Which Type of Estrogen Hormone Therapy Is Right for You?
Hormone replacement therapy HRT of the male-to-female MTF type is hormone replacement therapy and sex reassignment therapy used to change the secondary sexual characteristics of transgender people from masculine or androgynous to feminine.
It is one of two types of HRT for transgender people the other being female-to-male and is predominantly used to treat transgender women.
Some intersex people also receive this form of HRT, either starting in childhood to confirm the assigned sex or later if the assignment proves to be incorrect. The purpose of this form of HRT is to cause the development of the secondary sex characteristics of the desired sex , such as breasts and a feminine pattern of hair, fat, and muscle distribution. It cannot undo many of the changes produced by naturally occurring puberty , which may necessitate surgery and other treatments see below.
While HRT cannot undo the effects of a person's first puberty , developing secondary sex characteristics associated with a different gender can relieve some or all of the distress and discomfort associated with gender dysphoria , and can help the person to "pass" or be seen as the gender they identify with.
Introducing exogenous hormones into the body impacts it at every level and many patients report changes in energy levels, mood, appetite, etc. The goal of HRT, and indeed all somatic treatments, is to provide patients with a more satisfying body that is more congruent with their gender identity. Some medical conditions may be a reason to withhold hormone replacement therapy because of the harm it could cause to the patient. Such interfering factors are described in medicine as contraindications.
Absolute contraindications — those that can cause life-threatening complications, and in which hormone replacement therapy should never be used — include histories of estrogen-sensitive cancer e. Relative contraindications — in which the benefits of HRT may outweigh the risks, but caution should be used — include:. As dosages increase, risks increase as well. Therefore, patients with relative contraindications may start at low dosages and increase gradually.
Hormone therapy for transgender individuals has been shown in medical literature to be safe when supervised by a qualified medical professional.
Estrogen is one of the two major sex hormones in women the other being progesterone , and is responsible for the development and maintenance of feminine secondary sexual characteristics, such as breasts, wide hips, and a feminine pattern of fat distribution. 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. Androgens , such as testosterone and dihydrotestosterone DHT , are the major sex hormones in XY chromosomed individuals, and are responsible for the development and maintenance of masculine secondary sexual characteristics, such as a deep voice, broad shoulders, and a masculine pattern of hair, muscle, and fat distribution. 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.
Steroidal antiandrogens , namely spironolactone and cyproterone acetate , are the most commonly used antiandrogens for transgender women. 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. Cyproterone acetate is a powerful antiandrogen and progestin that suppresses gonadotropin levels which in turn reduces androgen levels , blocks androgens from binding to and activating the androgen receptor, and inhibits enzymes in the androgen biosynthesis pathway. It has been used as a means of androgen deprivation therapy to treat prostate cancer.
Nonsteroidal antiandrogens NSAAs used in HRT for transgender women include flutamide , nilutamide , and bicalutamide , all three of which are primarily used in the treatment of prostate cancer in cisgender men.
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. 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.
Certain antiandrogens do not reduce testosterone or prevent its action upon tissues, but instead prevent its metabolite, dihydrotestosterone DHT , from forming. 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. Progesterone , a progestogen , is the other of the two major sex hormones 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. 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.
Progestogens, in conjunction with the hormone prolactin , are involved in the maturation of the lobules , acini , and areola during pregnancy: Progestogens reportedly alter fat distribution e. Progesterone specifically is essential for bone health [ citation needed ] and seems to have a role in skin elasticity and nervous system function.
The psychological effects of hormone replacement therapy are harder to define than physical changes. 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.
Breast , nipple , and areolar development varies considerably depending on genetics, body composition, age of HRT initiation, and many other factors. Development can take a couple years to nearly a decade for some. However, many transgender women report there is often a "stall" in breast growth during transition, or significant breast asymmetry.
Transgender women on HRT often experience less breast development than cisgender women especially if started after young adulthood. For this reason, many seek breast augmentation. Transgender patients opting for breast reduction are rare. Shoulder width and the size of the rib cage also play a role in the perceivable size of the breasts; both are usually larger in transgender women, causing the breasts to appear proportionally smaller.
Thus, when a transgender woman opts to have breast augmentation, the implants used tend to be larger than those used by cisgender women. In clinical trials , cisgender women have used stem cells from fat to regrow their breasts after mastectomies. This could someday eliminate the need for implants for transgender women.
In transgender women on HRT, as in cisgender women during puberty, breast ducts and Cooper's ligaments develop under the influence of estrogen. Progesterone causes the milk sacs mammary alveoli to develop, and with the right stimuli, a transgender woman may lactate.
Additionally, HRT often makes the nipples more sensitive to stimulation. The uppermost layer of skin, the stratum corneum , becomes thinner and more translucent.
Spider veins may appear or be more noticeable as a result. Collagen decreases, and tactile sensation increases. The skin becomes softer,  more susceptible to tearing and irritation from scratching or shaving, and slightly lighter in color because of a slight decrease in melanin.
Sebaceous gland activity which is triggered by androgens lessens, reducing oil production on the skin and scalp. Consequently, the skin becomes less prone to acne. It also becomes drier, and lotions or oils may be necessary. Many apocrine glands — a type of sweat gland — become inactive, and body odor decreases. Remaining body odor becomes less metallic, sharp, or acrid, and more sweet and musky. As subcutaneous fat accumulates,  dimpling, or cellulite , becomes more apparent on the thighs and buttocks.
Stretch marks striae distensae may appear on the skin in these areas. Susceptibility to sunburn increases, possibly because the skin is thinner and less pigmented.