Hormone replacement therapy (trans female)

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This article is about hormone replacement therapy for trans women.

Contraindications

• Absolute: history of estrogen sensitive cancer (for example breast cancer), history of thromboembolic disease (unless provided with concurrent anti-coagulation therapy), or history of macroprolactinoma.
• Relative: Liver, kidney, or heart disease and stroke (or any of the risk factors for heart disease: high cholesterol, diabetes, obesity, smoking); Strong family history of breast cancer or thromboembolic disease; Gallbladder disease

Types of therapy

Estrogens

• Doses are often higher than replacement doses for cisgender women. Usually the dosage is reduced after an orchidectomy (the removal of the testes) or sex reassignment surgery.
• However, the practice of lowering estrogen doses after such operations has been carried over from the days when very high doses of estrogen were required to decrease testosterone since anti-androgens were not used. In fact, high doses (though in many cases not as high as those in years prior without the use of anti-androgens) are recommended during the first ten or so years of HRT to fully develop, with or without having had an orchiectomy or sex reassignment. After usually ten years or so the dosages can be reduced.
• Injected, implanted, nasal, oral, dermal gel and Transdermal patch formulations are available.
• As dosage increases, risks increase as well. Therefore, women with relative contraindications should start at lower doses and increase dosage more gradually.
• Transdermal estrogen may be preferable in older transwomen and smokers as it may have less of an increase in risk for thromboembolism. However, the number of patches needed and cost may make this less practical. Furthermore, transdermal estrogen carries the risk of localised skin irritation.

Progestogens

• Progestogens include progesterone and progestins (synthetic analogs of progesterone). There are oral, suppository, and injectable formulations available.
• Progestogens are involved in the full maturation of the breasts, particularly the mammary structures lobules, acini, and alveoli.
• Progestogens also help fat distribution, increase female libidinal feelings, increase appetite, slight increase in skin oil, increases blood flow to the skin, increases the ability to sweat and lose extra heat, increase in body temperature enabling one to better tolerate the cold, healthier nails, produce a sense of calm, and increase energy. Progesterone in particular is essential for bone health. However, progestogens may increase skin oil and libido too much for some and there may be acne breakouts due to the increase in skin oil.

Anti-androgens

• Spironolactone is the most frequently used anti-androgen in the United States because it is relatively safe and inexpensive. Cyproterone acetate is more commonly used outside of the US.
• Spironolactone is a ‘potassium sparing diuretic’ that is also used to treat hypertension, edema, hyperaldosteronism, and low potassium levels caused by other diuretics. It can cause high potassium levels, hyperkalemia, and is therefore contra-indicated in people with renal failure or who otherwise have elevated potassium levels.
• Cyproterone acetate is derived from 17-alpha-hydroxyprogesterone and suppresses luteinizing hormone (which in turn reduces testosterone levels), blocks dihydrotestosterone from binding to androgen receptors, and is a weak progestin. It has been used to treat prostate cancer. If used long-term in dosages of 200 milligrams or higher it can possibly lead to liver damage or failure. It is, arguably, the most potent anti-androgen.
• Other anti-androgens include bicalutamide, flutamide, and nilutamide. Unlike the two medications above, these do not lower testosterone levels but rather prevents testosterone and dihydrotestosterone from binding to androgen receptors. Because these have a weak action at the brain they do not lower libido or decrease erections.

GnRH agonists

• In both sexes, the hypothalamus releases GnRH (gonadotropin-releasing hormone) to stimulate the pituitary to produce LH (luteinizing hormone) and FSH (follicle stimulating hormone) which in turn cause the gonads to produce sex steroids. In adolescents of either sex with relevant indicators, GnRH agonists, such as goserelin acetate can be used to suspend the advance of sex steroid-induced, inappropriate pubertal changes for a period without inducing any changes in the gender-appropriate direction. GnRH agonists work by initially over stimulating the pituitary then rapidly desensitizing it to the effects of GnRH. After an initial surge, over a period of weeks, gonadal androgen production is greatly reduced. There is considerable controversy over the earliest age, and for how long it is clinically, morally and legally safe to do this. The current, sixth edition of the Harry Benjamin International Gender Dysphoria Association Standards of Care permit from Tanner stage 2, but do not allow the addition of gender-appropriate hormones until 16, which could be five or more years. The sex steroids do have important other functions. Also skeletal growth, which is often considered to be masculinising, is not hindered by GnRH agonists.
• GnRH agonists are often prescribed to prevent the reactivation of testicular function where surgeons require the cessation of estrogens prior to surgery.
• The high cost of GnRH agonists is often a significant factor.

Hormone effects

Overview

For trans women, taking estrogens causes among other changes:

• the growth of breasts, with concomitant enlargement of the nipples, and
• redistribution of body fat.
• thinning of skin.

For male-to-female transgendered people, HRT often includes antiandrogens in addition to the estrogens and progestagens mentioned above. HRT does not usually cause facial hair growth to be impeded; or the voice to change.

Irreversible changes

• breast development,
• enlarged nipples and areolae
• stretch marks (for some)

Reversible changes

• decreased libido and changes in sexual behaviour,
• redistribution of body fat,
• reduced muscle development,
• various skin changes,
• significantly reduced body hair,
• change in body odour and sweat production
• less prominence of veins
• ocular changes
• genital size

Psychological

The psychological changes are harder to define, since HRT is usually the first physical action that takes place when transitioning. This fact alone has a significant psychological impact, which is hard to distinguish from hormonally induced changes. Many also report feeling more confident.

Cardiovascular

• The most significant cardiovascular risk for transgender women is the pro-thrombotic effect of estrogens. (Increased blood clotting.) This manifests most significantly as an increased risk for thromboembolic disease: deep venous thrombosis (DVT) and pulmonary embolism (PE) which occurs when DVTs break off and migrate through the venous system to the lungs. It is important for any person on female hormones to immediately seek medical care if she develops pain or swelling of one leg (especially calf) as this is the predominant symptom of a DVT, or if she develops symptoms of PE: chest pain, shortness of breath, fainting, or palpitations (even without leg pain or swelling).
• In practice this becomes very important to transgender women undergoing surgery. Hormones should be withheld for a week before until two weeks after surgery.
• DVTs occur more frequently in the first year of treatment with estrogens. However this may represent a ‘screening by treatment’ of patients who may have genetic predispositions to thromboembolic disease, with those who are more likely to develop DVTs doing so early on in therapy. However, if patients have a family history of thromboembolic disease, screening for known disease may be appropriate.
• DVT risk is greater with oral rather than transdermal or injectable estrogens.
• DVT risk also increases with age and with smoking, so many clinicians advise using the safer transdermal formulations in patients who smoke or are older than age 40.
• If screening is undertaken for known pro-thrombotic mutations such as Factor V-Leiden, antithrombin III, and protein C or S deficiency, it should be done so to increase the safety of hormonal therapy and not as a screen for who may undertake hormonal therapy. Given that the risk of warfarin treatment in a relatively young, well-informed, and otherwise healthy population is quite low and that the risk of adverse physical and psychological outcome for untreated transgender patients is high, a prothrombotic mutation is not an absolute contraindication for hormonal therapy. (See: Levy, et al “Endocrine Intervention for Transsexuals”, Clin Endo 2003. 59:409-418.)

Hair

• Current facial hair is only slightly affected (some reduction in density, coverage, and slower growth) by anti-androgens. Those who are less than a decade past puberty and/or whose ethnicity generally lacks a significant amount of facial hair will have better results with anti-androgens. Those taking anti-androgens will have better results with electrolysis/laser hair removal than those who are not. If one is still in their teens or early twenties, there will be prevention of new facial hairs from developing if testosterone levels are within the female range.
• Body hair (chest, periareolar, shoulders, back, abdomen, rear, thighs, tops of hands, tops of feet, and even nose and ear) will, over time, turn from terminal (“normal”) hairs to vellus hairs (very tiny, blonde “baby” hairs). Hair on the arms, perianal, and perineal will reduce but may not turn to vellus hair on the latter two regions (some natal females also have some hair in these areas). Underarm hair will slightly change in texture and length, pubic hair becomes more typically female in pattern. Lower leg hair becomes less dense in concentration. All depending upon genetics.
• Head hair may slightly change in texture, curl, and color (new hairs that is, not hair that has already formed and reached the surface prior to HRT), this is especially likely with hair growth from previously bald areas.
• Eyebrow hair becomes less “bushy” or scattered.

Urogynecological effects

• Transgender women report a sometimes significant reduction in libido, all depending upon the dosage of anti-androgens. A small number of post-operative transsexual women may take small amounts of testosterone to boost the libido. Many pre-operative transsexual women simply wait until after sex-reassignment surgery to begin an active sex life (due to how they feel towards their genitals and/or, for heterosexual or bisexual transsexual women, an aversion to anal sex) and for post-operative transsexual women how satisfied they are with the results. Progestogens can both raise one’s libido and encourage female libidinal feelings.
• Spontaneous and morning erections decrease in frequency significantly, however some who have had an orchiectomy still experience morning erections. Voluntary erections can be maintaned since the brain is the most important sex organ, a developed repertoire of fantasies and good visualization is a must. It also depends on how one views their own genitals (disgust, strong aversion to, tolerable, etc.).
• Testi volume is reduced by about 25% with typical dosages and as much as 50% in higher dosages. This is in response to the decrease in Leydig cells, Sertoli cells, and interstitial tissue, which produce both sperm and testosterone. When testosterone is dramatically reduced spermatogenesis is halted almost completely, when the cells that are involved in these processes go unused they atrophy (shrink).
• The prostate shrinks
• The bladder shrinks
• The line that runs down the underside of the penis and down the middle of the scrotum, the peno-scrotal raphe (where the urogenital folds fused early in the womb), will darken.
• Minor water retention is likely

Childbearing

• Childbearing, as experienced by cisgender women and some trans men, is impossible with today’s technology.
• However, genetic offspring are possible. For transwomen wishing future genetic offspring, pre-operative sperm banking is available. This may be especially attractive to transgender lesbians as it would be possible for such a woman to have a genetic child even after SRS, with artificial insemination of her partner by previously banked sperm.

Bone

• Both estrogens and androgens are necessary in both biological males and females for healthy bone. (Young healthy women produce about 10 mg of testosterone monthly. Higher bone mineral density in males is associated with higher serum estrogen.)
• Bone is not static. It is constantly being reabsorbed and created. Osteoporosis results when bone formation occurs at a rate less than bone reabsorption.
• Estrogen is the predominant sex hormone that slows bone loss (even in men.)
• Both estrogen and testosterone help stimulate bone formation (T, especially at puberty.)
• The hips will rotate slightly forward due to changes in the tendons so hip discomfort is not uncommon.

Drug interactions

• Any drug can cause adverse reactions with other medications so it is wise to check with a doctor or pharmacist when starting any new medication
• Of the estrogen formulations commonly used, ethinyl estradiol (commonly found in birth control pills) has the greatest number of adverse reactions

Skin

• The skin becomes thinner and therefore more translucent and pinkish (spider veins may appear or be more noticeable), more susceptible to tearing and irritation from scratching or shaving, increased tactile sensation, and slightly lighter in colour due to a slight decrease in melanin (pigment).
• Skin becomes softer
• Sebaceous gland activity (which is triggered by androgens) lessens which lowers the amount of sebum (oil) production on the skin and scalp, consequently the skin becomes less prone to the formation of acne due to the less quantity of oil that is produced
• The skin’s pores become smaller due to the low quantities of sebum produced
• Body odor (skin, sweat, and urine) will become less “metallic,” “sharp,” or “acrid” and more “sweet” and “musky.”
• Many apocrine glands (type of sweat glands) become inactive and body odour decreases. Sebum also contributes to body odour, which the production of is reduced by anti-androgens (as described above).
• More subcutaneous (under skin) adipose (fat) tissue accumulates. This gives a more puffy/softer appearance. Consequently dimpling, or cellulite, will be more apparent on the thighs and buttocks due to this along with the thinness of the skin.
• Susceptibility to sunburn increases possibly due to the thinner skin and/or less skin pigment.
• Because of the increase in adipose tissue in the hips, thighs, and rear, stretch marks (striae distensae) may appear on the skin in these areas.

Ocular changes

• The lens of the eyes changes in curvature
• Due to decreased androgens, the meibomian glands (aka., tarsal, palpebral, or tarsoconjunctival glands. A type of sebaceous gland on the upper and lower eyelids that open at the edges of the lids) produce less oil (oil that makes up the lipid layer of tear film which prevents the evaporation of the watery layer beneath) and a tendency for dry eyes may be a problem.

Senses

• A male’s body odor becomes more noticeable (including male pheromones) particularly with higher doses of estrogen, overall the sense of smell becomes stronger. Progestogens, however, lowers the sensitivity to male pheromones.

Mammary glands

• Breast, nipple, and areolar development takes 4-6 years to complete depending upon genetics, sometimes as much as 10 years. It is normal for there to be a “stall” in breast growth during feminization or for the size of one breast to be a little bigger than the other. Unfortunately, MtF HRT doesn’t usually result in a big bosom (many seek breast augmentation), although some very rare cases actually have so much growth that they opt for breast reduction. The size of the rib cage and shoulder width will also play a role in the size of the breasts, natal females have smaller of both so if a natal female and a transsexual female were to have the same cup size the transsexual female’s breasts will most likely appear smaller (thus larger implants are typically used in transsexual females to compensate, these larger implants would appear too large for a natal female however).
• The nipples will become more sensitive to stimulation.

Adipose tissue

• Fat distribution in the body slowly changes over months and years. The body will now tend to accumulate new adipose tissue (fat) in a typically female pattern. This includes the hips, thighs, rear, pubis, upper arms, and breasts. The body now tends to use/burn the old adipose tissue in the waist making it smaller as well as in the shoulders and back.
• Subcutaneous adipose tissue increases in the face (cheeks and lips) making the face appear puffier, appears to “round out” the face, and the face appears less “drawn” or “hollow” with slightly less emphasis on the jaw due to the lower portion of the cheeks having filled in.

Gastrointestinal

• Estrogens may predispose to gallbladder disease – especially in older and obese people
• Estrogens (especailly oral forms) may cause elevations in transaminases (liver function tests) indicating liver toxicity. LFTs should therefore be periodically monitored in transgender women

Neurological and psychiatric

• Mood changes can occur – including the development of depression
• Migraines can be made worse or unmasked by estrogen therapy
• Estrogens can induce the development of prolactinomas, which is why prolactin levels should periodically be monitored in transgender women. Milk discharge from the nipples can be a sign of elevated prolactin levels. If a prolactinoma becomes large enough, it can cause visual changes (especially decreased peripheral vision), headaches, mood changes, depression, dizziness, nausea, vomiting, and symptoms of pituitary failure like hypothyroidism.

Metabolic

• Estrogen therapy causes decreased insulin sensitivity which places transgender women at increased risk of developing type II diabetes.
• One’s metabolism slows down and one tends to gain weight, lose energy, need more sleep, and become cold more easily. Due to androgen deprivation a loss of muscle tone, a slower metabolism, and physical weakness becomes more evident. Building muscle will take twice as much work than before. However, the addition of a progestogen may increase energy although an increase in appetite may be seen as well.

External links

• MtF Hormone FAQ
• Inhouse Pharmacy MTF Transgender medications – DIY resources