology, Croydon University
Hospital, UK
3
Department of Gynaecology, King’s College School of Medicine, UK

Endometriosis Corresponding author:

Paul D Simpson, Norfolk and Norwich University Hospital, Colney Lane,
Endometriosis is a common disease, affecting 5–10% of Norwich, Norfolk NR4 7UY, UK.
women of reproductive age.1,2 It is diagnosed in up to Email: paul.simpson@nnuh.nhs.uk
Simpson et al.
treatment and diagnosis and helps to avoid the cost and
potential morbidity of invasive surgical investigation. If
a patient fails to respond or their symptoms progress
after a period of effective symptom control, laparo-
scopic confirmation is required before pursuing
second-line medical therapy. This approach is sup-
ported by the European Society of Human
Reproduction and Embryology (ESHRE).4
Second-line medical therapy usually consists of con-
tinuous progestogen provision either as the levonorges-
trel intra-uterine system (LNG-IUS (MirenaÕ )),
continuous oral norethisterone (NET), an etonogestrel
implant or depot injections of medroxyprogesterone
acetate (MPA).5 If these are ineffective, treatment
may progress to complete suppression of the hypothal-
amic–pituitary–ovary (HPO) axis with a GnRH agon-
ist.6 The ESHRE guidelines recommend the use of
‘hormonal contraceptives, progestogens, anti-progesto-
gens or GnRH agonists’ as they reduce endometriosis
pain.4 There is no specific guidance as to the sequence
in which they should be trialled or the duration of treat-
ment, and no clear evidence exists to demonstrate
which is more effective. The authors find that this step-
wise three-tiered approach to medical therapy is useful
but remain flexible when planning treatment and take
into account patient preference, side effect profiles and
cost.
Such hormonal therapies are not suitable for every
patient and often a combination of ineffective symptom
control, progressive symptoms, intolerance of side
effects or contraindications limit their use. It is quite
common for patients to find that they have exhausted
all medical options and are left considering a surgical
solution. However, it should also be noted that there is
a significant post-operative recurrence rate – 10–55%
within 12 months.7 The risk of recurrence can be ame-
liorated by the use of simple medical treatment such as
the progestogen-only pill in the immediate post-opera-
tive period, which can be continued longer-term,
dependent on the patient’s fertility wishes. In situations
of recurrence, any repeat surgery is likely to be less
effective at managing pain and comes with greater
risk of morbidity and so with diminishing returns
from repeated surgery a greater reliance on medical
treatment may be needed.8 Consequently, there is a
clear need for more research into alternative medical
treatments, in particular ones in which the side effect
profile is more tolerable, so that longer term medical
treatment can be considered.
Fibroids
Uterine leiomyomas are common benign estrogen and
progesterone-dependent smooth muscle tumours. Their
prevalence increases with age with 20–25% of women
17
over 35 years and 70% of women over 50 having
fibroids.9,10 These are largely asymptomatic but 20–
50% of women have symptoms significant enough to
require intervention.11 The use of medical therapy and
interventional radiological procedures such as uterine
artery embolization have reduced the need for surgical
intervention but fibroids remain the leading indication
for hysterectomy in UK.12
The medical management of patients with fibroids
focuses on two key areas – bleeding symptoms and
pressure symptoms. The balance of these two symp-
toms, patient preference and family planning desires,
influences which treatment is most appropriate.
Heavy menstrual bleeding. Those with menorrhagia pre-
dominant symptoms are treated in line with the NICE
guidance on heavy menstrual bleeding.13 This usually
consists of the COCP, the LNG-IUS, depot MPA or
the use of tranexamic acid. A systematic review of pro-
gestogen therapy for uterine fibroids concluded that the
LNG-IUS was the most effective treatment at reducing
menstrual blood loss.14 However, the device can be dif-
ficult to fit and is more likely to be expelled in patients
with an enlarged uterus or leiomyomas greater than
3 cm in size.15
Pressure symptoms. Patients with pressure symptoms
such as lower abdominal aching or dragging and blad-
der dysfunction are more likely to need surgical inter-
vention. Medical treatment to reduce fibroid size
typically involves the use of GnRH agonist and was
first described by Maheux et al.16 The literature con-
sistently reports a 25–50% reduction in uterine volume
following a 3-month course. Unfortunately, this only
lasts for the duration of treatment and uterine size
returns to baseline within 6 months, making this treat-
ment of limited use other than pre-operatively. A sys-
tematic review of pre-operative GnRH agonists found
that they are effective in reducing uterine and fibroid
size and, in addition, correct pre-operative iron defi-
ciency anaemia, reduce intra-operative blood loss,
reduce the need for a mid-line incision and increase
the frequency of vaginal surgery for hysterectomy.17
Gonadotrophin receptor hormone analogues
(‘the on/off switch’)
There is clear evidence that GnRH agonists are effective
for the treatment of both endometriosis and
fibroids.17,18 However, the generation of the hypo-
estrogenic state carries a high-treatment burden. The
initiation of a ‘chemical menopause’ with a GnRHa
can be associated with short-term complications.
First, the agonistic nature of the drug can cause a
flare of symptoms in the first month prior to
18
downregulation of the GnRH receptors within the
hypothalamus and a resultant reduction in follicle sti-
mulating hormone and luteinising hormone. Second,
the sudden reduction in estradiol levels leads to pro-
nounced climacteric symptoms of hot flushes, vaginal
dryness, mood disturbance and decreased libido, which
can impact on compliance.
In addition, there are more long-term impacts on
bone mineral density (BMD) and cardiovascular risk.
The first of these is often the focus of concern. It is why
the duration of treatment is limited and also why the
ESHRE guidelines on the management of endometri-
osis recommend ‘careful consideration to the use of
GnRH agonists in young women and adolescents,
since these women may not have reached maximum
bone density’.4 As such, it is important to make an
assessment of any osteoporosis risk factors (see
Table 1) for all patients, before commencing GnRHa
therapy. A study of GnRHa therapy in endometriosis
demonstrated a reduction of bone density by 5.4% over
12 months and that only 3% was regained over the
subsequent 12 months off treatment.19 This level of
osteopenia means that treatment is often limited to 6
months to ensure that BMD can return to baseline fol-
lowing treatment.20 The duration of treatment can be
extended beyond this if steps are taken to protect
against this bone loss with the use of add-back therapy,
and these will be discussed later.
The increase in cardiovascular risk when women
enter the menopause is well documented.21–23 The
changes in lipid profile and atherosclerotic risk are
known but there is little evidence as to whether unop-
posed GnRHa therapy has a similar effect.24 We do
Table 1. WHO Fracture Risk Assessment Tool (FRAXÕ ).26
Osteoporosis risk factors
Known low BMD (DEXA at spine or hip)
Prior vertebral fracture or fragility fracture
Long-term glucocorticoid treatment
Rheumatoid arthritis
Other secondary causes:
 type 1 diabetes
 osteogenesis imperfecta in adults
 anorexia nervosa
 hyperparathyroidism
 untreated long-standing hyperthyroidism chronic malnutrition
or malabsorption (e.g. coeliac disease and inflammatory bowel
disease) and chronic liver disease
Family history of osteoporosis or hip fracture
Low BMI (less than 18.5 kg/m2)
Alcohol intake >14 U per week
Smoking
Long-term anticonvulsant therapy (phenytoin, phenobarbital and
carbamazepine)
Post Reproductive Health 21(1)
know that vascular endothelial cell function is
decreased in GnRHa-induced hypo-estrogenic states
and that this improves with the addition of add-back
therapy but the long-term impact of this is an area that
requires more research.25
The estrogen threshold hypothesis
The key to management of these two common, hormo-
nally responsive, gynaecological conditions is the estro-
gen threshold hypothesis that was proposed by
Barbieri.27–29 The hypothesis is based on the observa-
tion that different tissues have a different sensitivity to
estrogen, which means that some estrogen-dependent
cells will function normally at low-estrogen concentra-
tions but others will not. An example of this is the dif-
ference between bone metabolism and the growth of
ectopic endometrial cells found in endometriosis.
Endometriotic cells require a high estradiol concentra-
tion for growth whereas even at much lower concentra-
tions of estradiol, there is very little impact on bone
turnover. The difference between the dose-response
curves for these two cell types is represented in
Figure 1 and demonstrates that there is a clear thera-
peutic window (at an estradiol concentration of 30–
45 pg/mL) in which atrophy of endometriotic cells can
be achieved without having a negative impact on bone
health.
The estrogen threshold hypothesis is also supported
by studies and observations of patients with fibroids.
Leiomyomas initially present during the reproductive
years when estradiol levels are at their highest and
then usually regress during the menopause. The initiat-
ing factor for the development of these tumours is
unknown but clearly their growth depends on sex hor-
mones – both estrogen and progesterone.30 Uterine
fibroids have been shown to have significantly increased
concentrations of estrogen and progestogen receptors
compared with normal myometrium, which explains
their preferential growth.31
Alternative strategies
When considering ways to minimise menopausal side
effects whilst treating endometriosis and fibroids, four
clear strategies emerge. These strategies include those
treatment options that might be described as conven-
tional management but also highlight the new drugs,
either recently marketed or in development, which are
showing great promise.
Avoid the hormonal effects from GnRHa
Given that GnRHa therapy can lead to significant
menopausal side effects and clearly has a deleterious
Simpson et al.
Figure 1. Hormone treatment of endometriosis: the estrogen threshold hypothesis with the estradiol therapeutic window shown.
The concentration of estradiol required to cause growth of endometriosis lesions may be greater than the concentration required to
stabilise bone mineral density (Reproduced with permission).28
impact on long-term bone health, we must consider
whether it is an appropriate treatment for our patients.
To achieve this, a risk assessment should be performed,
and the advantages and disadvantages of treatment dis-
cussed with the patient. This process starts with a thor-
ough clinical history to ensure a clear understanding of
the main symptoms is known, the effect on quality of
life is appreciated and the reasons why previous thera-
peutic options have failed is explored.
Clear communication with the patient incorporating
all the alternative treatment options, a concise sum-
mary of pharmacology and the side-effect profiles,
allows the patient to consider which therapy is most
appropriate for them. Patients can easily get dis-
heartened by the ‘trial & error’ nature of hormonal
manipulation, particularly if symptoms are severe and
the trialled medication is completely ineffective or
poorly tolerated.
Although GnRHa therapy for endometriosis can be
very effective for some patients, it should be noted that
the evidence to support its use over other treatments is
not compelling. A randomised trial of GnRHa versus
continuous oral contraception was published by Guzick
et al.32 in 2011, which demonstrated that there was no
difference in the pain scores in the two treatment arms
and noted that continuous oral contraception is easier
to administer, carries a lower cost and has a better side
effect profile.32 In addition, a systematic review by
Brown and Farquhar,33 looking at all the previous
Cochrane reviews on endometriosis, concluded that
there was ‘no consistent evidence of a difference in
effectiveness between oral contraceptives and goserelin’.
It is also important not to pursue medical treatment
indefinitely and in situations where it is clear that sur-
gical management with or without adjuvant medical
therapy is more appropriate. Patients presenting with
large endometriomas, extensive rectovaginal disease
19
with palpable vaginal nodules or >14-week-size fibroid
uterus are unlikely to be served well by medical treat-
ment alone.
Correct the consequences of GnRHa
If GnRHa therapy is to be recommended, particularly
if treatment is to extend beyond 3 months, we must
consider add-back therapy. The aim of such therapy
is to preserve the therapeutic efficacy of the GnRHa
treatment whilst minimising or possibly eliminating
the negative side effects. Reducing the vasomotor side
effects makes the treatment more tolerable and
increases compliance whereas minimising the impact
on bone health or cardiovascular risk may allow more
prolonged GnRHa therapy. The possibility of pro-
longed GnRHa therapy is important for those patients
in whom surgical management has failed or those in
whom symptoms have returned after successful medical
treatment has been completed.
In those patients where GnRHa therapy is required,
we have three important questions to consider: How
long can we safely use GnRHa therapy? What type of
add-back therapy should we recommend, and Does
add-back therapy have an impact on the efficacy of
GnRHa in treating the disease? This subject has been
extensively explored in the literature. A review by
Surrey34 sets out the evidence to support the use of
hormonal add-back therapy. And a review by
McLaren et al.35 describes both hormonal and non-hor-
monal agents primarily aimed at lessening climacteric
symptoms and maintaining BMD (Table 2).
At first glance, the generation of a ‘chemical meno-
pause’ with GnRHa followed by hormone replacement
might seem counterintuitive. However, the hierarchy of
organ response to estradiol and the ‘therapeutic
window’ described by Barbieri28 makes it clear why
20
Table 2. Types of add-back therapy.
Progestogen only
Estrogen only
Progesterone and estrogen
Tibolone
Raloxifene
Bisphosphonates
Calcitonin
Vitamin D
Parathyroid hormone
add-back therapy can be effective. But it does not help
to answer the question as to which mixture of hormone
replacement is the most effective.
Progestogen only. Both MPA and NET alone have been
looked at as a hormone replacement in patients receiv-
ing GnRHa for endometriosis. Cedars et al.36 used
standard dose MPA and found that both vasomotor
symptoms and bone loss were improved compared to
controls but this combination was less effective at con-
trolling endometriosis symptoms. When Makarainen
et al.37 used a much higher dose of MPA, the endomet-
riosis was well treated but patients experienced signifi-
cant progestogenic side effects, e.g. fluid retention. A
study using NET by Surrey et al.38 showed improved
vasomotor symptoms and good control of endometri-
osis symptoms but reversible bone mineral loss.
Estrogen only. There is very little data to support the use
of estrogen only add-back therapy. Despite the fact that
the estrogen threshold hypothesis would indicate that
this approach to add-back therapy would be successful,
there has been a reluctance to pursue this.39 This may
be due to concerns about the possible stimulation of
endometriotic or fibroid growth. More recently, a
study by Kim et al.40 showed that a low-dose estro-
gen-only regimen was efficacious and tolerable as add-
back therapy during post-operative GnRHa treatment
for endometriosis. It is possible, however, that with
some of the more recent ultra-low dose estrogen, only
preparations combined with endometrial surveillance a
suitable estrogen only add-back regime could be
devised, though this requires further research.
Estrogen and progestogen combined. The use of conjugated
equine estrogens with MPA has been shown not to
affect the efficacy of GnRHa therapy whilst also redu-
cing the impact on BMD.41 The combination of estra-
diol and NET has also been shown to be efficacious and
to minimise vasomotor and bone loss side effects.42
Since these two studies, further work have again high-
lighted the benefits of estradiol or conjugated equine
estrogen in combination with NET.43,44 Currently,
Post Reproductive Health 21(1)
this regimen of hormone replacement is the most popu-
lar and well-studied.
Tibolone. This is a synthetic compound with estrogenic,
progestogenic and androgenic properties. Its use as
add-back therapy in UK is widespread but it is not
available in the USA. It has been evaluated in a
Cochrane review of two trials involving patients using
hormone replacement following a permanent surgical
menopause as a treatment for endometriosis. This
review showed that Tibolone performed similarly to
estrogen þ progestogen regimens.39
Currently, GnRHa use in patients with fibroids is
predominantly as a pre-operative treatment rather
than a long-term solution.45 However, for those
patients in which surgery is contra-indicated, longer-
term GnRHa treatment and the need for add-back
therapy must be considered. The majority of data
on add-back therapy in this situation support the use
of Tibolone, which decrease vasomotor symptoms
and bone loss without affecting the uterine volume
size.46
Prolonged treatment and therefore the need to con-
sider add-back therapy is mainly an issue when con-
sidering patients with endometriosis. The ESHRE
guidelines on the treatment of endometriosis are quite
clear on add-back therapy, recommending that clin-
icians prescribe add-back therapy to coincide with the
start of GnRH agonist therapy in order to prevent bone
loss and hypoestrogenic symptoms.4 A Cochrane
review, first published in 2003 and updated in 2010,
exploring the effect of GnRHa therapy on BMD,
included 15 prospective randomised controlled trials.
It concluded that estrogen and progestogen replace-
ment is protective for BMD whilst on treatment and
for 12 months afterwards.47 Unfortunately, despite the
wealth of data reviewed, no firm conclusions or guid-
ance can be offered as to the duration of GnRHa
treatment.
Prevent hypoestrogenic effects from treatment
An alternative to this ‘block & replace’ strategy is to use
GnRH antagonists, which act to block the action of
GnRH in a more controlled and dose-dependent
manner. This group of drugs has been likened to
‘volume control’ for the HPO axis as compared to the
‘on/off switch’ of GnRH agonists. These drugs are cur-
rently being explored and have shown some positive
results, raising the possibility that they may offer the
solution to long-term medical treatment for endometri-
osis and fibroids.
These antagonist compounds were first explored by
Altintas et al.48 The study involved a rat model of endo-
metriosis where peritoneal implants of endometrial
Simpson et al.
tissue were induced surgically. These rats were then
treated with either a GnRH antagonist, Cetrorelix or
the GnRHa, Leuprolide. At the end of 8 weeks of treat-
ment, it was noted that the rats treated with Cetrorelix
had a reduced volume of endometrial implants with
reduced glandular and stromal tissue. This was com-
parable to the effect of the Leuprolide, indicating that
Cetrorelix was as effective at supressing the peritoneal
implants.
The first-in-human trial was a double-blind, placebo-
controlled study of Elagolix, performed in 2009.49 The
administration of Elagolix was demonstrated to supress
the reproductive endocrine axis in healthy premenopau-
sal women, and the authors noted that this effect might
allow this drug to be used in the treatment of ‘repro-
ductive hormone-dependent disease states’. This was
followed up by Diamond et al.50 who conducted a
Phase II trial looking at the treatment of endometriosis
pain, which was published in March 2014. Elagolix
caused a significant reduction in mean dysmenorrhoea
scores at 8 and 12 weeks of treatment but non-men-
strual, and monthly mean pain scores were not signifi-
cantly reduced. However, the safety profile was
encouraging with only minimal BMD changes noted.
Minimise hormonal changes
The final strategy for minimising menopausal symp-
toms is to minimise the impact any treatment has on
estradiol concentrations by using selective progesterone
receptor modulators (SPRMs). SPRMs have both
agonistic and antagonistic properties depending on
the tissues being targeted. The balance and strength
of these properties is both dose and compound-specific
so they have a wide but ultimately unpredictable
response in vivo. The pharmacology and mechanism
of action of these drugs has been thoroughly reviewed,
as have the possible clinical applications: contracep-
tion, leiomyomata, dysfunctional uterine bleeding and
endometriosis.51,52
Selective progesterone receptor modulators have
been developed since the discovery of Mifepristone in
the 1970s. Mifepristone has largely antagonistic proper-
ties within the endometrium and myometrium and is
used for the termination of pregnancy. It has previously
been evaluated for the treatment of endometriosis and
fibroids. A Cochrane Systematic review of three trials
of its use in fibroids did demonstrate a positive effect on
heavy bleeding and fibroid-related quality of life but it
was unable to demonstrate an effect on fibroid
volume.53
Currently, there is only one SPRM licensed for use
in UK – ulipristal acetate (UPA) (EsmyaÕ ). UPA has
an anti-proliferative, anti-fibrotic and pro-apoptotic
effect on leiomyoma cells and is consequently used for
21
the pre-operative treatment of moderate-to-severe
fibroid-related symptoms. In the PEARL I study, a
clinically significant reduction in fibroid size was
achieved with ulipristal acetate compared to placebo
(41% vs 18%, p ¼ 0.01).54 It is marketed as an alterna-
tive to GnRHa for reducing fibroid size prior to myo-
mectomy or hysterectomy and it compares favourably.
The PEARL II study demonstrated a median time to
amenorrhoea of 7 days compared to the 21 days taken
with leuprolide acetate.55 This study also shows two
distinct benefits over GnRHa therapy – the effect of
Ulipristal Acetate is sustained for 6 months after com-
pleting the course of treatment and patients experience
fewer hot flushes, due to higher estradiol concentra-
tions, when compared to leuprolide acetate (p < 0.001).
Unfortunately, ulipristal acetate has a class-specific
effect on the endometrium, which has raised concerns
about the safety of these drugs in more prolonged use.
Progesterone receptor modulator-associated endomet-
rial changes are non-physiological epithelial architec-
tural distortion of the endometrium with cystically
dilated glands. These changes have been found in a
third of patients treated with UPA compared to less
than 1% of patients receiving GnRHa. Initially, these
changes were thought to be simple hyperplasia, raising
concerns about the safety of UPA but they have now
been recognised a unique histological response specific
to SPRMs.56 These changes resolve over 6 months and
are not thought to have any clinical significance.
Whilst UPA is only currently licenced for use in pre-
operative management of fibroids, some work has been
done suggesting that it may be effective in treating
endometriosis. Huniadi et al.57 have shown that UPA
contributed to the regression and atrophy of endome-
triotic lesions in rats. The immunohistochemical
expression found within the endometrial implants fol-
lowing UPA treatment would suggest that it has
pro-apoptotic and anti-proliferative actions within
endometrial tissue. This is an exciting prospect as it
opens the possibility of SPRMs becoming an effective
long-term treatment for endometriosis with minimal
menopausal side effects.
Conclusion
The increasing prevalence of these two conditions and
the impact they have on quality of life make holistic
management an important part of modern gynaecol-
ogy. Surgical management of endometriosis yields
diminishing results over time and has the potential to
negatively impact on a patient’s fertility plans.
Similarly, major surgery is becoming less attractive to
patients with fibroids who are increasingly considering
minimally invasive approaches rather than hysterec-
tomy. It is within this context that we must consider
22
all the medical management options, both currently
licenced products and those drugs in development.
The estrogen threshold hypothesis and the possibil-
ity of a ‘therapeutic window’ in which side effects and
bone loss are minimal but estrogenic drive to endomet-
riosis and fibroid cell growth is supressed is an import-
ant concept that has generated a lot of research interest.
Gonadotrophin receptor hormone antagonists have
shown promising results treating both endometriosis
and fibroids and may form part of medical manage-
ment in the future. In addition, the use of SPRMs in
the pre-operative management of fibroids has already
been very successful. The exploration of other indica-
tions for SPRMs in fibroid management and the possi-
bility of use in endometriosis is an exciting prospect.
Funding
This research received no specific grant from any funding
agency in the public, commercial, or not-for-profit sectors.
Conflict of interest
Mr Morris has the following declarations: (a) Owner of
patent for ‘‘Suresample’’ endometrial sampler (Marketed in
USA); (b) Received Speakers fees and honoraria from
Gedeon Richter, Abbott, Besins, Novo Nordisk, Cook
Medical and Lina Medical. The remaining authors declare
that there is no conflict of interest.
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