Hormone Replacement Therapy for Transgenders Do’s and Don'ts Steven M. Brown, MD

Hormone Replacement
Therapy for Transgenders
Do’s and Don'ts
Steven M. Brown, MD
University of Wisconsin School of Medicine
stevethediseaseslayer@yahoo.com
A Case Report
What is Hormone
Replacement Therapy?
What is a Hormone?



Organic compound, secreted by a gland, in minute
quantities, into the bloodstream, that has a
regulatory effect on the metabolism of tissue or
organs at a site different than the site of secretion
Alter the metabolism of cells or the synthesis and
secretion of other substances (“tropic hormones”)
Bind to receptors (specific proteins) to “turn on”
functions in target tissues
Endocrinology 101
Glands: Groups of cells which
specialize in the secretion of hormones

Some important glands
–
Pituitary
 Anterior
–
–
–
–
–
–
pituitary
Growth hormone
Thyroid stimulating hormone
Adrenocorticotropic hormone (ACTH)
FSH
LH
Prolactin
Additional glands


Thyroid
Pancreas
–



Insulin
Hypothalamus
Parathyroid glands
Adrenal glands
–
–
–
–
Cortisol
Testosterone
Estrogen
Aldosterone
The “sex glands”

Ovaries
–
–
–

Progesterone
Estrogen
Regulate reproduction, bone metabolism, regulation of
blood cholesterol, breasts, skin
Testes
–
–
Testosterone
Regulates reproduction, musculature, bone metabolism,
cholesterol levels, red blood cell production
Chemical origins of sex hormones






Derived from cholesterol
Chemical structures of estrogen, progesterone,
testosterone vary slightly
Testosterone is a metabolite of progesterone
Estrogen is a metabolite of testosterone
Production is governed by negative feedback loops
Present in males and females in differing
concentrations
Chemical origins of
sex hormones
Changes which occur in puberty





Pre-wired biological clock, probably in the hypothalamus,
coincides with practical reproductive considerations
Hypothalamus releases Leutinising Hormone-Releasing
Hormone (LHRH).
LHRH passes down nerve endings, stimulates pituitary gland
In girls, around age 10 to 13, FSH and LH are produced—starts
the cyclic activity of the ovaries in the production of estrogen
In boys, ages of 10 and 14 years, FSH and LH “switch on”
testicular function in males (FSH triggers sperm production), LH
triggers testosterone production
Why Use Hormone Replacement?





Change physical appearance to maximize
consistency between physical identity and internal
gender identity
Assist in “passing”
Create better skin and hair patterns for subsequent
cosmetic surgery such as facial feminization
Assist FTM transgenders with “beard growth”
For emotional well-being
What are some of the
obstacles to HRT?

Patient issues
–
–
–
–
–
–
–
Ambivalence, “coming out” issues, fears of violence, fears of
rejection, discrimination, social stigmatization
Not transsexual or not intensely transsexual
Financial considerations “social and economic
marginalization”
Access to health care
Mistrust of medical establishment
Ability to have sustained follow-up and monitoring
Medical/behavioral contraindications



Underlying disease states
Unfavorable family history
Unfavorable lifestyle (tobacco, alcohol)
What are some of the
obstacles to HRT?

Health care provider issues
–
–
–
–
–
–
–
–
Lack of education
Lack of clinical experience
Relative paucity of studies
Unanswered questions
Personal discomfort
Serious complications
Fear of litigation
Off-label administration of medications
Who Prescribes
Hormone Replacement?

Primary care physician
–
–
–





Internist
Family Practitioner
“Gender dysphoria” clinic
Endocrinologist
Gynecologist
Urologist
SRS Surgeon
Psychiatrists
Who SHOULDN’T
Prescribe Hormones







Yourself
Family
Friends
Internet “buddies”
“Urgent care” physicians
“On-line” doctors
“On-line” pharmacies
Where Transgenders
Get Hormones





“Black Market
Friends
Mexico
Internet
Local pharmacy
SOME IMPORTANT WARNINGS



NEVER use hormonal medication prescribed for
another person
DON’T self-medicate
Use caution in purchasing hormones from “Black
market sources”, the Internet, foreign countries, mail
order houses and vendors who can “get it or you”
–
–
–
Medication may be impure
May be contaminated
Temptation to bypass appropriate monitoring
SOME MORE WARNINGS


Don’t double dose
Don’t alter regimen without supervision
An HRT “Do”

A clinician should collaborate with a
mental health specialist who has
extensive experience with the diagnosis of
such patients to avoid mistreatment with
hormones or sex-reversing surgical
procedures
Standards of Care:
Harry Benjamin International
Gender Dysphoria Association:

Requirements for HRT in adults
– Age 18 or older
– Demonstrable knowledge of what hormones can and cannot do
– Knowledge of social benefits and risks
– Documented real-life test for at least 3 months before HRT
or
–
–
Period of psychotherapy of duration specified by a mental health
professional (usually 3 months)
A letter from the mental health professional to the prescribing
physician
www.hbigda.org.
Some important principles





There is a lot of misinformation, especially on the
Internet
Hormone therapy remains somewhat “hit and miss”
“Individual results will vary”, especially for MTF
Extremely important to let any treating physician and
pharmacist know of all your medications to avoid
“drug-drug” interactions and to reduce potential
complications
Need to keep spouse/significant others informed
Reproductive options




To give opportunity to obtain children who
are genetically “their own”
Sperm banking prior to HRT for MTF
FTM’s banking of ovarian tissue or oocytes
Embryo banking
Gender reassignment and assisted reproduction, Human Reproduction 16:
612-614 (2001)
“Real-Life Test” Pros and Cons

Pros
–

HRT can cause permanent changes including sterility and
gynecomastia. RLT may confirm that transitioning is the
right choice
Cons
–
–
–
HRT makes it easier to pass and easier to attempt RLT
Most people who would consider hormones are pretty sure
of what they want by that time
HRT is “diagnostic” itself—true transsexuals will feel calmer
and relieved upon starting HRT; if not truly transsexual,
changes will cause worsening anxiety
Purposes of Feminizing Hormones


Induce the development of female secondary
sexual characteristics
Anti-androgen treatment to reduce the effect
of endogenous male sex hormones
An important principle—
have realistic expectations
Feminizing Hormones DO NOT



Cause the voice to increase in pitch.
Dramatically reduce facial hair growth in
most people. There are some exceptions
with people who have the proper genetic
predisposition and/or are less than a decade
past puberty.
Change the shape or size of bone structure.
However, they may decrease the bone
density slightly.
Some important DO’s





DO review risks and benefits before starting any
hormones
DO be sure that this is what you really, really
want…permanent changes can occur within weeks
DO be patient
DO eat healthy and exercise
DO reduce alcohol intake (reduce stress on liver)
Some important DO’s







DO have regular medical checkups (every 2-3 months)
DO watch your blood pressure
DO take a good multi-vitamin/mineral supplement to help be
sure the body has everything it needs for new development
DO give the body time to adjust
Use the lowest hormone dosage that affords the desired
changes.
DO make sure you are not allergic to Provera tablets before
you use Depo-Provera sustained release intramuscular
injection
DO drink fluids, watch potassium intake if taking spironolactone
Some important DO’s of Doctoring







DO see a reputable doctor for your care
DO get regular check-ups
DO be honest and up front with your doctor about all
medications
DO make a list of questions prior to each visit—don’t
be afraid to ask questions
EDUCATE your doctor, especially if you disagree
DO keep records of all changes—physical and
emotional, and SHARE them with your doctors
SEE your doctor for any discharge from breasts
Some important DON’TS








DON’T go out on your own for meds
DON’T alter your medication regimen
DON’T BUY hormones on the Internet or through
Mexico
DON’T BELIEVE everything you read on the Internet,
including web pages, bulletin boards, and chat rooms
DON’T let your weight get out of control
DON’T smoke
DON’T taking the maximum planned dosage of all
hormones at once
DON’T take pre-operative dosages of hormones for
more than about 3 years
Effects of Feminizing Hormones on Males





Effects vary from patient to patient—familial, genetic
tendencies
Younger patients generally obtain and more rapid
results
Noticeable changes within 2-3 months
Irreversible effects within 6 months
Feminization continues at a decreasing rate for two
years or more, often with a “spurt” of breast growth
and other changes after orchidectomy
Effects of Feminizing Hormones on Males

Breast development
–
–
–
–
–
–
–
–
–
–
can take years, begins after 2-3 months
final size about 1 to 2 cup sizes less than
close female relatives
less satisfactory results in older patients
Only one-third more than a “B”-cup
45% don’t advance beyond an “A”
growth not always symmetric
Larger male thorax “dilutes” effect
enhanced by progesterone
nipples expand
areolae darken
clevelandplasticsurgery.com
Effects of Feminizing Hormones on Males



Loss of ability to ejaculate/maintain erection
(variable)
Fertility and “male sex drive” drop rapidly—
this may become permanent after a few
months
Increased female-type sex drive/attraction to
men
Effects of Feminizing Hormones on Males





Decreased testicular size (mostly flaccid)
The prostate shrinks but does not disappear and
prostate cancer is still possible (although risk is
reduced)
DO HAVE REGULAR PROSTATE EXAMINATIONS
Decreased penis size, scrotal size (25% within first
year), sometimes requiring the patient to stretch by
hand to maintain adequate donor material for SRS
Spontaneous erections suppressed within 3 months
(but not totally eliminated)
Effects of Feminizing Hormones on Males

Decreased facial/body hair
–
–
–
–
–
–
Body hair lightens in texture and color, frequently disappears
Cessation of male pattern baldness
Limited regrowth of scalp hair which has been lost
Improvement in thickness and texture of scalp hair
Enhanced action of 2% or 5% minoxidil (Rogaine®)
Not much effect on distribution of facial hair
 Enhanced effect of electrolysis
 Decreased rate of growth
Cutaneous Effects of Feminizing
Hormones on Males



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Redistribution of body and facial fat
– Face looks more “feminine”—reduced angularity, fuller
cheeks
– Redistribution of fat from waist to hips and buttocks
Skin softer/smoother/thinner, more translucent, less greasy
Skin sometimes becomes excessively dry
Improvement in spots and acne
Redistribution of fat to hips and buttocks
Brittle fingernails
Increased susceptibility to scratching and bruising
Tactile sensation becomes more intense
Oil and sweat glands become less active, resulting in dryer
skin, scalp, and hair
Effects of Feminizing Hormones on Males

Sensory changes
–
–

Heightened sense of touch
Increased sense of smell
Emotional changes
–
More labile
Effects of HRT on
Metabolism in MTF’s

Metabolism decreases
–
Given a caloric intake and exercise regimen
consistent with pre-hormonal treatment
 Weight
gain
 Decreased energy,
 Increased need for sleep
 Cold intolerance
Other effects of hormones
Reduced risk of Alzheimer’s
 Improved memory

Effects of Feminizing Hormones on Males



Loss of muscle mass
Loss of strength
Estrogen prevents bone loss after
testosterone deprivation
Long-term follow-up of bone mineral density and bone metabolism in transsexuals
treated with cross-sex hormones, Clinical Endocrinology, 48: 347-354
Changes in Sexual Orientation
“Of 20 transsexuals of various types that were
interviewed, 6 heterosexual male-to-female
transsexual respondents reported that their
sexual orientation had changed since
transitioning from male to female…three of
the respondents claimed that the use of
female hormones played a role in changing
their sexual orientation.”
Daskalos CT. Changes in the sexual orientation of six heterosexual male-tofemale transsexuals. Arch Sex Behav. 1998;27:605-614
Risks of Feminizing Hormones —
Some General Principles

Complete risks in transsexuals is not known
–
–
–
–
–
Most studies are performed in biological women
Limited research regarding risks
Safety data and Food and Drug Administration
approval do not acknowledge the use of
hormones in transsexuals
All administration is thus “off-label”
Mortality not necessarily increased
Risks of Feminizing Hormones

Blood clots—
–
–
–
–
–
–
12% over age 40
Usually start in the veins of the
legs
Can break off and block blood
supply to the lungs—a FATAL
complication (pulmonary
embolism)
20-fold increased risk in MTF’s
Risk increased with oral vs.
transdermal estrogens
Central retinal vein occlusion
has been reported
Mortality and morbidity in transsexual subjects treated with crosssex hormones, Clinical Endocrinology, 47: 37-342 (1997)
Risk factors for Venous Thromboembolism


Surgery
Trauma (major or lower extremity)
Immobility, paresis
Malignancy
Cancer therapy (hormonal,
chemotherapy, or radiotherapy)
Previous venous thromboembolism
Increasing age
Pregnancy and postpartum period

Estrogen therapies


Selective estrogen receptor
modulators



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
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
Geerts et al. CHEST
2004:338S-400S.
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Acute medical illness
Heart or respiratory failure
Inflammatory bowel disease
Nephrotic syndrome
Myeloproliferative disorders
Paroxysmal nocturnal
hemoglobinuria
Obesity
Central venous catheterization
Inherited or acquired thrombophilia
Varicose veins
Smoking
Risk Factors are
Cumulative
Reducing the Risk of Blood Clots

Smoking cessation
–
–
–



Pharmacologic support
Relaxation therapy
Behavioral therapy
Discontinue HRT for 3-6 weeks prior to any major
surgery, including SRS
Review HRT with surgeon and anesthesiologist prior
to minor surgery
Discontinue HRT in injuries which result in
immobilization
Risks of Feminizing Hormones


Fluid retention
Prolactin
–
–

14%, in one study developed elevations
Pituitary enlargement can sometimes require
surgery
Hypertension
–
May vary with hormone regimen
Mortality and morbidity in transsexual subjects treated with crosssex hormones, Clinical Endocrinology, 47: 37-342 (1997)
The Cardiac Risks of Feminizing
Hormones

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


Most studies have and are being done in biologic
women
Much evidence suggests that estrogen lowers
cholesterol levels, and raises HDL (good cholesterol)
Increases triglycerides, blood pressure,
subcutaneous and visceral fat
Decreased LDL particle size (bad)
Decreased insulin sensitivity (bad)
Estrogens and the Heart

Current studies
–
Women’s Health Initiative

–
–
27,500 enrollees without CAD to test estrogen or
estrogen plus progestin post-hysterectomy
Women’s Angiographic Vitamin and Estrogen
Women’s Estrogen/Progestin and Lipid Lowering
Hormone Atherosclerosis Regression Trial
(WELL-HART)
Hormones and the Heart

JAMA: July 17, 2002
–
“Risks and Benefits of Estrogen Plus Progestin in
Healthy Postmenopausal Women”



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16,608, ages 50-79 studied
Received placebo or Premarin® plus Provera®
Study stopped after 5.2 years because of significantly
increased risk of cancer in treatment group
Reduced risk of colorectal cancer and hip fractures
Increased risk of coronary artery disease, pulmonary
embolism, stroke
Hormones and the Heart

What is the risk-benefit ratio in postmenopausal women?
–

Decreased hot flashes
How does the risk-benefit ratio differ in
transgenders?
–
–
Physical feminization
Reduced emotional stress
Reducing the Odds of
Cardiac Complications

If there’s a history or strong family history of heart attack,
coronary artery disease, or stroke
–
–

Estradiol (Estrace® 1 or 2 mg), a naturally occurring estrogen, is
preferred to Premarin®
–



Close supervision by a cardiologist, stress test
Blood pressure, lipid control, blood thinners
Usual dose is 4 mg daily pre-op, 2 mg daily post-op
Natural progesterone (Prometrium®) does not have the adverse
effects of medroxyprogesterone (Provera®) on blood cholesterol
or blood pressure levels
Consider daily administration of aspirin 81 mg daily
Reduce risk factors
–
–
–
No smoking
Watch weight
Watch blood sugar
Risks of Feminizing Hormones




Gallstone disease
Liver disease (low risk)
Weight gain
Mood swings
Risks of Feminizing Hormones

Cancer risk
–
Fibroadenoma—the most common breast tumor


–
–
Influenced by estrogen
Estrogen receptors present in 28-100% of patients with
fibroadenoma
Breast cancer
Prostate cancer

Has been reported
Contraindications to HRT
in FTM Patients

Absolute
–
–
–
–

History of thromboembolism or thrombotic tendency
History of macroprolactinoma
History of breast cancer
Active substance abuse
Relative
–
–
–
–
–
–
–
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–
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Coronary artery disease
Cerebrovascular disease
Hepatic dysfunction or tumor
Strong family history of breast cancer
Cholelithiasis
Poorly controlled hypertriglyceridemia
Poorly controlled diabetes mellitus
Refractory migraine headaches
Heavy tobacco use
Uncontrolled hypertension
Endocrine Therapy of
Transsexualism and Potential
Complications of Long-Term
Treatment, Archives of Sexual
Behavior, 27: 209-226 (1998)
“DO” Get Appropriate Monitoring

Follow-up exams every 2 – 3 month
–
Breast exam


–
–
–
–
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Measurements
Looking for galactorrhea
Weight
Blood pressure
Testicular size
Examination of extremities for phlebitis, edema
Visual fields
Appropriate laboratory monitoring
–
–
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Liver function tests
Lipid profile
Renal (kidney) function
Blood pressure
Fasting glucose
Thyroid function
Blood clotting times (every 6 – 12 months)
Testosterone levels (<50 ng/dl) in MTF’s
Prolactin (rule out prolactinoma)
Breast self-examination
Prostate examination
Pregnancy testing (FTM’s)
Monitoring changes
–
–
Estrogen levels
Testosterone levels (especially in pre-ops) or if
considering antiandrogens in a post-op—can
usually be followed o clinical grounds
MTF Monitoring—Johns
Hopkins
Other Tests Which Can Be Followed


Calcium and phosphorus (skeletal health)
Bone densitometry every two or three years
Testosterone levels


300-1000 ng/dl
5-85 ng/dl
genetic males
genetic females
Estrogen levels


Levels may be misleading secondary to
insensitivity of assays
Dosing is more commonly made on “clinical
grounds”
Administration of Hormones

Orally (estrogens, progesterones,
androgens)
–
–
Advantage: convenience
Disadvantage: increased stress on the
liver
Administration of Hormones

Sublingual
–

Dissolve under the tongue
 Better absorption
 Avoid passing through the liver which may stimulate
clotting problems
Injections (estrogens, progesterones, androgens)
–
–
Advantages:
 Preferred in setting of liver disease
 Preferred mode of delivering androgens
Disadvantages:
 unsteady hormone levels (except for sustained-release
preparations in oil or microscopic beads)
 pain
 infection risk from hypodermic needle usage
Administration of hormones

Skin patches
–
Advantage:

–
Disadvantage:


Convenience
skin irritation, allergy to adhesive
Cream (estrogens):
–
Advantage

–
moister and healthier skin.
Disadvantage:


low transfer rate into the body,
requires frequent spread on very large skin surfaces.
Dosing of HRT in Male to Females


No generalized agreement
General principles
–
–
DON’T mix drugs within categories
Need drugs from these two categories


Anti-androgens (discontinued post-operatively)
Estrogens
Taking Just One Class of Medications

Anti-androgens alone
–

Serious bone density loss
Estrogens alone
–
Does not lower testosterone levels
Common anti-androgens

Cyproterone acetate (Androcur®, Cyprostat®) (antigonadotropic)
–
–
–
–
–
–



Not available in United States
Androgen receptor antagonist
50-150 mg/daily
Oral or injectable
Risk of liver damage, thromboembolic disease
Altered carbohydrate metabolism
Medroxyprogesterone
Nilutamide (androgen receptor blocker)
Finesteride Propecia (testosterone antagonist—decreases DHT)
–
–
5 mg daily
Reduces male pattern baldness
Androgen receptor antagonists

Flutamide (Eulexin)
–
–
–
–
–
–
–
Androgen receptor antagonist
Hepatotoxic
Reduced blood counts, including platelets
Hypertension
Fluid retention
Depression, anxiety, nervousness, lassitude,
insomnia, GI disturbances
250 mg one to three times daily
Antiandrogens

Spironolactone
–
–
–
–
–
Weak androgen receptor antagonist
Diuretic
Can cause elevated potassium levels
Antihypertensive
100 to 400 mg daily
GnRH Agonists

Act on pituitary
–
–
–
–
–
Overstimulating pituitary
Then desensitizing it to GnRH from hypothalamus
Used in adolescents to delay puberty or when hormones
are withdrawn prior to surgery to reduce reversion to male
Limited experience
Drugs:




Nafarelin acetate nasal spray
Goserelin acetate injection
Lupron
Leunrorelin acetate
A word about herbals



Not benign—potential for liver injury
Still a medication and self-medicating
Unregulated by FDA
Common estrogens

Estradiol valerate (Estrace®)
–
–
–
–
–
–
–
Equivalent to natural 17 b-estradiol
May be safer than ethinylestradiol
Reduced risk of breast cancer and thrombosis although how
much risk reduction in high doses of transsexuals is not
known
4-6 mg pre-op in divided doses
1-2 mg daily post-op
Best combined with an antiandrogen
If hot flushes, night sweats appear, switch to ethinylestradiol
may be helpful
Common estrogens

Ethinylestradiol (Estinyl®)
–
–
–
–
Slowly metabolized by the liver, resulting in
greater potency and longer half life
Regarded by many as pre-op drug of choice
More intense feminizing effects
50 mg twice daily, gradually reduced to 50 mg
Common estrogens

Conjugated natural estrogens (Premarin®)
–
–
–
–
–
From urine of pregnant mares
Ethical issues
More expensive
5 – 7.5 mg daily pre-op (divided doses)
1 – 2.5 mg daily post-op
Common estrogens

Estraderm® patches
50-100 µg/day
tramdermally
Common progestogens





Anti-androgenic
Not feminizing alone
Enhances feminization from estrogen
May help maintain libido
May reduce cancer risk associated with
estrogens
Medroxyprogesterone acetate
Provera®






Good safety record
May be slightly virilizing—may be
metabolized into testosterone
If virilization occurs, switch to dydrogesterone
Typical dose 5 mg twice daily pre-op for 10
days of the month
May enhance breast development
2.5 – 5 mg daily post-op
Natural Progesterone



Micronized progesterone
Progesterone USP
Prometrium
–
–
–
–
Molecular structure closer to the
progesterone produced in a natal
female's body
Provera has been linked to
depression in trans women
Less androgenic
More costly
Common HRT in the United States

Estrogen preparations
–
–
–
–
–

Conjugated estrogens (Premarin) 2.5-5.0 mg/day
Estradiol (Estrace) 2-6 mg/day
Ethinyl estradiol 0.100-0.300 mg/day
Estradiol transdermal patches 0.1-0.4 mg twice
weekly
Estradiol valerate 20-40 mg every 2 wk
Antiandrogens
–
Spironolactone 200-400 mg/day
Failure to Respond


In no changes are
seen (including
“tender nipples”)
within 2-3 months
or
Feminization is very
limited over a longer
period of time


Serum testosterone,
DHEAS levels to rule
out overproduction of
androgens
Referral to an
endocrinologist
FTM Hormone Replacement



Females respond quite well to hormone
replacement as adolescents and as adults
Experience all the changes that genetic
males experience during puberty
Most of these changes are irreversible
Why is FTM easier than MTF?




In FTM, addition of androgens excites
androgen receptors which are there but
dormant
Puberty occurs again, but differentiating as a
male this time
In MTF, bodies are already differentiated by
the natural presence of androgen
Males are thus “immune” to further pubertal
changes
Effects of Masculinizing Hormones on
Females





Acne
Male pattern baldness
Increased muscle mass and development
Growth of facial and body hair
Thickening of vocal cords and deepening of
voice (not always reversible), not always down
to typical male pitch
Effects of Masculinizing Hormones on
Females





Enlarged clitoris (3-8 cm) with increased libido—
can become overly, painfully sensitive, peaks
after 2-3 years
Atrophy of uterus and ovaries
Growth spurt, closure of growth plates before
puberty
Increased bone density
Reduced risk of blood clots
Testosterone increases bone mineral density in female-to-male transsexuals: a case series of
15 subjects, Clinical Endocrinology, 61: 560-566
Venous Thrombosis and Changes of Hemostatic Variables during Cross-Sex Hormone
Treatment in Transsexual People, J. Clin. Endocrin. Metab. 88: 5723-5729 (2003)
Effects of Masculinizing Hormones on
Females






Fertility decreases--menstrual cycle becomes irregular
then stops, usually within 5 months
Outer skin layer becomes rougher in feeling and
appearance
Prominence of veins
Fat is redistributed. The face becomes more typically
“male” in shape. Fat tends to move away from the hips
and toward the waist
Body odors (skin and urine) change. They become less
"sweet" or "musky" and become more "tangy" or
"metallic."
Emotions change. Aggressive and dominant feelings may
increase
Male hormones DO NOT

Significantly decrease the size
of the breasts.
–




However, they may soften
somewhat
Change the shape or size of
bone structure
Grow a penis
Prevent pregnancy
Work overnight
Risks of Masculinizing Hormones





Ovarian cancer—long-term exposure to endogenous and
exogenous androgens are associated with ovarian epithelial
cancer
Steroids increase epidermal growth factors and transforming
growth factor (TGF-a) which promote cancer growth
Polycystic ovaries
Endometrial hyperplasia—risk of endometrial cancer
Breast cancer—breast cells may remain even after mastectomy
Ovarian Cancer in Female-to-Male Transsexuals: Report of Two Cases,
Gynecologic Oncology 76: 413-415 (2000)
Risks of Masculinizing Hormones







Reduced HDL cholesterol (bad)
Reduced LDL particle size (bad)
Increases triglycerides
Polycythemia (elevated red blood cell levels)
Increased sweating
Increased metabolism
“Hot flashes”
Risks of Masculinizing Hormones






Water and sodium retention
Decreased carbohydrate tolerance
Obesity and insulin-resistance
Sleep apnea
Increased aggressive behavior,
hypersexuality (rare)
Excessive testosterone can convert to
estrogen, increase risk of breast cancer
Testosterone and the Liver

Testosterone-induced hepatotoxicity
–
Increased liver enzyme levels are a frequent
occurrence




occurs in about 15%
Hepatic adenomas
Hepatocellular carcinomas
Peliosis hepatitis—blood-filled cavities in the
liver
Contraindications of HRT in FTM’s


Absolute
– Pregnancy
– Active substance abuse
Relative
– History of breast or uterine cancer
– Polycythemia
– Hepatic dysfunction or tumor
– Coronary artery disease
– Hyperlipidemia
– History of violent behavior
– Severe obstructive sleep apnea
– Androgen sensitive epilepsy
– Migraines
– Bleeding disorders (for injected
testosterone)
Hormone replacement therapy (trans)
http://en.wikpedia.org/wiki/Hormone_replacement_therapy_(trans)
Common Androgen Replacement

Injectable testosterone
–
–
–

Testosterone enanthate 100-400 mg IM every 2-3 wk
Testosterone cypionate 100-200 mg IM every 2-3 wk
Can be self-administered
Transdermal testosterone
–
–
Testosterone transdermal patches† 2.5-7.5 mg/day
Testosterone gel 1% (AndroGel)† 2.5-10 g/day

Risk of inadvertent exposure to others who come into contact
with skin
EXCESSIVE TESTOSTERONE MAY LEAD TO STROKE
AND HEART ATTACK
Endocrine Therapy of Transsexualism and Potential Complications of Long-Term Treatment,
Archives of Sexual Behavior, 27: 209-226 (1998)
Other androgen replacement

Testosterone pellets (Testopel)
–
–
–

Oral
–
–

6 -12 pellets under the skin every three months
Local anesthetic
More constant blood levels
Andriol—not available in the US
Has to pass through liver
Sublingual/buccal lozenge
–
Striant—absorbed through oral mucosa, avoiding liver



Gum irritation
Taste changes
Headaches
Drug Interactions of Testosterone

Drugs which decrease levels of testosterone levels:
–
–
–

Drugs which increase levels of testosterone:
–
–
–
–
–

Phenobarbital and Dilantin (seizure medicines)
Rifampin
Alcohol!
Serzone, Prozac, Paxil (antidepressants)
Sporanox, Diflucan (antifungals)
Tagamet
Biaxin, Zithromax (antibiotics)
Protease Inhibitors (HIV treatment)
Testosterone can also alter the effects of other drugs:
–
–
–
Increase the blood thinning effect of Coumadin
Decreases the effectiveness of Inderal (propranolol) a blood-pressure
medicine
Increases the effect of some oral medicines for diabetes and can cause
dangerously low blood sugar levels
Progesterone Treatment in FTM’s

Short-course progesterone therapy to
–
Induce menstrual period in first 2 years to shed
build-up of endometrial lining (if a hysterectomy
has not been performed)


Reduces spot bleeding
Decreases risk of uterine cancer
FTM Monitoring—Johns
Hopkins
Some FTM Do’s

Prior to hormone therapy, consider hysterectomy and bilateral
salpingo-oophorectmy
–
–







Eliminates risk of ovarian cancer
Saves awkward situation of doing a hysterectomy on a masculinized
patient
Stress management
Giving blood
Be patient
PAP smears, pelvic examination if you still have a uterus
Check bone densitometry
Endometrial ultrasounds every two years
Take a calcium supplement
Some FTM Don’ts


Don’t buy too many shoes—your feet will
grow
More is not better