EDITION 1.

0
 Disclaimer
The information contained in this publication is for educational purposes only and is in no way a substitute
for the advice of a qualified health care provider. Appropriate medical therapy and the use of pharmaceutical
compounds like testosterone should be tailored for the individual, as no two individuals are alike. The author
does not recommend self-medicating with any compound, as you should consult with a qualified medical
doctor who can determine your situation. Any use of the information presented in this publication for
personal medical therapy is done strictly at your own risk, and no responsibility is implied or intended on the
part of the author, contributors, or the publisher.
ISBN- 978-0-9837739-3-1
Medicine, Health, Nutrition, Chemistry, Endocrinology
Library of Congress Control Number: 2010933334
Milestones Publishing
Copyright ©2020 Nelson Vergel. All rights reserved. No part of this publication may be reproduced, stored in
a retrieval system, or transmitted, in any form or by any means, electronic, photocopying, recording, or
otherwise, without the prior written permission of Nelson Vergel via the contact form on ExcelMale.com.
Nelson Vergel’s Previous Books.

2
 ABOUT THE AUTHOR
Nelson Vergel holds a chemical engineering degree and an MBA. After a HIV

diagnosis over 33 years ago, he explored therapies to reverse wasting syndrome to

save his life and those of his peers, leading him to co-author ―Built to Survive: The

Clinical Use of Anabolic Steroids for HIV+ Men and Women‖,‖ a book that became

the leading wasting treatment guide in the HIV field. He has been a member of

several U.S. National Institute of Health (NIH) and pharmaceutical advisory groups,

as well as FDA review panels. Nelson also founded the non-profit organizations

Body Positive Wellness Clinic and Program for Wellness Restoration in Houston,

providing health education and wellness services to HIV+ people. To expand help to

the general population using his hormone knowledge from HIV, he wrote;
―Testosterone: A Man’s Guide‖ and created ExcelMale.com and DiscountedLabs.com to provide men’s health education and

access to affordable blood testing. His latest project aims at improving access to testosterone and hormone replacement

treatments and care for men and women around the world by providing the largest hormone physician directory in the world

(HormoneClinicNetwork.com)

3
 This free eBook is dedicated to the hard-working volunteer moderators of
ExcelMale.com. They have kept the site free of spam and online trolls, while
faithfully answering questions posed by men across the globe. Their names
are James Tarbox, Jason Sypolt, Vince, Chris Shrenk, and, finally, Gene
Devine, who suggested – ten years ago – that I create ExcelMale.com. I
thank all of them for their ongoing altruism in helping thousands live better.

I also want to dedicate this eBook to Curt Moyers (a.ka. Lee Meyers), the
founder of PeakTestosterone.com, who tragically passed away in 2018. He
was my good friend and helped hundreds of people without seeking any
recognition.

4
 Table of Contents
INTRODUCTION 7

HOW TO USE THIS BOOK: 13

TESTOSTERONE 101 14

TESTOSTERONE IN WOMEN 49

HOW TO INCREASE TESTOSTERONE NATURALLY 57

DIAGNOSIS OF HYPOGONADISM (LOW TESTOSTERONE) 65

TESTOSTERONE TREATMENT OPTIONS 79

BENEFITS OF TESTOSTERONE REPLACEMENT 116

TESTOSTERONE SIDE EFFECT MANAGEMENT 124

TESTOSTERONE AND THE PROSTATE 137

TESTOSTERONE AND THE CARDIOVASCULAR SYSTEM 145

HUMAN CHORIONIC GONADOTROPIN (HCG) 151

IS ESTRADIOL AN ENEMY OF MEN ON TRT? 159

GYNECOMASTIA 200

TRT RELATED DIHYDROTESTOSTERONE (DHT) INCREASES 212

TRT-RELATED ACNE AND HAIR LOSS 220

TRT RELATED WATER RETENTION AND HIGH BLOOD PRESSURE 228

5
ERECTILE DYSFUNCTION/LOW LIBIDO- 232

CLINICAL USE OF FDA-APPROVED ANABOLIC STEROIDS 250

FERTILITY AND HPTA RECOVERY 259

GROWTH HORMONE RELEASING PRODUCTS 283

DHEA SUPPLEMENTATION 295

THYROID DYSFUNCTION: DIAGNOSIS AND MANAGEMENT 299

MENTAL HEALTH 312

NUTRITIONAL CONSIDERATIONS 315

EXERCISE CONSIDERATIONS 323

NELSON’S TIPS FOR TRT PATIENTS 327

HOW TO MONITOR TRT LAB TESTS 331

LA TESTOSTERONA: INFORMACION EN ESPAÑOL 368

EXPERT INTERVIEWS 370

TRT RESOURCES 374

6
 INTRODUCTION
It took me several years to gather the information contained in this eBook. That is why I am now making this information
available for free to the world, hoping that it spreads beyond boundaries to help millions that may have no access to
empowering health information on testosterone replacement and other important men’s health issues.

The purpose of this ―living‖ book is to give you a broad overview of the health topics discussed on the forums of
ExcelMale.com. I wanted to put the site in your hands.

I decided to provide live links so that the information contained in each linked section can be updated as new data and
practical, field experience is developed. I also decided to make this an illustrated eBook using slides I developed for physician
training since I have learned that most men learn faster with visual aids rather than with lengthy written discussions.

This eBook would not be possible without the 10 million users all over the world that have shared information on
ExcelMale.com. As of December 2019, we have had 155,000 posts with close to 10 million views since ExcelMale.com went live
on October 17, 2013. I never predicted there was such a need for a moderated forum for men!

Over the ten years, since I published ―Testosterone: A Man’s Guide‖ and created ExcelMale.com, I have seen a great deal of
progress – both in the science of hormone replacement and its clinical management. Much of it is heartening; some discourage
me.

7
 INTRODUCTION II
• Several misconceptions and myths related to the potential risks of testosterone replacement therapy (TRT) related to
prostate cancer and cardiovascular disease risk have been debunked as more solid data has been gathered.

• New testosterone formulations have been approved by the FDA. We now have two new testosterone gels (Axiron and
Fortesta), a long-acting testosterone undecanoate (Aveed), a nasal gel (Natesto), a subcutaneous testosterone enanthate
injection device (Xyosted), and oral testosterone undecanoate (Jatenzo) and generic gels.

• We have learned the vital role that estradiol plays in men’s health (estradiol is still a misunderstood puzzle in many
respects). We have also learned that the old estradiol blood test overestimates it and that a new test based on liquid
chromatography is now the preferred assay. We have seen many men complaining about their ―estradiol crash‖ after
having doctors over-prescribe the estrogen blocker anastrozole (Arimidex).

• Patients now know, even if their doctors don’t always understand, that the administration of testosterone injections
subcutaneously and in smaller, more frequent doses are as effective than deep intramuscular injections

• Side effects have been minimized as patient protocols are designed to produce lower peaks of serum testosterone levels.

8
 INTRODUCTION III
• The knowledgeable physician no longer has patients stop TRT due to fertility issues and fears since more data about
human chorionic gonadotropin (hCG) as an adjunct to a TRT protocol has shown to have a positive impact on sperm
production and motility.

• It is a relief to report that many physicians that once stopped TRT when hematocrit began to rise in their patient’s CBC
(chemistries and blood count panel) now understand that a simple blood donation (or therapeutic phlebotomy) can
manage this still too common TRT side effect.

• We are seeing more data about the benefits of testosterone for women, although we have no FDA approved
pharmaceutical brand for them. Luckily, testosterone creams (sometimes combined with estrogen, progesterone, and
DHEA) can be made by compounding pharmacies. We have also seen the first two products FDA approved specifically for
improving sexual desire in women in the past three years.

• Access to erectile dysfunction medications has increased as many telemedicine sites have started in the past three years
offering lower prices than pharmaceutical brands.

• Since January 2013, there have been over 113,252 studies and articles about testosterone in the medical literature. These
new data have brought new knowledge, but some have sparked considerable controversy.

9
 INTRODUCTION IV
This progress is all to the good. On the not so good side of the ledger, testosterone clinics pop up across the United States every
week. The level of care these practices offer varies widely.

• Too many clinicians have yet to catch up with the latest and best practices in the field. Some have not caught up on new
information about more uncomplicated injection techniques, still overprescribe anastrozole, make their patients drive to clinics
weekly for injections, do not know how to dose hCG to preserve fertility and testicular size, and do not adequately warn
patients about how to manage side effects.

• Even though we have several TRT treatment options in the U.S., most insurance companies restrict access to most and only
cover those that have given them discounted prices.

• It is still challenging for men to find physicians that take insurance and who not only prescribe testosterone, but that also
know how to manage side effects. This access issue has benefitted cash-based clinics.

• It is very difficult for a physician to get training on the best TRT management practices since most education comes from
pharmaceutical companies that only educate on their specific product.

• Many physicians still do not prescribe cheaper compounding pharmacy TRT products even in cases when insurance companies
refuse to pay for any of the ones made by pharmaceutical companies.

10
 INTRODUCTION V
• Many insurance companies disagree on what ―low testosterone‖ means as they arbitrarily use different minimum blood
level values (some require a man to have less than 250 ng/dL and others less than 350 ng/dL)

• Most clinical guidelines are still too basic in their approach to side effect management. Most recommend TRT in men with
an increased hematocrit and ignore the fact that this issue is easily managed by donating blood or getting therapeutic
phlebotomy. Others also have patients stop TRT when their PSA increases without performing the necessary exams to
determine if the increased PSA is caused by a treatable prostate infection.

• Most patients do not know that they can access treatment from telemedicine clinics and buy affordable blood tests online
without a doctor’s visit, no matter where they live in the U.S.

• Some physicians are still failing to explore hypothyroidism properly while performing a hypogonadism (testosterone
deficiency) work-up. Low thyroid function mimics a lot of the symptoms of hypogonadism. Thyroid hormone
replacement may increase testosterone blood levels before TRT is initiated or can improve TRT outcomes.

• One of the most frustrating things about our work is our inability to help men outside the United States and Canada to
find doctors who can provide successful treatment and help them in their effort to regain their health. This issue will
hopefully improve as we add more doctors to our HormoneClinicNetwork.com site.

11
 INTRODUCTION VI
We will get into more details about the observations listed above as you dig deeper into our content collected over ten years. I
hope this eBook helps you to make educated choices as a patient and also help clinicians provide proactive care.

This eBook covers:

• Testosterone and other hormones

• Nutrition

• Blood testing

• Expert interviews

• Resources (doctor finder, etc.)

• Workouts, general wellness tips, mental health, and more.

• Growth hormone-releasing peptides

• Thyroid, pregnenolone, prolactin, cortisol, and more

• Women’s issues related to HRT (men are very interested in this topic to help their significant others)

Each chapter will cover a wide range of topics and questions.

12
 HOW TO USE THIS BOOK:
This book consists of live links that will send you to our site, so you should have access to a web browser while you are
reading it. If you find yourself in a section and have a question, you can usually post it in the corresponding thread, but
you first need to register on ExcelMale.com.

To find out more information on how to maximize your benefits on ExcelMale.com, watch this video.

You can search for a particular topic by typing keywords here

I welcome suggestions for future editions, so please contact me via the contact form on ExcelMale.com

13
TESTOSTERONE 101
Change of Hormones as We Age

Estrogen
Progesterone
Testosterone
Growth Hormone
Thyroid
Insulin
Cortisol

20 Years 30 Years 40 Years 50 Years 60 Years 70 Years

15
 Testosterone and Aging
TESTOSTERONE
(plasma levels by decade)
24

22

20

nmol/l 18

16

14

12

10
25-34 35-44 45-54 55-64 65-74 75-84 85-100
Age

16
 History of Testosterone

1489 (Berthold) Transplanted the testes from roosters into abdomens of

capons

1931 (Butenandt) – Steroidal

Androgen first isolated from urine

1935 (David) – Testosterone was obtained in

crystalline form from bull testicles
1835 (Butenandt and Hanish) - testosterone
chemically synthesized

1957 (Junkman) – Longer acting testosterone esters

prepared

1986, 1992 (Coert and Nieschlag) –

Transdermal testosterone patches
applied to scrotal or non-scrotal
skin
2000 (Wang) Transdermal
Testosterone Gel

17
 Testosterone: Target Organs
BRAIN
Libido, mood

SKIN
Hair growth,
balding,
sebum production MUSCLE
Increase in
LIVER strength and
Synthesis of volume
serum proteins KIDNEY
Simulation of
erythropoietin production
MALE SEXUAL ORGANS
Penile growth
spermatogenesis prostate BONE MARROW
growth and function Simulation of stem cells
BONE
Accelerated linear growth
closure or epiphyses

18
Sex Hormone Synthesis Pathways

19
Symptoms of Testosterone Deficiency
• Decreased libido
• Decreased vitality
Q
Mild
• Fatigue
What
symptoms are • Mood changes
characteristic • Insomnia
of testosterone
Anemia

Degree of Deficiency
deficiency? •
• Delayed ejaculation
• Hot flushes
• Erectile dysfunction
• Decreased muscle mass
• Increased visceral body fat
• Testicular atrophy
• Weakness
Severe
• Osteopenia / Osteoporosis
• Loss of facial, axillary and pubic hair
Morales et al. CUAJ 2014;4:269-75; Bhasin et al. J Clin Endocrinol Metab 2010;95:2536-59

20
Other Symptoms of Low Testosterone

21
 Age-related Decline in Testosterone

Estimates of prevalence depend

on arbitrary cut points for total
or free compared to lower limit of
young males:
• Total < 250 ng/dL= 8%1
• Total < 320 ng/dL = 20%1
• Free < 50 pg/dL = 33%2,3

1 Tenover JL. Mayo Clin Proc 2000;75(Suppl):S77

2 Morley JE et al. Metabolism 2002;51:554
3 Harman, SM, et al. J Clin Endocrinol Metab 2001; 86:724.

22
 Diurnal Variation of Testosterone

Bremner et al. J Clin Endocrinol Metab 1983;56:1278-81.

Because of diurnal variation and to avoid misdiagnosis of hypogonadism, always obtain

testosterone levels in early morning

23
Absent Diurnal Variation In Serum Testosterone In
Men With Baseline Low Testosterone

J. Sexual Medicine. April 2019 Volume 16, Issue 4, Supplement 1, Pages S35–S36

24
Total vs. Free Testosterone Levels Are Lower in Obesity

Data from Glass, AR, Swerdloff, RS, Bray, GA, et al, J Clin Endocrinol Metab 1977; 45:1211.

Reduction in total testosterone with normal free testosterone due to diminished protein
binding in obesity

25
High Intra-individual Variability of Testosterone

Because of significant intra-individual variability, always confirm low

testosterone by repeating AM testosterones at least once

26
 Variability of Testosterone: A Single Low Value DOES
NOT Diagnose Hypogonadism

• 30% of men with testosterone in mildly hypogonadal range will be normal

on repeat measurements
• 15% of healthy young men may have a testosterone transiently below the
normal range in a 24-hour period
• A substantial number of men ages 65 - 80 who have low serum
testosterone in the afternoon will have normal testosterone in the morning

Brambilla DJ, O’Donnell AB, Matsumoto AM, McKinlay JB 2007 Intraindividual variation in levels of serum testosterone and other reproductive and
adrenal hormones in men. Clin Endocrinol (Oxf) 67:853-862

27
 Improved Cognitive Capacity/Mood

Increased Libido

Increased Stamina

Benefits of
Testosterone
Lower Cardiovascular Risks if Properly Managed

Replacement Improved Body Composition

Therapy Improved Glucose control

Improved Exercise Tolerance and Functional Capacity

Improved Longevity/Survival?

28
Testosterone Metabolites and Their Functions

LH

Dihydrotestosterone (DHT)
10% of T (by 5α-reductase) Androgen
genitals, prostate gland, Receptor
seminal vesicles, skin, and
hair follicles
Direct Effect (Free T)
Testosterone Androgen
5-7 mg/day Muscle, Brain Receptor

Estradiol (by Aromatase) 0.4% of T Estrogen

Hair, Brain, Bone, Fat Receptor

Oxidation by Liver
Elimination by Kidneys

29
 Gonadotropins: LH, FSH and hCG
• The gonadotropins are peptide hormones that regulate ovarian and testicular function and are essential for
normal growth, sexual development and reproduction.

• The human gonadotropins include follicle stimulating hormone (FSH) and luteinizing hormone (LH) which
are made in the pituitary, and chorionic gonadotropin (hCG) which is made by the placenta through
pregnancy.

• They are under the control of gonadotropin releasing hormone (GnRH), a decapeptide produced in the
hypothalamus

• FSH is essential for sexual maturation and reproduction in both men and women. It is involved in ovulation and
sperm production.

• LH is essential to activate Leydig cells in the testicles to produce testosterone.

• hCG is an analog of LH that has been used to improve fertility in men and women. It’s extracted from pregnant
women’s urine or made by recombinant DNA process.

30
 Production and Regulation of Testosterone
Free T,
Hypothalamus 2%
GnRH

Pituitary
Albumin
-bound
T, 38%
Hypothalamic- Testosterone LH FSH SHBG-
bound
Pituitary- T, 60%

Testicular
Axis (HPTA) Testis
SHBG: Sex Hormone Binding Globulin
Free T SHBG-bound T Albumin-bound T
GnRH: Gonadotropin Releasing Hormone
Testosterone T = testosterone
LH: Luteinizing Hormone
Only 2% is free testosterone
FSH: Follicle Stimulating Hormone
and 98% is bound

Sperm

Adapted from Bagatell CJ, Bremner WJ. N Engl J Med. Adapted from Braunstein GD. In: Basic & Clinical Endocrinology.
1996;334:707-715. 5th ed. Stamford, Conn: Appleton & Lange; 1997:403-433.

31
 Circulating Testosterone Fractions
SHBG-bound T (tight) Albumin bound T
44% (weak)
54%

“Bioavailable”
Testosterone
= Free T + Albumin
Bound T

Free T 1- 2%
Dunn JF. et al, JCEM 1981
Testosterone Sex Hormone Binding Globulin (SHBG)
• Strong binding 50-60% of total testosterone
• Total 350-1000 ng/dL
• No dissociation during tissue transit time (inactive)
• Free 50-210 pg/dL (1-2%)
• 98% of Testosterone is protein-bound Albumin
• Loose binding 40-50% of total testosterone (active). Releases
T as needed by the body.

32
Total, Free and Bioavailable Testosterone

Free
Testosterone

33
 Laboratory Assays: Free Testosterone
„Direct‟ free T
• Common analog displacement assay
• Flawed methodology- not reliable- should not be used.
Calculated free T
• Better than analog assay but affected by accuracy of assays used to measure
total testosterone and serum binding proteins
Free T by equilibrium dialysis
• Reliable and gold standard but more expensive
• Available only at certain reference labs
Bioavailable Testosterone:
• Accurate measure of ―free‖ and albumin-bound (i.e. biologically active)
testosterone
J Clin Endocrinol Metab, June 2010, 95(6):2536–2559
AACE Hypogonadism Guidelines, Endocr Pract. 2002;8(No. 6)

34
 Sex Hormone Binding Globulin (SHBG)
Conditions associated with decreased SHBG concentrations
• Moderate obesity*
• Nephrotic syndrome*
• Hypothyroidism
• Use of glucocorticoids, progestins, and androgenic steroids*
• Acromegaly
• Diabetes mellitus*
Conditions associated with increased SHBG concentrations
• Aging*
• Hepatic cirrhosis and hepatitis*
• Hyperthyroidism
• Use of anticonvulsants*
• Use of estrogens
• HIV disease

* Particularly common conditions associated with alterations in SHBG concentrations

35
Age-related Decline in Free and Total Testosterone
Levels
Free Test (nmol/l) SHBG Test (nmol/l) Total Test (nmol/l)

0.75 8 25

0.625

0.5 7 20

0.375 6 15

0.25 5 10

0.125

0
Years:18-29 30-49 50-59 60-69 70-79 80-89 90-100 >100

SHBG Total Test Free Test

36
 What T Level Is Too Low? Review Of Studies
(Avg. T levels that increases risks)

< 450 ng/dl (15.3 nmol/l) - Risk of metabolic syndrome

< 400 ng/dl (15.3 nmol/l) - Venous leakage (internal penile damage) risk

< 350 ng/dl (11.9 nmol/l ) - All cause death risk and anemia risk

< 300 ng/dL (10.2 nmol/L) - Lowered libido, weight gain & Diabetes risk increased

< 300 ng/dL (10.2 nmol/L) - Quartile risk of fractures (osteoporosis), memory- elated issues & depression risk
increases

< 250 ng/dl (8.5 nmol/l) - Arterial plaque (arteriosclerosis) & sleep quality affected

< 235 ng/dl (8.0 nmol/l) - Hardening of arteries (dialysis patients)

< 200 ng/dl (6.8 nmol/l) - Morning erections decrease

< 150 ng/dl (5.1 nmol/l)- Increased inflammation (TNF-alpha)

References in ExcelMale.com

37
 What T Level is Defined as “Low”? Different
Guidelines Disagree

Body Total Testosterone Free Testosterone (calculated or EqD)

J Sex Med. 2019 Jun;16(6):812-820.

38
Cutoff Low Testosterone Values From Different Guidelines and
Clinical Groups Do Not Fully Coincide

J Sex Med. 2019 Jun;16(6):812-820.

39
Different Patients Are Treated Differently by Different Guidelines

The Journal of Sexual Medicine

Volume 16, Issue 6, June 2019, Pages 812-820
TD: Testosterone Deficiency
TT: Total Testosterone
TRT: Testosterone Therapy

40
Types of Hypogonadism

41
 Testosterone Deficiency Causes
Secondary (hypothalamic-pituitary dysfunction) Primary (testicular dysfunction) Mixed

Chromosomal abnormalities (Klinefelter's, XX male

Idiopathic GnRH deficiency, Kallman syndrome,
gonadal dysgenesis), defects in androgen
Congenital Prader-Willi syndrome, Laurence-Moon-Biedl
biosynthesis, myotonia dystrophia, cryptorchidism,
syndrome, panhypopituitarism, pituitary hypoplasia
varicocele
Orchitis (mumps, human immuno-deficiency virus Chronic infection (HIV,
Inflammatory
[HIV], viral, leprosy) tuberculosis, fungal infection)

Trauma Postsurgical blunt head trauma Orchiectomy Irradiation

Tumor Pituitary adenoma, craniopharyngioma

Vascular Insult Pituitary infarct/apoplexy, carotid aneurysm Testicular torsion

Sex steroids, drug-induced hyperprolactinemia, Cytotoxic drugs, ketoconazole, cimetidine,

Drugs Corticosteroids
opioids spironolactone
Malnutrition, chronic renal
Systematic
Anorexia nervosa failure, liver failure, chronic
Illness
inflammatory disease

Autoimmune Autoimmune hypophysis

Sarcoidosis, histiocytosis,
Infiltrative
hemochromatosis

Toxins Alcohol, fungicides, insecticides, heavy metals

Other Obesity, aging

42
 Medications that Lower Testosterone
• Ketoconazole (Extina, Nizoral, Ketoderm) is used to treat infections caused by fungi or yeast (e.g.,
athlete’s foot, yeast infection of the skin, seborrheic dermatitis, or dandruff.) Ketoconazole can be
taken as a pill or used as a cream, foam, gel, or shampoo.
• Cimetidine (Tagamet) is often prescribed to people with ulcers or gastroesophageal reflux disease
(GERD). It’s also available in an over-the-counter form to treat heartburn. It comes in tablet and
liquid forms.
• Spironolactone (Aldactone) may be used with other medicines to treat high blood pressure and
heart failure. It may also help people who have too much aldosterone, a hormone, or people who
have edema (fluid retention) from heart, liver, or kidney disease.
• Certain antidepressants may lower testosterone levels. A doctor can advise a patient on which
antidepressant is most suitable.
• Chemotherapy drugs have been shown to lower testosterone levels, possibly because they can
damage the testes, the organs that produce testosterone in men.

43
• Corticoids
• Antiepileptic and antipsychotic drugs can increase prolactin which can lower testosterone
• Opioids are pain relievers like morphine, codeine, hydrocodone (Vicodin), and oxycodone
(OxyContin, Percocet).
• Emerging data on statins’ testosterone lowering effects.
• Anabolic steroids

44
 Testosterone and Weight Loss: The Evidence

Waist circumference
(WC) decreases even
after years of TRT
use.

Curr Opin Endocrinol Diabetes Obes. 2014 Oct; 21(5): 313–322.

45
Hormone Unit Conversion Calculator

Click Here to Convert Units

46
Who Prescribes Testosterone ?

Testosterone Replacement Therapy. FDA Advisory Committee Briefing Document. Sept 17, 2014

47
Who Prescribes Testosterone ? II

Testosterone Replacement Therapy. FDA Advisory Committee Briefing Document. Sept 17, 2014

48
TESTOSTERONE IN
WOMEN
Hormone Replacement Therapy (HRT) for Women
Benefits of Testosterone for Post-menopausal Women

Hormone products for women: Dosing protocols

The Use of Testosterone in Women - Is it Worth it and Safe?

Rekynda (bremelanotide) (final brand: Vyleesi) for Female Sexual Disorder

Treatments that may increase sex drive in women

Estrogens and progestins treatment for women

Timing of female hormone testing

Female Sexual Dysfunction- Causes and Treatments: Video

FDA approves bioidentical hormone therapy for menopausal hot flashes

50
Hormone Replacement Therapy (HRT) for Women II
Sexual Dysfunction in Women: A Practical Approach

HRT and Weight Loss in Women: Videos

Table: FEMALE HORMONE THERAPY OPTIONS

Webinar Video and Transcript: Latest Advances in HRT for Women

Video: Testosterone in Women: Friend or Enemy?

Is HRT for Menopause Staging a Comeback?

Slide Presentation: HRT in Women

Video: Postmenopausal hormone replacement

Dr. Saya speaks about HRT

Dr. Eugene Shippen Lectures About HRT in Women

Bioidentical vs. Synthetic Hormones for Women

51
 Testosterone Production in Women
ACTH Anterior LH
Cortisol Pituitary Estradiol

DHEA-S

DHEA
Adrenal
Ovaries
Gland
Androstenedione

Testosterone

Buster JE, et al. In: Lobo RA, ed. Treatment of the Postmenopausal Woman: Basic and Clinical Aspects.
2nd edition. Philadelphia, Pa: Lippincott, Williams & Wilkins; 1999:142.

52
Signs and Symptoms of Testosterone Deficiency in
Women
Signs
• Decreased lean body mass
• Increased body fat
• Thinning or loss of hair
• Osteopenia or Osteoporosis
Symptoms
• Decline in sexual motivation or
libido
• Fatigue and lack of energy
• Lack of sense of well being
• Lack of concentration
• Orgasmic dysfunction
• Arousal disorder
• Depression
53
Medical Therapy for Female Sexual Dysfunction
Hormonal Therapy Non-hormonal Therapy
• Estrogen • Bremelanotide PT-141
• Local or systemic (Vyleesi)
• Progesterone • Viagra / PDE5i
• DHEA-S • Wellbutrin
• Testosterone • Dostinex and other dopamine
(compounded) agonists (i.e. Mirapex)
• Addyi

54
55
Join the Women‟s Health and HRT Group on Facebook

56
HOW TO INCREASE
TESTOSTERONE
NATURALLY
 How Can One Increase Testosterone Naturally?

Avoiding
Good Sleep Quality Weight Loss if
Environmental
and Hygiene Overweight
Toxins

Note: There is no
effective OTC
Glucose Control Exercise
testosterone
booster

58
Effect of Sleep on Hormones

59
 Sleep Apnea, Testosterone and ED
• Low testosterone may affect overall sleep quality which is improved by replacement doses.
Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are
associated with abnormalities of sleep duration and architecture.

• Erectile dysfunction improved with the use of Continuous Positive Airway Pressure (CPAP) in
men with sleep apnea. Testosterone did not increase.

• Sleep apnea has been linked to higher cardiovascular risks, fatigue, depression, fat gain,
poor memory, low testosterone, ED, and other health issues.

• If you snore and are tired during the day, ask your doctor to refer you to a sleep study.

Asian J Androl. 2014 Jan 7. Arch Sex Behav. 2015 Sep 14.

60
Disruptors of Testosterone and Sperm Around Us

Endocrine
Disruptors

61
Health Consequences of Poor Sleep
Sleep Apnea- CPAP Masks

62
Effects of Sleep Deprivation

63
 Factors Involved in Good Sleep Hygiene

Doing relaxation
Don’t watch TV Spend time in
Stay hydrated exercises before
before bed the day light
bed

Go to bed and
get up at the Read a paper
same time every book in bed
day
Helps you
sleep
Have a light
Don’t do the
dinner, and not
things below!!!
too late

Keep Your Room

Avoid Cell
Dark and Cool
Phones, iPad,
etc.

64
 DIAGNOSIS OF
HYPOGONADISM
(LOW TESTOSTERONE)
HYPOGONADISM DIAGNOSIS (American Urology Association)
• Requires signs/symptoms + low total testosterone level
o Normal and low testosterone levels should be defined for each assay. There is an ongoing effort by the US Centers for Disease Control and
Prevention (CDC) to harmonize testosterone assays to the same standard, which should help to harmonize normal ranges. The International
Society of Andrology defines low testosterone as levels <231 ng/dL and borderline levels 231-346 ng/dL. The Endocrine Society uses <300 ng/dL

• Initial labs: fasting 7-10 AM serum total testosterone; if low total testosterone, repeat and include LH, FSH,
• Measure free or bioavailable testosterone level in men with borderline low total testosterone or whom alterations in SHBG are
suspected
• Evaluation of androgen deficiency should not be done during any acute or subacute illness
• DEXA scan recommended for all men with severe testosterone deficiency or fragility fracture
Avoid Testosterone Therapy if:
• Breast or untreated prostate cancer
• Hematocrit >50% (explore sleep apnea or smoke cessation)
• Untreated severe obstructive sleep apnea
• Severe lower urinary tract symptoms (American Urological Association (AUA) International Prostate Symptom Score (IPSS) >19)
• Uncontrolled Chronic Heart Failure (New York Heart Association (NYHA) Class III or IV)
• Desire for fertility (talk to pt about the use of TRT+ HCG and/or FSH)

66
 HYPOGONADISM RELATED PHYSICAL EXAM
• Breast tenderness or gynecomastia
• Eunuchoid (sexual development) proportions (arm span >=2 inches greater than height;
lower segment [floor to pubis] >=2 inches greater than upper body segment [pubis to
crown])
• Hair patterns: decreased facial/axillary/chest/pubic hair, female (triangular) escutcheon
• Increased body and visceral fat
• Acne
• Genital Urologic Exam: penis length, urethra for hypospadias, prostate exam for
small/atrophied prostate (can be obscured by benign prostatic hyperplasia [BPH])
• Scrotal exam for testicular descent, consistency, and size )<4 x 2 cm or <20 mL),
varicocele
• Musculoskeletal development, strength, muscle atrophy, bone deformity/fractures

67
 Blood Tests and Physical Exam
• Total testosterone (TT) blood level of 400 ng/dL or below along with
hypogonadism symptoms not caused by temporary factors (lack of
sleep, recent excess weight gain, thyroid dysfunction, temporary
illness, and anabolic steroid use).

• For men with TT > 400 ng/dL, lifestyle modification counseling to

lower BMI (If BMI >26), improve sleep hygiene, and exercise is
recommended.

68
 LH, FSH, and Prolactin at Baseline
• LH and FSH should be measured at baseline to document if hypogonadism is primary

(Testicular-high LH and FSH and low T) or secondary (Pituitary- Low LH and/or FSH). LH

and FSH are suppressed by TRT, so no need to measure at follow up.

• If Total Testosterone< 200 ng/dL at baseline with no history of medication induced

suppression, measure prolactin to rule out prolactemia induced by pituitary adenoma. If

prolactin is over 50 ng/mL, a referral to an endocrinologist is needed. Pituitary MRI and

cabergoline treatment may be needed

• Note: Substantial elevation in prolactin (>150 ng/mL) usually indicates a pituitary tumor.

Very high levels of prolactin are associated with larger tumors.

69
 Prolactin and Thyroid Measurement at Baseline
• Modest levels of prolactin elevation (25–100 ng/mL) may be associated with the use of several
medications. All other causes of hyperprolactinemia should be excluded before a tumor is considered.
Primary hypothyroidism and chronic renal disease is associated with elevations in prolactin, probably
because of altered metabolism or clearance of prolactin. The following medications can cause elevated
prolactin and very low TT blood levels:

• Link: Prolactin: Should Men with Erectile Dysfunction Be Tested?

• Hypothyroidism (TSH>3.5 U/mL or below normal free T3) can lead to hypogonadism. If patient is
experiencing cold intolerance in extremities, fatigue and weight gain TSH should be measured . Free T3
and T4, thyroid antibodies, and reverse T3 tests may be needed to determine the root cause of high
TSH (Potential Hashimoto’s Disease).

70
 Digital Rectal Exam (DRE) and Other
Considerations
• A digital-rectal exam (DRE) is recommended at baseline prior to starting testosterone replacement to document
any BPH. BPH is not a contraindication but urinary track symptoms should be closely monitored to detect
worsening due to TRT associated prostate volume increase. Prostate volume increases plateau after 4 months on
TRT.

• Physical exam should also include a list of medications taken by the patient. Ketoconazole (current use),
cimetidine (current use), opiates (current or prior use), anabolic steroids (current or prior use), glucocorticoids
(current or prior use), finasteride (current or prior use), Accutane (current or prior use) and OTC supplements can
decrease TT and FT levels. Hypertension medications like beta blockers and diuretics can decrease libido and
worsen ED (ACE inhibitors may have a lower incidence of these issues). Antidepressants (exception: bupropion-
Wellbutrin), anxiolytics, and statins have also been associated with lower libido, ED, and/or orgasmic issues.

• Traumatic head injury has been associated with low TT blood levels in young men, so please ensure that this is
noted in the chart if present.

71
 CONTRAINDICATIONS TO TESTOSTERONE
REPLACEMENT THERAPY
Patients with the following issues should not be treated with TRT unless the issue is corrected:

1. Severe sleep apnea not treated with CPAP

2. Hematocrit > 50 (without TRT)

a. For patients with hematocrit > 50, inquire about recent testosterone or anabolic steroid use,
sleep apnea, heavy smoking, or family history of congenital polycythemia or lung disease.

3. PSA> 4

NOTE:

a. Men with prior history of prostate cancer that has been successfully treated and whose PSA
has remained stable over a year are not excluded from TRT. This determination should be
made by a qualified urologist.
72
 CONTRAINDICATIONS TO TESTOSTERONE
REPLACEMENT THERAPY II
b. If PSA increases by > 1 ng/mL or approaches 4 ng/mL by follow up visit, ensure that
potential prostatitis is addressed. Increased sexual activity may also expose some men to
higher risks of prostate infections. Inquire about potential symptoms of UTI.

c. If PSA does not decrease after 4 weeks of antibiotic treatment, a referral to urology is
required. TRT cessation may be discussed with patient at that moment.

4. The FDA has sent a warning to inform that men with prior history of clotting disorders (DVT, etc.)
may have relapse on TRT . No studies have been performed to determine if blood thinners can
enable a patient to start TRT safely. Two percent of men may have genetic mutations that
predispose them to blood clots. Several studies have shown no association of DVT and TRT.

5. TRT is not contraindicated for obese patients, patients with diabetes and those with a history of
MI/CDV.

73
 This basic questionnaire can be very useful for men
to describe the kind and severity of their low
testosterone symptoms.
• 1. Do you have a decrease in libido (sex drive)? Yes No
• 2. Do you have a lack of energy? Yes No
ADAM Questionnaire • 3. Do you have a decrease in strength and/or endurance? Yes No
• 4. Have you lost height? Yes No
about Symptoms of •
•
5. Have you noticed a decreased "enjoyment of life" Yes No
6. Are you sad and/or grumpy? Yes No

Low Testosterone •
•
7. Are your erections less strong? Yes No
8. Have you noticed a recent deterioration in your ability to play

(Androgen Deficiency in
sports? Yes No
• 9. Are you falling asleep after dinner? Yes No
• 10. Has there been a recent deterioration in your work
the Aging Male) performance? Yes No

If patient answers Yes to number 1 or 7 or if he

answers Yes to more than 3 questions, he may have
hypogonadism.

74
 Sample Testosterone Deficiency Diagnosis Algorithm
Clinical suspicion of TRT
• Osteoporosis
• Type II diabetes • End-stage renal disease
• Insulin resistance • COPD
• Metabolic syndrome • Obstructive sleep apnea
• HIV-associated weight loss • Infertility
• Treatment with opioids, • Frailty
glucocorticoids or ketoconazole • Hyperprolactinemia
• Chronic alcohol abuse or heroin use • Sellar region mass, disease, radiation or trauma
• Hemochromatosis • Testicular cancer treatment

Measure testosterone in morning

(between 7am and 11am, or within 3 Normal No TRT
The Journal of Sexual Medicine hours after waking)
Volume 1, Issue 1, pages 6-23, 3 AUG 2004
Borderline low or low-normal testosterone
Low testosterone
(repeat for confirmation)

Comprehensive laboratory evaluation

Consider referral to TRT expert if strong
• FSH, LH • TSH clinical manifestations and low-normal
• Prolactin • Ferritin (or %iron testosterone
• SHBG saturation)
• TT, FT • CBC, PSA
• Prolactin

Secondary hypogonadism Consider treatment or referral to TRT expert

Primary hypogonadism (testicular)
(pituitary / hypothalamic) if clear manifestations of TRT but borderline
Low testosterone + high LH/FSH
Low testosterone + normal LH/FSH biochemical levels

75
By Nelson Vergel

76
By Nelson Vergel

77
By Nelson Vergel

78
 TESTOSTERONE
TREATMENT OPTIONS
Approval Timeline of Testosterone Products in the
U.S.
(2000)
Testosterone
solution

(1940s) (1977) (2000) (Phase III) SC self-

Testosterone Oral Testosterone administered testosterone, oral
implants testosteronea gel testosterone undecanoate,
testosterone gel

1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s

2003
Transbuccal
(1954)
Intramuscular (1994) testosterone (Phase II) Unmodified oral
testosterone
injecUons Transdermal
Spray-on testosterone
scrotal patch-b

(1995) (2014)
Nonscrotal patch Intranasal
testosterone

80
Commonly Prescribed Forms of Testosterone
Replacement

10% 3%

17%

70%

Gels Injectables Patches Other

IMS NPA; 2006.

81
 There are several things that your doctor may fail to tell you when you start
testosterone replacement therapy (TRT):

1- TRT decreases your sperm count.

2- TRT may increase your blood viscosity (hematocrit). Some doctors want to stop
your TRT when this happens, but this side effect can be managed easily with blood
donations.

Twelve Facts To 3- TRT shuts down your own testosterone production. It may recover after a few
weeks and up to 6 months after you stop.

Know About TRT 4- TRT works to improve your sex drive, muscle mass, and burn fat. But it does not
work for everyone and dose/frequency are important along with other factors like
side effect management. It is not a magic bullet.

5- Testosterone can be injected under the skin (Most doctors think you should inject
deeply into muscle)

6- Testosterone gels and creams can be effective, but most doctors do not use the
right dose or do not adjust dose based on your blood level.

82
 7- Many doctors still prescribe testosterone injections at 200 mg
every two weeks. Many are moving towards 100 mg/week or 50 m
twice per week with insulin syringe.

8- TRT can worsen sleep apnea

Twelve Facts To
9- TRT only improves erectile function in younger men. It improves
libido in most men regardless of age, though.

Know About TRT- 10- You can monitor your own blood tests via companies that sell

II
discounted labs without a doctor visit.

11- You can access a testosterone doctor via telemedicine if you

don’t have one close by.

12- TRT does not cause prostate cancer or heart attacks

(cardiovascular outcomes depend on proper monitoring of
hematocrit, HDL, and blood pressure, though)

83
84
Newer Testosterone Products

Long
Acting

85
 Injectable
Testosterone
Esters Approved
in the U.S.

86
Sustanon-250
• Most common injectable testosterone used
worldwide.
• Entered the market in the early 70’s
• Each milliliter of the oily solution contains
the following:
• testosterone propionate, 30 mg
• testosterone phenylpropionate, 60 mg
• testosterone isocaproate, 60 mg
• testosterone decanoate, 100 mg
• Not available in the U.S.
• Available over-the-counter in some countries
• Usual dose: 250 mg every 10 days

87
Oral Testosterone Undecanoate Twice Per Day Testosterone enanthate injected
subcutaneously once per week

Latest FDA Approved TRT Options

88
Average Cost/Month of Testosterone Treatment Options in
the U.S. (2016)

The Journal of Nurse Practitioners. April 2017 Volume 13, Issue 4, Pages 241–249

89
Average Cost/Month of Testosterone Treatment
Options in the U.S. (2016) II

The Journal of Nurse Practitioners. April 2017 Volume 13, Issue 4, Pages 241–249

90
 TRT-RELATED
COMPOUNDED
PRODUCTS

Pellets
91
 Why Use Compounded Products for TRT?
There are several brand name TRT options that are covered by insurance for men with diagnosed hypogonadism,
so why would a patient prefer to use a product customized by a compounding pharmacy?
• Most report high co-pay cost of brand name options

• Limitations on what type of brand an insurance company may

be willing to cover

• Other restrictions that make it impractical for physicians to

prescribe or for patients to afford. Example: Insurance definition
of low testosterone.

• Compounded TRT options can be manufactured with varying

concentrations of testosterone and/or blends of different esters
usually at a lower cost than most co-pays

92
 TRT DOSING
Testosterone Cypionate Injections:

• 100 mg per week or 50 mg twice per week. Check TT and FT at follow up and titrate dose
to achieve TT >600 ng/dL while assessing symptoms. Max dose: 250 mg/week (or 125 mg
twice per week). Injections can be performed using a 26 or 27-gauge ½ inch insulin
syringe subcutaneously in the abdominal area or intramuscularly on glutes, shoulders or
hamstrings

Compounded Testosterone Cream (2 %):

• 1 ml on shoulders or inner thighs after daily showering. Advise patient of risk of

transferring testosterone to females or children during the first 12 hours of application

93
 TRT Options And Dosing
Route Formulation Dose regimen Pharmacokinetics Advantages Disadvantages
• Gel (AndroGel 1% or 1.6%, Testim
1%)
AndroGel 1% • Start 5-10 g of 1% gel/day Quick onset. Physiologic
(provides 50-100 mg T Cost or insurance issues.
AndroGel 1.62% pattern Stable serum levels.
daily) Possible site irritation with
Fortesta, 2% Easy self-administration.
Transdermal gels • Lotion (Axiron): 60 mg once daily Steady state in 48-72 h alcohol based gels. Transference
Axiron, 2% applied to axilla (30-120 mg/d) Compounded cream can be
risk. Variable response.
Testim, 1% • Fortesta 2% gel 60 mg/d applied to scrotum for
Unreliable absorption.
Compounded creams: 200mg/cc • Compounded cream: 1 cc daily. New increasing DHT.
method: scrotal application

Gum/mouth irritation/altered
Quick onset. Physiologic
Oral buccal Striant 30 mg tablet 30 mg BID Peak serum levels within 30 min taste. Twice per day. Kissing
pattern .Easy to use
transference.
Enanthate 200 mg/ml injection- Supraphysiologic levels. Pain.
Injection (shorter 200 mg q 2 weeks or 100-150 mg Half-life 5-7 days, rapid onset and Inexpensive.
Cypionate 100 or 200 mg/ml May cause higher hematocrit.
acting) IM q week offset
injection Peaks and nadirs.
Long duration Stable serum Large IM injection
Injection 750 mg IM q week x2, then q 10 Normal serum levels maintained for
Aveed (undecanoate) 750 mg/ml levels. Less frequent injections. Office injection. Rare post-
(longer acting) weeks thereafter up to 10-12 weeks
Better compliance. injection cough.
Testopel 75 mg pellet Testopel 16 pellets q 3-4 months. Serum level peaks at 1-month, Procedural insertion. Pellet
Long duration. Stable serum
Subcutaneous pellets Compounded pellets (100-200 Compounded 6 pellets q 3-4 normal levels maintained 3-4 extrusion. Potential bruising or
levels. Better compliance.
mg) months months infection
Topical Mimics circadian patterns Ease Skin irritation at application site.
Androderm 2 and 4 mg patches 2-6 mg (1-3 patches) q day Maintain physiologic levels for 24 h
patches of use Disclosure
Peak serum levels within 40 min, Quick onset. Easy to use. Intranasal irritation. High peaks.
Nasal Natesto 5.5 mg 11mg (2 pump actuations) TID
short half-life Minimal contact transference Twice per day
IM: intramuscular; TID: three times daily; BID: twice daily

Modified and Adapted from McBride JA, Carson CC, Coward RM. Diagnosis and management of testosterone deficiency. Asian J Androl 2015;17:177-86

94
Twice Per Day Oral Testosterone Undecanoate – Jatenzo
FDA Approved on March 27, 2019

Source: FDA approved label

95
 Testosterone Replacement Therapy: Bio-identical?
―Bioidentical‖ testosterone replacement therapy

• Trendy and popular, some proponents claim more ―natural‖ and safer than traditional
options

• Never shown to be safer/more effective in any RCT

• Long term safety and efficacy unknown

• Not approved or monitored by the FDA

• The Endocrine Society and American Association of Clinical Endocrinology have position
statements advising against the use of ―bioidentical‖ HRT

AACE Hypogonadism Guidelines, Endocr Pract. 2002;8(No. 6)

96
 Scrotal Testosterone Cream

• Applying compounded (non-alcohol based)

testosterone cream (200 mg/ml) on scrotal skin has
been shown to increase DHT levels more effectively
than applying it on other areas of the body. This may
be important for men with low sex drive at follow up
visits.

• AndroGel, Testim, Axiron and Fortesta are alcohol

based, so DO NOT apply to scrotum since they may
cause irritation.

Andrology. Volume5, Issue4. July 2017. Pages 725-731

97
Testosterone Replacement Therapy: Transdermal Gels

Disadvantages and Side effects

• Technique of application important for consistent

absorption- teach patients how to apply correctly

• Sticky feeling on skin

• Odor (Testim)

• Skin irritation- rare

• Risk of inter-personal transfer

98
 Testosterone Transdermal Gel: Risk of inter-
personal transfer
• After receiving reports of secondary exposure in 8 children ages 9 months
to 5 years, the FDA added a boxed warning to testosterone gels1,2

• Reports included penile or clitoral enlargement, premature development of

pubic hair, advanced bone age, increased libido, and aggressive behavior3

• Most symptoms regressed after testosterone eliminated (with exception of

penile/clitoral enlargement).3
1. Repas T. “New Boxed Warning for Testosterone Gels” Endocrine Today. May 27, 2009.
http://www.endocrinetoday.com/comments.aspx?rid=40285#com
2. http://www.fda.gov/bbs/topics/NEWS/2009/NEW02011.html (Accessed on 5/26/09).
3. Bhowmick, SK, et al. Sexual precocity in a 16-month-old boy induced by indirect topical exposure to
testosterone. Clin Pediatr (Phila) 2007; 46:540.

99
 Testosterone Transdermal Gel: Risk of inter-
personal transfer
• Risk of this complication is extremely rare (8 cases/1.8 million prescriptions)

• However, patients must be advised to take appropriate precautions to prevent exposing others.

Always remind patient to:

• Wash hands thoroughly after application.

• Avoid skin contact until the gel has dried completely.

• Keep the application site covered.

1. Repas T. “New Boxed Warning for Testosterone Gels” Endocrine Today. May 27, 2009.
http://www.endocrinetoday.com/comments.aspx?rid=40285#com
2. http://www.fda.gov/bbs/topics/NEWS/2009/NEW02011.html (Accessed on 5/26/09).

100
 Most Men on
AndroGel and
Testim Stop Using
Them
• Included were 15,435 hypogonadal
men, from the Thomson Reuters
MarketScan® Database, who had an
initial topical testosterone
prescription in 2009 and who were
followed for 12 months.

• No reasons for treatment

discontinuation were given.

101
 Injectable Testosterone Ester Basic
Structure
• To optimize testosterone therapeutic potential, three
approaches have been used:

1. Altering the route of admin

2. Esterification of position 17

3. Chemical modification of the molecule

• Unmodified Testosterone has a T ½ (half life) of 10 min

o Esterification at position 17 (ex: propionic acid or

enanthic acid) prolongs the activity of testosterone
in proportion to the length of the side chain

102
 Testosterone Esters
• Most common testosterone replacement used worldwide is intramuscular
testosterone injection

• Oldest and most economical way to increase blood levels of testosterone

Esterified testosterone is used in injectable to create a timed release

from the injection site

• An 'ester' is a chain composed of hydrogen, carbon, and oxygen atoms, which are
attached to the testosterone molecule which must be broken down creating a
timed release in the body once injected

• Even though the testosterone molecule remains the same no matter the ester,
each one can yield different results by the way they are metabolized in the body
once injected

• Example: injecting 50mg of test prop every other day versus 200mg of test
cypionate every 7 days

103
 Identical Profiles: T Cypionate vs T
Enanthate
• 6 Healthy men 20 – 29
• 194 mg TE vs 200 mg TC
• Results
o Serum T profiles were identical after
injection, including max concentration
and duration of elevation above basal
levels
o TC and TE had comparable
suppressive effects on LH
o TC = TE pharmokinetically

Schulte-Beerbuhl and Nieschlag 1980

104
 Most Commonly-Used Injectable TRT
Regimens in the U.S.

• Testosterone Cypionate or Enanthate:

o 200 mg every two weeks (package insert of commercial
products)
o 100-200 mg very week
o 50-75 mg twice per week
• Testosterone Propionate:
o 25-50 mg three times per week
• Sustanon 250 (not available in the US)
o 250 mg every two 10 days to 2 weeks
• Nebido (Overseas) – Aveed (US) (testosterone undecanoate)
o 1000 mg every 10 weeks (overseas)
o 750 mg at week 0 & 4, then every 10 weeks (US)

105
200 mg of Testosterone Enanthate Injections Every Two Weeks in 33
men age 22-65 : Effect on Total and Bioavailable Testosterone,
Estradiol, and DHT

Adapted from Dabs AS, et al. J Clin Endocrinol Metab. 1999;84:3469-3478.

106
 Testosterone Intramuscular Injections: Monitoring
Testosterone Levels During Therapy
Intramuscular:

• Check trough testosterone on day of injection (before injection) and peak testosterone 24-
48 hrs. after injection.

• Goal is to avoid too low of a trough and too high of a peak

• Smaller doses given more frequently decreases severity of peaks and troughs (100-150 mg
IM q week or 50-75 mg twice per week)

• Alternative testing is to measure testosterone mid-way between injections and aim for
testosterone 400-700 ng/dl

• Decrease or increase dose as needed.

• If too much variation in blood T levels, consider switching to transdermal preparations

107
Testosterone Injection Sites for Deep and Shallow IM
& Subcutaneous Methods

INTRAMUSCULAR (IM) SHALLOW IM SUBCUTANEOUS (SC)

108
 Shallow Intramuscular Injections
• 27-gauge ½ inch insulin syringe

• Injection at 90 degrees

• T dose: 50 to 75 mg twice per week

• hCG dose: 350-500 IU two or three times per week

• Injection sites: Shoulders and glutes

• Fewer site reactions (if any) site reactions or bumps

compared to subcutaneous injections

• As effective at raising T levels as deep IM or

subcutaneous injections

• Only one hand needed for injecting

109
 Testosterone Injections: Then and Now
Then: 18-gauge loading syringe, 23-gauge 1 inch injection syringe

Now: 27-gauge ½ inch syringe used for loading

AND injecting:

• Less pain

• Less testosterone and supply waste

• Good penetration Then

• Only one hand needed

• No aspiration needed

• Not advised for testosterone injection Now

volume over .5 cc

• Sites:

• Shallow IM: Deltoids, Quads, Glutes

• Subcutaneous: Abdominal area

110
 International
Physician
Directory
(Testosterone ,
HRT and Thyroid
Replacement)

Contact us on excelmale.com/contact-us
if you want your clinic listed

111
 Testosterone Pellet
Regimens
• Testopel (65mg T per pellet)

− 12-14 pellets every 2-3 months depending on

lowest T level.

• Compounded pellets (100 to 200 mg per pellet)

− 4-5 pellets every 2-3 months

112
 Testosterone Replacement Therapy:
Testosterone Implants (Pellets)
Testosterone Implants
• Pure crystalline testosterone cylinders
• Excellent profile of release over 3-4 months
• May not be covered by insurance
Disadvantages and Side effects
• Need for insertion procedure
• Pellet extrusion ~ 10%
• Risk of infection and bruising
Usual Dose:
• 600-800 mg implanted every 3-4 months (three to 6 cylinders of 200 mg)
• 12 Testopel pellets every 3-4 months

113
Testosterone Pellet Insertion Procedure

114
 Testosterone Pellets:
Good and Bad Insertion Technique

115
 BENEFITS OF
TESTOSTERONE
REPLACEMENT
How Long Does it Take to See TRT Benefits?: Review
of Studies
Time Course of Testosterone Effects in Weeks

Inflammation 12
3

Glycaemic control 52
12

156
Bone mineral density
26

52
Body composition 16
12
Maximum benefit reached
30
Depressive mood 6
3 Upper
78
Quality of life 4
Lower
3

26
Erections/ejaculations 26
12

6
Sexual Interest
3

0 20 40 60 80 100 120 140 160 180

Eur J Endocrinol. 2011 Nov; 165(5): 675–685.

117
Effects of Testosterone Therapy on Body Composition:
10 Weeks of 100 mg/week of Injectable Testosterone

Increase in fat-free mass compared to

baseline in 7 hypogonadal men on
testosterone enanthate 100 mg/week
x 10 weeks

Bhasin, S. et. al. J Clin Endocrin Metab 1997;82:407

118
Nat Rev Endocrinol. 2013;9(7):414-24.

119
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How to decrease SHBG and increase free testosterone

123
 TESTOSTERONE SIDE
EFFECT MANAGEMENT
Testosterone Replacement Monitoring Targets and Their Management
(Consult your Physician before any treatment, cessation or dose changes)
Total Testosterone >= 500 ng/dL for If low or hypogonadal symptoms are not improved, increase testosterone dosage. High T levels (over 1500 ng/dL) with high hematocrit, low HDL and/or side effects
improvement in hypogonadism symptoms may require dosage reduction.
If low, test for sex hormone binding globulin. Higher TRT dose may increase free T by decreasing
Free Testosterone >= 2% of total T
SHBG. Low SHBG may be present in diabetes.
If high, donate blood or ask doctor for therapeutic phlebotomy order. If low, investigate anemia or stop
Hematocrit <= 53%
donating blood more than every 3 months.

PSA <= 4ng/mL If high, talk to your doctor about potential prostatic infection or a referral to a urologist. TRT is contraindicated if PSA is 4 ng/mL or greater.
Most men on TRT do not need to use an aromatase inhibitor like anastrozole (Arimidex). Some physicians prescribe low dose
anastrozole for what they consider high estradiol. If low, higher testosterone dose and/or cessation of AI may be required.
The lab range was derived from men with heart disease and low testosterone, so there is still debate on what the range
Estradiol (Sensitive Test) = 20-50 (Debate) should be for men on TRT since 0.3 to 0.4 % of testosterone aromatizes to estradiol, so men with high T due to TRT will
have higher estradiol. No upper range value has been determined for men on TRT. Studies have shown that
pg/mL for gynecomastia to occur, high estradiol in the presence of low T and high IGF-1 may be required. Read Estradiol In Men –
Why Is It Important For Optimal Health And Fitness Performance and The Top 18 Things You Did not Know About Estradiol in
Men

Blood pressure <= 135/85 mmHg
Estimated Glomerular Filtration Rate (eGFR)
(kidney function) >=
60 mL/min/1.73 m2
If high, weight loss, exercise, T dose reduction and/or blood pressure medications may be needed. If too low, blood pressure medication dose needs to be reduced,
electrolytes checked or hypoglycemia excluded.
If low, good hydration, use of blood pressure medications, and/or stopping offending oral supplements may improve eGFR. Exercise, high protein intake and higher
muscle mass can also increase creatinine and decrease eGFR. Use Cystatin C in obese and very muscular patients.

Liver enzymes <= 1.2 x top value of reference If high, stopping oral supplements can help. AST and ALT can increase with exercise but this is not clinically relevant. If high AST and ALT, test GGT and bilirubin to
range ensure no liver toxicity is present.
TSH <= 2.5 U/mL If high, test for other thyroid tests like free T3, free T4 and antibodies to detect hypothyroidism.

Free T3 >= 3.7 pg/mL If low, hypothyroidism may be present. See comment on TSH. If high (>5 pg/mL),explore hyperthyroidism

Ferritin 55-270 ng/mL & Iron 55-160 If low, reduce frequency of blood donations or phlebotomies and supplement with iron until it is back
micrograms/dL to normal. If high, donate blood or get therapeutic phlebotomy

HDL >= 40 mg/dL The most difficult parameter to manage. Higher TRT doses decrease HDL. Niacin may help increase HDL but may cause flushing.

Test if Total Testosterone is below 150 ng/dL before TRT to detect potential pituitary adenoma or other issues. High levels (> 30 ng/dL) may cause sexual
Prolactin (<= 30 nd/dL)
dysfunction and galactorrhea in men (milk production)

125
TRT Side Effect Management Posts on ExcelMale.com
Testosterone and Anabolic Side Effect Management Table
Testosterone Replacement Monitoring Targets and Their Management
Role of Estradiol in Men and Its Management
How to Manage Increased Blood Thickness (Hematocrit) Caused by Testosterone Replacement Therapy
The Use of HCG to Prevent / Reverse Testicular Shrinkage and Preserve Fertility
Does Testosterone Cause Prostate Cancer? Can Men Treated for Prostate Cancer Use TRT?
Does Testosterone Increase the Chance for a Heart Attack?
Testosterone and Hair Loss: What You Need to Know
Can Testosterone Induce Blood Clots and Thrombosis? Interview with Dr. Charles Glueck
Water Retention Caused by Testosterone May Have Nothing to Do with Estradiol
Why does testosterone therapy decrease HDL cholesterol in some men?
I am always hot: Is this a high estradiol symptom?

126
 TRT Side Effect Management Posts on ExcelMale.com II
Is HCG safe for long term use
How to improve penile sensitivity?
Effect of Low and High Doses of Testosterone Injections on Hematocrit, PSA and HDL
How to Avoid Getting Gynecomastia
The Hidden Benefits of DHT and How to Increase & Reduce It
Testosterone Replacement Therapy (TRT) Effect on Men's Fertility
Getting Off Testosterone or Anabolics? You May Want to Read These PCT protocols
What high blood pressure meds are the most erection-friendly?
Can Testosterone Replacement Affect Kidneys?
Water Retention Caused by Anabolics and Testosterone
Testosterone, BPH and Lower Urinary Tract Symptoms

127
Testosterone Replacement Therapy: Potential Risks
Risk Degree of Concern Precautions Contraindications

Stimulation of Rarely of clinical Test PSA, DRE Avoid in untreated prostate

Prostate Tissue significance before/during tx cancer, be cautious in severe
BPH
Low HDL Only with oral T Avoid oral T Avoid oral T

Secondary Primarily with injectable CBC before and during Be cautious in COPD and
erythrocytosis therapy (up to 44%) or tx; avoid untreated sleep apnea. Smoke
excess doses supratherapeutic cessation should be discussed.
levels, use transdermal
tx

CV risk Data mixed; no None None

confirmed definitive
harm
Venous thrombosis No clinical evidence None None

128
Testosterone Replacement Therapy: Potential Risks (2)
Risk Degree of Concern
Hepatotoxicity Can be severe but seen only
with oral T
Mood swings, aggression or Rare, usually from injectable
―testotoxicosis‖ therapy or supratherapeutic
levels
Acne & increased body hair Usually minor and of no
concern in men
Testicular atrophy/ Sperm count decreases
decreased fertility sharply on TRT. Testicle
volume may decrease 20-
30% with long term use.
Precautions Contraindications
Avoid oral T except T Avoid oral T except T undecanoate
undecanoate
Avoid excess doses; start Be careful in men with underlying
low and go slow in older aggression or psych disorders
men or men with history of
prior issues
Avoid excess doses. Use None
ketoconazole shampoo as
body wash. Antibiotics or
low dose Accutane many be
required for extreme cases.
Discuss use of hCG plus TRT. None
Add FSH for non-
responders (sperm
count/quality)
129
 Systematic Risks Associated with TRT
Risk Comment

Oily skin, acne, skin reactions Skin irritation more common with nonscrotal patches

Often transient and abates with continued treatment (generally not seen when T levels are
Breast enlargement or tenderness
maintained in physiological range, as with TRT patches and gel)

Not reported as a consequence of treatment, but considered COPD in heavy smokers or

Sleep apnea??
overweight persons a relative contraindication

Polycythemia Uncommon, but associated with age, sleep apnea, smoking history, and COPD

Liver function abnormalities or tumors Rare with injectable esters and transdermal formulations

Lower extremity edema May occur in first few months of treatment

Symptomatic BPH and

Modest and inconsistent increases in prostate volume and minor PSA elevation reported
prostate cancer

COPD=chronic obstructive pulmonary disease; BPH=benign prostatic hyperplasia Waid M, et al. J Androl. 2006;27:12-132.

130
 TESTOSTERONE REPLACEMENT (TRT) SIDE131
EFFECT MANAGEMENT

Problem Solution and Comments

Acne/oily skin • Retin-A/Tretinoin cream

Caused by • Accutane– a powerful prescription item - 40 mg/day for one week sometimes stops acne if started
Dihydrotestosterone
at the first sign or as directed by your doctor. Accutane is potentially highly liver toxic and can
(DHT) effect on
lower testosterone. Do not use unless as last resort.
increased oil production
• Sporanox – Effective for some acne-like eruptions that are caused by fungi. Some doctors also
prescribe antibiotics, like tetracycline, for acne with good results.
• Minocycline
• Shower with Nizoral shampoo
• Anti-bacterial soaps - Use a scrubbing brush and wash twice a day, especially after sweating during a
workout.
UV light or sunlight with moderation.
• Zinc/copper supplements or zinc soaps may help some men with acne.
• Other options: How to treat and prevent acne

Hair loss • Nizoral shampoo– Available by prescription and over-the-counter as a lower dose product.
Caused by DHT effect on • Rogaine – Available over the counter
hair follicles • Compounded foams and lotions including several products
• Propecia (finasteride) - Available by prescription. A few males experience decreased erections with
finasteride. Do not use.
TESTOSTERONE REPLACEMENT (TRT) SIDE EFFECT MANAGEMENT
Problem Solution and Comments

Unresolved erectile • Viagra, Cialis, Levitra – Available by prescription; enables strong erections in 60% of men. If you have sinus congestion or
function headaches/backaches (Caused by Cialis) take non-drowsy allergy medication and ibuprofen. ED drugs can be combined with alpha-
blockers and/or nitric oxide precursor amino acids (arginine or citrulline) but be careful with low blood pressure.
• Yohimbine (Yocon) - Available by prescription; increases sex organ sensitivity. Can increase heart rate and blood pressure. Not very
effective.
• Muse - Available by prescription; pellet inserted into the urethra to produce an erection. Unpopular
• Trimix, BiMix or Quadmix – Available by prescription from compounding pharmacies. The best and cheapest formula for injection
into the penis for lasting erections.
• Caverject - Available by prescription. An injection into the penis that produces an erection that can last 1 to 2 hours. Be careful with
injecting too much since it can produce dangerously ling erections that need to be treated in emergency rooms! Follow instructions
from your urologist.
• Papaverine – An older injectable medication, less expensive than Caverject.
• Wellbutrin – Prescription at 300 to 450 mg/day; increases dopamine.
• Human chorionic gonadotropin (HCG) – First dose is 2,000 IU, then 250-500 IU twice or three times a week. No protocol has been
proven in controlled studies yet.
When Testosterone Replacement Doesn’t Lead to Better Erections

Insomnia • Sleeping medications – e.g. Ambien, Sonata, Lunesta, Restoril. Concerns about habituation.
• Melatonin- 1 to 3 mg before bedtime. If you wake up groggy after 6 hours your dose should be lower.
Usually, this is caused by • Avoid working out too close to bedtime.
dosages that are too high. • Limit caffeine, especially after 3 pm.
Find the least amount that • You may want to try a sleep formula with tryptophan, melatonin, and magnesium. Nutrients do not work as well as drugs, but they can
gives you a good result. help some people.
• Article: How to protect your circadian rhythm

132
 TESTOSTERONE REPLACEMENT
(TRT) SIDE EFFECT MANAGEMENT
Problem Solution and Comments

Sleep Apnea • Have your doctor prescribe a sleep study if you snore and wake up tired even after 7 hours of
sleep. Some people may have to wear a C-PAP machine to breathe at night. Visit Home -
SleepApnea.org for more information. There are also oral devices for those people who fail
CPAP. Fatigue- When Testosterone Is Not Enough

Testicular • Human Chorionic Gonadotropin (hCG)– One 2,000 unit injection per week for 2 weeks, followed
atrophy by maintenance of 350-500 IU twice a week. For men who want to remain fertile while on TRT,
500 IU every other day has been studied. Watch this video on hCG and men

Enhanced • Make sure you are getting enough sleep.

assertiveness or • Count until 10 and be aware of your interaction with others.
reactivity. • Decrease caffeine. Be careful with pre-workout drinks.
• Meditation, mindfulness, yoga, breathe from your belly for a few minutes when overreacting.
• Your testosterone dosage may be too high.
• Ask yourself: Do I need to always be right?
• Vent extra energy at the gym, sex, and sharing with your buddies at www.excelmale.com

133
TESTOSTERONE REPLACEMENT (TRT) SIDE EFFECT MANAGEMENT
Problem
High blood pressure/water
retention
Gynecomastia- RARE in
TRT (male breast development)
Caused by overproduction of
estrogen in the presence of low
testosterone and high IGF-1
Solution and Comments
• Blood pressure medications - Elevated blood pressure may be transient or not. Try ACE or ARBs since they seem to have
fewer sexual dysfunction related effects.
• Magnesium (600 mg/day); vitamin B6 (100 to 200 mg/day); may help reduce water retention.
• Water - Drink extra water every day to help flush the kidneys.
• Avoid salty or extra sweet foods
• Make sure you are doing cardio exercise at least 3 times a week for 30 min. Sweat and lower your salt intake since TRT
increases sodium retention in some men.
• Arimidex (anastrozole) Inhibits estrogen production. Available by prescription. 0.5 mg/week max. Ensure that your estradiol
is never under 20 pg/ml (by sensitive test) since it is needed for bone, skin, brain, lipids, libido, good lipids and hair health.
Only 0.3-0.4% of testosterone is aromatized to estradiol. Current lab ranges were derived from men not on TRT. Most men
on TRT do not need anastrozole. Be careful not to crash your estradiol.
• Nolvadex (tamoxifen)– Competes with estrogen for receptors. Available by prescription, 10 to 20 mg/day. Use of Nolvadex
may reduce T’s net anabolic effect, as it decreases the production of GH and IGF-1, factors also involved in gynecomastia. A
tamoxifen cream can also be purchased by prescription from Empower Pharmacy.
• Severe cases may require removal of the breast tissue by surgery.
• DHT cream- Some people have obtained great results by rubbing a 10% DHT cream on their nipples. Not available in the US
but some people order it online from Germany
• Read about medications/foods to avoid if you have gynecomastia.
• Those who do know to respond to the above, check other reasons
Watch this video about estradiol in men
Check your estradiol with the right sensitive test and make sure your testosterone is not low.
134
 Side Effect: Increased Number of Red Blood Cells
(Erythrocytosis or Polycythemia)
High Hematocrit Increases Blood Pressure and
Cardiovascular Risks.
Portion of red
blood cells Aim at Hematocrit Under 52
f

• Solution for High Hematocrit: Donate blood or therapeutic

phlebotomy (every 3-6 months) if hematocrit approaches 53

• Careful with iron and ferritin loss due to frequent blood

donations!

• Hematocrit stabilizes in most patients after 6 months.

Exceptions occur in smokers and men with sleep apnea.

• Sleep apnea and smoking can increase hematocrit

135
 Why is High Hematocrit Dangerous?
High Hematocrit Increases Coagulation Risks High Hematocrit Increases Blood Pressure

High Hematocrit Increase Blood Viscosity

Haematologica. 2010 Feb; 95(2): 182–184.

International Journal of Epidemiology 2013;42:601–615
Chem Eng Science. Volume 64, Issue 22, 16 November 2009,
Pages 4701-4706
Hypertension. 2012;60:936–941

136
TESTOSTERONE AND
THE PROSTATE
 Increased prostate size (benign prostatic
hypertrophy)

Prevention: BPH does not worsen in men on TRT

Digital Rectal Exam (DRE)
Prostatic Specific Antigen (PSA) blood test

138
 Prostate Related Posts on ExcelMale.com
Seven causes of a high PSA that are not cancer

What Every Man Should Know About Prostatitis

Cialis versus Flomax in Men with Prostate Enlargement

Does Testosterone Cause Prostate Cancer? Can Men Treated for Prostate Cancer Use TRT?

Effect of DHT on Prostate and Sexual Function: Review of Studies

The Prostate and Testosterone: Lecture by Dr. Joseph LaBoissiere

PSA numbers increasing on testosterone- Should I stop TRT?

139
Challenging beliefs of Testosterone Therapy and Prostate Cancer

• The relationship between

testosterone therapy and prostate
cancer continues to challenge
historic and current beliefs.

• A new cohort analysis revealed a

~33% reduction in prostate cancer
incidence in men with increased
testosterone use.

• The mechanisms underlying this

protective effect are unclear, but
these findings challenge current
paradigms and warrant further
investigation.

Nat Rev Urol (2019) doi:10.1038/s41585-019-0253-8

140
 Published Series of TRT in Men with Treated Prostate Cancer
TRT is not linked to prostate cancer
Cases of
Prostate cancer Follow-up (mean/median,
Authors (year) Sample size biochemical
treatment range)
recurrence
Kauman & Graydon
7 RP NR, 1-12 years 0
(2004)
Agarwal & Oefelein 0
10 RP 19 months, 9-29 months
(2005)
Khera et al. (2009) 57 RP 12 months, 1-60 months 0
Sathyamoorthy et al.
133 RP 363 days, NR 0
(2010)
Nabulsi et al. (2008) 22 RP 24 months, 14-30 months 1

Sarosdy et al. (2007) 31 Brachy 60 months, 18-108 months 0

Morales et al. (2009) 5 EBRT 14-6 months, 6-27 months 0

12 months aftër RP/9 months
Davila et al. (2008) 20 RP (14) EBRT (6) 0
aftër EBRT, NR
RP (24) EBRT (12) Brachy
Leibowitz et al. (2010) 96 15 months, 1-83 months 41
(1) ADT (59)

ADT, androgen deprivation therapy; EBRT, external bean radiotherapy; NR, not reported; RP, radical prostatectomy; TRT, testosterone replacement therapy.

141
 Does Testosterone Cause Prostate Cancer?

Prostate enlargement and cancer happen in

later years when testosterone is lower

Meta Analysis of Studies from 1950-2016:

―This historical perspective reveals that there is not now — nor has there ever been — a
scientific basis for the belief that testosterone causes prostate to grow.‖ – Abraham
Morgentaler. MD.
Morgentaler, Abraham “Testosterone and Prostate Cancer: Is There a Link?” March 16, 2017.
Accessed Nov 2019. https://grandroundsinurology.com/testosterone-prostate-cancer-link

142
PSA/DRE (Digital Rectal Exam) MONITORING
• Stop TRT therapy and refer to urology if
• PSA increases > 1.4 ng/mL within 12 months
• PSA>4 ng/mL
• PSA velocity >0.4 ng/mL per year over >6 months (must have
PSA levels >= 2 years)
• Abnormal Digital Rectal Exam (DRE)
• AUA/IPSS >19

Explore potential prostatitis before doing more advanced testing

143
 Age

Prostatitis

BPH (benign prostatic hyperplasia)

Seven Causes of UTI (urinary track infection)
High PSA that
are not Cancer DRE (digital rectal exam)

Bike Riding

Recent Ejaculation
144
 TESTOSTERONE AND
THE CARDIOVASCULAR
SYSTEM
Testosterone and Cardiovascular Disease (CVD)
• Two trials in 2014 suggested that testosterone replacement therapy may increase the risk of heart
disease and/or stroke. Media and the FDA reacted to these studies.

• These were poorly designed studies which conflict with numerous previous medical trials that show
the beneficial effects of testosterone on the heart and that low testosterone levels in males are
associated with an increased risk in the development of heart disease. There will also later found to
have major flaws.

• On 17 September 2014, the advisory committee voted 20‐1 to restrict the indicated population for
TRT and require the pharmaceutical companies to perform a cardiovascular safety study.

• The European Medicines Agency performed its own review and declined to add a new CV warning.

Vigen, R., et al., “Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels,”
JAMA 2013; 310(17):1829- 36.
Finkle, W., et al., “Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men,” PLOS January 29,
2014.

146
 Testosterone and Cardiovascular Disease (CVD) II
• The weight of evidence does not support the contention that TRT increases CV risk. Indeed, for approximately two

decades there was suggestive evidence that a normal endogenous serum T, or TRT itself, provided protective benefits

against adverse CV outcomes. This view was challenged by two observational studies published in quick succession in

late 2013 and early 2014 that reported increased CV risks and gained enormous media attention. However, a spate of

new studies—controlled as well as observational—over the last few years has failed to support concerns of increased CV

risk and has provided additional evidence that T therapy may offer CV protection in men with T deficiency. (1)

• Two meta‐analyses regarding CV risk with testosterone compared with placebo have been published since the

September 2014 FDA Advisory committee meeting. One study reviewed 24 randomized controlled trials (RCTs) (2) and

the other reviewed 30 RCTs. (3) Neither showed increased CV risk with T treatment compared with placebo.

• The International Expert Consensus Conference on Testosterone Deficiency and its Treatment and the American

Association of Clinical Endocrinologists have concluded the evidence does not indicate increased CV risk with TRT.

1- Clinical Endocrinology. Volume 89, Issue1. July 2018. Pages 3-10

2- Expert Opin Drug Saf. 2014; 13: 1327‐ 1351.
3- Am J Med. 2017; 130: 293‐ 305.

147
 Testosterone and Cardiovascular Disease (CVD) III
• Publicity regarding the potential for increased CV risk with TRT has led to litigation

against pharmaceutical companies that sell testosterone products. Attorneys spread

advertising to recruit potential plaintiffs, which increased patient and physician

exposure to the hysteria surrounding TRT and CVD. Most of these lawsuits have ended

with mixed outcomes.

• Although this issue has been getting better since 2014 as more data comes in, the

two flawed studies have intensified fear of litigation among providers of TRT and

reduced the willingness to write a prescription as well as halting educational initiatives

around testosterone therapy.

Clinical Endocrinology. Volume 89, Issue1. July 2018. Pages 3-10

148
FDA Statement on Testosterone and Cardiovascular Risks

― There is insufficient evidence of a causal link

between testosterone therapy
and adverse cardiovascular outcomes‖

Testosterone Replacement Therapy and Cardiovascular Risk: A Review. World J Men's Health. 2015 Dec; 33(3): 130–142.

149
Properly Managed Testosterone Replacement Does Not
Increase Risks of Heart Disease
(click on links)
• Flawed Testosterone Studies Fuel Concerns and Lawsuits
• Opposition from Medical Groups Heats Up Against Flawed Testosterone Paper
• A new study of 25,420 older men showed that testosterone does not cause heart attacks
• EMA Finds Little Evidence That Testosterone Ups CV Risk
• 56% Less Likely to die when tot T is "normalized": a study of 83,000 older veterans on TRT
• Placebo Controlled Testosterone Trial Finds No Link to Hardening of the Arteries
• American Association of Clinical Endocrinologists Position Statement on the Association of Testosterone and
Cardiovascular Risks
• A Meta-Analysis of Placebo Controlled Testosterone Studies Finds TRT Safe
• Dr Morgentaler Clarifies Misperceptions of Testosterone and Heart Disease Risk
• An update on the role of testosterone replacement therapy in the management of hypogonadism
• A Review of Testosterone CV Studies Based on Prescription Data

150
 HUMAN CHORIONIC
GONADOTROPIN (HCG)
• Beyond Testicular Atrophy
 Human Chorionic Gonadotropin (HCG)
• Produced by human placenta, sterile product derived from urine of pregnant females
• In men HCG mimics LH from pituitary to stimulate Leydig cells of testes to produce
testosterone. However, it is not detected as LH in blood tests.

• Can increase TRT-related side effects like edema, increased hematocrit, & acne
• Normal lyophilized vial contains 6,000-12,000 units HCG by compounding pharmacies
(commercial products cost 3X compounding)

• Used by fertility specialists to induce ovulation to harvest eggs, etc.

• Latest data show that men on TRT + HCG were able to remain fertile at 500 IU 3 times
per week. 2/3 of men responded. Age and prior testosterone exposure time were
limiting factors.

• It can improve sperm production in men on TRT even with the absence of FSH.
• Usual recommended dose is 350-500 IU twice per week for prevention/reversal of
testicular atrophy (anecdotal)

• Anecdotal effect on raising sex drive

152
 hCG- Typical
• For boosting testosterone and
maintaining sperm production in
hypogonadal men (monotherapy): 1000-
2500 IU 3 times per week
• To maintain fertility in men on TRT: 500
IU every other day.
• To prevent/reverse testicular atrophy
and boost libido (anecdotal) in men on
TRT: 250-500 IU twice per week (non-
validated dose)
• Timing of hCG dose in men on TRT varies
among clinics. There is some anecdotal
efficacy of combining hCG + T in same
syringe.
• Monitoring increases in hematocrit,
estradiol and DHT may be needed.
• Rarely covered by insurance but available
cheaply from compounding pharmacies.

153
 Higher Doses of hCG Result in Higher E2 and T

Mean of plasma estradiol (upper

panel) and testosterone levels (lower
panel) in normal men in response to
one injection of
Left Column: Vehicle alone (⧫) or 50 (▵),
500 (□), and 5000 IU (▪) hCG

Right Column: 5000 IU (black box)

and 6500 IU (white box)

Cailleux-Bounacer A et al. Eur J Endocrinol 2008;159:171-178

154
Fertility on Testosterone Therapy (TRT): Baylor
Algorithm

hCG: human chorionic gonadotropin;

FSH: Follicle Stimulating Therapy
Asian J Androl. 2015 Mar-Apr; 17(2): 197–200

155
 Sample algorithm for
management of hypogonadal
men who wish to preserve
fertility.

hCG: human chorionic gonadotropin;

q.o.d.: every other day;
TST: testosterone supplementation therapy.

Asian J Androl. 2015 Mar-Apr; 17(2): 197–200.

156
 Treatments for Male Infertility

Aromatase Inhibitors Carry the Risk of Low Estradiol

Asian J Androl. 2015 Mar-Apr; 17(2): 197–200

157
hCG Use While on Anabolic Cycle Preserves
Sperm Counts
hCG 500IU 2x weekly Cycle ends
1 2
0 30 mill/mL@1.5 mos.
70 mill/mL@ 6 mos.
Anabolics 33 mill/mL
1/18 azoospermic

•N=18 Finnish power athletes on ―massive anabolic doses‖

•Instructed to also take hCG 500 IU 2x weekly with anabolics
•Followed semen quality over time on combination therapy
•Spermatogenesis maintained despite prolonged, massive doses of anabolics

Karila et al. Int J Sports Med. 2004, 25: 257

158
 IS ESTRADIOL AN
ENEMY OF MEN ON
TRT?
 Hormone Stigma & “Bad” Hormones
Common Wrong Beliefs
• ―Women don’t have or need testosterone‖

• ―Men should knock down their estradiol‖

• ―Testosterone will make you aggressive.‖

• ―Estradiol will make a man moody, bloated and asexual, and make him grow boobs‖

• ―Testosterone will make me super-human‖

160
Role of Estradiol in Men

0.3% T= E2

161
The Role of Estrogen in Male Reproduction

162
 Limitations of Current Data on
Estradiol in Men
• Most data comes from men with total testosterone under 350 Nd/dl

• Most studies used old E2 (Immunoassay) test instead of the LC/MS based one (sensitive E2)

• No upper limits have been studied in men on TRT.

• Lower limit is becoming clear (10-15 pg/mL) to prevent bone loss, fat gain and decreased
sexual function.

• Only 3 studies explored T/E2 ratios

• Only 2 contradictory studies (epileptic men) using anastrozole in men on TRT at 1 mg/day to
improve libido.

163
 Estrogen Receptors Alpha and Beta are
Everywhere
• The two best-characterized estrogen receptors (Ers) are ER-alpha and ER-beta. They
are found in a variety of tissues in both genders including brain, liver, fat, lung,
bladder, and bone marrow (1).

• Histologic studies have also found both ERs in corpora cavernosa in the penis,
neurovascular bundles, urethra, seminal vesicles, and prostate (2), although ERb
generally dominates in urogenital tissues (3).

• The individual role of ERa and ERb are not known.

[1] Nilsson S, Gustafsson JA. Estrogen receptors: Therapies targeted to receptor subtypes. Clin Pharmacol Ther 2011;89: 44–5
[2] Mowa CN, Jesmin S, Miyauchi T. The penis: A new target and source of estrogen in male reproduction. Histol Histopathol 2006;21:53–67
[3] Saunders PT, Sharpe RM, Williams K, Macpherson S, Urquart H, Irvine DS, Millar MR. Differential expression of oestrogen receptor alpha
and beta proteins in the testes and
male reproductive system of human and non-human primates. Mol Hum Reprod 2001;7:227–36

164
 Role of Estradiol in Men: Bone
• Longitudinal studies have shown that low total and bioavailable E2 levels are
associated with increased rate of bone loss, with increased risk at a threshold
of 40 pmol/L (11 pg/mL) [1].

• Androgen deprivation therapy with GnRH agonists for prostate cancer, which
leads to dramatic reductions in both T and E2, leads to a decrease in bone
mineral density of up to 13% annually and an increased risk of fracture [2].

[1] Khosla S, Melton J, Atkinson EJ, O’Fallon WM. Relationship of serum sex steroid levels to longitudinal
changes in bone density in young versus elderly men. J Clin Endocrinol Metab 2001;86:3555–61
[2] Guise TA, Oefelein MG, Eastham JA, Cookson MS, Higano CS, Smith MR. Estrogenic side effects of androgen
deprivation therapy. Rev Urol 2007;9:163–80

165
Low Estradiol Increased Fat Mass and Decreased
Gains in Libido and Erectile Function
Low blood level of estradiol was associated with significant increases
in the percentage of body fat (P<0.001), subcutaneous fat area
(P<0.001), and intra abdominal fat area (P = 0.002), and relative less
improvement in sexual desire (P<0.001) and erectile function (P =
0.022)

Reference: Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men N Engl J Med 2013;369:1011-22.

166
 Role of Estrogen in Men- Lipids and
Prostate Cancer
• A balance between T and E2 may regulate lipid accumulation and glucose homeostasis.
Further study is needed, but excess T in the absence of E2 could potentially be harmful.

• The importance of estrogens in prostate health is a hotly debated topic, with some
studies showing changes in ER distribution in high grade prostate cancer [1].

• Treatment with estradiol in men with prostate cancer undergoing testosterone blockage
improved mood and bone density. No accelerated progression of cancer was seen.

[1] Bonkoff H, Berges R. The evolving role of oestrogens and their receptors in the
development and progression of prostate cancer. Eur Urol 2009;55:533–42

167
 Balanced Estradiol in Men: Benefits
• Estradiol is involved in maintenance of proper
• Bone density

• Percent body fat

• Erectile Function and Penile Sensitivity

• HDL cholesterol

• Cognitive function/mood

• Inflammation modulation

168
 Causes of High Estradiol
• Estradiol Treatment
• Increased Aromatization of T to E2
• Genetic mutations or aromatase enzyme excess
• Low T/E2 ratio: Testosterone blockage (prostate cancer)
• Medications (anti-seizure meds, HIV meds, etc)
• Higher BMI
• Older age?
• Other hormone effects
• Certain foods?
• Environmental toxins
• Certain micronutrient deficiencies?

169
 Potential Symptoms of High (Relative) Estradiol
Reasons Men Use Aromatase Inhibitors
• Nipple sensitivity? No proof that it leads to gynecomastia.
• Fluid retention? There are no studies on anastrozole’s effect on androgen
associated edema. TRT can increase sodium retention and edema/blood
pressure regardless of E2 levels
• Low mood? . One study
• Decreased libido. Some evidence
• Increased venous leakage?. Small pilot study
• Most men assume above are high E2 related but fail to corroborate with
E2 blood test.
• No T/E2 ratio reported in most studies

170
 Accuracy of E2 Blood Test
Importance of lab methodology and the sensitive E2 test in men

• Electrochemiluminescence immunoassay (ECLIA) overestimates

estradiol because of interference with C-Reactive Protein (CRP)
(inflammation).

• Testing with Liquid chromatography/mass spectrometry (LC/MS)

accurately measures E2 and free E2 (and most hormones).

• A study done in Europe found an average E2 overestimation of

30% using the old ECLIA assay.

171
LC/MS (Sensitive) E2 Test on
DiscountedLabs.com

Estradiol (sensitive): $51

Free E2 (sensitive): $103

Click Here

172
 High Estradiol Increases Heart Disease Only in Men
with Low Testosterone
• Study showed that high estradiol in males with low T was associated with an increased risk of stroke. (1)

• Study showed that elevated circulating estradiol is a predictor of progression of carotid artery intima media thickness in middle age men
with low T. (1)

• High estradiol levels in men with low T were associated with acute myocardial infarctions. (2)

• High estrone and low testosterone levels were associated with promoting the development of atherogenic lipid milieu in men with
coronary heart disease. (3)

• Low testosterone and elevated estradiol was associated in this study with lower extremity peripheral artery disease in older men. (4)

• Men with myocardial infarction had high estradiol and low testosterone levels. (4)

• Elevated levels of estradiol in men were associated with an increase incidence of strokes, peripheral vascular disease, and carotid artery
stenosis compared to subjects with lower estradiol levels. (5)

• Elevated levels of estrogen in men with low T are associated with an increased risk of heart disease. (5)
• Should we be following Testosterone to Estradiol ratios?
1. Abbott, R., et al., “Serum estradiol and risk of stroke in elderly men,” Neurology 2007; 68(8):563-68.
2. Mohamad, M., “Serum levels of sex hormones in men with acute myocardial infarction,” Neuro Endocrinol Lett 2007; 28(2):182-86.
3. Dunajska, K., et al., “Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis,” Aging Male 2004; 7(3):197-204.
4. Tivesten, A., et al., “Low serum testosterone and high serum estradiol associated with lower extremity peripheral arterial disease in elderly men. The MrOS
Study in Sweden,” Jour Amer Coll Cardiol 2007; 50(11):1070-76.
5. Lerchbaum, E., et al., “High estradiol levels are associated with an increase in mortality in older men referred to coronary
angiography,” Exp Clin Endocrinol Diabetes 2011; 119(8):490-96.

173
 Study: Men with Higher Estradiol and
Testosterone Had Greater Libido
• In a study of 423 men on TRT, Dr Ramasamy at Baylor College of Medicine measured men’s
testosterone and estradiol levels and asked them to rate the quality of their libido using a five-
point Likert scale (1= terrible, 5 = excellent).

• The researchers categorized the men as having low or high testosterone (below or above 300
ng/dL, respectively) and low or high estradiol (below 5 and above 50 pg/ml, respectively)

• Men with high serum testosterone levels reported significantly greater libido than men with
low level and those with high serum estradiol levels had significantly greater libido than
subjects with low levels.

From the March 2014 Issue of Renal And Urology Journal

174
 Calculated Free T and T:E Ratio but not Total Testosterone
and Estradiol Predict Low Libido
• In summary, free T and T:E ratio were predictive of
positive libido response on IIEF11 & 12 questions in
the IIEF questionnaire (see Table)

• Estradiol, even at a cutoff of 50 pg/ml, was not

independently associated with improved libido.

• Surprisingly, no correlation was found between total

testosterone and IIEF11 (desire frequency).

• The effect of testosterone and estradiol on libido

requires further research with prospective studies.

Reference: Presented By Nikhil Gupta, Springfield, IL at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA

175
 Benefits of Higher Testosterone/Estradiol Ratios
• Lengthening of telomere length (a measure of slower aging) (1)

• Lower LDL and higher HDL cholesterol (2)

• Decreased inflammation and plaque formation (2)

• Improved semen quantity and quality (3)

• Improved libido (4)

• Above studies hint at ratios over 10 as beneficial (T in Nd/dL divided by E2 in

pg/mL)

1- Exp Gerontol. 2019 Mar;117:38-44

2- Cardiovascular Research, Volume 115, Issue 2, 01 February 2019, Pages 453–462
3- The Journal of Urology Volume 165, Issue 3, March 2001, Pages 837–841
4- Presented By Nikhil Gupta, Springfield, IL at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA

176
 Testosterone/Estradiol Ratio In Fertile vs
Unfertile Men (No Data on Libido)
Ratio=T in ng/dL 16
14.5
divided by 14
E2 in pg/mL
12

10
Example:

RATIO
8
6.9
800 ng/dL (T) divided by
42 pg/mL (E2)= 19 6

4
For 14.5 ratio=
55 pg/mL E2 2

0
Caveat: E2 test done by ECLIA Fertile Patients Testicular Failure
Patients

The Journal of Urology Volume 165, Issue 3, March 2001, Pages 837–841

177
Estradiol Response in Testosterone Therapy (non sensitive test)
Impact
Trial Subjects Intervention Baseline E2 on E2 Comment

60 men aged > 55 with RCT (52 weeks)

No significant change in E2. Specific
Allan et al. [97] T < 15 nmol/L 1) Androderm 5 mg daily 1) 50.9 ± 4.1 pmol/L
and BMI < 30 2) Placebo 2) 53.6 ± 5.0 ↔ values not reported.

RCT (36 months) Significant increase in E2 for all men

1) 83.3 ± 44.4 receiving T. Greater increase in E2
75 men aged > 65 with 1) T enanthate 200 mg IM q 2 week
Amory et al. [98] for men receiving both T and
T < 12.1 nmol/L 2) T + finasteride 2) 71.5 ± 33.7 ↑ finasteride.
3) Placebo 3) 84.0 ± 33.3 pmol/L
Specific values not reported.
38 men aged 20–75 RCT (3 months) 1) 54.5 ± 24.7
Chiang et al. [99] with T < 300 ng/dL 1) Daily androgel 5 g 1) 46.1 ± 23.7
or FT < 8.7 pg/mL 2) Placebo 2) 52.1 ± 16.0 pg/mL ↔ 2) 2) 47.3 ± 21.8
Nonsignificant increase in E2
Retrospective study: gel (137 points), All: 26.0 ± 9.93 pg/mL
211 men, mean age
T enanthate (65), patch (8), buccal (1) Specific values for each group not
55.2 ± 9.7, with
Reyes-Vallejo et al. [100]
T < 300 ng/dL or FT <
1) T levels: 0–200 1) 21.3 ± 12.9
2) 28.3 ± 10.8
↑ provided. Mean increase of 2.37 pg/mL
2) 201–300 in E2 for all subjects.
1.5 ng/dL 3) 26.7 ± 7.85
3) 300+
RCT (30 weeks)
1) T ethanate 250 mg q 3 weeks 1) 27.5 ± 9.33
40 men aged 18–64 1) 23.1 ± 4.96 2) 2) 29.6 ± 8.02
Schubert et al. [101] 2) 2) T undecanoate 1,000 mg q 6–9 weeks
with T < 5 nmol/L
3) Prolonged TRT (N = 32): T undecanoate 2) 2) 21.6 ± 6.91 ↑ E2 rose in parallel with T. Decline in E2
4) 1,000 mg q 8–12 weeks over time with prolonged TRT.

BMI = body mass index; E2 = estradiol; FT = free testosterone; IM = intramuscular; RCT = randomized controlled trial; T = testosterone; TRT = testosterone therapy
Journal of Sexual Medicine . Volume9, Issue6. June 2012. Pages 1681-1696

178
The Effects of Injected Testosterone Enanthate Dose and Age on the
Conversion of Testosterone to Estradiol (E2) and
Dihydrotestosterone (DHT) in Young and Older Men
• Blood samples were derived from healthy young men (aged 18–35 yr) and older men (aged 60–75 yr) with
normal testosterone levels who were participants in a testosterone dose-response study.

• After a 4-wk control period, participants received monthly injections of a GnRH agonist (leuprolide depot, 7.5
mg) to suppress endogenous testosterone production. Concomitantly, the participants were randomized to
receive weekly im injections of TE (Delatestryl, 200 mg/ml) in one of five doses: 25, 50, 125, 300, or 600 mg per
week. Treatment duration was 20 wk.

• Blood was drawn before receiving the hormone injections 7 d after the previous TE injection.

• The Data and Safety Monitoring Board stopped the 600-mg TE dose group due to a number of serious adverse
events in older men in this dose group. After this point, randomization was limited to one of four TE dose
groups: 25, 50, 125, or 300 mg weekly.

J Clin Endocrinol Metab. 2010 Aug; 95(8): 3955–3964.

179
The Effects of Injected Testosterone Enanthate Dose (25-600 mg/week) and
Age on the Conversion of Testosterone to Estradiol (E2) and
Dihydrotestosterone (DHT) in Young and Older Men

Blood Levels of
Total
Testosterone VS
Estradiol and
DHT blood levels

Correction: E2
in pg/mL not
ng/dL

J Clin Endocrinol Metab. 2010 Aug; 95(8): 3955–3964.

180
Serum E2, DHT, E2:T ratios, and DHT:T ratios in response to administration of different
testosterone enanthate doses (25 to 600 mg/week)
Young men (black bars) and older men (white bars)

To convert total testosterone

in ng/dL to nanomoles per
liter, multiply by 0.03467; to
convert free testosterone to
picomoles per liter, multiply
by 3.467. To convert estradiol
concentrations in pg/mL to
picomoles per liter, multiply
by 3.671. To convert total
DHT in ng/dL to nanomoles
per liter, multiply by 0.0344;
to convert free DHT ng/dL to
picomoles per liter, multiply
by 3.44.

181
The Effects of Injected Testosterone Enanthate Dose and Age
on the Conversion of Testosterone to Estradiol (E2) and
Dihydrotestosterone (DHT) in Young and Older Men
• Estradiol and DHT increased with increased T dose. The increase was not directly proportional and reached a

plateau at high T doses.

• Young men’s E2 increased up to 80 pg/ml and older men’s up to 140 pg/ml at 600 mg/week of testosterone

enanthate

• DHT increased as high as 140 ng/dL in younger men versus 230 ng/dL in older men with increased T dose.

• The ratio of metabolites (DHT, E2, and their free fractions) to testosterone decreased with increased T dose. This

means that the percent aromatization to E2 and DHT production by aromatase enzyme decreased with increased

testosterone blood levels.

• E2 and DHT increased more in older men than in younger men. This difference cannot be explained when

considering body composition alone. Age was the main determining factor.

J Clin Endocrinol Metab. 2010 Aug; 95(8): 3955–3964.

182
hCG‟s Effect on Estradiol Stabilizes with Time

Dose:
3,000 IU hCG daily
for 3 days

Ishimaru, T. Plasma Estradiol Concentrations and Effect of hCG on

Plasma Estradiol and Testosterone in Normal Subjects and Patients
with Endocrine Disorders. Endocrinol. Japon. 1975, 22 (4), 287 296

183
DHEA Supplementation Increases Estradiol
Weighted standardized differences (with 95% confidence interval) of E2 at endpoint across RCTs evaluating the
effect of DHEA vs Placebo therapy
Diff. In LL, 95% CI UL, 95% CI P
Source
mean
Nestler et al.,1988 (12) 9.40 -6.60 25.40 0.25
-40 -20 0 20 40 60 80 100 120 26.00 -20.46 72.46 0.273
Morales et al.,1994 (13) 140

85.81 50.32 121.30 0.000

Flynn et al., 1999 (16)
77.94 34.86 121.02 0.000
Flynn et al., 1999* (16)
1.67 -8.09 11.42 0.738
Baulieu et al., 2000 (18)
1.00 -6.71 8.71 0.799
Arlt et al., 2000 (18)
2.57 -27.60 32.75 0.867
Jedrzejuk et al., 2001 (19)
E2 mean Villareal et al., 2004 (24)
41.18 23.65 58.70 0.000
differences 16.00 3.45 28.55 0.012
(pmol/L) Martina et al.m 2006 (26)
20.00 10.62 29.38 0.000
Nair et al., 2006 (27)
50.40 34.30 66.50 0.000
Villareal et al., 2006 (28)
59.50 27.75 91.25 0,000
Jankowski et al., 2008 (29)
3.00 -7.58 13.58 0.578
Von Muhlen et al., 2008 (30)
23.16 8.81 37.52 0.002
Weiss et al., 2009 (33)
24.76 14.14 35.39 0.000
Overall

Placebo E2 w DHEA sup Corona G et al. JCEM 2013;98:3615-3626

184
 TRT ADJUNCTIVE MEDICATIONS: Anastrozole

Anastrozole – Compounded 0.25 mg and 0.5 mg capsules

• This drug inhibits aromatase activity. Over-prescribed due to lack
of data and wrong selection of testing method. Prescribed only if
the patient has a sensitive estradiol value over 50 pg/ml AND
potential gynecomastia (rare) at follow up. Starting dose is 0.25 mg
per week. Most men do not need it. Never prescribe it at TRT start.
• Caution: Low estradiol of 11 ng/mL or below has been associated
with low libido, bone loss, and higher fat gains. Very high estradiol
may cause gynecomastia only in the presence of low testosterone
(low T/E ratio), high IGF-1 along with genetic predisposition.

185
 High Estradiol Management
• Several physicians prescribe anastrozole if estradiol by sensitive test is over 40-50 pg/mL
at follow up. There is controversy about this upper range value for men with higher T.
• 0.25 mg/week is the usual starting dose to be readjusted at second follow up visit.
• Several physicians also prescribe doses as high as 1 mg/day. This is NOT recommended
• Some even prescribe anastrozole when starting TRT irrespective of baseline estradiol . Not
recommended
• Many physicians are still dosing based on the wrong E2 test
• Tamoxifen has been shown in studies to be more effective at reversing early to moderate
gynecomastia than anastrozole. It does so by decreasing estradiol and IGF-1. No data on
the use of other SERMS beyond clomiphene for improved testosterone/estradiol ratios
• Surgery may be required for advanced cases that do not respond to treatment.
• Should we be monitoring or treating based on T/E2 ratio?
• Evolving anecdotal evidence: Lower dose, more frequent testosterone subcutaneous or
intramuscular testosterone injections may cause lower estradiol and hematocrit increases.

186
 Aromatase Inhibitor (AI) Misuse
1- AIs should not be prescribed at TRT start.
2- Sensitive estradiol should be measured after 6-8 weeks
3- A ratio of testosterone to estradiol of 14 and higher may not be a cause of gynecomastia (divide
ng/dL by pg/mL). All men on TRT have that kind of ratios.
4- Unless you have strong genetic predisposition to gynecomastia, AI's should not be used. If AIs are
used, most men do not need doses over 0.25- 0.5 mg per week.
5- Water retention and sensitive nipples are usually NOT a symptom of high estradiol.
6- Using AIs have never been proven to decrease water retention. Water retention on TRT is caused by
sodium retention.
7- It is not easy to recover from crashing your estradiol. Low estradiol can decrease sex drive and penis
sensitivity, bone density and increase fat mass.

187
 Estradiol in Men- Mismanagement Issues
Many physicians are still using the old CLIA test assay that over-estimates E2. The sensitive LC/MS E2 test is recommended.
This results in prescribing anastrozole to men on TRT who do not need it.

Current lab ranges (20- 40 pg/mL) were derived for men who were not on TRT and total testosterone <500 ng/dL. The upper
range max value does not apply to men on TRT.

0.3-0.4 % of T aromatizes to E2, so higher T -> Higher E2. A man on TRT with high T levels can expect his estradiol blood
level to be over the upper limit of the range (>40-50 pg/ml depending on the lab).

In recent studies, low E2 has been associated with low bone density, higher fat mass, worse lipids, and lower libido in men.
Anecdotally, men complain of low penile sensitivity with low E2.

Many clinics are over-prescribing anastrozole and causing low E2 in TRT patients. Most men using normal TRT doses do not
need anastrozole.

Some patients and physicians wrongly associate water retention and nipple sensitivity with high E2 and ignore the increased
TRT-related sodium retention as a cause. Anastrozole treatment is started without E2 testing.

Many TRT patients are afraid of gynecomastia, which is rare in men with high T ( low T/E2 ratio, genetics and high IGF-1 are
contributing factors). Note: Nipple sensitivity is not a sign of early gynecomastia.
Note: Estradiol management is not mentioned by any testosterone guidelines group.
For studies on estradiol in men, Google ―estradiol excelmale.com‖

188
Aromatase Inhibitors

189
 Tamoxifen or Raloxifene (SERM)
• For boys and men with severe gynecomastia that is causing substantial tenderness or
embarrassment, a short course of tamoxifen (sample brand name: Nolvadex, 20 mg daily
for 3-6 months) or raloxifene (brand name: Evista, 60 mg every other day) may be
recommended.

• These drugs block the effects of estrogen (and IGF-1) in the body and can reduce the size
of the breasts somewhat. However, neither of these drugs is approved in the United States
for the treatment of gynecomastia, but they can be prescribed off-label and purchased at
compounding or regular pharmacies.

190
 Other Estradiol Blockers
1. Letrozole (Femara). One study (in women) showed that Arimidex could achieve almost total suppression of estradiol
levels but was still detectable. However, letrozole was even more powerful and could achieve total suppression of
estradiol to where it could not even be detected! Be careful in going too low with estradiol as it can actually lead to
osteoporosis, body aches, mood, and erectile issues, etc

However, in some cases, that slight extra horsepower from letrozole can help with gynecomastia, at least according to
the "common knowledge" on the steroid forums. The general feedback is that anastrozole can prevent gyno usually,
but letrozole can actually reverse it (in some cases). Discuss with your physician of course as letrozole has a reputation
for more side effects.

2. Suicide Inhibitors (such as Aromasin). These "type I" type of aromatase inhibitors do their work using a little different
technique: they actually bind to the aromatase enzyme and permanently and irreversibly take it out of
commission. This may seem really concerning, but the body rebuilds those enzymes after a few weeks. These type of
inhibitors are popular in the steroid community on their own. It may also have mild androgenic properties

One study on young men showed that 25 and 50 mg dosages both reduced plasma estradiol levels by about a third in
14 days.

191
Estradiol Unit Conversion Site

192
 Estrogens- Isoflavones and SERMS
• Nonsteroidal compounds such as isoflavones are sometimes classified as ―phytoestrogens‖ as they are found
in a variety of plants, notably soy. These compounds have a spatial relationship between hydroxyl groups
similar to those found in E2 and can bind estrogen receptor ERb, although only at one-third of the affinity [1].

• Equol, a metabolite of soy isoflavones, can also bind estrogen receptor ERa. However, the bacteria required to
produce equol are not universally present in human flora and circulating serum concentrations are low even
when these bacteria are present [2].

• Isoflavones may also act as E2 agonists (similar to E2) on cell membrane receptors and lead to rapid ER
independent effects [3].

• Pharmaceuticals such as clomiphene citrate and tamoxifen are classified as selective ER modulators (SERMs).
These compounds bind to both ERa and ERb and have agonist and antagonistic activity specific to target
tissues.
[1] Molla MDJ, Hidalgo-Mora JJ, Soteras MG. Phytotherapy as alternative to hormone replacement therapy. Front Biosci 2011;S3:191–204
[2] Messina M. Soybean isoflavone exposure does not have feminizing effects on men: A critical examination of the clinical evidence. Fertil Steril
2010;97:2095–104
[3] Ricketts ML, Moore DD, Banz WJ, Mezei O, Shay NF. Molecular mechanisms of action of the soy isoflavones includes activation of promiscuous
nuclear receptors. A review. J Nutr Biochem 2005;16:321–30

193
 Elevated Estradiol and T Deficiency
• Low T is most often associated with reduced concentrations of E2, not elevated E2. In population-based
studies, total T parallels total E2, even at lower T levels [1].

• A study of men undergoing TRT suggested a limited relationship between T and E2 levels in men. No
difference in E2 was found between men with very low (<200 ng/dL), low (200–300 ng/dL), or ―normal‖ (>300
ng/dL) serum T [2].

• Although the data indicate that most T-deficient men have low or normal levels of E2, some of these men will
have elevated E2. It remains to be determined whether these men respond differently to TRT compared with
men without elevated E2. In addition, it is unknown whether reducing serum E2 provides additional benefits to
these men. While E2 is measured in many studies of TRT, they did not identify any studies that examined the
relationship between E2 and response to TRT. This is a topic that merits investigation

[1] Orwoll E, Lambert L, Marshall LM, Phipps K, Blank J, Barrett-Connor E, Cauley J, Ensrud K, Cummings S. Testosterone
and estradiol among older men. J Clin Endocrinol Metab 2006;91:1336–44
[2] Reyes-Vallejo L, Lazarou S, Morgentaler A. Subjective sexual response to testosterone replacement therapy based on
initial serum levels of total testosterone. J Sex Med 2007;4:1757–62

194
 Elevated E2 During TRT: To Treat or Not To
Treat?
• TRT may lead to elevations in serum E2 and in some cases to levels above the upper limit of normal. The
development of nipple or breast tenderness or frank gynecomastia has been reported in association
with TRT, and in these cases there is a clear indication for the use of aromatase inhibitors to reduce E2.
Some authors recommend withdrawal first of TRT with subsequent resolution of symptoms, followed by
the use of aromatase inhibitors together with reinitiation of TRT [1].

• Some clinicians, particularly in the antiaging community, advocate the routine use of aromatase
inhibitors with TRT even in the absence of symptoms of estrogen excess. These clinicians believe that
maintaining a relatively low estrogen concentration improves male health and the efficacy of TRT.
Emerging data shows that this belief is ill-founded. Blocking estradiol may be as detrimental as
blocking DHT, a metabolite associated with libido.

[1] Rhoden EL, Morgentaler A. Treatment of testosterone induced gynecomastia with the aromatase inhibitor, anastrozole. Int J Impot Res 2004;16:95–7

195
Elevated E2 During TRT: To Treat or Not To
Treat? (2)
• In one randomized controlled trial, treatment of men with low T with anastrozole normalized T
levels, but there was no improvement in symptoms of low T or changes in body composition,
muscle strength, or hematocrit [1]. Further studies of this nature are needed. Furthermore, E2 levels
in some men treated with aromatase inhibitors decreased below 40 pmol/L (11 pg/mL) considered
the threshold at which there is increased risk of developing bone loss changes [2]

• Additionally, case reports of men with congenital aromatase deficiency suggest that aromatase
inhibition may risk decreasing insulin sensitivity, potentially worsened by TRT . Low estradiol may
increase LDL cholesterol and decrease HDL. [3]

[1] Burnett-Bowie AM, Roupeniean KC, Dere M, Lee H, Leder B. Effects of aromatase inhibition in hypogonadal older men: A randomized, double-
blind, placebo controlled trial. Clin Endocrinol (Oxf) 2009;70:116–23
[2] Maffei L, Murata Y, Rochira V, Tubert G, Aranda C, Vazquez M, Clyne CD, Davis S, Simpson ER, Carani C. Dysmetabolic syndrome in a man with
a novel mutation of the aromatase gene: Effects of testosterone, alendronate, and estradiol treatment. J Clin Endocrinol Metab 2004;89:61–70
[3] Rochira V, Madeo B, Zirilli L, Caffagni G, Maffei L, Carani C. Oestrasiol replacement treatment and glucose homeostasis in two men with
congenital aromatase deficiency: Evidence for a role of oestradiol
and sex steroids imbalance on insulin sensitivity in men. Diabet Med 2007;24:1491–5.

196
 Does Adding Anastrozole Improve Libido in
Men on TRT with High E2?
• The only two trials identified in this review that compared the use of TRT with and without an aromatase
inhibitor were conducted in men with hyposexuality (low sex drive) and seizure disorders. Anti-
seizure medications can cause increased prolactin and estradiol. One trial showed a significant benefit in
sexual interest from the addition of testolactone (an aromatase inhibitor) therapy [1].

• A second trial involving 40 men reported a trend toward improved libido in men treated with T and
anastrozole over T alone, although this did not reach statistical significance. Some men in the T-only
group reported improvement in libido despite increases in E2 with TRT [2].

• ExcelMale invites researchers to prove that adding an AI to TRT has any quality of life or lab test variable
benefits.

[1] Herzog AG, Klien P, Jacobs AR. Testosterone versus testosterone in treating reproductive and sexual dysfunction in men with epilepsy and
hypogonadism. Neurology 1998;50: 782–4.
[2] Herzog AG, Farina EL, Drislane FW, Schomer DL, Smithson SH, Fowler KM, Dworetzky BA, Bromfeld EB. A comparison of anastrozole and
testosterone versus placebo and testosterone for treatment of sexual dysfunction in men withepilepsy and hypogonadism. Epilepsy Behav
2010;17:264–71

197
 Elevated E2 During TRT: To Treat or Not To
Treat? – Dr. Morgentaler‟s Opinion
• We find no evidence to support the contention that relative reductions in E2 via the use of aromatase inhibitors
or other agents in conjunction with TRT offer benefits beyond that offered by TRT alone. We do not recommend
the routine use of aromatase inhibitors with TRT.

• Anecdotally, in our practice, there have been rare cases of men who failed to experience symptomatic benefits
from TRT and were found to have elevated E2 concentrations. Some of these men have responded to steps to
lower E2 concentrations, either by reduction in T dosage or by addition of aromatase. However, these cases are
anecdotal, and even if treatment was beneficial, the rarity of such occurrences does not justify the routine use of
aromatase inhibitors together with TRT.

• Moreover, aromatase inhibitors may reduce E2 levels below a crucial threshold for bone health, and dual-energy
X-ray absorptiometry (DXA) monitoring should therefore be considered for individuals receiving such therapy. It
does not appear that naturally occurring elevations in E2 are harmful with respect to T levels or sexual function.

198
 Elevated E2 During TRT: To Treat or Not To Treat? –
Dr. Morgentaler‟s Opinion II
• E2 may increase during TRT, but elevations above the normal range are uncommon. Elevations in E2 may
resolve with prolonged TRT.

• Symptoms of estrogen excess, such as gynecomastia or nipple tenderness, are rare.

• In the absence of signs of estrogen excess, we also find no reason to recommend the use of aromatase
inhibitors in men who experience positive benefits from TRT despite elevated or high-normal E2
concentrations.

Journal Sexual Medicine.Volume9, Issue6. June 2012 . Pages 1681-1696

199
GYNECOMASTIA:
• Not a Simple Diagnosis
Gynecomastia (breast enlargement in men)

Treatment: Estrogen Blocker Medications or surgery (in worst cases)

201
 Gynecomastia: Potential Hormone Factors.
It‟s never one hormone!
Gynecomastia can be affected by:
• Low T, high E2. Low T/E2 ratio?

• Low DHT, high E2

• Normal-high T, high E2, high IGF-1

• None of the above unless there is a genetic polymorphism present

• What is ―High E2‖? Should the level of T determine that value?

• What’s a good range for E2? 20-50 pg/mL? Treating numbers vs symptoms

202
A Longitudinal Study of Growth, Sex Steroids, and IGF-1 in
Boys With Physiological Gynecomastia

Conclusion: Gynecomastia is frequent in pubertal boys. Increased IGF-1 levels and pubertal
growth appear to be associated, whereas changes in estrogen to testosterone ratio seem
negligible.

Mieritz et al; The Journal of Clinical Endocrinology & Metabolism 2015, 100, 3752-3759.

203
 PATHOGENESIS OF GYNECOMASTIA
Absolute deficiency of androgens (hypogonadism)

• Primary hypogonadism

• Klinefelter syndrome

• Testicular trauma

• Cancer chemotherapeutic agents

• Testicular radiation

• Infections (for example, mumps orchitis, leprosy)

• Disorders in enzymes of testosterone biosynthesis: drugs (for example, ketoconazole,

spironolactone, metronidazole); inherited defects in androgen biosynthesis

• Secondary hypogonadism (pituitary and/or hypothalamic damage from disease, surgery or

radiation)
204
 PATHOGENESIS OF GYNECOMASTIA II
Altered serum androgen to estrogen ratio
• Puberty
• Aging
• Refeeding gynecomastia (weight gain after severe illness)
• Renal failure and dialysis
• Hepatic cirrhosis
• Hyperthyroidism
• Drugs (for example, ketoconazole)
Decreased androgen action
• Drugs (for example androgen blockers like spironolactone, bicalutamide, cimetidine)
• Androgen receptor defects
• Absent or defective androgen receptors (complete and partial androgen insensitivity syndromes)
• Expansion of CAG repeats in the androgen receptor gene (such as in spinobulbar muscular atrophy)

205
 PATHOGENESIS OF GYNECOMASTIA III
Increased serum levels of estrogens or estrogen-like activity

• Exposure to exogenous estrogens (intentional or unintentional)

• Increased aromatization of androgens to estrogens (androgens, ethanol abuse)

• Estrogen agonist activity (digitoxin)

Decreased serum testosterone levels

• Hypogonadotropic hypogonadism (Low LH) (caused by gonadotropin-releasing hormone agonists/antagonists

and possibly HAART therapy for HIV)

• Hypergonadotropic hypogonadism (High LH) (possible causes: destruction of inhibition of Leydig cells by
chemotherapeutic/cytotoxic agents (for example, alkylating agents, vincristine, methotrexate, nitrosoureas,
cisplatin, imatinib) or

• Inhibition of testosterone or DHT biosynthesis by ketoconazole, metronidazole, spironolactone or finasteride

and dutasteride)

206
 PATHOGENESIS OF GYNECOMASTIA IV
Androgen receptor blockage caused by • Digoxin
medications • HAART therapy for HIV infection
• Flutamide, bicalutamide, enzalutamide • Human growth hormone
• Cimetidine • Amiodarone
• Marijuana • Calcium channel blockers (for
• Spironolactone example, nifedipine, verapamil,
diltiazem)
• Increased serum prolactin levels
• Amphetamines
• Antipsychotic agents
• Anti epileptic agents
• Metoclopramide
• Possibly calcium channel blockers
• Isoniazid

207
Diagnostic Workup of Patients with
Gynecomastia

Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2017/1504

208
Tests Included in Panel:

TESTOSTERONE, Free and Total

DHT ( Dihydrotestosterone)

Low blood levels of testosterone and DHT in the

presence of high estradiol, IGF-1, thyroid
hormones or prolactin may accelerate the
growth of breast tissue in men

SENSITIVE ESTRADIOL

IGF-1 (Insulin Growth Factor 1)

PROLACTIN

TSH (Thyroid Stimulating Hormone)

FREE T3 (Free Triiodothyronine )

Click here: Gynecomastia Panel

209
Gynecomastia Treatment Studies

Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2017/1504

210
Gynecomastia Treatment Studies II

Journal compilation © Blackwell Verlag GmbH, Berlin | JDDG | 1610-0379/2017/1504

211
 TRT RELATED
DIHYDROTESTOSTERONE
(DHT) INCREASES
• Should We Be Concerned?
The Effects of Injected Testosterone Enanthate Dose and
Age on the Conversion of Testosterone to
Dihydrotestosterone (DHT) in Young and Older Men

J Clin Endocrinol Metab. 2010 Aug; 95(8): 3955–3964.

213
Effect of High Dose DHT Supplementation in Men
• 114 healthy, eugonadal men who received 2 years of either DHT treatment with a
transdermal, pharmacologic dose of 70 mg DHT gel daily, or matching placebo gel.
• they report no DHT-specific effects on prostate volume, with both the treatment
• Compared to placebo, the DHT group demonstrated a decrease in total body fat
mass and in bone mineral density at the spine, but not at the hip, and increased
lean body mass, serum hemoglobin and creatinine.
• The extremely high serum levels of DHT achieved in this study lead to significant
gonadotropin suppression, thereby reducing circulating testosterone levels to
nearly castrate levels and reducing circulating estradiol levels by 90%.
• Bone density decreases were due to decreased estradiol
• Note: There are no FDA approved DHT products in the US. Many doctors are now
prescribing compounded testosterone cream applied to the scrotum skin, rich in
alpha reductase and able to increase DHT moderately.
• Note: A separate study found that DHT cream applied to the nipple area decreased
gynecomastia in HIV+ men. DHT is a powerful estradiol blocker.
• DHT has been linked to libido but using it as monotherapy is not recommended
due to shut down of testosterone and estradiol.

Asian J Androl. 2011 Mar; 13(2): 199–200.

214
 Review of the Effects of DHT on Prostate, Heart
and Body Composition
• The benefits associated with lowered serum DHT levels after 5a-
reductase inhibitor (finasteride) therapy in men have contributed
to a misconception that circulating DHT levels are an important
stimulus for androgenic action in target tissues (e.g., prostate).
• Yet evidence from clinical studies indicates that intracellular
concentrations of androgens (particularly in androgen-sensitive
tissues) are essentially independent of circulating blood levels.
• To assess the clinical significance of modest elevations in serum
DHT and the DHT/testosterone (T) ratio observed in response to
common T replacement therapy, a comprehensive review of the
published literature was performed to identify relevant data.
• Although the primary focus of this review is about DHT in men, we
also provide a brief overview of DHT in women.
Endocrine Reviews 38: 220 – 254, 2017

215
Increased DHT due to TRT: Lack of Effect on the Prostate
• The available published data are limited by the lack of large, well-controlled studies of
long duration that are sufficiently powered to expose subtle safety signals.

• Nonetheless, the preponderance of available clinical data indicates that modest

elevations in circulating levels of DHT in response to androgen therapy should not
be of concern in clinical practice.

• Elevated DHT has not been associated with increased risk of prostate disease (e.g.,
cancer or benign hyperplasia) nor does it appear to have any systemic effects on
cardiovascular disease safety parameters (including increased risk of polycythemia)
beyond those commonly observed with available T preparations.

• Well-controlled, long-term studies of transdermal DHT preparations have failed to identify

safety signals unique to markedly elevated circulating DHT concentrations or signals
materially different from T.

Endocrine Reviews 38: 220 – 254, 2017

216
 Increased DHT Due to TRT: Blood Levels Not Equal to
Tissue Levels
• Circulating levels of DHT in response to testosterone replacement therapy (TRT) do not
correlate with those found in androgen sensitive tissue (e.g., prostate, adipose, muscle)
due to local regulatory mechanisms that tightly control intracellular androgen
homeostasis.

• The modest increases observed in serum DHT and in the DHT/T ratio observed after TRT
are unlikely to be a cause of clinical concern, particularly when viewed in the context of
changes observed in these parameters for currently marketed T-replacement products
and those under development for which DHT data are available.

Endocrine Reviews 38: 220 – 254, 2017

217
 Increased DHT due to TRT: Cardiovascular Disease
Effects?
• While well-controlled, long-term studies designed to specifically examine the effects of androgen
exposure on risk for prostate need to be conducted, the current clinical data base is relatively reassuring
that circulating levels of androgens (or changes in such) apparently do not play as pivotal a role as once
thought in the development of prostate disease.

• Robust epidemiologic or clinical trial evidence of a deleterious DHT effect on cardiovascular disease
CVD is lacking. There is some evidence that DHT therapy in men with CVD may improve clinical status – a
finding that needs confirmation. Data from a longitudinal data base of older normal (i.e., not
hypogonadal) indicated an association between serum DHT and incident CV disease and mortality.
Conversely, others have reported that higher DHT levels in older men were associated with decreased all
cause mortality and reduced ischemic heart disease mortality. Additional exploration in prospective,
placebo-controlled intervention studies of TRT with CVD as the primary endpoint is needed to resolve the
long-term effects of androgens on CVD risks.

Endocrine Reviews 38: 220 – 254, 2017

218
 DHT Effect on Body Composition, Cognition
and Diabetes
• DHT does not play a substantive role in body composition compared to T under normal conditions. Thus,
elevated levels of DHT in response to TRT are unlikely to appreciably impact lean or fat mass. Nonetheless,
data from animals suggest a role for DHT in adipose tissue that inhibits biochemical pathways involved in
lipid synthesis and promotes several transcripts associated with apoptosis of adipocytes. Whether these
DHT-induced effects also occur in human adipose tissue remains an area for future study.

• There is very limited data available regarding DHT and effects on cognition. Further research is needed,
particularly in light of animal data where DHT positively modified synaptic structure and significantly
delayed cognitive impairment in a well-regarded animal model for Alzheimer’s disease.

• Recent data indicating that higher levels of DHT were inversely associated with insulin resistance and
risk of diabetes merit further mechanistic investigation to understand whether this action is separate
from that of T.

Endocrine Reviews 38: 220 – 254, 2017

219
TRT-RELATED ACNE
AND HAIR LOSS
• Treatment Strategies
 Managing TRT-Related Acne
Caused by Dihydrotestosterone (DHT) effect on increased oil production.

More common in those with history of acne at young age. Back and shoulders more common than face and legs.

· Accutane – a powerful prescription item - 40 mg/day for one week sometimes stops acne if started at the first sign.
Accutane is potentially highly liver toxic and can lower testosterone. Do not use unless as last resort and for a short
time. Another safer option is Retin-A/Tretinoin cream

- Minocycline (antibiotic and anti-inflammatory)

· Sporanox – Effective for some acne-like eruptions that are caused by fungi. Some physicians also prescribe
antibiotics, like tetracycline or minocycline, for acne with good results.
. Shower with Nizoral shampoo· Anti-bacterial soaps - Use a scrubbing brush and wash twice a day, especially after
sweating during a workout.
· UV light or sunlight with moderation.

. Avoid whey and creatine supplementation

. Zinc/copper supplements, zinc-based soaps and benzoyl peroxide creams/washes may help some men with acne.
Some reports of increased acne with the use of whey protein and creatine.

221
 FDA Approved Branded
Products for Acne
• Sarecycline
• Tetracycline based (antibiotic)
• Altreno
• Tretinoin 0.05% (drying agent)
• Onextron
• Clindamycin phosphate (antibiotic) and benzoyl peroxide (drying
agent)
• Differin Gel
• Over the counter retinoid. Adapalene Gel 0.1%
• Aczone Gel
• Dapsone 7.5% (antibiotic)
• Trifarotene Cream
• New retinoid

Note: Acne can be confused with folliculitis

222
Acne Creams and Lotions Made by Compounding Pharmacies

223
 Managing Potential TRT-Related Hair Loss

· Nizoral shampoo– Available by

prescription and over-the counter as a
Caused by DHT effect on hair follicles.
lower dose product.
Mostly not an issue in men over 45
· Rogaine – Available over the counter
years of age. High DHT, nutrition,
· Propecia (finasteride) - Available by
stress , medication side effects and
prescription. Warning: Men
genetic factors play a role in hair loss.
experience decreased erections with
finasteride. Do not use.

224
Post- Finasteride Syndrome: DHT Blocker Decreases
Libido and Mood in Some Men

Source

225
 Biotin (also known as vitamin B7 or vitamin H) is a water-soluble vitamin that
serves as an essential cofactor for carboxylase enzymes in multiple metabolic
pathways.

Warning: It has been shown in some studies to work well only in people with biotin
deficiency. However, most Americans get enough biotin in their diets.

Biotin
Supplements Biotin can interfere with hormone blood tests. Most of the published
research on biotin interference covers hormone tests, such as parathyroid
for Hair hormone (PTH), thyroid stimulating hormone (TSH), T4 and T3 tests, as well
as tests for troponin. However, because biotin is used in so many

Growth immunoassays, scientists say it could interfere with many others.

If you are taking a biotin supplement, please stop it at least 4 days before
getting your blood drawn.

226
 Andro-Block for Hair Restoration
• Empower Pharmacy offers custom compounded scalp solutions for hair restoration.

• Andro-Block products combine these ingredients into a single solution designed for
specific goals

• Multiple formulas available to allow for treatment customization

• Latanoprost: Active Ingredient of Latisse (eye lash growth liquid)

• No data on scalp hair growth

227
 TRT RELATED WATER
RETENTION AND HIGH
BLOOD PRESSURE
• Misconceptions and Concerns
 Testosterone-Related Water Retention
• Some men can gain a few pounds during the first 8 weeks of treatment due to water retention. This
issue may resolve after a few weeks.
• TRT can reduce urinary sodium excretion from the kidneys. The body compensates by diluting
sodium with water.
• TRT reduces Aldosterone production. Aldosterone regulates the retention of sodium, the secretion
of potassium, and water reabsorption, all of which may result increased blood pressure.
• Most men assume that water retention is due to high estradiol (most do not get tested to confirm
this belief and start AI treatment)
• Anastrozole has not been shown to decrease water retention.
• The as-needed use of potassium sparing diuretics is sometimes prescribed.
• Severe edema cases require a cardiovascular workup if lower extremity edema is present to rule out
risk of peripheral artery disease.
• Some men report improvements in water retention with cardiovascular exercise and reduction in salt
intake.

The Journal of Clinical Endocrinology & Metabolism, Volume 90, Issue 7, 1 July 2005, Pages 3989–3994

229
 High Blood Pressure Consequences: Effect of BP
Meds on ED
• Consequences of uncontrolled hypertension : ocular/renal/vascular disease. Loss of visual
acuity, end stage renal disease (dialysis), Erectile dysfunction/vascular dementia/Hypertensive
heart disease.

Journal of Clinical Hypertension, Volume 8, Issue5. May 2006. Pages 359-363

230
TRT-Induced Lower Extremity Edema:
Concerns for Peripheral Artery Disease

TRT water retention occurs because of

changes in sodium retention. Many men
wrongly assume it is due to high estradiol.

231
ERECTILE DYSFUNCTION/
LOW LIBIDO-
• Causes and Treatments
 When Testosterone is not Enough
Fatigue- When Testosterone Is Not Enough

When Testosterone Doesn’t Lead to Better Erections

Penis Injections for Hard Erections: TRIMIX

Erectile Dysfunction 101 – Facts, Causes, and Management Options

Where to Buy Cheaper Generic Cialis Without a Prescription

Treatments for Men who Fail to Benefit from ED Medications

The benefits of long-term use of Cialis

The Effect of Sleep on Your Hormones, Erections, Body, and Quality of Life

Effect of Blood Pressure Medications on ED

Are you tired even with normal testosterone? Adrenal fatigue may be the problem.

Erection Pills- Do They Work?

233
 When Testosterone is not Enough II
New Affordable Erectile Dysfunction Panel at Discounted Labs

Erectile Dysfunction Risk Linked to How Many Medications Are Taken

How Do ED Drugs Compare? Cialis vs. Viagra vs Levitra vs Stendra

Video: How to Inject Trimix

Where to find syringes, ED drugs, doctors, HCG, and much more.

Most Important Testosterone, HCG, Anastrozole, Trimix, etc. Fact Sheets on

ExcelMale

Download Nelson Vergel's Testosterone and Erectile Function Lecture Handout

234
 Causes of Erectile Dysfunction
Risk factors Examples
Stress
Diabetes Aging
Anxiety
Antihypertensives, antidepressants,
Heart Medication
digoxin, spironolactone
Depression disease
Smoking, obesity, sedentary lifestyle, alcohol
Lifestyle
Obesity High Blood and drug abuse
Pressure
Psychological Depression, performance anxiety or
Neurological disorders stress
Smoking diseases
Atherosclerosis, ischemic heart disease,
Vascular disorders
Vascular peripheral vascular disease
Lack of disease
exercise
Stroke, multiple sclerosis, spinal cord injury,
High Neurological disease
pelvic trauma or prostrate surgery
Alcohol cholesterol
abuse
Endocrine
Relationship Low testosterone
abnormalities
Problems
Hypertension, dyslipidemia, diabetes
mellitus, cardiovascular disease, chronic
Chronic illness
renal failure, heart failure, chronic
obstructive pulmonary disease

235
 Erectile and
Libido
Questionnaire
Used
By Physicians

236
237
MEDICATIONS ASSOCIATED ALTERNATE SOLUTIONS MEDICATIONS ASSOCIATED ALTERNATE SOLUTIONS
WITH ED WITH ED

Cardiovascular Antidepressants
Betablockers Hydralazine ACE inhibitors SSRI Buproprion
Methyldopa ACE II inhibitors Tricyclic antidepressants Mirtazapine
Alpha-blockers Ca++ channel blockers MAOI

Diuretics Antipsychotic agents

Thiazide diuretics Furosemide Conventional neuroleptics Quetiapine
Spironolactone (loop diuretics) Risperidone Olanzapine

Hormone agents Gastroesophageal reflux & ulcers

Anti-androgens (e.g. Varies depending on Cimetidine Other H2 antagonist or PPI
cyproterone) indication
Corticosteroids
Antiparkinsonian agents Anticonvulsants
Levodopa At the neurologist’s discretion Carbamazepine At the neurologist’s discretion
Phenytoin
Miscellaneous:
Phenothiazine antiemetics, opioids (chronic use), digoxin, ketoconazole, lithium

Drug-induced male sexual dysfunction. Pharmacist's Letter/Prescriber’s Letter 2006; 22(9):220907.

238
 Heart Cholesterol Surgery
Disease
Alcohol &
Obesity
Drugs

High Blood Organ

Pressure Failure

Low Sexual
Desire
High
Diabetes
Prolactin

Poor
Medications
Sleep
Low Stress and
Injury
Testosterone Depression

239
 Current ED Treatment Approaches
Male patient diagnosed with ED

~75%
1st line Oral ED therapies Prescribed by both
therapies
(Viagra, Cialis, Levitra, Staxyn) Urologists & PCPs

~5% <10% <5%

2nd line Urethral Injectable Vacuum

therapies (Trimix, Caverject,
gels etc) pump
Primarily prescribed
by Urologists
~5% <1%

3rd line Corrective

therapies Penile implant vascular surgery

Source: Adapted from American Urologic Association Treatment of ED Guidelines, emedicine.com,

L.E.K. Consulting Interviews and analysis.

240
 Medication
Medication Viagra (sildenafil) Levitra (vardenafil) Cialis (tadafil) Stendra (avanafil)

Type PDE-5 Inhibitor PDE-5 Inhibitor PDE-5 Inhibitor PDE-5 Inhibitor

Dose 25-100 mg 5-20 mg 5-20 mg 50-200 mg

Peak Time 1 hour 42-54 minutes 2 hours 15-30 minutes

Gone from body 8-12 hours 8-12 hours 36 hours 8-12 hours

Contra-indicated Nitrates Nitrates Nitrates Nitrates

FDA Approval 3/29/98 8/20/03 2/02/04 4/1/12

No food or drink 1-2 hours

Effects of eating and drinking Not effected by food or alcohol Not effected by food or alcohol Not effected by food or alcohol
before

Headache, flushing, nasal Headache, flushing, nasal

Headache, flushing, nasal
Side Effects congestion, abnormal vision,
heartburn, bloodshot eyes
Headache, flushing, nasal
congestion, heartburn, congestion, heartburn,
congestion, abnormal vision,
bloodshot eyes, backache, leg bloodshot eyes, backache, leg
heartburn, bloodshot eyes
cramps cramps

For many patients the most

Greater selectivity (and thus Greater selectivity (and thus
potent. Negatives are shorter Greater selectivity (and thus
usually fewer side effects) than usually fewer side effects) than
Other half-life (than Cialis), less usually fewer side effects) than
Viagra. Slower to take effect Viagra. Slower to take effect
effective when taken with fatty Viagra.
when taken with fatty meal. when taken with fatty meal.
meal. Most side effects.

241
 38% of Men Do Not Respond Well to Oral ED
Medications

Most important considerations Most important reasons for

when staring ED medications: discontinuing ED medications:

Av. Reasons for discontinuation (quantitative data) %

Variables No. Pts Importance Score Importance Rank
Rank
Non-effectiveness 38.0
Cure 1.57 30 2.67 1
Erection recovery 22.3
Pleasure 2.63 40 3.35 2
Concerns about cardiovascular safety of PDE5 15.7
Partner Satisfaction 2.04 27 3.85 3
Cost 13.7

Reproduction 2.16 19 5.80 4 Secondary effects 12.3

Naturalness 2.13 16 6.79 5
Lack of sexual opportunity 11.5
Control 2.57 14 9.36 6
Other treatments 9.3
Duration 2.33 12 9.90 7
Lack of spontaneity 8.7
Spontaneity 2.78 9 15.75 8
Fear of drug dependence 6.0
Penetration 2.00 6 17.00 9
Decreased sexual interest 5.4
Times/wk. 2.75 8 17.53 10
Constrain/embarrassment in obtaining the drug 2.7

242
Compounded Erectile Dysfunction Products

243
Intracavernosal Penile
Injections
• Tri-Mix is a mixture of Papaverine, Phentolamine, and Prostaglandin
• Only offered by compounding pharmacies
• More effective in smaller doses than if these compounds were used
individually
• 503B Outsourcing Facilities who specialize in ED offer numerous
strengths and combinations that include aprostadil
• Lyophilized version preferred for longer shelf-life (lower cost to the
patient)

244
245
246
247
 Penile
Prosthesis
Indications:
• Patients who have
failed other therapies
• Pyronine's disease
• Severe vasculogenic
disease

248
 Three-Piece Inflatable Penile Prosthesis
• Most closely approximates the feel of a natural erection

• Cylinders expand in girth

• Some cylinders have the potential to expand in length

• When inflated, it feels firmer and fuller than other prosthetic erections

• When deflated, it feels softer and more flaccid with better conceal ability than with other
prosthetic devices

• Negative: An average loss in length of 0.5-1 inch has been reported

249
CLINICAL USE OF FDA-
APPROVED ANABOLIC
STEROIDS
 Clinical Use of FDA Approved Anabolic Steroids
Nandrolone (Deca Durabolin) Studies in Humans

Steroid Belly: Anabolic Steroids Increase Visceral and Decrease Subcutaneous Fat in Bodybuilders

Does anyone use Nandrolone (Deca Durabolin)?

All About Oxandrolone

Recovery of sperm production following testosterone replacement or anabolic steroids

Use of Testosterone and Anabolic Steroids in Patients Who Have HIV

How to decrease HIV related belly fat accumulation

Starting TRT with stage IV Bowel Cancer age 35 in the U.K.

Anabolic Steroid Side Effects- Part 1

Anabolic/Androgenic Hormone Prescribing Indications

FREE Nelson's First Book: Built to Survive- Medical Use of Anabolic Steroids

251
 Injectable:
• Testosterone Cypionate and Enanthate, 100

FDA mg/ml, 200 mg/ml (compounded and

branded)

Approved
• Testosterone decanoate (Aveed), 750
mg/3ml

Anabolic
• Nandrolone decanoate (compounded), 200
mg/ml

Steroids for
Human Use-
Clinical Label and
Oral:
• Oxandrolone (compounded and generic. Old
Off Label Uses brand name: Oxandrin), 20 mg
• Stanozolol (Winstrol), 5 mg
• Oxymetholone (Anadrol-50), 50 mg

252
 Presentation: Injectable (IM-Depot) 100mg/mL; 200mg/mL
X 10mL

Nandrolone Common dose range: 100-200 mg per week along with TRT

Decanoate: Active-life: 7-10 days post injection

The Most Like all anabolics, it shuts down endogenous T production

Researched
Injectable Treatment and Indication:

Anabolic FDA approved in 1983 for treatment of Osteoporosis; anemia;

Steroid
and to treat some forms of neoplasia including breast cancer.

Indicated for the treatment of anemia associated with chronic

and acute renal failure.

253
 Nandrolone is indicated for Cachexia, most
commonly in the form of HIV/AIDS wasting
syndrome; Wasting caused by tuberculosis

Nandrolone
and cancer cachexia

Decanoate
Clinical Off- To induce an increase in nitrogen retention and feed-

Label Uses efficiency for patients suffering metabolic acidosis.

To treat musculoskeletal injuries and soft tissue trauma.

Nandrolone is also prescribed to improve joint pain/injury.

To treat muscle loss due to M.S and other neurological

disease.

For more information click here

254
• Hypogonadal men taking injectable testosterone
therapy ( presenting to a single andrology clinic
between July 2018 and October 2018) were evaluated
for the presence of joint pain.

• Men who reported significant joint pain and denied

prior nandrolone usage were invited to take part in the
study.

• Study participants completed the Rheumatoid Arthritis

Pain Scale (RAPS), a validated questionnaire initially
developed to assess/characterize pain levels in adults
with rheumatoid arthritis.

255
 Nandrolone and Joint Pain- Results
• 48 eligible patients completed the initial survey and 18 men (37.5%) responded to follow-up requests at

the time of this review.

• Mean duration of therapy was 63 days.

• 13 men reported marked improvements in joint pain (JP) (72%) with 5 (27.8%) reporting a decreased

need for pain medication

• Nandrolone (ND) is a promising new adjunctive therapy for hypogonadal men with JP. It reduced pain

scores by an average of 52% in responding patients and decreased pain medication requirements in

27.8% of patients

• Reducing pain medication needs is paramount in today’s opioid crisis climate. Further studies are

required to better characterize ND’s effects across a larger study population and understand it’s efficacy.

256
 Oxandrolone is indicated as an adjunctive therapy to promote weight-gain after weight
loss following extensive surgery, chronic infections; or severe trauma, and in some
patients who without definite pathophysiologic reasons fail to gain or maintain normal
weight. Over 48 studies in humans.

Oxandrolone: Presentation: Oral Capsule; Tablet; Sublingual Troche

The Most
Researched
$1500 for 60 – 10 mg tablets (Commercial Product)

Oral Anabolic
Steroid
Compounded oxandrolone: $230 for 30- 25 mg capsules

Approved by Common daily dose range: 2.5mg (children), 10mg (women), 20-50mg (men) daily

the FDA
Active life: 9h-12h. Minimal effect on liver enzymes. It decreases HDL cholesterol.

For more information click here

257
For more information on
nandrolone and
oxandrolone: Free
Download Here

https://powerusa.org/books/Built_to_Survive.pdf

258
FERTILITY AND HPTA
RECOVERY
 Hypothalamic-
Pituitary-Testicular Axis
Hypothalamus
H
GnRH

Pituitary
P (HPTA)
Testosterone LH FSH

TRT or anabolic steroids shut down

the HPTA due to a negative feedback
Testis
mechanism. LH, FSH and sperm
T
count decrease dramatically.

• GnRH: Gonadotropin Releasing

Testosterone
Hormone

• LH: Luteinizing Hormone

Sperm

• FSH: Follicle Stimulating Hormone

Adapted from Bagatell CJ, Bremner WJ. N Engl J Med.

1996;334:707-715.

260
Micronutrients and Sperm Count/Quality

261
Can Men That Stop Anabolic Steroids Normalize their
Sperm Count and Quality Without PCT (Post Cycle
Therapy)?

Factors that Predict Normalization: Younger age, normal T at baseline, & shorter exposure time

262
 HPTA Restoration Facts
• There is no agreement on what the best HPTA restoration protocol is for
men with history of testosterone and anabolic steroid use whose sperm
quality/count and testosterone remain suppressed after weeks of
treatment cessation. No controlled studies have been performed due to
the stigma associated with anabolic steroids.

• Men with low testosterone at baseline may never restore normal T

production even after a HPTA protocol.

263
 Mechanism of Action of HPTA Restoration
Therapies

Endocrinology, Diabetes and Metabolism. 17-0055; July 2017

264
Medications used for Hypothalamic-Pituitary-
Testicular (HPTA) Stimulation
• Clomiphene is a SERM used to stimulate pituitary output of LH
and FSH

• HCG can be used as a short term mono-therapy to stimulate

testicular production of T

• Clomid and HCG stimulation protocols are typically

administered separately; HCG can cause negative feedback
within the pituitary resulting in blunted LH and FSH release

265
Commonly Used Medications for Maintenance or Restoration of Sperm
Production After Anabolic Steroid or Testosterone Use

• Predictors of successful treatment: Baseline testosterone, younger age and shorter exposure to androgens.
• AIs not recommended due to health risks associated with low estradiol.

Asian J Androl. 2016 May-Jun; 18(3): 373–380.

266
267
Clomiphene (Clomid) Use for Fertility and HPTA
Recovery

How to Improve Sperm Quality, LH, FSH and Testosterone in Infertile Men

Are guys that do well on low dose Clomid unicorns...or do they really exist?

FSH dosage effect on conventional sperm parameters: a meta-analysis of RCTs

FSH therapy for idiopathic male infertility: four schemes are better than one

Clomid & Testosterone: Why they don't work together - By Mike Gaiso

Clomid for Men: What Every Man Needs to Know

Post - PCT Blood Test Panel

Is Clomid (Clomiphene) Effective to Increase Testosterone, Fertility, and Sperm Volume?

268
 Clomiphene Citrate
Nonsteroidal hormone
An anti-estrogen (SERM) E22
Increases GnRH output
GnRH
Rx T
12.5-25 mg/day T
Labs: LH, FSH, T @ 4 wks.
Monitor semen q 3 mos.
LH
Side Effects: gynecomastia, FSH
weight gain, visuals, acne, Leydig Cells
low sex drive

Courtesy of Dr. Paul Turek

269
 Algorithm for Treatment
Anabolic steroid–induced of Anabolic
hypogonadism (ASIH): Steroid
diagnosis and treatment

Induced Hypogonadism

SQ: Subcutaneous
hCG: Human Chorionic
Gonadotropin
SERM: Selective Estrogen
Receptor Modulator- clomiphene
Endogenous: Natural Production Fertility and Sterility Volume 101, Issue 5, Pages 1271-1279 (May 2014)
T: Testosterone Fertility and Sterility 2014 101, 1271-1279DOI: (10.1016/j.fertnstert.2014.02.002)

270
 Example of HPTA Normalization Protocol
HCG 350-500iu daily X 14 days, FOLLOWED by

Clomiphene 25mg daily X 28 days (6 week cumulative

regimen).

Labs Needed at the end of the protocol (Before HPTA protocol start and at 6 weeks after
cessation): Testosterone Free and Total, Sensitive Estradiol, semen analysis, LH, FSH, CBC &
CMP

If the patient does not respond to the HCG + Clomid after 2 cycles, then it can be
assumed there is possible primary hypogonadism.

In this case it is best to suggest continuing TRT so that T levels remain optimal and the
patient’s life quality and health also remain optimal. hCG plus FSH may be used in fertility
is desired.

271
Anabolics: Spontaneous Recovery of Sperm Count
3 mill/mL 20 mill/mL
0 @ 2.5 mos. @ 3.4 mos.
1 67% @ 6 mos.
90% @ 12 mos.
100%@ 24 mos.
4
Stop 10 mill/mL
Anabolics @ 3 mos.

•Analysis of 1549 eugonadal men age 18-51 years (90% of published data)
• Patients followed after discontinuation of androgens.
•Variables: older age, Asian, shorter treatment duration, higher baseline counts, less time to
suppression, lower baseline LH
•It took at least a year for the majority of men to normalize sperm count.

Liu et al. Lancet. 2006, 367: 1412

272
 Gonadotropins
(hCG, hMG, FSH)
Give LH and FSH formulations to drive testicle function

Rx hCG, 1,500-3,000 IU S.Q. 3x weekly

hMG 75-150 IU S.Q 2x weekly
rFSH 150 IU SQ 3x weekly
Check serum testosterone levels after 4 weeks
Follow semen analyses q 3 months.

Side Effects: expensive, compliance, injection site reaction.

Efficacy: No controlled trials.

Courtesy of Dr. Paul Turek

273
 Anabolics: Recovery of Spermatogenesis with
Gonadotropins
hCG 2500 IU 3x weekly
+/- rFSH 150 IU 3x weekly
2 3 4 mos.
1
0

Taper off
Reduce Gtropes Stop Gtropes
anabolics
by 50%

• Goal: drive native testosterone production while tapering off anabolics

• Goal: earlier return of endogenous T levels and sperm production (unproven)

Menon DK. Fertil Steril. 2003, 79: suppl 3, 1659

274
hCG Preserves Sperm Counts While on Anabolic
Steroids
hCG 500IU 2x weekly 1 2 Cycle ends
0 30 mill/mL@1.5 mos.
70 mill/mL@ 6 mos.

Anabolics 33 mill/mL
1/18 azoospermic

• N=18 Finnish power athletes on ―massive anabolic doses‖

• Instructed to also take hCG 500 IU 2x weekly with anabolics
• Followed semen quality over time on combination therapy
• Spermatogenesis maintained despite prolonged, massive doses of anabolics
Karila et al. Int J Sports Med. 2004, 25: 257

275
 Recovery of Testosterone with SERMS (Selective
Estrogen Receptor Modulators)
Clomiphene citrate 25mg q.d
Tamoxifen 10mg q.d

3 4 mos.
1 2
0

Reduce SERM Stop SERM

by 50%

• Goal: support testosterone production during stress

• Goal: taper off SERM as stress falls
• Reasonable to consider for mild hypogonadotropic hypogonadism and sexual symptoms

Moskovic et al. BJU Int. 2012. Epub March 28

276
 Recovery of Testosterone with SERMS
3 Yr. response to clomiphene citrate
• N=46 men with T < 300 ng/mL from 2002-2006
• Given clomiphene 25mg/day. Titrated dose to T 500-600 ng/dL
• Followed labs q 6 mos. (T/gonadotropins)
• Mean age 44 yrs. Mean baseline T=228 ng/mL
• Mean T @ 1 yr. = 612 ng/dL
• Mean T @ 2 yrs. = 562 ng/dL
• Mean T @ 3 yrs. = 582 ng/dL
• Mean femoral neck and lumbar spine bone density higher
• ADAM scores 7 to 3 at 3 yrs.
Moskovic et al. BJU Int. 2012. Epub March 28

277
hCG + FSH Studies: Effect on Sperm
Production

Asian J Androl. 2016 May-Jun; 18(3): 373–380.

278
Commercial Menotropin Product
MENOPUR®
Contents: 75iu FSH/75iu LH*

Presentation: Each box contains 5 bottles containing lyophilized HMG

Problems:

• High cost making it unaffordable to many patients ($85/75iu vial)

• 1:1 ratio making it difficult and costly to titrate individual gonadotropins

• Increased injection pain due to higher volume injections

• Increased risk of non-compliance due to labor needed to reconstitute

multiple vials or administer multiple injections needed to achieve
desired dose

• Lower Cost FSH or HMG from compounding pharmacies can make

fertility seeking more economical than using this brand name product.

279
Follicle Stimulating Hormone (FSH)
• Available as lyophilized FSH both
commercial and compounded

• Used concurrently with hCG to increase

fertility in males

• Compounded version significantly lower

cost than commercial

• Empower Pharmacy offers the lowest

cost FSH in the U.S.

280
 HMG Custom Compounded Product

• Effective for Improving Fertility in Men on TRT

• Proposed Formula: FSH 4000iu/LH 2000iu

• Contents: 4000iu of Urinary FSH + 334iu

urinary HCG

• Dosage Form: Subcutaneous injection

• Presentation: Lyophilized powder for injection:

containing 4000 IU FSH and 2000 IU of LH
activity, supplied as lyophilized powder cake in
sterile vials with diluent vial

281
 FSH :1200iu
Compounded HCG
Gonadotropins • 6,000iu
Used in Fertility • 12,000iu
• 50,000iu

282
 GROWTH HORMONE
RELEASING PRODUCTS
 Peptide Information and Descriptions
Oral growth hormone enhancer MK-677 (ibutamoren)
Thoughts on ipamorelin?
Libido Peptide for Men and Women: PT 141 (Brand: Vyleesi for
General Premenopausal women)

Growth
IGF-1 Roles and Benefits
Sermorelin Use - Good Information to help you.

Hormone How to care for and store your HCG (or any peptide)
Growth Hormone Product Review
Releasing Increase your growth hormone: Slide Handout

Secretagogue Video: Growth Hormone Releasing Hormones and Peptides: Research

History

Information Sermorelin, GHRP2, and GHRP6: How does your Doc Prescribe?
Growth Hormone versus GHRH Peptides- Legalities and other
considerations

284
Hypothalamic/Pituitary Hormone Release

285
Growth Hormone (GH) Release, Effects and
Inhibition

286
 Ways to Increase Growth Hormone and IGF-1
• IGF-1 (Insulin Growth Factor 1) level is surrogate marker for GH activity in the body due to
diurnal and pulsatile secretion pattern. (for GH section). It can be increased by:

• Exercise

• Fasting

• Recombinant hGH

• Sermorelin and other growth hormone release hormones (GHRP 2, Ipamorelin)

• Ibutamoren (oral Ghrelin analog)

• Higher dose testosterone

• Arginine or Citrulline

287
 GH Legalities
• Human growth hormone is not controlled under the Controlled Substances Act (CSA).

• However, as part of the 1990 Anabolic Steroids Control Act,

• the distribution and possession, with the intent to distribute, of GH “for any use…

other than the treatment of a disease or other recognized medical condition, where such use has been
authorized by the Secretary of Health and Human Services…

and pursuant to the order of a physician…” was criminalized as a five-year felony under the penalties chapter
of the Food, Drug, and Cosmetics Act of the FDA.

• Prescribing GH for adult growth hormone deficiency has to be based on strict GH stimulation tests to justify it.
Many insurance companies refuse reimbursement and the cash price is prohibiting to most patients.

• GH secretagogues are also not controlled and can be used without the requirements imposed on GH use.
They provide physiologic GH levels and are cost-effective.

288
 Proving GH Deficiency-GH Stimulation
Tests: Labor Intensive
• A GH level by itself is meaningless in the evaluation of GH deficiency

• Provocative agents include clonidine, L-dopa, arginine, insulin, glucagon,

and GHRH

• Fasting 8-12 hours

• 5 blood samples, first between 6-8 am, then the provocative agent is
administered via IV. 30 minutes after that another blood sample,
repeated every 30 minutes
• Normal peak value, at least 10 nanogram per milliliter (ng/mL) or 10 microgram/L

• Indeterminate, 5 to 10 ng/mL or 5 to 10 microgram/L

• Subnormal, 5 ng/mL or 5 microgram/L

• (A normal value rules out GH deficiency; in some laboratories, the normal level is 7 ng/mL
or 7 microgram/L.)

• An easier test uses a recently approved Ghrelin analog called Macrilen

289
Insurance: Medical necessity GH use
requirements
• Aetna considers GH treatment of adults with documented GH deficiency
medically necessary when all of the following criteria are met at initiation
of treatment as an adult:
– Member has GH deficiency as a result of hypothalamic or pituitary disease (e.g.,
panhypopituitarism, pituitary adenoma, trauma, cranial irradiation, pituitary surgery) and at
least one other hormone deficiency diagnosed (except for prolactin deficiency); and

– Member is already receiving adequate replacement therapy for any other pituitary hormone
deficiencies; and

– Member has a severe GH deficiency, defined as a peak GH response of less than 9 mIU/liter (3
ng/ml) during an insulin tolerance test or a cross-validated GH threshold in an equivalent test
(growth hormone releasing hormone, arginine, or glucagon); and

– Member has a perceived impairment of quality of life (QoL), as demonstrated by a reported

score of at least 11 in the disease-specific 'Quality of life assessment of growth hormone
deficiency in adults' (QoL-AGHDA) questionnaire .

– Aetna considers this treatment medically necessary for an initial 9 months, allowing for an
initial 3-month period of GH dose titration, followed by a 6-month therapeutic trial
period. Subsequent GH treatment is considered medically necessary only if, upon subsequent
testing of the effect of this treatment, the member demonstrates a QoL improvement of 7 or
more points in QoL-AGHDA score

290
Available Products Involved in GH Release

Hormones involved and related analog drugs

1 2 3 4
Growth Hormone Ghrelin Somatostatin Growth Hormone
Releasing Agonists: 1. Synthetic human
Hormones: 1. GHRP 2 & 6 growth hormone
1. Sermorelin 2. Ipamorelin (rHCG)
2. Tesamorelin 3. Ibutamoren

291
 Growth Hormone Releasing Hormone
(GHRH)
• Produced by hypothalamus

• Stimulates GH synthesis and RELEASE

• Binds to GHRH-R in pituitary

• Short half-life

• Increases number of somatotrophs AND amount of

GH from each

• No down regulation with supplementation

• Natural production inhibited by fatty acids

292
 Growth Hormone
Secretagogues (GHS)
• GHRS belong to a broader class of compounds all of
which share the common trait of being able to bind to the
Growth Hormone Secretagogue Receptor (GHS-R) and
effect GH release.

• These compounds include the synthetic peptides (GHRP-

6, GHRP-1, GHRP-2, Ipamorelin) and smaller synthetic
non-peptide molecular compounds such as Ibutamoren as
well as the natural ligand Ghrelin.

• This broad class which includes all of the above but not
Growth Hormone Releasing Hormone (GHRH) is termed
Growth Hormone Secretagogues (GHSs).

293
 hGH vs GHRH / GHRS
• GHRH / GHRS significantly less expensive than rHCG

• HGH overdosing is minimized or completely avoided with GHRH / GHRS

• Tissue exposure to hGH released by the pituitary under the influence of GHRH / GHRS is episodic
not ―square wave‖, preventing diminished response by mimicking normal physiology

• By stimulating the pituitary, GHRH / GHRS preserves more of the growth hormone
neuroendocrine axis which fails first during aging

• GHRH / GHRS blocks the cascade of hypophyseal hormone failure that occurs during aging,
thereby preserving youthful anatomy and physiology

294
DHEA SUPPLEMENTATION
 DHEA Supplementation
• Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are steroid hormones mainly secreted by the adrenal
gland with a daily production rate of approximately 5 to 8 mg and 6 to 20 mg, respectively.

• DHEA-S is generally considered a large plasma reservoir of DHEA because the 2 hormones can be interconverted
by extra-adrenal sulfotransferase and sulfatase enzymatic activities

• Several experimental and uncontrolled studies have documented that DHEA and DHEAS might be implicated in a
broad range of biological abnormalities including obesity, diabetes, osteoporosis, sexual dysfunction, cancer, and
mental disorders, leading to speculation that a relative DHEAS deficiency may contribute to the development of
common age-related diseases or diminished longevity. Accordingly, there is a widespread, although non
supervised, use of DHEA as a dietary supplement for elderly people, in the hope of finding the fountain of youth.

• A metanalysis has found no effect of DHEA supplementation in comparison with placebo was observed for
various clinical parameters including lipid and glycemic metabolism, bone health, sexual function, and quality of
life.

• DHEA has been found to increase estradiol in men.

296
 DHEA Supplementation II
• DHEAS is secreted by the adrenal zona reticularis of the adrenal glands only, whereas DHEA can also be
produced by the testes and ovaries and can be synthesized within the brain. Although in women, adrenal
production of DHEA and DHEAS contributes substantially to overall androgen production, in men, the
adrenal contribution to the pool of biologically active androgens is very small

• In females, DHEAS levels gradually decline with aging, although no specific reduction is associated with
menopause. In postmenopausal women, adrenal DHEA and DHEAS represent the major precursors of
estrogen and androgen production. An age-dependent reduction of circulating DHEAS has also been
reported in men.

• The role of DHEA in elderly men is still considered conflicting. Meta-analysis of available trials did not
support a beneficial effect of DHEA supplementation on cognitive function in non demented middle-aged or
elderly people, whereas other authors reported possible positive effects on other outcomes

297
 DHEA and Women
• A meta-analysis of the placebo-controlled trials has demonstrated no significant effect of DHEA
on anxiety and sexual well-being in women with adrenal insufficiency, although DHEA may
improve, in a small and perhaps trivial manner, quality of life (QOL), and depression in these
women.

• Cross-sectional studies have indicated a link between low DHEA levels and impaired sexual
function, well-being, and cognitive performance, placebo RCTs do not show any benefit on these
outcomes or any favorable effect of oral DHEA on lipids and carbohydrate metabolism

• DHEA has been shown to increase testosterone in women.

298
THYROID DYSFUNCTION:
DIAGNOSIS AND
MANAGEMENT
 Types of Hormone Axes and Their Functions
Prolactin: Should Men with Erectile Dysfunction Be
Tested?
Beyond Does Testosterone Replacement Affect the Thyroid?
Testosterone: Animated Video: All You Need to Know About Thyroid
Thyroid, Hormone Replacement
DHEA Supplementation
Prolactin, Hypothyroidism: Facts, Interactions, and Resources
DHEA, and Pregnenolone – By Gene Devine
Pregnenolone Reverse T3 (rT3): Should it be measured in patients with
hypothyroidism?

300
 Pregnenolone 101: What You Need to Know About
this Precursor Hormone
IGF-1 Roles and Benefits
Beyond DHEA Supplementation: What Do Studies Show?
Testosterone: The TSH Reference Range Wars: What's "Normal?"
Who is Wrong, who is Right...
Thyroid, Prolactin, Article: Armour, Desiccated, Levothyroxine, &
DHEA, and Liothyronine- Any Differences?

Pregnenolone II New Comprehensive Thyroid Panel at

www.DiscountedLabs.com
29 Medications That May Cause Adverse Interactions
with Thyroid Drugs

301
Symptoms of Low and High Thyroid Hormone
Blood Levels

Hypothyroidism (Low thyroid function) increases risk of:

• Heart Disease
• Kidney Dysfunction
• Mental health Issues
• Peripheral neuropathy.
• Myxedema (intense cold intolerance and drowsiness followed
by profound lethargy and unconsciousness)
• Infertility
• Birth defects

Source: Mayo Clinic

302
Hypothalamic-Pituitary-Thyroid Axis
Hypothalamus TRH -

- Pituitary gland TSH

Thyroid gland
T4 & T3 T4 T3 T4 & T3

Peripheral tissues
T4 >>>> T3

303
Factors that Affect Thyroid Function
Factors that contribute to
proper production of Factors that inhibit proper
thyroid hormones production of thyroid
• Nutrients: iron, hormones
iodine, tyrosine, zinc, • Stress
• Infection, trauma,
selenium, vitamin E,
radiation, medications
B2, B3, B6, C, D
• Fluoride (antagonists to
T4 iodine)
• Toxins: pesticides,
Factors that increase mercury, cadmium, lead
conversion of T4 to RT3 • Autoimmune disease:
• Stress Celiac
• Trauma
• Low-calorie diet
• Inflammation Factors that increase
(cytokines, etc.) conversion of T4 to T3
• Toxins • Selenium
• Liver/kidney • Zinc
dysfunction
• Certain medications
RT3 RT4
T3 and RT3 compete for binding
sites

Factors that improve

cellular sensitivity to
Nucleus / thyroid hormones
Mitochondri • Vitamin A
a
• Exercise
• Zinc
Cell

304
 Challenges in Thyroid Hormone Replacement
Therapy
Drug formulation Drug Interactions
- T4 - Calcium carbonate Thyroid Hormone Metabolism
- T3 - Iron - Deiodinase distribution
- Combination T4/T3 - Phenytoin - Peripheral conversion
- Generic vs. Brand - Rifampin

Co-existing Conditions
Variability of Outcome Measures
- Pregnancy
- Subjective Neurocognitive outputs
- Renal Failure
- Lack of standardization
- Hepatic Disease
- Placebo effects

Treatment Patient Compliance

Dosing
- Lean vs. obese Efficacy
- Endogenous Production Comorbidities
- Malabsorption
- GI surgery

Drug Distribution
- Circulation
Thyroid Hormone Action Disease Cause
- Plasma proteins Drug Absorption
- Neurological - Stable vs. Progressive
- Food intake
- Metabolism - Residual Thyroid Tissue
- Timing
- Endocrine
- GI monthly
- Receptor regulation

Source: The Challenges and Complexities of Thyroid Hormone Replacement Shayri M. Kansagra, BS,1 Christopher R. McCudden, PhD,2 Monte S. Willis, MD, PhD2,3 (1Department of
Molecular Biology, University of North Carolina at Chapel Hill, 2Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, 3McAllister Heart Institute,
University of North Carolina at Chapel Hill, Chapel Hill, NC)

305
 Clinical Presentation* of Hypothyroidism

Symptoms Fatigue, low energy, weakness, arthralgias, myalgias, cold intolerance, weight gain,
depression, constipation, sexual dysfunction, menorrhagia, dry skin, coarse brittle hairs
and nails, decreased concentration, memory impairment, slow speech, periorbital
puffiness, headaches hoarseness

Signs Bradycardia, hypertension, periorbital edema, reflex delay, +/- goiter, lateral thinning of
eyebrows (Queen Anne's sign), pericardial effusions, pleural effusion
ascites

laboratory Macrocytic anemia, elevated creatine kinase, hypercholesterolemia, hyponatremia

findings
*Clinical presentation is highly variable, and individual findings have low sensitivity and low specificity

306
 Thyroid Function: What‟s a Normal TSH?
Several Clinical Guidelines Disagree
Thyrotropin Upper Normal
Group, Study, Society TSH Upper Normal Comments

NACB 2.5 When there is no evidence of thyroid disease

No self-reported thyroid disease

NHANES III, disease free 4.5
Not on thyroid medications
No self-reported thyroid disease
Not on thyroid medications
NHANES III, reference population 4.12 Negative anti-thyroid antibodies
Not pregnant
Not on estrogens, androgens, lithium
No evidence of thyroid disease
Negative anti-thyroid antibodies
Hanford Thyroid Disease Study 4.10
Not on thyroid medications
Normal ultrasound (no nodules or thyroiditis)

Pregnancy, first trimester 2.0-2.5 See section L-thyroxine treatment of hypothyroidism and Hypothyroidism during pregnancy

Pregnancy, second trimester 3.0 See section L-thyroxine treatment of hypothyroidism and Hypothyroidism during pregnancy

Pregnancy, third trimester 3.5 See section L-thyroxine treatment of hypothyroidism and Hypothyroidism during pregnancy
Sources: Stagnaro-Green et al., 2011 (10); Hollowell et al., 2001 (11); Hamilton et al., 2008 (81); Baloch et al., 2003 (85)
NACB, National Academy of Clinical Biochemists; NHANES, National Health and Nutrition Examination Survey

307
 The Trouble of Using Only TSH for Diagnosis

• Using only TSH sometimes misses hypothyroid patients that may show low
levels of free T3 under further exploration.

• Some physicians only use total T3 and T4 instead of their free fractions (free T3
and free T4)

• Using solely TSH to diagnose hypothyroidism is analogous to using only

LH/FSH and ignoring serum testosterone test to diagnose hypogonadism.

308
Diagnosis of Thyroid Dysfunction
Serum TSH and Free
Thyroxine

TSH TSH TSH normal TSH normal

Free T4 Free T4 normal Free T4 Free T4 normal

Central hypothyroidism
Mild or subclinical
Primary hypothyroidism Non-thyroidal illness Normal
hypothyroidism Drug effect

Laboratory assessment of hypothyroidism

309
 Thyroid Blood Tests Optimal Ranges
The 6 Key Thyroid Tests to Request from Your Are Your Thyroid Levels Optimal?
Optimal Levels
Doctor

TSH 1-2 mU/L

Test Panel 1
Thyroid Hormones: TSH OPTIMAL BETTER
(initial)
Free T3 >3.2 .5µIU/mL 1.5 2.5 4.5

Free T4 >1.1
Free OPTIMAL
T4
.8ng/dL 1.3 2.8

Free BETTER OPTIMAL

Thyroid Antibodies:
T3
If TSH > 3 +
Antithyroglobulin antibody Ideally, negative or < 4 2.3pg/mL 3.2 3.7 4.2
symptoms
Thyroperoxidase antibody
then Test
Panel 2
Reverse T3 <than a 10:1 ratio RT3:FT3

310
 • T4 only medications (synthetic)
o Levothroid, Levoxyl, Synthroid, Unithroid

Thyroid
• T3 only medications (synthetic)
o Liothyronine, Cytomel
Medications
• T4/T3 combo medications (synthetic)
o Liotrix, Euthroid, Thyrolar, Compounded Products
o Desiccated Thyroid (Armour) and Compounded
Desiccated Thyroid

311
MENTAL HEALTH
 Ketamine Could Be the Key to Reversing America’s Rising Suicide
Rate

Improving How to Stop Antidepressants Safely

Are You Neurotic? Take This Test and Find Out Your Score
and Can a person be on psychiatric medications and be on TRT?

Maintaining Psychedelic drugs could treat depression and other mental

illnesses

Mental Health Results from Study on Testosterone and Depression in Older

Men
Helping a man at risk of suicide
Testosterone Increases Response to Stress

313
 Nelson recommends: This is why you may not be happy
Male depression and suicide: it's time for a change
What other non-psychiatry treatments for depression
are there?

Improving and
Ways to Deal with Depression and Anxiety
Nelson Recommends: Soul Sickness by Jason Silva

Maintaining Hormones and Neurotransmitters - Effects on Mood

Mental Health II
Psychiatric Manifestations of Endocrine Disorders
What is Your Chronotype and It Can Be Used to
Improve Mood?
Benzodiazepine Dependency and Withdrawal
Hormones and mood– the first steps to feeling better

314
 NUTRITIONAL
CONSIDERATIONS
 Clean nutrition for health, muscle gain, and fat loss.
Best Vitamins and Supplements by Nelson Vergel
Gene's Nitric Oxide Stack
Top 5 Must-Have Supplements for Men Over 40
List of Nootropics: Brain supplements and medications to increase
Nutrition and focus and mood.

Supplements
Testosterone and Supplements
Antioxidants for the treatment of male infertility: an overview
NAC Benefits: HDL and More
Can Oral Glutathione Supplements Work?
The Truth About Magnesium Supplements
Creatine: Everything You Need to Know

316
 What Every Man Should Know About Nitric Oxide
Whey Q&A
A low-carb diet for beginners
Fast Easy Meals from the One Pot Chef
Higher Magnesium Intake Is Associated with Lower Fasting Glucose
and Insulin

Nutrition and The ―KETO‖ Diet (GOOD OR BAD) just when I was almost convinced...
How to lower blood pressure naturally
Supplements II What is the optimum blood level of Vitamin D for maximum
testosterone?
High estradiol / Hematocrit: What supplements to avoid?
Collection Of 250+ Studies: Supplements, Vitamins, Bioavailability,
Micronutrients

317
 ExcelMale.com Meal Plan
What You Should Know About Weight Loss Supplements
Nelson's Top Tricks for Fat Loss
Overcoming Challenges in Weight Management

Nutrition and Supplements that lower LDL cholesterol and triglycerides and
increase HDL.

Supplements III Slide Show: Nutrition Considerations in HIV

Low Carb Diet Better Than Low Fat for Weight Loss and Heart
Video: Truth and Lies About Fat Loss Supplements
Nelson’s Tips on Nutrition, Exercise, and Supplements
Lifestyle factors that can affect semen quality

318
What Your
Plate Should
Look Like….

319
 Nutritional
Considerations
• Reduce fried foods and hydrogenated oils

• Eat omega-3 fish oil-rich foods- salmon, tuna, sardines or

flax seed oil (alternative)

• Use monounsaturated fats: olive oil

• Minimize sugar, fructose (sweets, sodas, foods with high

fructose corn syrup )

• Eat adequate amounts (0.7-1 gm/lb./day) of protein (fish,

eggs, cottage cheese, lean meats, chicken, whey, nuts, etc.)
 Do not skip breakfast (keep an eye on sugar and refined flower products!)

Try to eat several smaller meals or snacks instead of 2-3 large ones

Eat more almonds, walnuts, pecans and pistachios (good cholesterol lowering fats)

More Nutritional Eat fruits and vegetables of all colors

Considerations ( varied antioxidant profile)

Eat a high protein, complex carbohydrate- rich meal after work outs

Minimize caffeine (it reduces appetite)

321
 Grocery Shopping List

• Almonds and other nuts • Eggs

• Beans and other legumes
• Spinach and other green leafy vegetables
• Low fat dairy, yogurt
• Whey protein
• Oatmeal
• One or two glasses of red wine
• Lean meats and fish
• Flaxseed , pumpkin and sunflower seeds
• Whole grain breads
• Sweet potatoes
• Peanut, almond , cashew butters
• Green tea
• Olive oil and avocados
• Raspberries and all berries. Fruits (avoid fruit juices)

322
 EXERCISE
CONSIDERATIONS
 Exercise videos: Click on the body part you want to exercise
Cable Exercises Can Develop the Body Fully and Safely
Interval Training Superior to Others in Improving Muscle Aging

Key Exercise Exercise Tips to Lose Fat and Gain Muscle

Information
Anabolic Resistance: Why It Is Harder to Add Muscle Mass as
We Age and How to Fight It
Scientific Recommendations for Strength and Hypertrophy
Training From 150+ Studies (Part 1 Of 3)
Practical Exercise Tips

324
 Aerobic (Cardiovascular)
Exercise
• Start with a brisk walk every day if tired

• Concentrate in low impact or no impact exercises (e.g.

Elliptical Trainers)

• Do what you enjoy (bicycling, roller skating, etc.)

• Good for burning fat, triglycerides, blood sugar, but it may

decrease muscle mass

• 20 - 30 minutes 3-4 times a week is enough for many people

• Cardiovascular exercise may increase fat loss under the skin

325
 Progressive Resistance
Exercise (PRE)
• Warm up and stretch before a session

• Lift maximum weight for muscular failure (exhaustion) at 8-

12 repetitions

• One-hour sessions 3-4 times a week

• Three sets per body part

• If no access to a gym, start with crunches, push ups, and

squats at home

• For more details, visit exrx.net

326
NELSON‟S TIPS FOR TRT
PATIENTS
 Use of over-the-counter testosterone ―boosters‖

Wrong product choice

Wrong dosing

What are the Not knowing how to prevent and manage side effects.

top 10 Use of black-market hormones

mistakes Inadequate communication with physicians

men make Unrealistic expectations

on TRT? Forgetting about the effect of other hormones

Lifestyle choices

Provider selection

328
 How to Effectively Choose and
Speak to Your Physician
• Do your research before selecting him/her. Call office and ask if the doctor uses HCG and hematocrit management.

• Be educated and courteous.

• Prepare for the consult. Show him/her a note as soon as he/she walks in

• Ask ―What would you do if you were me?‖ when presented with options

• When questioning, never say you ―read it on the internet‖ but instead bring a copy of a study

• Sweeten your relationship with the front desk and mid-level clinicians (RNs, PAs, etc.)

• In your choice of doctors, favor the ones with email access

• If you are happy, refer your friends and have them tell the doctor that you did so.

• Dilemma:

• Insurance-based versus cash-based doctors

• Face-to-face versus telemedicine doctors

329
 Have reasonable expectations. Testosterone is not a magic bullet.

Do not fall prey to testosterone booster scams.

Do not obsess about estradiol without testing it with right (sensitive) test.

Monitor your hematocrit every 2-3 months during first year of therapy. Donate blood if it reaches 52,

Nelson‟s Top 10
but be careful with donations more frequent than every two months (low iron or ferritin).

TRT
Explore easier ways to inject like subcutaneous and shallow IM.

Commandments
Never cycle TRT on and off.

You can’t change what you don’t measure. Monitor your blood tests and quality of life. Know your
trends. Use DiscountedLabs.com, MyHealthGraphs.com & TRT Analyzer App.

Do not change more than one variable at a time. You will lose track of what works and what doesn’t.

Protect your fertility, testicles and upstream hormones (HCG)

Don’t stay behind in this evolving field. Register on ExcelMale.com

330
HOW TO MONITOR TRT
LAB TESTS
 Monitoring Your Blood Tests While on Testosterone

Why Use Discounted Labs .com and How it Works?

Blood Tests Needed Before and During Testosterone Replacement
Therapy
What blood assay to pull when having low libido

Blood Test Is the Cystatin- C Kidney Function Test Best for Muscular Men?
LAB TEST RANGES AND COMPLICATIONS OF HIGH OR LOW

Discussion VALUES
FACTORS THAT CAN AFFECT THE ACCURACY OF YOUR BLOOD
TEST RESULTS
Why All Men Should be Tested with the Sensitive Estradiol Test
Description and Tests Included in DiscountedLabs Panels
Types of Testosterone Blood Test Methods- Which One to
Choose?

332
 Nelson Vergel 's New Lab Test Graph Site:
MyHealthGraphs.com
How to Read Your CBC and CMP Blood Tests- Interpretation
Guide and Videos

Blood Test
Sensitive e2 Test Now Available in Canada
Ten Percent Off Blood Tests on DiscountedLabs.com- No

Discussion II Doctor Visit- Most US Cities

Nelson's Coaching Session
Creatine Phosphokinase (CPK) - Does Testosterone Impact It?
Canadian Patients: Dynacare Sensitive Estradiol Test

333
 Most Affordable Basic Semen Analysis Now on
DiscountedLabs.com
Two Blood Test Companies in the United Kingdom (UK)
Important Testosterone Blood Test Articles
Blood Test Post PCT Bloodwork

Discussion III Hormone unit conversion calculator

Kidney Function 101
Resistance Exercise Can Increase Liver Enzymes
How to convert mmol/L to mg/dl or pg/mL (or vice versa) of
different hormones

334
 TRT BLOOD TEST MONITORING SCHEDULE:
What Do the Guidelines Say?
The monitoring guidelines of many established TRT clinics are more strict than all current TRT medical guidelines.
You can see a summary of blood testing and examinations required by the main four medical groups in this table:

335
Testosterone Replacement Monitoring Targets and
Their Management
(Consult your Physician before any treatment, cessation or dose changes)
Total Testosterone >= 500 ng/dL for
improvement in hypogonadism
symptoms
Free Testosterone >= 2% of total T
Hematocrit <= 53%
PSA <= 4ng/mL
Estradiol (Sensitive Test) = 20-50
(Debate) pg/mL
Blood pressure <= 135/85 mmHg
If low or hypogonadal symptoms are not improved, increase testosterone dosage. High T levels (over 1500 ng/dL) with high hematocrit,
low HDL and/or side effects may require dosage reduction.
If low, test for sex hormone binding globulin. Higher TRT dose may increase free T by decreasing
SHBG. Low SHBG may be present in diabetes.
If high, donate blood or ask doctor for therapeutic phlebotomy order. If low, investigate anemia or stop
donating blood more than every 3 months.
If high, talk to your doctor about potential prostatic infection or a referral to a urologist. TRT is contraindicated if PSA is 4 ng/mL or
greater.
Most men on TRT do not need to use an aromatase inhibitor like anastrozole (Arimidex). Some physicians prescribe low dose
anastrozole for what they consider high estradiol. If low, higher testosterone dose and/or cessation of AI may be required. The lab range
was derived from men with heart disease and low testosterone, so there is still debate on what the range should be for men on TRT
since 0.3 to 0.4 % of testosterone aromatizes to estradiol, so men with high T due to TRT will have higher estradiol. No upper range
value has been determined for men on TRT. Studies have shown that for gynecomastia to occur, high estradiol in the presence of low T
and high IGF-1 may be required. Read Estradiol In Men – Why Is It Important For Optimal Health And Fitness Performance and The Top
18 Things You Did not Know About Estradiol in Men
If high, weight loss, exercise, T dose reduction and/or blood pressure medications may be needed. If too low, blood pressure medication
dose needs to be reduced, electrolytes checked or hypoglycemia excluded.
336
Testosterone Replacement Monitoring Targets and
Their Management
(Consult your Physician before any treatment, cessation or dose changes)
Estimated Glomerular Filtration If low, good hydration, use of blood pressure medications, and/or stopping offending oral supplements may
Rate (eGFR)
improve eGFR. Exercise, high protein intake and higher muscle mass can also increase creatinine and decrease
(kidney function) >=
60 mL/min/1.73 m2 eGFR. Use Cystatin C in obese and very muscular patients.

Liver enzymes <= 1.2 x top value of If high, stopping oral supplements can help. AST and ALT can increase with exercise but this is not clinically relevant. If high
reference range AST and ALT, test GGT and bilirubin to ensure no liver toxicity is present.

TSH <= 2.5 U/mL If high, test for other thyroid tests like free T3, free T4 and antibodies to detect hypothyroidism.

Free T3 >= 3.7 pg/mL If low, hypothyroidism may be present. See comment on TSH. If high (>5 pg/mL),explore hyperthyroidism

Ferritin 55-270 ng/mL & Iron 55- If low, reduce frequency of blood donations or phlebotomies and supplement with iron until it is back
160 micrograms/dL to normal. If high, donate blood or get therapeutic phlebotomy

The most difficult parameter to manage. Higher TRT doses decrease HDL. Niacin may help increase HDL but may cause
HDL >= 40 mg/dL
flushing.

Test if Total Testosterone is below 150 ng/dL before TRT to detect potential pituitary adenoma or other issues. High levels
Prolactin (<= 30 nd/dL)
(> 30 ng/dL) may cause sexual dysfunction and galactorrhea in men (milk production)

337
 MONITORING SCHEDULE
Every 6-12
Parameter Baseline 2-3 Months 6 Months 12 Months
Months

Symptom Response √ √ √ √

Adverse Events √ √ √ √

Testosterone Level √ √ √ √

Hematocrit* √ √ √ √ √

PSA** √ √ √ √

DRE** √ √ √

BMD*** √ √

DRE = digital rectal exam

If Hct>53, have patient donate blood or order a therapeutic phlebotomy if excluded from donation.
** After 3 months, continue to follow PSA and DRE per age and race-appropriate guidelines
*** For patients with osteoporosis or fragility fracture; recheck at 12-24 months

338
 TRT Patient Monitoring
• Initial Blood Test – New Patient
o Testosterone, Free & Total, if under 150 ng/dL test for prolactin.
o PSA
o LH & FSH
o Lipids
o CBC
o
o
CMP
TSH, free T3 (if high TSH, test for thyroid antibodies)
Lowest Cost Blood
• 8-6wk Follow up after initial RX
o CBC
Tests Online:
o CMP
o Lipids
o Testosterone, Free & Total
o Estradiol (sensitive)
o TSH
• 6 Month Follow up – 6 months after initial RX
o Testosterone, Free & Total
o PSA
o Lipids
o CBC
o CMP
o Estradiol (sensitive)
• Annual Blood Test – Same as 6 months

ADAM questionnaire at every visit

339
 BLOOD TEST MONITORING SCHEDULE: Baseline
• The following are the required blood tests and how to use them for clinical decision making. Physicians can sign up to a
blood test lab cooperative at 4PMD.com. Patients can get affordable blood tests in most U.S. cities at
DiscountedLabs.com
Note: q-ADAM questionnaire during every visit
Initial Blood Test – New Patient Starting TRT

• Testosterone, Free & Total

• PSA
• LH & FSH
• Lipids
• CBC
• CMP
• TSH, Free T3 & Free T4
• Sensitive Estradiol
• Post baseline:
• If T <200 ng/dL and no current/past use of anabolic steroids or
opiates, test for prolactin.
• If free T3 is low and/or TSH is high (> 2.5), perform a complete
thyroid panel including antibodies.

340
BLOOD TEST MONITORING SCHEDULE – Follow Up

01

Fasted, morning and well- 03

hydrated conditions:
• CBC
• CMP
• Testosterone, Free 02
& Total
• Estradiol Sensitive
• Free T3
• TSH • Testosterone, Free & Total
• PSA • PSA (optionally based on week 6 results)
• Low libido: DHT • Lipids
• CBC
• CMP
• Estradiol, sensitive
• Free T3 (if abnormal FT3 was found at baseline
por follow up and thyroid treatment was provided)

341
 MANAGEMENT OF KEY TRT VARIABLES AT
WEEK 6 OR 8 FOLLOW UP
Adjust TRT , hCG and/or anastrozole dose if
needed based on blood test values and If patient has a TT >600 ng/dL and he is still
symptoms. If total testosterone (TT) has ‘ fatigued, check TSH and free T3 and inquire
decreased from week 6, investigate patient about sleep apnea symptoms. If TT <600
treatment adherence. If hematocrit is ng/dL, increase T dose by 50%. Some men are
approaching 54, have pt donate blood or order fast metabolizers of testosterone. Adherence
a therapeutic phlebotomy. Donations should
to TRT should be investigated if TT < 500
not be done more frequently than every 2.5
ng/dL.
months
\\\\\\\
You may increase the initial hCG dose from 350 IU
to 500 IU 2-3 times per week if pat'ient reports
low libido even with TT> 600 ng/dL. Increased Very low HDL (< 35 mg/dL) may indicate
hCG dose may also increase DHT, an important high T dose or anabolic steroid use.
metabolite linked to libido. Most patients do not Triglycerides usually decrease with TRT.
complain about testicular atrophy with these hCG LDL may decrease to a smaller degree.
doses. Some physicians are prescribing scrotal T
creams to improve DHT and libido as
monotherapy or in combination with T injections.

342
Blood Test
Ranges

343
344
HOW DOES DISCOUNTEDLABS.COM WORK?

1. Go to the "Find a Location" page to find the closest lab location. No need to
make an appointment since walk-ins are welcomed. Once you have identified
your closest location, go to step 2.
NOTE: We serve all states in the U.S. except New York, New Jersey, Massachusetts,
New Hampshire, Rhode Island, Maine, Vermont, and Hawaii.
2. Go to "Choose a Test" and add your selection (s) in the shopping cart.
3. If you have a discount coupon code, add it to your cart.
4. A $6 blood draw fee will be added to your total.
5. Pay using a credit card.
6. You will receive order confirmation and instructions on how to download your
lab request form from your profile on our site by logging into your account and
clicking on My Labs.
7. Print lab request form that you downloaded.
8. Take that form to the closest LabCorp location with a picture ID. Get your blood
drawn.
9. You will receive an email when the results are ready for you to download from
our site following the same procedure as item 6.

345
 Blood Tests Reference Ranges -High and Low Values
Blood test
Alanine aminotransferase (ALT, SGPT)
Range
Male 10-55 U/liter. Female10-55 U/liter
Complications
Levels are extremely increased in cases of liver cell
necrosis of any cause, right heart failure, acute anoxia,
extensive trauma, or left heart failure. A slightly high level
may indicate cirrhosis, obstructive jaundice, liver tumors,
extensive myocardial infarction, myositis, muscular
dystrophy, fatty liver, chronic alcohol abuse, or severe
pancreatitis. Levels will by low in cases of pyridoxal
phosphate deficiency

Albumin 3.1-4.3 g/dl There is no naturally occurring hyperalbuminemia. Any

condition that results in the decrease of plasma water will
increase the concentration of all plasma proteins,
including albumin. Low concentrations of blood albumin
may be due to acute and chronic inflammation, decreased
synthesis by the liver, increased loss via body surfaces,
increased catabolism, or increased blood volume.
*albumin is the principal oncotically active component of
plasma. As the major plasma protein, albumin acts as a
nitrogen pool. Its role in transporting bilirubin, bile acids,
metal ions, and drugs will be markedly affected by
variations in concentrations.

346
Alkaline phosphatase (adult)
Androstenedione (adult)
Aspartate aminotransferase (AST,
SGOT)
Male 45-115 U/liter. Female 30-100
U/liter
50-250 ng/dl
Male 10-40 U/liter. Female 9-25 U/liter
Origins of the major phosphatases are liver, bone, intestine,
endometrium, and lung. Ingestion of a meal increases the
intestinal isoenzyme of alp in serum, especially in
individuals who are blood type o or b and who are Lewis-
positive secretors. Increased levels of alp may indicate
increased bone metabolism (during healing of fracture,
primary and secondary hyperparathyroidism, osteomalacia,
or juvenile rickets). May also indicate bone disease, renal
disease, or liver disease. Low levels may indicate
hypothyroidism, scurvy, gross anemia, vitamin b12
deficiency or nutritional deficiency of zinc or magnesium.
Androstenedione is a major precursor in the biosynthesis of
androgens and estrogens. It is produced in adrenals and
gonads and serves as prohormone for testosterone and
estrone. The test is useful in conjunction with other tests in
the evaluation and management of androgen disorders
Increased levels may indicate liver cell necrosis or injury of
any cause, including cholestatic and obstructive jaundice,
chronic hepatitis, or drug-induced injury to liver. May also
be associated with hepatic metastases and hepatoma,
necrosis or trauma to heart or skeletal muscle,
inflammatory disease of heart or skeletal muscle, heart
failure, Forbes’s disease, heat stroke, hypothyroidism,
intestinal obstruction, lactate acidosis, or toxic shock
syndrome. Also distinguishes neonatal hepatitis from biliary
atresia.
347
Bilirubin, direct 0.0-0.4 mg/dl High serum blood levels are associated with intrahepatic and
extrahepatic biliary tree obstruction, hepatocellular damage,
cholestasis, Dubin-Johnson syndrome, or rotor’s syndrome.

Bilirubin, total 0.0-1.0 mg/dl High serum levels may indicate hepatocellular damage
(inflammatory, toxic, neoplastic), intrahepatic and extrahepatic
biliary tree obstruction, hemolytic diseases, fructose intolerance,
hypothyroidism or neonatal physiological jaundice

Calcium 8.5-10.5 mg/dl High blood calcium levels may indicate primary and tertiary
hyperparathyroidism, malignant disease with bone involvement
(in particular metastatic carcinoma of the breast, lung, kidney,
multiple myeloma, lymphomas, and leukemia), vitamin d
intoxication, milk-alkali syndrome, Paget’s disease with
immobilization, thyrotoxicosis, acromegaly, diuretic phase of
acute tubular necrosis or dehydration. Low levels of calcium may
indicate hypoparathyroidism; vitamin d deficiency, chronic renal
failure, magnesium deficiency, prolonged anticonvulsant therapy,
acute pancreatitis, anterior pituitary hypofunction,
hypoalbuminemia, or inadequate nutrition.

348
Carbon dioxide 24-30 mmol/liter High levels may indicate respiratory acidosis caused by poor gas exchange or
content, total depression of respiratory center; generalized respiratory disease; metabolic acidosis
(after severe vomiting in pyloric stenosis, hypokalemic states, or excessive alkali intake).
Low levels may indicate compensated respiratory alkalosis, metabolic acidosis in
diabetes mellitus, renal glomerular or tubular failure, renal tubular acidosis and
intestinal loss of alkali with coexisting increase in c1 and normal anion gap
Chloride 100-108 mmol/liter High chloride levels may be attributed to dehydration, renal tubular acidosis, acute renal
failure, diabetes insipidus, metabolic acidosis associated with prolonged diarrhea with
loss of nahco3, respiratory alkalosis, and some cases of primary hyperparathyroidism.
Low serum chloride levels may be due to excessive sweating, prolonged vomiting from
any cause or gastric suction, persistent gastric secretion, salt-losing nephritis,
aldosteronism, potassium depletion associated with alkalosis, respiratory acidosis
Cholesterol Desirable < 200 mg / dl. Borderline high High total cholesterol levels may indicate familial or polygenic hyperlipoproteinemia
200-239 mg/dl. High > 239 mg/dl types IIa and IIb, hyperlipidemia, hyperlipoproteinemia's secondary to hepatocellular
disease, intra- and extrahepatic cholestasis, chronic renal failure, malignant neoplasms
of pancreas and prostate, hypothyroidism, gout, ischemic heart disease, pregnancy,
diabetes, alcoholism, an albuminemia, dysglobulinemia, anorexia nervosa, idiopathic
hypercalcemia, acute intermittent porphyria, or isolated hGH deficiency. Low levels may
be associated with lipoprotein deficiency, hepatocellular necrosis, malignant neoplasm
of liver, hyperthyroidism, malabsorption, malnutrition, megaloblastic anemias, chronic
obstructive lung disease, mental retardation, rheumatoid arthritis, or intestinal
lymphangiectasia. *secondary disorders that elevate cholesterol levels should be ruled
out prior to initiating therapy with cholesterol-lowering drugs. *factors that have
variable effects on cholesterol levels in different people include posture before and at
time of blood sampling, a recent meal, emotional stress, and menstrual cycle.

349
Creatinine 0.6-1.5 mg/dl
Dehydroepiandrosterone (DHEA) Male 10-619 µg/dl. Female
sulfate (adult) Premenopausal 12-535 µg/dl. Female
Postmenopausal 30-260 µg/dl
Estradiol (ultra sensitive) Female Menstruating
Follicular phase 50-145 pg/ml Midcycle peak
112-443 pg/ml Luteal phase50-241 pg/ml
Postmenopausal <59 pg / ml
Male < 50 pg / ml
High serum or plasma levels may indicate renal function
impairment, both acute and chronic; active acromegaly and
gigantism, hyperthyroidism, and meat meals. Creatine
supplements can increase creatinine. It is always good to
calculate your eGFR to make sure it is not under 60
Decreased levels may be associated with increased age in men
and women, hyperlipidemia, psychosis, or psoriasis. Weakly
androgenic
Estradiol is the most active of endogenous estrogens. The test is
of value, together with gonadotropins, in evaluating menstrual
and fertility problems in adult females. Measurement is also
useful in the evaluation of gynecomastia or feminization states
due to estrogen or producing tumors.
350
Follicle-stimulating Female Menstruating In hypogonadism, FSH and LH levels lower than normal for
hormone (FSH) Follicular phase 3.0-20.0 U/liter Ovulatory phase9.0-26.0 the patient’s age indicate hypothalamic or pituitary
U/liter Luteal phase 1.0-12.0 U/liter problems; higher levels indicate a primary gonadal defect
Postmenopausal 18.0-153.0 U/liter Male 1.0-12.0 U/liter

Globulin 2.6-4.1 g/dl High levels may be associated with chronic hepatitis, plasma
cell dyscrasias/ lymphoproliferative disorders, cirrhosis,
chronic liver diseases, chronic infections or certain
autoimmune disorders. Low levels may indicate immune
deficiency or suppression or lymphoproliferative disorder.
Decreases in all fractions may be seen in bulk loss of proteins
into the gut.

Glucose, fasting 70-110 mg/dl Serum glucose levels may be high due to diabetes mellitus,
strenuous exercise, increased epinephrine, pancreatic disease
or an endocrine disorder. A high serum level may also be
related to acute myocardial infarction or severe angina,
chronic liver disease, or chronic renal disease.

351
(gamma)-Glutamyl transferase
(GGT)
Growth hormone (resting)
Hemoglobin A1C
Male 1-94 Very high levels can be associated with obstructive liver disease and post hepatic
U/liter obstruction. Moderately high levels may indicate liver disease (inflammation,
Female 1-70 cirrhosis, space-occupying lesions), infectious mononucleosis, renal transplant,
U/liter hyperthyroidism, myotonic dystrophy, diabetes mellitus, pancreatitis, or alcohol-
induced liver disease. Low GGT levels will indicate hypothyroidism. *useful marker
for pancreatic cancer, prostatic cancer, and hepatoma because levels reflect
remission and recurrence.
2-5 ng/ml Secretion of GH is episodic and pulsatile; highest values occur during periods of
deepest sleep. Ability to secrete GH in response to a conventional challenge
declines with age. Random levels of GH provide little diagnostic information; GH
secretion is best assessed during tests that stimulate or suppress release. Patients
with GH-producing pituitary disorders often release GH in response to TRH or
GnRH; and patients with suspected GH deficiencies have subnormal responses to
stimulation tests (i.e. GH stimulation test after arginine, insulin, L-dopa, glucagon,
propranolol and insulin tolerance test.)
3.8-6.4% Glycated hemoglobin concentration appears to reflect the mean blood glucose
concentration over the previous 4-8 wks. This test, while not useful for the diagnosis
of diabetes mellitus, has been shown to be useful in monitoring its long-term
control. Glycated hemoglobins are increased as a reflection of hyperglycemia during
the lifespan of erythrocytes
352
High-density lipoprotein
cholesterol, as major risk factor
Insulin
Lactate dehydrogenase (LDH)
Males above 40 Epidemiological studies demonstrate the inverse association between HDL-c
mg/dl levels and the incidence and prevalence of coronary heart disease (CHD). It is
Females above 50 suggested that for every 5 mg/dl decrease in HDL-c below the mean, the risk of
mg/dl CHD increases 25%. Another approach in assessing CHD risk is to calculate the
ratio of HDL-c to either LDL-c or total cholesterol. The following primary disease
states can lead to secondary decrease in HDL-c: uncontrolled diabetes, premature
coronary heart disease, hepatocellular disorders, cholestasis, nephrotic syndrome,
and chronic renal failure.
2-20 U/ml Decreased serum levels indicate inadequately treated type I diabetes mellitus.
High serum levels may indicate insulin overdose, insulin resistance syndromes, or
endogenous hyperinsulinemia
110-210 U/liter Extremely high levels may indicate megaloblastic and pernicious anemia, extensive
carcinomatosis, viral hepatitis, shock, hypoxia or extreme hyperthermia. Very high
levels are associated with cirrhosis, obstructive jaundice, renal diseases, neoplastic
diseases, skeletomuscular diseases, or congestive heart failure. Mildly high levels
are associated with any cellular injury that results in loss of cytoplasm, myocardial
or pulmonary infarction, leukemias, hemolytic anemias, hepatitis (nonviral), sickle
cell disease, lymphoma, renal infarction, or acute pancreatitis.
353
Lipoprotein(a) Low-density 0-30 mg/dl. Desirable < 130 mg/ dl, Borderline LDL encompasses all of the lipoproteins with density greater
lipoprotein cholesterol high risk 130-159 mg/dl than 1.006 kg/l and less than or equal to 1.063 kg/l. High levels
High risk greater than or equal to 160 mg/dl may indicate primary hyperlipoproteinemia types IIa and IIb;
tendon and tuberous xanthomas, corneal arcus, and premature
coronary heart disease. The following diseases can lead to
secondary elevation of LDL-c: hyperlipoproteinemia secondary
to hypothyroidism, nephrotic syndrome, hepatic obstruction,
hepatic disease, pregnancy, anorexia nervosa, diabetes, chronic
renal failure, and Cushing’s syndrome.
Iron 45-180 ug/dL High serum levels may indicate pernicious, aplastic, and
hemolytic anemias; hemochromatosis, acute leukemia, lead
poisoning, acute hepatitis, vitamin b6 deficiency, excessive iron
supplementation/therapy, repeated transfusions, or nephritis.
Low serum iron levels may indicate iron-deficiency anemia,
remission of acute and chronic infection, carcinoma, nephrosis,
hypothyroidism, or postoperative state. *symptoms of iron
poisoning include abdominal pain, vomiting, bloody diarrhea,
cyanosis, lethargy, and convulsions. Levels may vary widely for
an individual within the same day or from day to day.
Luteinizing hormone (LH) Female Menstruating Test used to determine the preovulatory LH surge; also provides
Follicular phase 2.0-15.0 an integrated picture of LH secretion throughout the day. Shows
Ovulatory phase 22-105 pituitary or hypothalamic impairment or overproduction
Luteal phase 0.6-19
Postmenopausal 16-64
Male 2.0-12.0

354
Magnesium 1.4-2.0 meq/liter Magnesium plays a vital role in glucose metabolism by facilitating the formation of muscle and
liver glycogen from blood-borne glucose. Also participates as a cofactor in the breakdown of
glucose, fatty acids, and amino acids during energy metabolism. High serum levels may indicate
dehydration, renal insufficiency, uncontrolled diabetes mellitus, adrenocortical insufficiency,
Addison’s disease, hypothyroidism or lupus erythematosus. Phytate, fatty acids, and an excess
of phosphate impair mg absorption. Symptoms of deficiency usually do not occur until serum
levels are above 1 meq / liter

Phosphorus, 2.6-4.5 mg/dl Serum phosphorus concentrations have a circadian rhythm (highest level in late morning,
inorganic (adult) lowest in evening) and are subject to rapid change secondary to environmental factors such as
diet (carbohydrate), phosphate-binding antacids, and fluctuations in growth hormone, insulin,
and renal function. High levels may indicate osteolytic metastatic bone tumors, myelogenous
leukemia, milk-alkali syndrome, vitamin d intoxication, healing fractures, renal failure,
hypoparathyroidism, pseudohypoparathyroidism, diabetes mellitus with ketosis, acromegaly,
portal cirrhosis, pulmonary embolism, lactic acidosis or respiratory acidosis.

Potassium 3.4-4.8 mmol/liter High potassium levels are associated with reduced renal excretion of potassium or
redistribution of potassium in the body (i.e. Massive hemolysis, severe tissue damage, severe
acute starvation-anorexia nervosa, hyperkinetic activity, malignant hyperpyrexia following
anesthesia, hyperkalemic periodic paralysis, and dehydration).

355
Progesterone Female
Follicular phase > 1 ng / ml
Midluteal phase 3-20 ng/ml
Male < 1 ng / ml
Prolactin Female
Premenopausal 0-20 ng/ml
Postmenopausal 0-15 ng/ml
Male 0-15 ng/ml
Prostate-specific antigen Female 0
(PSA) Male less than 40 years of age 0.0-
2.0 ng/ml
greater than or equal to 40 yr. old
0.0-4.0 ng/ml
Prostate-specific antigen Males 45-75 yr. old, with PSA values
(PSA), Free between 4 and 20 ng/ml. Above
25% associated with benign
prostatic hyperplasia
The diagnostic value of this test lies in its detection of ovulation
and in the evaluation of the function of the corpus luteum.
Serial sampling during the menstrual cycle is required. During
menopause, levels drop to 0
May help assess Prolactin reserve and abnormal Prolactin
secretion by the pituitary. May indicate pituitary tumors.
PSA is prostate-tissue specific, not prostate-cancer specific.
Used for early detection of the recurrence of prostatic cancer.
The test is of great value as a marker in the follow-up of
patients at high risk for disease progression. PSA values
increase with age.
PSA is prostate-tissue specific, not prostate-cancer specific.
Used for early detection of the recurrence of prostatic cancer.
The test is of great value as a marker in the follow-up of
patients at high risk for disease progression. PSA values
increase with age.
356
Protein, total 6.0-8.0 g/dl High blood levels may be associated with anabolic steroid use, androgens,
corticosteroids, corticotrophin, epinephrine, insulin, progesterone, or thyroid
preparations. Severe protein deficiency, chronic liver disease, malabsorption
syndrome, and malnutrition may also lead to abnormal levels. Serum total protein
decreases in the third trimester of pregnancy.

Sodium 135-145 mmol/liter High serum levels are associated with water loss in excess of salt through skin,
lungs, GI tract, and kidneys. Also may indicate increased renal sodium
conservation in hyperaldosteronism, Cushing’s syndrome or disease, inadequate
water intake because of inadequate thirst mechanism, dehydration, or excessive
saline therapy. Low sodium levels may indicate low sodium intake, sodium losses
due to vomiting, diarrhea, excessive sweating with adequate water intake and
inadequate salt replacement, diuretics abuse, or salt-losing nephropathy

Somatomedin C 16-24 yr. 182-780 ng/ml

(Insulin-like growth 25-39 yr. 114-492 ng/ml Blood concentrations of IGF-1 are constant during the day and after eating. In
factor I) 40-54 yr. 90-360 ng/ml acromegaly, the test may serve as an indicator of the severity of the disease; serial
> 54 yr. 71-290 ng/ml determinations may be used to monitor efficacy of treatment. In dwarfism IGF-1
may be used to determine the response to GH therapy. Concentrations of IGF-1
rise during the first year of life, reaching the highest values in preadolescent or
early adolescent years. Normal values tend to decline progressively until age 50

357
Testosterone, total (morning
sample)
Testosterone, unbound
(morning sample)
Thyroid-stimulating
hormone (TSH)
Female 6-86 ng/dl
Male 350-1070 ng/dl
Male 20-40 yr. 15.0-40.0 pg/ml
41-60 yr. 13.0-35.0 pg/ml
61-80 yr. 12.0-28.0 pg/ml
Female 20-40 yr., 0.6-3.1 pg/ml
41-60 yr. 0.4-2.5 pg/ml
61-80 yr. 0.2-2.0 pg/ml
0.5-3.5* U/ml
This test is a measure of total circulating testosterone, both
protein bound and free. In adult men, serum levels peak in the
early morning, decreasing 25% to the evening minimum. Levels
increase after exercise and decrease after immobilization and
after glucose load. Progressive decreases begin after age 50
Free (nonprotein-bound) testosterone is independent of
changes in concentrations of the principal testosterone
transport protein, sex hormone-binding globulin.
First-line test for hyper- and hypothyroidism. Test is considered
by some to be the preferred screening test for evaluation of
thyrometabolic states. Moderately high TSH is often found in
euthyroid patients during treatment of hyperthyroidism. *
There is disagreement among guidelines about what the max
value of normal range should be.
358
Thyroxine, total 4.5-10.9 g/dl Used in conjunction with other tests to measure thyroid function. T4 testing is frequently used
(T4) when TSH levels are abnormally high or low. In hypothyroidism, total serum t4 falls before t3. High
serum levels may represent hyperthyroidism.

Transferrin 191-365 mg/dl Transferrin is the major plasma transport protein for iron. High serum levels may indicate iron
deficiency (high levels often precede the appearance of anemia by days to months). Serum ferritin
levels fall with iron deficiency and with generalized malnutrition but remain normal in the presence
of inflammation and iron deficiency

Triglycerides 40-150 mg/dl Increased triglyceride levels indicate hyperlipoproteinemia types I, IIb, III, IV, and V due to familial or
(fasting) sporadic endogenous hypertriglyceridemia. The following primary disease states or conditions can
lead to secondary elevation of triglycerides: obesity, impaired glucose tolerance, viral hepatitis,
alcoholism, alcoholic cirrhosis, biliary cirrhosis, acute and chronic pancreatitis, extrahepatic biliary
obstruction, nephrotic syndrome, chronic renal failure, essential hypertension, acute myocardial
infarction, chronic ischemic heart disease, cerebral thrombosis, hypothyroidism, diabetes mellitus,
gout, pregnancy, glycogen storage diseases types I, II, III, and IV, down syndrome, respiratory
distress syndrome, Werner’s syndrome, anorexia nervosa, or idiopathic hypercalcemia. Low levels of
triglycerides may indicate chronic obstructive lung disease, brain infarction, hyperthyroidism,
hyperparathyroidism, lactosuria, malnutrition, malabsorption syndrome, intestinal lymphangiectasia
or end-stage parenchymal liver disease.

359
Triiodothyronine, total (T3)
Urea nitrogen (BUN) (adult)
Uric acid
Differential blood count
60-181 ng/dl Used in conjunction with other tests to measure thyroid function. High
serum levels may indicate hyperthyroidism while low levels may
indicate hypothyroidism. At least 80% of circulating T3 is derived from
Monod iodination of T4 in peripheral tissues. Free T3 and free T4 can
also be of great value in thyroid work-ups. T3 is 4 to 5 times more
potent in biological systems than T4.
8-25 mg/dl High serum blood levels may indicate impaired kidney function
associated with an increase with age or protein content of diet.
Male 3.6-8.5 mg/dl High serum levels may indicate gout, renal failure, leukemia,
Female 2.3-6.6 mg/dl lymphoma, psoriasis, polycythemia, multiple myeloma, kidney disease,
and or chronic lead nephropathy. Associated with hyperlipidemia,
obesity, hypertension, arteriosclerosis, diabetes mellitus,
hypoparathyroidism, acromegaly, and liver disease.
Neutrophils 45-75% Neutrophils a white blood cell.
Bands 0-5% Bands: increase in band neutrophils means the bone marrow has been
Lymphocytes 16-46% signaled to release white blood cells
Monocytes 4-11% Lymphocytes a form of small leukocyte (white blood cell), occurring
Eosinophils 0-8% especially in the lymphatic system.
Basophils 0-3% Monocytes a large phagocytic white blood cell
Eosinophils a white blood cell containing granules
Basophils a basophilic white blood cell.
360
Erythrocyte count Male 4.50-5.30 X 106/mm3 Red Blood Cell count. Low Values may mean blood loss, hemorrhage, bone marrow failure
Female 4.10-5.10 X 106/mm3 deficiencies in iron, folate vitamins B6 or B12, hemolysis, certain cancers. High values may mean
living at high altitudes, congenital heard disease, cor pulmonale, pulmonary fibrosis,
dehydration, smoking, COPD, testosterone or anabolic steroid use.

Folate (folic acid) Normal 3.1-17.5 ng/ml Water soluble vitamin involved with amino acid metabolism, may presage loss of red blood cells.
Borderline deficient 2.2-3.0 ng/ml LOW values may mean inability to process B12 exhaustion, muscle weakness, vision disturbances,
Deficient < 2 ng / ml neurological and psychiatric disturbances including depression and confusion. HIGH values have
Excessive above 17.5 ng/ml not been found to be associated with morbidities.

Hematocrit (adult) Male 37.0-49.0 % of Red Blood Cells present in total blood. Low values may mean anemia, blood loss, bone
Female 36.0-46.0 marrow disease hemolysis, certain cancers, deficiencies in iron, folate, B6 or b12, or cirrhosis.
HIGH values may mean dehydration, polycythemia, smoking, testosterone or anabolic steroid
use, sleep apnea, COPD, or living at high latitudes.

Hemoglobin (adult) Male 13.0-18.0 g/dl Oxygen-carrying compound of blood. Numerical value of hemoglobin present in Red Blood
Female 12.0-16.0 g/dl Cells. LOW values may mean anemia, blood loss or deficiencies in iron, folate, B6 or B12. HIGH
values may mean sickle cell anemia, Thalassemia, a transfusion reaction, hemolysis dehydration,
polycythemia, anabolic steroid or testosterone use, or living in a high altitude.

Iron 30-160 g/dl Constituent of hemoglobin (transport of oxygen in blood) and enzymes involved in energy
metabolism. LOW values may mean iron deficiency anemia, chronic blood loss, anemia due to
infection or chronic illness, Nephrosis, hypothyroid, frequent blood donations, or menstruation in
women. HIGH values may mean hemolytic anemia, hepatitis, acute iron toxicity, thalassemia,
hemochromatosis

361
Leukocyte count (WBC) 4.5-11.0X103/mm3 Ferritin should also be measured in those undergoing
phlebotomies or blood donation to ensure it is not low.
LOW values may mean bone marrow failure, presence of
toxins, autoimmune disease, aplastic anemia, liver or
spleen disease, or radiation exposure. HIGH values may
mean bacterial, viral protozoal or parasitic illnesses,
inflammatory illnesses, leukemia, severe emotional or
physical stress, tissue damage.

Mean corpuscular hemoglobin (MCH) 25.0-35.0 pg/cell Value is calculated from hemoglobin and erythrocyte
count. formula is MCH= Erc÷Hb LOW volume may mean
microcytic or normal anemia, iron deficiency HIGH values
may macrocytic anemia, hereditary spherocytosis

Mean corpuscular hemoglobin concentration 31.0-37.0 g/dl Mean cell hemoglobin concentration is calculated from
(MCHC) Hb and hematocrit (Hct)
formula is MCHC= Hct÷Hb LOW volume may mean
hypochromic anemia, Iron deficiency Thalassemia HIGH
values may mean hereditary spherocytosis

362
Mean corpuscular Male 78-100 m3 Mean cell volume may not be reliable when a large number of abnormal erythrocytes
volume (MCV) (adult) Female 78-102 m3 or a dimorphic population of erythrocytes is present. It may also be calculated from
the hematocrit and erythrocyte count formula is MCV= Erc÷Hct LOW values may
mean microcytic anemia, Iron deficiency, thalassemia. HIGH Values may mean
macrocytic anemia, folic acid or B12 deficiencies, alcoholism hereditary spherocytosis

Platelet count 150-350X103/mm3 Helps mediate the blood clotting that prevents loss of blood after injury. LOW values
may mean chemotherapy, hemolytic anemia, hypersplenism, idiopathic
thrombocytopenic purpura, B12 or folate deficiency, leukemia, prosthetic heart valves,
sequelae of massive blood transfusion, disseminated intravascular coagulation. HIGH
values may mean post-splenectomy syndrome, primary thrombocytosis, certain
malignancies, early chronic myelogenous leukemia, polycythemia, rheumatoid
arthritis

Mean platelet volume 6.4-11.0 m3 Mean platelet volume is a measurement of the average size of platelets found in
blood and is typically included in blood tests as part of the CBC LOW MPV values
may mean platelets are destroyed, usually by antibodies, an infection, or toxins. HIGH
MPV values may mean a genetic mutation or chronic myelogenous leukemia

363
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Watch the video here

367
 LA TESTOSTERONA:
INFORMACION EN ESPAÑOL
Libro La Testosterona de Nelson Vergel
Video: La Testosterona: Lo Que Todo Hombre Debe Saber
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Información básica sobre la testosterona
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EXPERT INTERVIEWS
 Controversies with Testosterone Therapy: Interview
with World Expert Dr. Mohit Khera
Can Testosterone Induce Blood Clots and Thrombosis?
Interview with Dr. Charles Glueck
Is Metformin a Miracle Drug? Nelson Vergel Explains
Expert Beyond Testosterone: Interview with Dr. Lynese Lawson

Interviews New Testosterone Nasal Gel (Natesto) Data- Video

Interview with Dr. Ramasamy
Nelson Interviews Dr. Spencer Nadolsky- The Online
Fitness Doctor
Estradiol in Men: Myths and Facts- by Nelson Vergel

371
 Interview with Lee Myer, Author of "Natural vs. Testosterone Therapy"
Comprehensive Evaluation of Erectile Function: Interview with Dr.
Lisbeth Roy
Growth Hormone Releasing Hormones and Peptides: Research History
Adversity, Breakthrough and a Hero’s Battle with Death -Jay Campbell
Expert Interviews Nelson Vergel

Interviews II
Estradiol in Men: Interview with Urology Professor Dr. Ranjith
Ramasamy
Nelson Vergel Speaks to Paul Burguess from the UK about
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Gynecomastia Surgery: Interview with Dr. Joseph Cruise
Interview with NYC urologist Dr. Michael Rotman
Video: Interview with Dr. Rand McClain About Testosterone and More

372
 Interview with Nelson Vergel by Performance Health
Podcast in Australia
Penile Implants- Interview with Dr. Robert Cornell in
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Expert Webcast: Doctors Speak About Men's Health Issues

Interview with Jerry Brainum: Truth and Lies About Fat Loss
Interviews III Supplements
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Side Effects- Part 1

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 Doctor and Clinic Reviews

Compounding Pharmacy Product Reviews

ExcelMale Supplement Reviews

Member Blood Testing Company Reviews

Reviews Book Reviews

Gadget and App Reviews

Other Men's Health Product or Company Reviews

376
 Websites
• ExcelMale.com
• PeakTestosterone.com
• HormoneClinicNetwork.com ( International TRT and
HRT doctor directory)

Books
TRT • Testosterone: A Man’s Guide
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