Types of therapy[ edit ] See also: Estrogens act by binding to and activating the estrogen receptor ER , their biological target in the body.
A variety of different forms of estrogen are available and used medically. The most common estrogens used in transgender women include estradiol which is the predominant natural estrogen in women and estradiol esters such as estradiol valerate and estradiol cypionate which are prodrugs of estradiol.
Conjugated estrogens CEEs , marketed as Premarin among other brand names, and ethinylestradiol are also sometimes used, but this is becoming less common. Estrogens may be administered orally , sublingually , transdermally via patch , topically via gel , by intramuscular or subcutaneous injection , or by an implant.
Prior to sexual reassignment surgery, dosages of estrogen for transgender people are often higher than replacement dosages used for cisgender women. However, that practice has been carried over from an era in which very high doses of estrogen were required to decrease testosterone , since antiandrogens were not used concurrently.
Today, high doses of a less potent estrogen — estradiol, which is endogenous to the human body, rather than the riskier ethinylestradiol and conjugated estrogens used in the past — are recommended during the first ten or so years of HRT, with or without an orchiectomy or genital reassignment.
After that period, dosages can be reduced. In addition, they stimulate sex drive and the frequency of spontaneous erections and are responsible for acne, body odor, and masculine-pattern scalp hair loss. Androgens act by binding to and activating the androgen receptor AR , their biological target in the body. In contrast to androgens, antiandrogens are drugs that prevent the effects of androgens in the body.
They do this by preventing androgens from binding to the AR or by preventing the production of androgens. The most commonly used antiandrogens in transgender women are cyproterone acetate , spironolactone , and GnRH analogues. Spironolactone, which is relatively safe and inexpensive, is the most frequently used antiandrogen in the United States. Cyproterone acetate, which is unavailable in the United States, is more commonly used in Europe and the rest of the world.
Spironolactone is a potassium-sparing diuretic that is mainly used to treat low- renin hypertension, edema , hyperaldosteronism , and low potassium levels caused by other diuretics.
It can cause high potassium levels hyperkalemia and is therefore contraindicated in people who have renal failure or already-elevated potassium levels. Spironolactone prevents the formation of androgens in the testes though not in the adrenal glands by inhibiting enzymes involved in androgen production. It has been used as a means of androgen deprivation therapy to treat prostate cancer. They do not lower androgen levels; rather, they act solely by preventing the binding of androgens to the androgen receptor.
However, they do so very strongly, and are highly effective antiandrogens. Bicalutamide has improved tolerability and safety profiles relative to cyproterone acetate, as well as to flutamide and nilutamide, and has largely replaced the latter two in clinical practice for this reason.
Enzalutamide is a more recently introduced NSAA with even greater potency and efficacy as an antiandrogen than bicalutamide, but it is still under patent protection and in relation to this is currently and for the foreseeable future extremely expensive. However, bicalutamide does have a very small risk of hepatotoxicity itself, as well as of interstitial pneumonitis. GnRH analogues[ edit ] In both sexes, the hypothalamus produces gonadotropin-releasing hormone GnRH to stimulate the pituitary gland to produce luteinizing hormone LH and follicle-stimulating hormone FSH.
This in turn cause the gonads to produce sex steroids such as androgens and estrogens. In adolescents of either sex with relevant indicators, GnRH analogues such as goserelin acetate can be used to stop undesired pubertal changes for a period without inducing any changes toward the sex with which the patient currently identifies.
GnRH agonists work by initially overstimulating the pituitary gland, 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 at which it is clinically, morally, and legally safe to use GnRH analogues, and for how long.
The sixth edition of the World Professional Association for Transgender Health 's Standards of Care permit it from Tanner stage 2 but do not allow the addition of hormones until age 16, which could be five or more years later. Sex steroids have important functions in addition to their role in puberty, and some skeletal changes such as increased height that may be considered masculine are not hindered by GnRH analogues.
GnRH analogues are often prescribed to prevent the reactivation of testicular function when surgeons require the cessation of estrogens prior to surgery.
The high cost of GnRH analogues is a significant factor in their relative lack of use in transgender people. However, they are prescribed as standard practice in the United Kingdom. Two medications are currently available to prevent the creation of DHT: These medications have also been found to be effective in the treatment of hirsutism in women.
Unlike estrogen, progesterone is not overtly involved in the development of female secondary sexual characteristics, and is instead involved mainly in the menstrual cycle and pregnancy. For this reason, progestogens are not commonly prescribed for transgender women. However, there may be a role of progestogens in breast development though controversial and disputed and in regulation of skin and hair,[ citation needed ] and progesterone specifically may have positive effects on sex drive, sleep, and levels of anxiety.
The most common progestogens used in transgender women include progesterone and progestins synthetic progestogens like CPA and medroxyprogesterone acetate MPA. These drugs are usually taken orally, but may also be administered by intramuscular injection. Antiandrogenic and androgenic effects[ edit ] High doses of progestogens exert negative feedback on the hypothalamic—pituitary—gonadal axis by activating the progesterone receptor. As a result, they have antigonadotropic effects — that is, they suppress the gonadal production of sex hormones such as androgens.
As such, sufficient dosages of progestogens, such as cyproterone acetate , gestonorone caproate , hydroxyprogesterone caproate , megestrol acetate , and MPA, can considerably lower androgen levels. In addition, certain other progestogens, such as cyproterone acetate, megestrol acetate, drospirenone , and nomegestrol acetate , bind to and block the activation of the androgen receptor. Because HRT is usually the first physical step taken to transition, the act of beginning it has a significant psychological effect, which is difficult to distinguish from hormonally induced changes.