Feminizing hormone therapy

Requirements

Main article: Transgender hormone therapy#Requirements, Transgender hormone therapy#Accessibility}}{{See also, DIY transgender hormone therapy

Many physicians operate by the World Professional Association of Transgender Health (WPATH) Standards of Care (SoC) model and require psychotherapy and a letter of recommendation from a psychotherapist in order for a transgender person to obtain hormone therapy. Other physicians operate by an informed consent model and have no requirements for transgender hormone therapy aside from consent.

Medications used in transgender hormone therapy are also sold without a prescription on the Internet by unregulated online pharmacies, and some transgender women purchase these medications and treat themselves using a do-it-yourself (DIY) or self-medication approach. One reason that many transgender people turn to DIY hormone therapy is due to long waiting lists of up to years for standard physician-based hormone therapy in some parts of the world such as the United Kingdom, as well as due to the often high costs of seeing a physician and the restrictive criteria that make some ineligible for treatment, or simply medical malpractice by physicians that are not adequately trained.

The accessibility of transgender hormone therapy differs throughout the world and throughout individual countries.

Medications

A variety of different sex-hormonal medications are used in feminizing hormone therapy for transgender women. These include estrogens to induce feminization and suppress testosterone levels; antiandrogens such as androgen receptor antagonists, antigonadotropins, GnRH modulators, and 5α-reductase inhibitors to further oppose the effects of androgens like testosterone; and progestogens for various possible though uncertain benefits. An estrogen in combination with an antiandrogen is the mainstay of feminizing hormone therapy for transgender women.

Estrogens

Estrogens are the major sex hormones in women, and are 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 estrogens 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 (Premarin), which are used in menopausal hormone therapy, and ethinylestradiol, which is used in birth control pills, have been used in transgender women in the past, but are no longer recommended and are rarely used today due to their higher risks of blood clots and cardiovascular problems. Estrogens may be administered orally, sublingually, transdermally/topically (via patch or gel), rectally, by intramuscular or subcutaneous injection, or by an implant.{{bulleted list| | |

The pharmacokinetics of estradiol's routes of administration vary greatly. Sublingual and rectal administration result in peak concentrations up to ten times higher than oral administration, and higher trough concentrations. This makes frequent, small sublingual or rectal doses, a very efficient way to create a stable and constant increase in trough levels. A large amount of estradiol consumed sublingually, and especially orally is converted by the GI tract into estrone and other compounds, causing a higher estrone:estradiol (E1:E2) ratio. This means oral doses are more subject to individual variances in enzymes and physiological chemistry. The extent of the estrone ratio's effects are unclear but, as a weaker estrogen agonist than estradiol, a high estrone level can reduce feminization by competitive antagonism. A high estrone ratio is linked to reduced skeletal growth in pubertal boys and insulin resistance in PCOS. The ratio is also known to be higher in early female puberty (~1:3), and lower in the later stages (~1-5). An average dose intramuscular injection can vary from far above to far below the average female range over the course of a week, depending on an individual's body.

In addition to producing feminization, estrogens have antigonadotropic effects, suppressing testosterone and other gonadal sex hormones. Levels of estradiol of 200 pg/mL and above suppress testosterone levels by about 90%, while estradiol levels of 500 pg/mL and above suppress testosterone levels by about 95%, or to an equivalent extent as surgical castration and GnRH modulators. Lower levels of estradiol can also considerably but incompletely suppress testosterone production. When testosterone levels are insufficiently suppressed by estradiol alone, antiandrogens can be used to suppress or block the effects of residual testosterone. Oral estradiol often has difficulty adequately suppressing testosterone levels, due to the relatively low estradiol levels achieved with it.Prior to orchiectomy (surgical removal of the gonads) or sex reassignment surgery, the doses of estrogens used in transgender women are often higher than replacement doses used in cisgender women. This is to help suppress testosterone levels. The Endocrine Society (2017) recommends maintaining estradiol levels roughly within the normal average range for premenopausal women of about 100 to 200 pg/mL. However, it notes that these physiological levels of estradiol are usually unable to suppress testosterone levels into the female range. A 2018 Cochrane review proposal questioned the notion of keeping estradiol levels lower in transgender women, which results in incomplete suppression of testosterone levels and necessitates the addition of antiandrogens. The review proposal noted that high-dose parenteral estradiol is known to be safe. The Endocrine Society itself recommends dosages of injected estradiol esters that result in estradiol levels markedly in excess of the normal female range, for instance 10 mg per week estradiol valerate by intramuscular injection. A single such injection results in estradiol levels of about 1,250 pg/mL at peak and levels of around 200 pg/mL after 7 days. Dosages of estrogens can be reduced after an orchiectomy or sex reassignment surgery, when gonadal testosterone suppression is no longer needed.

Antiandrogens

Antiandrogens are medications that prevent the effects of androgens in the body. Androgens, such as testosterone and dihydrotestosterone (DHT), are the major sex hormones in individuals with testes, and are responsible for the development and maintenance of masculine secondary sex characteristics, such as a deep voice, broad shoulders, and a masculine pattern of hair, muscle, and fat distribution. In addition, androgens stimulate sex drive and the frequency of spontaneous erections and are responsible for acne, body odor, and androgen-dependent scalp hair loss. Androgens also have functional antiestrogenic effects in the breasts and oppose estrogen-mediated breast development, even at low levels.{{bulleted list| | | | |

Antiandrogens that directly block the androgen receptor are known as androgen receptor antagonists or blockers, while antiandrogens that inhibit the enzymatic biosynthesis of androgens are known as androgen synthesis inhibitors and antiandrogens that suppress androgen production in the gonads are known as antigonadotropins. Estrogens and progestogens are antigonadotropins and hence are functional antiandrogens. The purpose of the use of antiandrogens in transgender women is to block or suppress residual testosterone that is not suppressed by estrogens alone. Additional antiandrogen therapy is not necessarily required if testosterone levels are in the normal female range or if the person has undergone orchiectomy. However, individuals with testosterone levels in the normal female range and with persisting androgen-dependent skin and/or hair symptoms, such as acne, seborrhea, oily skin, or scalp hair loss, can potentially still benefit from the addition of an antiandrogen, as antiandrogens can reduce or eliminate such symptoms.

Steroidal antiandrogens

Steroidal antiandrogens are antiandrogens that resemble steroid hormones like testosterone and progesterone in chemical structure. They are the most commonly used antiandrogens in transgender women. Spironolactone (Aldactone), which is relatively safe and inexpensive, is the most frequently used antiandrogen in the United States. Cyproterone acetate (Androcur), which is unavailable in the United States, is widely used in Europe, Canada, and the rest of the world. Medroxyprogesterone acetate (Provera, Depo-Provera), a similar medication, is sometimes used in place of cyproterone acetate in the United States.

Spironolactone is an antimineralocorticoid (antagonist of the mineralocorticoid receptor) and potassium-sparing diuretic, which is mainly used to treat high blood pressure, edema, high aldosterone levels, and low potassium levels caused by other diuretics, among other uses. Spironolactone is an antiandrogen as a secondary and originally unintended action. It works as an antiandrogen mainly by acting as an androgen receptor antagonist. The medication is also a weak steroidogenesis inhibitor, and inhibits the enzymatic synthesis of androgens. However, this action is of low potency, and spironolactone has mixed and inconsistent effects on hormone levels. In any case, testosterone levels are usually unchanged by spironolactone. Studies in transgender women have found testosterone levels to be unaltered with spironolactone or to be decreased. Spironolactone is described as a relatively weak antiandrogen. It is widely used in the treatment of acne, excessive hair growth, and hyperandrogenism in women, who have much lower testosterone levels than men. Because of its antimineralocorticoid activity, spironolactone has antimineralocorticoid side effects and can cause high potassium levels. Hospitalization and/or death can potentially result from high potassium levels due to spironolactone, but the risk of high potassium levels in people taking spironolactone appears to be minimal in those without risk factors for it. As such, monitoring of potassium levels may not be necessary in most cases. Spironolactone has been found to decrease the bioavailability of high doses of oral estradiol. Although widely employed, the use of spironolactone as an antiandrogen in transgender women has recently been questioned due to the various shortcomings of the medication for such purposes.

Cyproterone acetate is an antiandrogen and progestin which is used in the treatment of numerous androgen-dependent conditions and is also used as a progestogen in birth control pills. It works primarily as an antigonadotropin, secondarily to its potent progestogenic activity, and strongly suppresses gonadal androgen production. Cyproterone acetate at a dosage of 5 to 10 mg/day has been found to lower testosterone levels in men by about 50 to 70%, while a dosage of 100 mg/day has been found to lower testosterone levels in men by about 75%. The combination of 25 mg/day cyproterone acetate and a moderate dosage of estradiol has been found to suppress testosterone levels in transgender women by about 95%. In combination with estrogen, 10, 25, and 50 mg/day cyproterone acetate have all shown the same degree of testosterone suppression. In addition to its actions as an antigonadotropin, cyproterone acetate is an androgen receptor antagonist. However, this action is relatively insignificant at low dosages, and is more important at the high doses of cyproterone acetate that are used in the treatment of prostate cancer (100–300 mg/day). Cyproterone acetate can cause elevated liver enzymes and liver damage, including liver failure. However, this occurs mostly in prostate cancer patients who take very high doses of cyproterone acetate; liver toxicity has not been reported in transgender women. Cyproterone acetate also has a variety of other adverse effects, such as fatigue and weight gain, and risks, such as blood clots and benign brain tumors, among others. High dosages of cyproterone-based medication have been linked with meningioma. Periodic monitoring of liver enzymes and prolactin levels may be advisable during cyproterone acetate therapy.

Medroxyprogesterone acetate is a progestin that is related to cyproterone acetate and is sometimes used as an alternative to it. It is specifically used as an alternative to cyproterone acetate in the United States, where cyproterone acetate is not approved for medical use and is unavailable. Medroxyprogesterone acetate suppresses testosterone levels in transgender women similarly to cyproterone acetate. Oral medroxyprogesterone acetate has been found to suppress testosterone levels in men by about 30 to 75% across a dosage range of 20 to 100 mg/day.{{bulleted list| | | | | |

Numerous other progestogens and by extension antigonadotropins have been used to suppress testosterone levels in men and are likely useful for such purposes in transgender women as well.{{bulleted list| | | | | | | |

Nonsteroidal antiandrogens

Nonsteroidal antiandrogens are antiandrogens which are nonsteroidal and hence unrelated to steroid hormones in terms of chemical structure. These medications are primarily used in the treatment of prostate cancer, but are also used for other purposes such as the treatment of acne, excessive facial/body hair growth, and high androgen levels in women. Unlike steroidal antiandrogens, nonsteroidal antiandrogens are highly selective for the androgen receptor and act as pure androgen receptor antagonists. Similarly to spironolactone however, they do not lower androgen levels, and instead work exclusively by preventing androgens from activating the androgen receptor. Nonsteroidal antiandrogens are more efficacious androgen receptor antagonists than are steroidal antiandrogens, and for this reason, in conjunction with GnRH modulators, have largely replaced steroidal antiandrogens in the treatment of prostate cancer.

The nonsteroidal antiandrogens that have been used in transgender women include the first-generation medications flutamide (Eulexin), nilutamide (Anandron, Nilandron), and bicalutamide (Casodex).{{bulleted list| | |

Nonsteroidal antiandrogens like bicalutamide may be a particularly favorable option for transgender women who wish to preserve sex drive, sexual function, and/or fertility, relative to antiandrogens that suppress testosterone levels and can greatly disrupt these functions such as cyproterone acetate and GnRH modulators. However, estrogens suppress testosterone levels and at high doses can markedly disrupt sex drive and function and fertility on their own.{{bulleted list| | |

GnRH modulators

GnRH modulators are antigonadotropins and hence functional antiandrogens. In both males and females, gonadotropin-releasing hormone (GnRH) is produced in the hypothalamus and induces the secretion of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. The gonadotropins signal the gonads to make sex hormones such as testosterone and estradiol. GnRH modulators bind to and inhibit the GnRH receptor, thereby preventing gonadotropin release. As a result of this, GnRH modulators are able to completely shut-down gonadal sex hormone production, and can decrease testosterone levels in men and transgender women by about 95%, or to an equivalent extent as surgical castration. GnRH modulators are also commonly known as GnRH analogues. However, not all clinically used GnRH modulators are analogues of GnRH.

There are two types of GnRH modulators: GnRH agonists and GnRH antagonists. These medications have the opposite action on the GnRH receptor but paradoxically have the same therapeutic effects. GnRH agonists, such as leuprorelin (Lupron), goserelin (Zoladex), and buserelin (Suprefact), are GnRH receptor superagonists, and work by producing profound desensitization of the GnRH receptor such that the receptor becomes non-functional. This occurs because GnRH is normally released in pulses, but GnRH agonists are continuously present, and this results in excessive downregulation of the receptor and ultimately a complete loss of function. At the initiation of treatment, GnRH agonists are associated with a "flare" effect on hormone levels due to acute overstimulation of the GnRH receptor. In men, LH levels increase by up to 800%, while testosterone levels increase to about 140 to 200% of baseline. Gradually however, the GnRH receptor desensitizes; testosterone levels peak after about 2 to 4 days, return to baseline after about 7 to 8 days, and are reduced to castrate levels within 2 to 4 weeks. Antigonadotropins such as estrogens and cyproterone acetate as well as nonsteroidal antiandrogens such as flutamide and bicalutamide can be used beforehand and concomitantly to reduce or prevent the effects of the testosterone flare caused by GnRH agonists.{{bulleted list| | | |

GnRH modulators are highly effective for testosterone suppression in transgender women and have few or no side effects when sex hormone deficiency is avoided with concomitant estrogen therapy. However, GnRH modulators tend to be very expensive (typically to per year in the United States), and are often denied by medical insurance.{{bulleted list| | |

In adolescents of either sex, GnRH modulators can be used to suppress puberty. The eighth edition of the World Professional Association for Transgender Health's Standards of Care permit its use from Tanner stage 2 and recommends GnRH agonists as the preferred method of puberty blocking.

5α-Reductase inhibitors

5α-Reductase inhibitors are inhibitors of the enzyme 5α-reductase, and are a type of specific androgen synthesis inhibitor. 5α-Reductase is an enzyme that is responsible for the conversion of testosterone into the more potent androgen dihydrotestosterone (DHT). There are three different isoforms of 5α-reductase, types 1, 2, and 3, and these three isoforms show different patterns of expression in the body. Relative to testosterone, DHT is about 2.5- to 10-fold more potent as an agonist of the androgen receptor. As such, 5α-reductase serves to considerably potentiate the effects of testosterone. However, 5α-reductase is expressed only in specific tissues, such as skin, hair follicles, and the prostate gland, and for this reason, conversion of testosterone into DHT happens only in certain parts of the body. Furthermore, circulating levels of total and free DHT in men are very low at about one-tenth and one-twentieth those of testosterone, respectively, and DHT is efficiently inactivated into weak androgens in various tissues such as muscle, fat, and liver. As such, it is thought that DHT plays little role as a systemic androgen hormone and serves more as a means of locally potentiating the androgenic effects of testosterone in a tissue-specific manner. Conversion of testosterone into DHT by 5α-reductase plays an important role in male reproductive system development and maintenance (specifically of the penis, scrotum, prostate gland, and seminal vesicles), male-pattern facial/body hair growth, and scalp hair loss, but has little role in other aspects of masculinization. Besides the involvement of 5α-reductase in androgen signaling, it is also required for the conversion of steroid hormones such as progesterone and testosterone into neurosteroids like allopregnanolone and 3α-androstanediol, respectively.

5α-Reductase inhibitors include finasteride and dutasteride. Finasteride is a selective inhibitor of 5α-reductase types 2 and 3, while dutasteride is an inhibitor of all three isoforms of 5α-reductase. Finasteride can decrease circulating DHT levels by up to 70%, whereas dutasteride can decrease circulating DHT levels by up to 99%. Conversely, 5α-reductase inhibitors do not decrease testosterone levels, and may actually increase them slightly. 5α-Reductase inhibitors are used primarily in the treatment of benign prostatic hyperplasia, a condition in which the prostate gland becomes excessively large due to stimulation by DHT and causes unpleasant urogenital symptoms. They are also used in the treatment of androgen-dependent scalp hair loss in men and women. The medications are able to prevent further scalp hair loss in men and can restore some scalp hair density. Conversely, the effectiveness of 5α-reductase inhibitors in the treatment of scalp hair loss in women is less clear. This may be because androgen levels are much lower in women, in whom they may not play as important of a role in scalp hair loss. 5α-Reductase inhibitors are also used to treat hirsutism (excessive body/facial hair growth) in women, and are very effective for this indication. Dutasteride has been found to be significantly more effective than finasteride in the treatment of scalp hair loss in men, which has been attributed to its more complete inhibition of 5α-reductase and by extension decrease in DHT production. In addition to their antiandrogenic uses, 5α-reductase inhibitors have been found to reduce adverse affective symptoms in premenstrual dysphoric disorder in women. This is thought to be due to prevention by 5α-reductase inhibitors of the conversion of progesterone into allopregnanolone during the luteal phase of the menstrual cycle.

5α-Reductase inhibitors are sometimes used as a component of feminizing hormone therapy for transgender women in combination with estrogens and/or other antiandrogens. They may have beneficial effects limited to improvement of scalp hair loss, body hair growth, and possibly skin symptoms such as acne. However, little clinical research on 5α-reductase inhibitors in transgender women has been conducted, and evidence of their efficacy and safety in this group is limited. Moreover, 5α-reductase inhibitors have only mild and specific antiandrogenic activity, and are not recommended as general antiandrogens.

5α-Reductase inhibitors have minimal side effects and are well tolerated in both men and women. In men, the most common side effect is sexual dysfunction (0.9–15.8% incidence), which may include decreased libido, erectile dysfunction, and reduced ejaculate. Another side effect in men is breast changes, such as breast tenderness and gynecomastia (2.8% incidence). Due to decreased levels of androgens and/or neurosteroids, 5α-reductase inhibitors may slightly increase the risk of depression (~2.0% incidence). There are reports that a small percentage of men may experience persistent sexual dysfunction and adverse mood changes even after discontinuation of 5α-reductase inhibitors.{{bulleted list| | |

Progestogens

Progesterone, a progestogen, is the other of the two major sex hormones in women. It is mainly involved in the regulation of the female reproductive system, the menstrual cycle, pregnancy, and lactation. The non-reproductive effects of progesterone are fairly insignificant. Unlike estrogens, progesterone is not known to be involved in the development of female secondary sexual characteristics, and hence is not believed to contribute to feminization in women. One area of particular interest in terms of the effects of progesterone in women is breast development. Estrogens are responsible for the development of the ductal and connective tissues of the breasts and the deposition of fat into the breasts during puberty in girls. Conversely, high levels of progesterone, in conjunction with other hormones such as prolactin, are responsible for the lobuloalveolar maturation of the mammary glands during pregnancy. This allows for lactation and breastfeeding after childbirth. Although progesterone causes the breasts to change during pregnancy, the breasts undergo involution and revert to their pre-pregnancy composition and size after the cessation of breastfeeding. Every pregnancy, lobuloalveolar maturation occurs again anew.

There are two types of progestogens: progesterone, which is the natural and bioidentical hormone in the body; and progestins, which are synthetic progestogens. There are dozens of clinically used progestins. Certain progestins, namely cyproterone acetate and medroxyprogesterone acetate and as described previously, are used at high doses as functional antiandrogens due to their antigonadotropic effects to help suppress testosterone levels in transgender women. Aside from the specific use of testosterone suppression however, there are no other indications of progestogens in transgender women at present. In relation to this, the use of progestogens in transgender women is controversial, and they are not otherwise routinely prescribed or recommended. Besides progesterone, cyproterone acetate, and medroxyprogesterone acetate, other progestogens that have been reported to have been used in transgender women include hydroxyprogesterone caproate, dydrogesterone, norethisterone acetate, and drospirenone.{{bulleted list| | | |

Clinical research on the use of progestogens in transgender women is very limited. Some patients and clinicians believe, on the basis of anecdotal and subjective claims, that progestogens may provide benefits such as improved breast and/or nipple development, mood, and libido in transgender women. There are no clinical studies to support such reports at present. No clinical study has assessed the use of progesterone in transgender women, and only a couple of studies have compared the use of progestins (specifically cyproterone acetate and medroxyprogesterone acetate) versus the use of no progestogen in transgender women. These studies, albeit limited in the quality of their findings, reported no benefit of progestogens on breast development in transgender women. This has also been the case in limited clinical experience.

Progestogens have some antiestrogenic effects in the breasts, for instance decreasing expression of the estrogen receptor and increasing expression of estrogen-metabolizing enzymes,{{bulleted list| | | | |

In terms of the effects of progestogens on sex drive, one study assessed the use of dydrogesterone to improve sexual desire in transgender women and found no benefit. Another study likewise found that oral progesterone did not improve sexual function in cisgender women.

Progestogens can have adverse effects. Oral progesterone has inhibitory neurosteroid effects and can produce side effects such as sedation, mood changes, and alcohol-like effects. Many progestins have off-target activity, such as androgenic, antiandrogenic, glucocorticoid, and antimineralocorticoid activity, and these activities likewise can contribute unwanted side effects. Furthermore, the addition of a progestin to estrogen therapy has been found to increase the risk of blood clots, cardiovascular disease (e.g., coronary heart disease and stroke), and breast cancer compared to estrogen therapy alone in postmenopausal women. Although it is unknown if these health risks of progestins occur in transgender women similarly, it cannot be ruled out that they do. High-dose progestogens increase the risk of benign brain tumors including prolactinomas and meningiomas as well. Because of their potential detrimental effects and lack of supported benefits, some researchers have argued that, aside from the purpose of testosterone suppression, progestogens should not generally be used or advocated in transgender women or should only be used for a limited duration (e.g., 2–3 years). Conversely, other researchers have argued that the risks of progestogens in transgender women are likely minimal, and that in light of potential albeit hypothetical benefits, should be used if desired. In general, some transgender women respond favorably to the effects of progestogens, while others respond negatively. A 2025 study found that 72% of progesterone users were satisfied with progesterone use, and 73.5% would recommend progesterone to others.

Progesterone is most commonly taken orally. However, oral progesterone has very low bioavailability, and produces relatively weak progestogenic effects even at high doses. In accordance, and in contrast to progestins, oral progesterone has no antigonadotropic effects in males even at high doses. Progesterone can also be taken by various parenteral (non-oral) routes, including sublingually, rectally, and by intramuscular or subcutaneous injection. These routes do not have the bioavailability and efficacy issues of oral progesterone, and accordingly, can produce considerable antigonadotropic and other progestogenic effects. Transdermal progesterone is poorly effective, owing to absorption issues. Progestins are usually taken orally. In contrast to progesterone, most progestins have high oral bioavailability, and can produce full progestogenic effects with oral administration. Some progestins, such as medroxyprogesterone acetate and hydroxyprogesterone caproate, are or can be used by intramuscular or subcutaneous injection instead. Almost all progestins, with the exception of dydrogesterone, have antigonadotropic effects.

Miscellaneous

Galactogogues such as the peripherally selective D2 receptor antagonist and prolactin releaser domperidone can be used to induce lactation in transgender women who wish to breastfeed. An extended period of combined estrogen and progestogen therapy is necessary to mature the lobuloalveolar tissue of the breasts before this can be successful. There are several published reports of lactation and/or breastfeeding in transgender women.{{bulleted list| | | |

The World Professional Association for Transgender Health (WPATH) Standards of Care for the Health of Transgender and Gender Diverse People Version 8 (SOC8), released in September 2022, recommends against therapeutic strategies including supraphysiological estradiol levels (200 pg/mL), use of progesterone (including rectal progesterone), use of bicalutamide, and monitoring of the ratio of estrone to estradiol. This is due to lack of data to support these approaches in transfeminine people as well as potential risks. The WPATH SOC8 also recommends against the use of 5α-reductase inhibitors such as finasteride in transfeminine people.

Interactions

Many of the medications used in feminizing hormone therapy, such as estradiol, cyproterone acetate, and bicalutamide, are substrates of CYP3A4 and other cytochrome P450 enzymes. As a result, inducers of CYP3A4 and other cytochrome P450 enzymes, such as carbamazepine, phenobarbital, phenytoin, rifampin, rifampicin, and St. John's wort, among others, may decrease circulating levels of these medications and thereby decrease their effects. Conversely, inhibitors of CYP3A4 and other cytochrome P450 enzymes, such as cimetidine, clotrimazole, grapefruit juice, itraconazole, ketoconazole, and ritonavir, among others, may increase circulating levels of these medications and thereby increase their effects. The concomitant use of a cytochrome P450 inducer or inhibitor with feminizing hormone therapy may necessitate medication dosage adjustments.

Effects

The spectrum of effects of hormone therapy in transfeminine people depend on the specific medications and dosages used. In any case, the main effects of hormone therapy in transfeminine people are feminization and demasculinization, and are as follows:

Mental changes

The psychological effects of feminizing hormone therapy are harder to define than physical changes. Because hormone therapy 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.

Changes in mood and well-being occur with hormone therapy in transgender women.

Side effects of hormone therapy have the ability to significantly impact sexual functioning, either directly or indirectly through the various side effects, such as cerebrovascular disorders, obesity, and mood fluctuations. Some transgender women report a significant reduction in libido, depending on the dosage of antiandrogens. The effects of long-term hormonal regimens have not been conclusively studied and are difficult to estimate because research on the long-term use of hormonal therapy has not been noted. One study found that sex drive returned to baseline after three years of hormone therapy. It is possible to approximate outcomes of these therapies on transgender people based on their observed effect in cisgender men and women. Firstly, if one is to decrease testosterone in feminizing gender transition, it is likely that sexual desire and arousal would be inhibited; alternatively, if high doses of estrogen negatively impact sexual desire, which has been found in some research with cisgender women, it is hypothesized that combining androgens with high levels of estrogen would intensify this outcome. To date there have not been any randomized clinical trials looking at the relationship between type and dose of transgender hormone therapy, so the relationship between them remains unclear. Typically, the estrogens given for feminizing gender transition are 2 to 3 times higher than the recommended dose for HRT in postmenopausal women. Pharmacokinetic studies indicate taking these increased doses may lead to a higher boost in plasma estradiol levels; however, the long-term side effects have not been studied and the safety of this route is unclear.

Several studies have found that hormone therapy in transgender women causes the structure of the brain to change in the direction of female proportions.{{bulleted list| | | | |

Fat distribution

In hormone therapy, trans women often experience slight weight gain as men generally carry higher levels of visceral fat compared to subcutaneous fat, and less fat overall compared to women. Over months and years, HRT causes the body to accumulate new fat in a feminine pattern (gynoid fat). Unlike abdominal fat, gynoid fat has little effect on overall health except in the case of severe excess or postural changes. Gynoid fat will accumulate in the hips, lower belly, thighs, buttocks, pubis, upper arms, and breasts while the body burns fat in the ribcage, upper waist, shoulders, and back. However, fat will not simply move from one spot to another. There must be sufficient caloric intake to deposit gynoid fat, and sufficient activity to burn android fat.

Breast development

Significant breast development in transgender women begins within two to three months of the start of hormone therapy and continues for up to two years or more. Breast development seems to be better in transgender women who have a higher body mass index. This indicates that weight gain in the early phases of hormone therapy may be beneficial not only for fat distribution, but for breast development. Different estrogens, such as estradiol valerate, conjugated estrogens, and ethinylestradiol, appear to produce equivalent results in terms of breast sizes in transgender women. The sudden discontinuation of estrogen therapy has been associated with onset of galactorrhea (lactation).

Breast, nipple, and areolar development varies considerably depending on genetics, nutrition, 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.

Fertility

The effect of feminizing hormone therapy on fertility is not clear, but it is known that testosterone suppression can prevent sperm production. The age of starting and stopping hormone therapy seems to be a significant factor, but no direct causation has been found between length of treatment and ability to reproduce.

There is some research showing effective restoration of fertility by alternative means than HRT cessation alone. Dr. Will Powers has demonstrated the effectiveness of clomifene in restoring spermatogenesis in trans women. His study also includes an in-depth description of other methods for fertility restoration.

Skin

Estrogens cause the accumulation of subcutaneous fat and an increased epidermal thickness, softening the skin. Some skin conditions, including melasma, are found in trans women at the same rate at cisgender women. Body odor and sweat patterns are changed by feminizing hormone therapy, while sebaceous gland activity 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.

Skeleton

Sex hormones play an important role in bone growth and maintenance. The effects of hormone therapy on bone health are not fully understood, and may depend on whether hormone therapy is started before or after puberty. Bone density continue to grow and change over time.

Significant changes to bone structure have been observed, and transgender women have statistically poorer bone health even before beginning the transition process, possibly due to a lack of physical exercise or other risk factors such as low vitamin D, eating disorders, and substance abuse.

Approximately 14% of transgender women suffer from osteoporosis. Transgender women below the age of 50 show increased fracture risk compared to age-matched cisgender women, equal to the risk to cisgender men of equivalent age. Transgender women above the age of 50 have a similar fracture risk to post-menopausal women — higher than that of age-matched cis men. In both cases, trans women's fracture patterns follow that of cis women, suffering long-term stress fractures concentrated in the hip, spine, and arms, typical of chronic low bone mineral density, rather than the fracture patterns typical of external injury suffered by cis men. Current clinical guidelines are for bone health to be monitored regularly throughout the transition process, particularly if risk factors are present. Transgender individuals are encouraged to ingest at least 1g of Calcium and 1000 IU of Vitamin D daily, engage regularly in weight-bearing physical activity, and reduce alcohol and smoking consumption.

The effects of hormone therapy on bone health are reversible should treatment be interrupted. However, withdrawing hormone therapy after gonadectomy can lead to bone loss, and poor compliance with prescribed hormone therapy after gonadectomy may account in part for the observed fracture risk.

Hair

As male-pattern hair loss is caused by androgens, particularly dihydrotestosterone, feminizing hormone therapy causes the rapid cessation and reversal of hair loss, though the degree of regrowth may vary. In many cases, the use of estrogens and antiandrogens have a more profound impact on hair loss compared to treatments used in men such as finasteride due to the greater suppression of dihydrotestosterone. Occasionally, hormones can also have effects on scalp hair texture, depending on various genetic factors.

Antiandrogens affect existing facial hair only slightly; patients may see slower growth and some reduction in density and coverage. This reduction of density is due to the decreasing hair diameter and slower terminal growth rate. Effects on hair size and density were noticeable in the first four months following the start of hormone therapy, but later subsided, with measurements staying constant. In patients in their teens or early twenties, antiandrogens prevent new facial hair from developing if testosterone levels are within the normal female range.

Body hair (on the chest, shoulders, back, abdomen, buttocks, thighs, tops of hands, and tops of feet) turns, over time, from terminal ("normal") hairs to tiny, blonde vellus hairs. Arm, perianal, and perineal hair is reduced but may not turn to vellus hair on the latter two regions (some cisgender women also have hair in these areas). Underarm hair changes slightly in texture and length, and pubic hair becomes more typically female in pattern. Lower leg hair becomes less dense. All of these changes depend to some degree on genetics. Eyebrows do not change because they are not androgenic hair.

Eye morphology

The lens of the eye changes in curvature.{{bulleted list| | | | | | | | |

Cardiovascular effects

The most significant cardiovascular risk for transgender women is the prothrombotic effect (increased blood clotting) of estrogens. This manifests most significantly as an increased risk for venous thromboembolism (VTE): deep vein thrombosis (DVT) and pulmonary embolism (PE), which occurs when blood clots from DVT break off and migrate to the lungs. Symptoms of DVT include pain or swelling of one leg, especially the calf. Symptoms of PE include chest pain, shortness of breath, fainting, and heart palpitations, sometimes without leg pain or swelling.

VTE occurs more frequently in the first year of treatment with estrogens. The risk of VTE is higher with oral non-bioidentical estrogens such as ethinylestradiol and conjugated estrogens than with parenteral formulations of estradiol such as injectable, transdermal, implantable, and intranasal.Multiple sources:{{bulleted list| | | | | | | | | | | | | | | | | | | | | Increased risk of VTE with estrogens is thought to be due to their influence on liver protein synthesis, specifically on the production of coagulation factors. Non-bioidentical estrogens such as conjugated estrogens and especially ethinylestradiol have markedly disproportionate effects on liver protein synthesis relative to estradiol. In addition, oral estradiol has a 4- to 5-fold increased impact on liver protein synthesis than does transdermal estradiol and other parenteral estradiol routes.

Because the risks of warfarin – which is used to treat blood clots – in a relatively young and otherwise healthy population are low, while the risk of adverse physical and psychological outcomes for untreated transgender patients is high, prothrombotic mutations (such as factor V Leiden, antithrombin III, and protein C or S deficiency) are not absolute contraindications for hormonal therapy.

A 2018 cohort study of 2842 transfeminine individuals in the United States treated with a mean follow-up of 4.0 years observed an increased risk of VTE, stroke, and heart attack relative to a cisgender reference population. The estrogens used included oral estradiol (1 to 10 mg/day) and other estrogen formulations. Other medications such as antiandrogens like spironolactone were also used.

A 2019 systematic review and meta-analysis found an incidence rate of VTE of 2.3 per 1000 person-years with feminizing hormone therapy in transgender women. For comparison, the rate in the general population has been found to be 1.0–1.8 per 1000 person-years, and the rate in premenopausal women taking birth control pills has been found to be 3.5 per 1000 patient-years. There was significant heterogeneity in the rates of VTE across the included studied, and the meta-analysis was unable to perform subgroup analyses between estrogen type, estrogen route, estrogen dosage, concomitant antiandrogen or progestogen use, or patient characteristics (e.g., sex, age, smoking status, weight) corresponding to known risk factors for VTE. Due to the inclusion of some studies using ethinylestradiol, which is more thrombotic and is no longer used in transgender women, the researchers noted that the VTE risk found in their study may be an overestimate.

In a 2016 study that specifically assessed oral estradiol, the incidence of VTE in 676 transgender women who were treated for an average of 1.9 years each was one individual, or 0.15% of the group, with an incidence of 7.8 events per 10,000 person-years. The dosage of oral estradiol used was 2 to 8 mg/day. Almost all of the transgender women were also taking spironolactone (94%), a subset were also taking finasteride (17%), and fewer than 5% were also taking a progestogen (usually oral progesterone). The findings of this study suggest that the incidence of VTE is low in transgender women taking oral estradiol.

Cardiovascular health in transgender women has been reviewed in recent publications.

Gastrointestinal

Estrogens may increase the risk of gallbladder disease, especially in older and obese people.

Cancer risk

Studies are mixed on whether the risk of breast cancer is increased with hormone therapy in transgender women. Two cohort studies found no increase in risk relative to cisgender men, whereas another cohort study found an almost 50-fold increase in risk such that the incidence of breast cancer was between that of cisgender men and cisgender women. There is no evidence that breast cancer risk in transgender women is greater than in cisgender women. Twenty cases of breast cancer in transgender women have been reported as of 2019.

Cisgender men with gynecomastia have not been found to have an increased risk of breast cancer. It has been suggested that a 46,XY karyotype (one X chromosome and one Y chromosome) may be protective against breast cancer compared to having a 46,XX karyotype (two X chromosomes). Men with Klinefelter's syndrome (47,XXY karyotype), which causes hypoandrogenism, hyperestrogenism, and a very high incidence of gynecomastia (80%), have a dramatically (20- to 58-fold) increased risk of breast cancer compared to karyotypical men (46,XY), closer to the rate of karyotypical women (46,XX). The incidences of breast cancer in karyotypical men, men with Klinefelter's syndrome, and karyotypical women are approximately 0.1%, 3%, and 12.5%, respectively. Women with complete androgen insensitivity syndrome (46,XY karyotype) never develop male sex characteristics and have normal and complete female morphology, including breast development, yet have not been reported to develop breast cancer. The risk of breast cancer in women with Turner syndrome (45,XO karyotype) also appears to be significantly decreased, though this could be related to ovarian failure and hypogonadism rather than to genetics.

Prostate cancer is extremely rare in gonadectomized transgender women who have been treated with estrogens for a prolonged period of time. Whereas as many as 70% of men show prostate cancer by their 80s, only a handful of cases of prostate cancer in transgender women have been reported in the literature. As such, and in accordance with the fact that androgens are responsible for the development of prostate cancer, HRT appears to be highly protective against prostate cancer in transgender women.

The risks of certain types of benign brain tumors including meningioma and prolactinoma are increased with hormone therapy in transgender women. These risks have mostly been associated with the use of cyproterone acetate.

Estrogens and progestogens can cause prolactinomas, which are benign, prolactin-secreting tumors of the pituitary gland. 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, depression or other mood changes, dizziness, nausea, vomiting, and symptoms of pituitary failure, like hypothyroidism.

Unaffected characteristics

Established changes to the bone structure of the face are also unaffected by HRT. A significant majority of craniofacial changes occur during adolescence. Post-adolescent growth is considerably slower and minimal by comparison.

Facial hair develops during puberty and is only slightly affected by HRT.

A person's voice is unaffected by feminizing hormone therapy. Transgender individuals who have undergone male puberty often opt for vocal training, which can take up to years of practice to achieve the desired results. Some may also opt for vocal surgery, though surgeons recommend this in addition to vocal training, not as an alternative.

Monitoring

Especially in the early stages of feminizing hormone therapy, blood work is done frequently to assess hormone levels and liver function. The Endocrine Society recommends that patients have blood tests every three months in the first year of HRT for estradiol and testosterone, and that spironolactone, if used, be monitored every two to three months in the first year. Recommended ranges for total estradiol and total testosterone levels include but are not limited to the following:

The optimal ranges for estrogen apply only to individuals taking estradiol (or an ester of estradiol), and not to those taking synthetic or other non-bioidentical preparations (e.g., conjugated estrogens or ethinylestradiol).

Physicians also recommend broader medical monitoring, including complete blood counts; tests of renal function, liver function, and lipid and glucose metabolism; and monitoring of prolactin levels, body weight, and blood pressure.

If prolactin levels are greater than 100 ng/mL, estrogen therapy should be stopped and prolactin levels should be rechecked after 6 to 8 weeks. If prolactin levels remain high, an MRI scan of the pituitary gland to check for the presence of a prolactinoma should be ordered. Otherwise, estrogen therapy may be restarted at a lower dosage. Cyproterone acetate is particularly associated with elevated prolactin levels, and discontinuation of cyproterone acetate lowers prolactin levels. In contrast to cyproterone acetate, estrogen and spironolactone therapy is not associated with increased prolactin levels.

History

Effective pharmaceutical female sex-hormonal medications, including androgens, estrogens, and progestogens, first became available in the 1920s and 1930s, and might have been prescribed for transitions as early as the late 30s or 40s. The earliest report of hormone therapy in transgender women was published by Danish endocrinologist Christian Hamburger in 1953. One of his patients was Christine Jorgensen, who he had treated starting in 1950. Additional reports of hormone therapy in transgender women were published by Hamburger, the German-American endocrinologist Harry Benjamin, and other researchers in the mid-to-late 1960s. However, Benjamin had several hundred transgender patients under his care by the late 1950s, and had treated transgender women with hormone therapy as early as the late 1940s or early 1950s. In any case, Hamburger is said to be the first to treat transgender women with hormone therapy.

One of the first transgender health clinics was opened in the mid-1960s at the Johns Hopkins School of Medicine. By 1981, there were almost 40 such centers. A review of the hormonal regimens of 20 of the centers was published that year. The first International Symposium on Gender Identity, chaired by Christopher John Dewhurst, was held in London in 1969, and the first medical textbook on transgenderism, titled Transsexualism and Sex Reassignment and edited by Richard Green and John Money, was published by Johns Hopkins University Press in 1969. This textbook included a chapter on hormone therapy written by Christian Hamburger and Harry Benjamin. The Harry Benjamin International Gender Dysphoria Association (HBIGDA), now known as the World Professional Association for Transgender Health (WPATH), was formed in 1979, with the first version of the Standards of Care published the same year. The Endocrine Society published guidelines for the hormonal care of transgender people in 2009, with a revised version in 2017.

Hormone therapy for transgender women was initially done using high-dose estrogen therapy with oral estrogens such as conjugated estrogens, ethinylestradiol, and diethylstilbestrol and with parenteral estrogens such as estradiol benzoate, estradiol valerate, estradiol cypionate, and estradiol undecylate. Progestogens, such as hydroxyprogesterone caproate, medroxyprogesterone acetate, and other progestins, were also sometimes included. The antiandrogen and progestogen cyproterone acetate was first used in transgender women by 1977. Its use was standard at the Center of Expertise on Gender Dysphoria (CEGD; Kennis- en Zorgcentrum Genderdysforie, or KZcG) in Amsterdam, the Netherlands by 1985. Spironolactone, another antiandrogen, was first used in transgender women by 1986. These agents were described as allowing the use of much lower doses of estrogen than previously required, and this was considered advantageous due to risks of high doses of estrogens such as cardiovascular complications. Antiandrogens were well-established in hormone therapy for transgender women by the early 1990s. Estrogen doses in transgender women were reduced following the introduction of antiandrogens. Ethinylestradiol, conjugated estrogens, and other non-bioidentical estrogens largely stopped being used in transgender women in favor of estradiol starting around 2000 due to their greater risks of blood clots and cardiovascular issues.

In modern times, hormone therapy in transgender women is usually done with the combination of an estrogen and an antiandrogen. In some places however, such as Japan, use of antiandrogens is uncommon, and estrogen monotherapy, for instance with high-dose injectable estradiol esters, is still frequently used.

References

References

1. (November 2017). "Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism.
2. (2012). "Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7". [[International Journal of Transgenderism]].
3. (17 June 2016). "Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People". Center of Excellence for Transgender Health.
4. (March 2017). "Hormonal and Surgical Treatment Options for Transgender Women and Transfeminine Spectrum Persons". The Psychiatric Clinics of North America.
5. (2015). "Endocrine Therapy for Transgender Adults in British Columbia: Suggested Guidelines". [[Vancouver Coastal Health]].
6. (February 2010). "Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes". Clinical Endocrinology.
7. (January 2016). "A Systematic Review of the Effects of Hormone Therapy on Psychological Functioning and Quality of Life in Transgender Individuals". Transgender Health.
8. (2021). "Short-Term Effects of Gender-Affirming Hormone Therapy on Dysphoria and Quality of Life in Transgender Individuals: A Prospective Controlled Study". Frontiers in Endocrinology.
9. (31 August 2016). "Sketchy Pharmacies Are Selling Hormones to Transgender People: Burdened by cost and medical discrimination, many people are taking a do-it-yourself approach to transitioning".
10. (16 November 2016). "Fears of 'DIY transitioning' as hormone drugs sold to transgender women without checks".
11. (21 August 2014). "Adolescent Medicine, An Issue of Primary Care: Clinics in Office Practice, E-Book". Elsevier Health Sciences.
12. (28 June 2017). "Women's Health Care in Advanced Practice Nursing". Springer Publishing Company.
13. (October 2006). "Therapy Insight: parenteral estrogen treatment for prostate cancer--a new dawn for an old therapy". Nature Clinical Practice. Oncology.
14. (December 2006). "Parenteral estrogens for prostate cancer: can a new route of administration overcome old toxicities?". Clinical Genitourinary Cancer.
15. (2024-03-05). "Comparison of Estrone/Estradiol Ratio and Levels in Transfeminine Individuals on Different Routes of Estradiol". Transgender Health.
16. (2016-08-19). "Correlations between Prepubertal and Pubertal Estrogen Levels and Final Height Out-Come in Growth Hormone (GH) Treated Boys with Silver Russell syndrome". Bioscientifica.
17. (December 2021). "Association between the serum estrone-to-estradiol ratio and parameters related to glucose metabolism and insulin resistance in women with polycystic ovary syndrome". Clinical and Experimental Reproductive Medicine.
18. (October 2023). "Distinct roles of estrone and estradiol in endothelial colony-forming cells". Physiological Reports.
19. (December 2016). "Hormone therapy for transgender patients". Translational Andrology and Urology.
20. (2018). "Hormonal Treatment of Transgender Women with Oral Estradiol". Transgender Health.
21. (1988). "Single drug polyestradiol phosphate therapy in prostatic cancer". American Journal of Clinical Oncology.
22. (May 2003). "Transdermal estradiol therapy for advanced prostate cancer--forward to the past?". The Journal of Urology.
23. (June 2014). "Variable Response to Oral Estradiol Therapy in Male to Female Transgender Patients". Endocrine Reviews.
24. (February 2018). "Testosterone Levels Achieved by Medically Treated Transgender Women in a United States Endocrinology Clinic Cohort". Endocrine Practice.
25. (January 2008). "Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience". The Journal of Clinical Endocrinology and Metabolism.
26. (2009). "Recommendations of endocrine treatment for patients with gender dysphoria". Sexual and Relationship Therapy.
27. (3 March 2015). "Management of Gender Dysphoria: A Multidisciplinary Approach". Springer.
28. (November 2020). "Antiandrogen or estradiol treatment or both during hormone therapy in transitioning transgender women". The Cochrane Database of Systematic Reviews.
29. (1975). "Longacting steroid preparations". Acta Clinica Belgica.
30. (January 1980). "Serum oestrone, oestradiol and oestriol concentrations in castrated women during intramuscular oestradiol valerate and oestradiolbenzoate-oestradiolphenylpropionate therapy". Maturitas.
31. (May 1996). "Pharmacokinetics and testosterone suppression of a single dose of polyestradiol phosphate (Estradurin) in prostatic cancer patients". The Prostate.
32. (2017). "Endocrinology of the Testis and Male Reproduction".
33. (11 November 2015). "Williams Textbook of Endocrinology". Elsevier Health Sciences.
34. (3 August 2018). "Transgender Health Issues". [[ABC-CLIO]].
35. (April 2018). "Androgens and androgen receptor: Above and beyond". Molecular and Cellular Endocrinology.
36. (August 2001). "Androgen deprivation therapy for prostate cancer chemoprevention: current status and future directions for agent development". Urology.
37. (2006). "Encyclopedia of Molecular Cell Biology and Molecular Medicine".
38. (April 2000). "Pharmacodynamics of oestrogens and progestogens". Cephalalgia.
39. (1978). "The physiological action of progesterone and the pharmacological effects of progestogens--a short review". Postgraduate Medical Journal.
40. (April 2017). "Oestrogen and anti-androgen therapy for transgender women". The Lancet. Diabetes & Endocrinology.
41. (2015). "European Handbook of Dermatological Treatments".
42. (October 2015). "Evidence-based approach to cutaneous hyperandrogenism in women". Journal of the American Academy of Dermatology.
43. (2017). "Testosterone".
44. (February 2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Current Medicinal Chemistry.
45. (22 September 2016). "Surgical Management of the Transgender Patient". Elsevier Health Sciences.
46. (7 February 2017). "Clinical Issues and Affirmative Treatment with Transgender Clients, An Issue of Psychiatric Clinics of North America, E-Book". Elsevier Health Sciences.
47. (12 May 2014). "Trans Bodies, Trans Selves: A Resource for the Transgender Community". Oxford University Press.
48. (July 2019). "Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy". Endocrine Connections.
49. (July 2017). "30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development". The Journal of Endocrinology.
50. (December 1993). "Hirsutism and the effectiveness of spironolactone in its management". Journal of Endocrinological Investigation.
51. (November 1976). "Spironolactone and endocrine dysfunction". Annals of Internal Medicine.
52. (1993). "Drug-induced gynecomastia". Pharmacotherapy.
53. (February 1991). "Spironolactone in dermatologic therapy". Journal of the American Academy of Dermatology.
54. (April 2017). "Oral Spironolactone for Acne Vulgaris in Adult Females: A Hybrid Systematic Review". American Journal of Clinical Dermatology.
55. (May 2001). "The spironolactone renaissance". Expert Opinion on Investigational Drugs.
56. (18 October 2012). "Comprehensive Dermatologic Drug Therapy E-Book". Elsevier Health Sciences.
57. (15 December 1990). "Chronic Hyperandrogenic Anovulation". CRC Press.
58. (2 March 2009). "Meyler's Side Effects of Cardiovascular Drugs". Elsevier.
59. (December 2015). "Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone". International Journal of Cardiology.
60. (August 2004). "Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study". The New England Journal of Medicine.
61. (May 2016). "Guidelines of care for the management of acne vulgaris". Journal of the American Academy of Dermatology.
62. (September 2015). "Low Usefulness of Potassium Monitoring Among Healthy Young Women Taking Spironolactone for Acne". JAMA Dermatology.
63. (1994). "The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research". Experimental and Clinical Endocrinology.
64. (2003). "Progestogens with antiandrogenic properties". Drugs.
65. (August 1976). "Continuous oral low-dosage cyproterone acetate for fertility regulation in the male? A trend analysis in 15 volunteers". Contraception.
66. (1978). "Effects of Cyproterone Acetate (CPA) on Pituitary Gonadotrophin Release and on Androgen Secretion Before and After LH-RH Double Stimulation Tests in Men". International Journal of Andrology.
67. (March 1980). "Use of low-dosage oral cyproterone acetate as a male contraceptive". Contraception.
68. (April 1980). "Medium dose cyproterone acetate (CPA): effects on hormone secretion and on spermatogenesis in men". Contraception.
69. (November 1984). "Effect of flutamide or cyproterone acetate on pituitary and testicular hormones in normal men". The Journal of Clinical Endocrinology and Metabolism.
70. (June 1980). "Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial". British Journal of Urology.
71. (2017). "Is a lower dose of cyproterone acetate as effective at testosterone suppression in transgender women as higher doses?". International Journal of Transgenderism.
72. (February 2020). "Safety and rapid efficacy of guideline-based gender-affirming hormone therapy: an analysis of 388 individuals diagnosed with gender dysphoria". European Journal of Endocrinology.
73. (December 1997). "Treatment of androgen excess in females: yesterday, today and tomorrow". Gynecological Endocrinology.
74. (6 December 2012). "Pharmacology of the Skin II: Methods, Absorption, Metabolism and Toxicity, Drugs and Diseases". Springer Science & Business Media.
75. (2004). "Hepatotoxicity induced by antiandrogens: a review of the literature". Urologia Internationalis.
76. (1990). "Hair and Hair Diseases". Springer.
77. (December 2018). "Testosterone undecanoate and testosterone enanthate injections are both effective and safe in transmen over 5 years of administration". Clinical Endocrinology.
78. (18 May 2010). "Endocrinology - E-Book: Adult and Pediatric". Elsevier Health Sciences.
79. (20 May 2016). "Principles of Transgender Medicine and Surgery". Routledge.
80. (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric.
81. (March 1999). "Distinguishing androgen receptor agonists and antagonists: distinct mechanisms of activation by medroxyprogesterone acetate and dihydrotestosterone". Molecular Endocrinology.
82. (August 2003). "Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety". Contraception.
83. (September 1986). "Comparison of diethylstilbestrol, cyproterone acetate and medroxyprogesterone acetate in the treatment of advanced prostatic cancer: final analysis of a randomized phase III trial of the European Organization for Research on Treatment of Cancer Urological Group". The Journal of Urology.
84. (25 August 2011). "Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set". Elsevier Health Sciences.
85. (27 November 2013). "Androgens II and Antiandrogens / Androgene II und Antiandrogene". Springer Science & Business Media.
86. (1983). "Gonadotropin-releasing hormone analogues for palliation of carcinoma of the prostate". World Journal of Urology.
87. (2009). "Hormone Therapy in Breast and Prostate Cancer". Humana Press.
88. (March 1987). "Current concepts in the treatment of prostate cancer". Drug Intelligence & Clinical Pharmacy.
89. (March 2017). "Flutamide-induced hepatotoxicity: ethical and scientific issues". European Review for Medical and Pharmacological Sciences.
90. (2013). "Update on idiopathic hirsutism: diagnosis and treatment". Acta Clinica Belgica.
91. (March 2018). "Combined Oral Contraception and Bicalutamide in Polycystic Ovary Syndrome and Severe Hirsutism: A Double-Blind Randomized Controlled Trial". The Journal of Clinical Endocrinology and Metabolism.
92. (January 1997). "Maximum androgen blockade in advanced prostate cancer: a meta-analysis of published randomized controlled trials using nonsteroidal antiandrogens". Urology.
93. (8 November 2010). "Cancer Chemotherapy and Biotherapy: Principles and Practice". Lippincott Williams & Wilkins.
94. (November 2018). "Androgen Receptor Targeted Treatments of Prostate Cancer: 35 Years of Progress with Antiandrogens". The Journal of Urology.
95. (2018). "Enzalutamide and blocking androgen receptor in advanced prostate cancer: lessons learnt from the history of drug development of antiandrogens". Research and Reports in Urology.
96. (November 2014). "Safety of antiandrogen therapy for treating prostate cancer". Expert Opinion on Drug Safety.
97. (1 January 2008). "Controversies in the Treatment of Prostate Cancer". Karger Medical and Scientific Publishers.
98. (20 December 2011). "Prostate Cancer". Demos Medical Publishing.
99. (10 March 2010). "Bicalutamide BPCA Drug Use Review in the Pediatric Population". [[United States Department of Health and Human Services.
100. (14 September 2010). "Drug Management of Prostate Cancer". Springer Science & Business Media.
101. (January 1996). "Worldwide activity and safety of bicalutamide: a summary review". Urology.
102. (September 2012). "Enzalutamide--a major advance in the treatment of metastatic prostate cancer". The New England Journal of Medicine.
103. (5 June 2007). "Prostate Cancer". Springer Science & Business Media.
104. (2018). "Bicalutamide-Associated Acute Liver Injury and Migratory Arthralgia: A Rare but Clinically Important Adverse Effect". Case Reports in Gastroenterology.
105. (August 2018). "Understanding and Addressing Hair Disorders in Transgender Individuals". American Journal of Clinical Dermatology.
106. (January 2001). "Nonsteroidal antiandrogens: a therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function". BJU International.
107. (March 2001). "Effects of long-term treatment with the anti-androgen bicalutamide on human testis: an ultrastructural and morphometric study". Histopathology.
108. (2003). "Principles & Practice of Urology: A Comprehensive Text". Universal-Publishers.
109. (December 1995). "Estrogens in the treatment of prostate cancer". The Journal of Urology.
110. (February 2007). "Drug Insight: clinical use of agonists and antagonists of luteinizing-hormone-releasing hormone". Nature Clinical Practice. Endocrinology & Metabolism.
111. (1 January 2016). "Williams Textbook of Endocrinology". Elsevier Health Sciences.
112. (6 December 2012). "Genitourinary Cancer: Basic and Clinical Aspects". Springer Science & Business Media.
113. (January 2015). "Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain". Women's Health.
114. (January 1991). "Gonadotropin-releasing hormone and its analogues". The New England Journal of Medicine.
115. (13 September 2013). "Yen and Jaffe's Reproductive Endocrinology". Elsevier Health Sciences.
116. (2001). "Flare Associated with LHRH-Agonist Therapy". Reviews in Urology.
117. (January 2019). "Risk of Testosterone Flare in the Era of the Saturation Model: One More Historical Myth". European Urology Focus.
118. (25 February 2015). "Endocrinology: Adult and Pediatric E-Book". Elsevier Health Sciences.
119. (December 2005). "Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist". Experimental and Clinical Endocrinology & Diabetes.
120. (23 June 2018). "Gender Confirmation Surgery, An Issue of Clinics in Plastic Surgery, E-Book". Elsevier Health Sciences.
121. (25 July 2018). "FDA approves drug to control endometriosis pain". UPI.
122. (June 2017). "Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels". Endocrine Reviews.
123. (March 2013). "Clinical biochemistry of dihydrotestosterone". Annals of Clinical Biochemistry.
124. (18 September 2011). "Handbook of Drug Interactions: A Clinical and Forensic Guide". Springer Science & Business Media.
125. (2004). "5alpha-reductase: history and clinical importance". Reviews in Urology.
126. (13 February 1996). "Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects". John Wiley & Sons.
127. (March 2001). "Steroid 5alpha-reductases and 3alpha-hydroxysteroid dehydrogenases: key enzymes in androgen metabolism". Best Practice & Research. Clinical Endocrinology & Metabolism.
128. (1992). "Dihydrotestosterone is a peripheral paracrine hormone". Journal of Andrology.
129. (1996). "Role of dihydrotestosterone in androgen action". The Prostate. Supplement.
130. (December 2014). "5-Alpha reductase deficiency: a 40-year retrospective review". Current Opinion in Endocrinology, Diabetes, and Obesity.
131. (December 2002). "Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency". Molecular and Cellular Endocrinology.
132. (2018). "Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone". Chronic Stress.
133. (April 2000). "Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia". European Urology.
134. (August 2010). "Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride". Hormone Molecular Biology and Clinical Investigation.
135. (January 2019). "Do 5α-Reductase Inhibitors Raise Circulating Serum Testosterone Levels? A Comprehensive Review and Meta-Analysis to Explaining Paradoxical Results". Sexual Medicine Reviews.
136. (September 2012). "Role of 5α-reductase inhibitors in benign prostatic diseases". Prostate Cancer and Prostatic Diseases.
137. (December 2014). "5α-Reductase inhibitors in androgenetic alopecia". Current Opinion in Endocrinology, Diabetes, and Obesity.
138. (2017). "Dutasteride in Androgenetic Alopecia: An Update". Current Clinical Pharmacology.
139. (June 2010). "Finasteride treatment of hair loss in women". The Annals of Pharmacotherapy.
140. (July 2014). "Androgenetic alopecia: an evidence-based treatment update". American Journal of Clinical Dermatology.
141. (26 June 2008). "Hair Growth and Disorders". Springer Science & Business Media.
142. (17 April 2015). "Hair Loss and Restoration, Second Edition". CRC Press.
143. (13 February 2014). "Male Alopecia: Guide to Successful Management". Springer Science & Business Media.
144. (2008). "Foye's Principles of Medicinal Chemistry". Lippincott Williams & Wilkins.
145. (July 2016). "Clinical Potential of Neurosteroids for CNS Disorders". Trends in Pharmacological Sciences.
146. (March 2016). "5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder". Neuropsychopharmacology.
147. (January 2012). "Medical management of adult transsexual persons". Pharmacotherapy.
148. (March 2015). "Cross-sex hormone therapy for gender dysphoria". Journal of Endocrinological Investigation.
149. (July 2016). "Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review". The Journal of Clinical and Aesthetic Dermatology.
150. (May 2013). "Side Effects of 5-Alpha Reductase Inhibitors: A Comprehensive Review". Sexual Medicine Reviews.
151. (September 2016). "Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials". The Journal of Sexual Medicine.
152. (May 2018). "Effects of 5-alpha reductase inhibitors: new insights on benefits and harms". Current Opinion in Urology.
153. (March 2011). "Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients". The Journal of Sexual Medicine.
154. (2018). "The Post-finasteride Syndrome: Clinical Manifestation of Drug-Induced Epigenetics Due to Endocrine Disruption". Current Sexual Health Reports.
155. (January 2018). "What's New in Epidemiology?". European Urology Focus.
156. (June 2014). "The dark side of 5α-reductase inhibitors' therapy: sexual dysfunction, high Gleason grade prostate cancer and depression". Korean Journal of Urology.
157. (June 2017). "Discriminating in favour of or against men with increased risk of finasteride-related side effects?". Experimental Dermatology.
158. (24 January 2012). "Foye's Principles of Medicinal Chemistry". Lippincott Williams & Wilkins.
159. (2012). "Mammary gland development". Wiley Interdisciplinary Reviews. Developmental Biology.
160. (2018). "The Breast". Elsevier.
161. (March 1999). "Breast growth and the urinary excretion of lactose during human pregnancy and early lactation: endocrine relationships". Experimental Physiology.
162. (August 2004). "Progestogen therapies: differences in clinical effects?". Trends in Endocrinology and Metabolism.
163. (8 September 2015). "Pharmacology for Women's Health". Jones & Bartlett Publishers.
164. (12 March 2007). "The Health of Sexual Minorities: Public Health Perspectives on Lesbian, Gay, Bisexual and Transgender Populations". Springer.
165. (November 2015). "Endocrine care of transpeople part II. A review of cross-sex hormonal treatments, outcomes and adverse effects in transwomen". Clinical Endocrinology.
166. (August 2009). "Effects of transdermal testosterone or oral dydrogesterone on hypoactive sexual desire disorder in transsexual women: results of a pilot study". European Journal of Endocrinology.
167. (May 2014). "Clinical review: Breast development in trans women receiving cross-sex hormones". The Journal of Sexual Medicine.
168. (April 1986). "Physical and hormonal evaluation of transsexual patients: a longitudinal study". Archives of Sexual Behavior.
169. (1979). "Reproductive endocrinology, infertility, and contraception". F. A. Davis Co..
170. (February 2011). "Dydrogesterone and other progestins in benign breast disease: an overview". Archives of Gynecology and Obstetrics.
171. (December 2001). "Cyclic progestin therapy for the management of mastopathy and mastodynia". Gynecological Endocrinology.
172. (June 2015). "Progestogens in menopausal hormone therapy". Przeglad Menopauzalny = Menopause Review.
173. (2001). "Principles and Practice of Endocrinology and Metabolism". Lippincott Williams & Wilkins.
174. (2005). "Manual of Vascular Diseases". Lippincott Williams & Wilkins.
175. (2018). "Case Report: Induced Lactation in a Transgender Woman". Transgender Health.
176. (January 2000). "Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men". The American Journal of Surgical Pathology.
177. (2007). "The Health of Sexual Minorities". Springer.
178. (2009). "Rosen's Breast Pathology". Lippincott Williams & Wilkins.
179. (March 2016). "Hormones and Female Sexual Dysfunction: Beyond Estrogens and Androgens--Findings from the Fourth International Consultation on Sexual Medicine". The Journal of Sexual Medicine.
180. (October 2000). "Using progestins in clinical practice". American Family Physician.
181. (September 1990). "Clinical use of oestrogens and progestogens". Maturitas.
182. (February 2014). "Allopregnanolone and mood disorders". Progress in Neurobiology.
183. (2018). "Multiple meningiomas in two male-to-female transsexual patients with hormone replacement therapy: A report of two cases and a brief literature review". Surgical Neurology International.
184. (July 2018). "The occurrence of benign brain tumours in transgender individuals during cross-sex hormone treatment". Brain.
185. Chang, Julia J.. (2025-11-01). "Progestogen Experience Among Transgender Women and Gender Diverse Adults Assigned Male at Birth in the United States". Endocrine Practice.
186. (2011). "Pharmacology of Progestogens". Journal für Reproduktionsmedizin und Endokrinologie-Journal of Reproductive Medicine and Endocrinology.
187. (August 2013). "Progesterone--promoter or inhibitor of breast cancer". Climacteric.
188. (October 2018). "Menopausal hormone therapy: a better and safer future". Climacteric.
189. (2000). "Progesterone and progestins: applications in gynecology". Steroids.
190. (June 2005). "Over-the-counter progesterone cream produces significant drug exposure compared to a food and drug administration-approved oral progesterone product". Journal of Clinical Pharmacology.
191. (October 2007). "Progesterone: review of safety for clinical studies". Experimental and Clinical Psychopharmacology.
192. (1993). "Progesterone reduces sympathetic tone without changing blood pressure or fluid balance in men". Gynecologic and Obstetric Investigation.
193. (2006). "The Use of Progesterone in Clinical Practice: Evaluation of its Efficacy in Diverse Indications Using Different Routes of Administration". Current Drug Therapy.
194. (April 2003). "Demonstration of progesterone receptor-mediated gonadotrophin suppression in the human male". Clinical Endocrinology.
195. (November 2014). "Systemic progesterone therapy--oral, vaginal, injections and even transdermal?". Maturitas.
196. (1 June 1999). "Hormone Replacement Therapy". Springer Science & Business Media.
197. (May 2019). "Medication and Facilitation of Transgender Women's Lactation". Journal of Human Lactation.
198. (2019). "Transgender Medicine". Humana Press.
199. (March 1958). "Disturbances of lactation". Clinical Obstetrics and Gynecology.
200. (1985). "[Case of galactorrhea in a transsexual male patient]". Problemy Endokrinologii.
201. (1982). "Prolactin: Physiology, Pharmacology, and Clinical Findings". Springer-Verlag.
202. (19 August 2022). "Standards of Care for the Health of Transgender and Gender Diverse People, Version 8". [[International Journal of Transgender Health]].
203. (2023). "Psychopharmacological Considerations for Gender-Affirming Hormone Therapy". Harvard Review of Psychiatry.
204. (April 2020). "Sexual Desire Changes in Transgender Individuals Upon Initiation of Hormone Treatment: Results From the Longitudinal European Network for the Investigation of Gender Incongruence". The Journal of Sexual Medicine.
205. (September 2010). "Androgen deprivation therapy for prostate cancer: recommendations to improve patient and partner quality of life". The Journal of Sexual Medicine.
206. (February 2003). "Side effects of androgen deprivation therapy: monitoring and minimizing toxicity". Urology.
207. (October 2012). "Sexuality and intimacy after definitive treatment and subsequent androgen deprivation therapy for prostate cancer". Journal of Clinical Oncology.
208. (29 June 2013). "Andrology: Male Reproductive Health and Dysfunction". Springer Science & Business Media.
209. (2015). "Guidelines and Protocols for Comprehensive Primary Care for Trans Clients". Sherbourne Health Centre.
210. (August 2003). "Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects". The Journal of Clinical Endocrinology and Metabolism.
211. (1993). "Hormone Treatment in Transsexuals". Journal of Psychology & Human Sexuality.
212. (October 2003). "Endocrine intervention for transsexuals". Clinical Endocrinology.
213. (2016). "Breast development in male-to-female transgender patients after one year cross-sex hormonal treatment". Endocrine Abstracts.
214. (February 2018). "Breast Development in Transwomen After 1 Year of Cross-Sex Hormone Therapy: Results of a Prospective Multicenter Study". The Journal of Clinical Endocrinology and Metabolism.
215. (October 2018). "Gender-Affirming Hormone Use in Transgender Individuals: Impact on Behavioral Health and Cognition". Current Psychiatry Reports.
216. (November 2009). "Sexual functioning in transsexuals following hormone therapy and genital surgery: a review". The Journal of Sexual Medicine.
217. (2020). "Mp45-20 Effects of Feminizing Hormone Therapy on Sexual Function of Transgender Women". The Journal of Urology.
218. (December 2015). "The transsexual brain--A review of findings on the neural basis of transsexualism". Neuroscience and Biobehavioral Reviews.
219. (1992). "Hormone Treatment in Transsexuals".
220. (18 August 2011). "Atlas of Pelvic Anatomy and Gynecologic Surgery". Elsevier Health Sciences.
221. (16 April 2002). "Recent Advanced in Gender Dysphoria, Gender Identity Disorder: Towards a Uniform Treatment Approach".
222. (November 2015). "Testicular Functions and Clinical Characterization of Patients with Gender Dysphoria (GD) Undergoing Sex Reassignment Surgery (SRS)". The Journal of Sexual Medicine.
223. de Nie, Iris. (January 2023). "Successful restoration of spermatogenesis following gender-affirming hormone therapy in transgender women". Cell Reports. Medicine.
224. Yau, Mabel. (January 2023). "The return of spermatogenesis in transgender women ceasing gender-affirming hormone therapy". Cell Reports. Medicine.
225. Powers, William J.. (March 20, 2024). "A Gender-Affirming Approach to Fertility Care for Transgender and Gender-Diverse Patients".
226. Braun, Hayley. (October 2020). "Transgender patients and their skin".
227. (1999). "Feminizing Hormonal Therapy For The Transgendered". Together Lifeworks.
228. (February 2023). "Characterizing Dermatological Conditions in the Transgender Population: A Cross-Sectional Study". Transgender Health.
229. (August 2000). "Effects of sex steroid deprivation/administration on hair growth and skin sebum production in transsexual males and females". The Journal of Clinical Endocrinology and Metabolism.
230. (November 2022). "Impact of gender-affirming treatment on bone health in transgender and gender diverse youth". Endocrine Connections.
231. (November 2017). "Effect of Sex Steroids on the Bone Health of Transgender Individuals: A Systematic Review and Meta-Analysis". The Journal of Clinical Endocrinology and Metabolism.
232. (June 2019). "Bone Health in the Transgender Population". Clinical Reviews in Bone and Mineral Metabolism.
233. (January 2015). "Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study". Osteoporosis International.
234. (May 2013). "Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy". Bone.
235. (January 2022). "Bone health in transgender people: a narrative review". Therapeutic Advances in Endocrinology and Metabolism.
236. (January 2020). "Fracture Risk in Trans Women and Trans Men Using Long-Term Gender-Affirming Hormonal Treatment: A Nationwide Cohort Study". Journal of Bone and Mineral Research.
237. (June 2019). "Osteoporosis and Bone Health in Transgender Persons". Endocrinology and Metabolism Clinics of North America.
238. (September 2019). "Bone Mineral Density in Transgender Individuals After Gonadectomy and Long-Term Gender-Affirming Hormonal Treatment". The Journal of Sexual Medicine.
239. (November 2020). "Fracture risk assessment in an Italian group of transgender women after gender-confirming surgery". Journal of Bone and Mineral Metabolism.
240. Stevenson, Mary O.. (2016). "Scalp Hair Regrowth in Hormone-Treated Transgender Woman". Transgender Health.
241. (2000). "The hair follicle: a paradoxical androgen target organ". Hormone Research.
242. (28 March 2012). "Clinical Gynecologic Endocrinology and Infertility". Lippincott Williams & Wilkins.
243. (November 2018). "Acute Clinical Care for Transgender Patients: A Review". JAMA Internal Medicine.
244. (November 2018). "Venous thromboembolism and women's health". British Journal of Haematology.
245. (August 2018). "Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study". Annals of Internal Medicine.
246. (January 2019). "Venous Thrombotic Risk in Transgender Women Undergoing Estrogen Therapy: A Systematic Review and Metaanalysis". Clinical Chemistry.
247. (August 2015). "Epidemiology of venous thromboembolism". Nature Reviews. Cardiology.
248. (2019). "Transgender and Gender Nonconforming Health and Aging". Springer.
249. (November 2016). "Incidence of Venous Thromboembolism in Transgender Women Receiving Oral Estradiol". The Journal of Sexual Medicine.
250. (August 2017). "Cardiovascular Disease Among Transgender Adults Receiving Hormone Therapy: A Narrative Review". Annals of Internal Medicine.
251. (September 2018). "Cardiovascular health in transgender people". Reviews in Endocrine & Metabolic Disorders.
252. (February 2019). "Interdisciplinary Management of Transgender Individuals at Risk for Breast Cancer: Case Reports and Review of the Literature". Clinical Breast Cancer.
253. (December 2013). "Breast cancer development in transsexual subjects receiving cross-sex hormone treatment". The Journal of Sexual Medicine.
254. (January 2015). "Incidence of breast cancer in a cohort of 5,135 transgender veterans". Breast Cancer Research and Treatment.
255. (May 2019). "Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands". BMJ.
256. (2019). "Health considerations for transgender women and remaining unknowns: a narrative review". Therapeutic Advances in Endocrinology and Metabolism.
257. (October 2018). "Breast cancer in transgender patients: A systematic review. Part 1: Male to female". European Journal of Surgical Oncology.
258. (March 2014). "Gynecomastia: Clinical evaluation and management". Indian Journal of Endocrinology and Metabolism.
259. (March 2008). "Gynaecomastia and breast cancer in men". BMJ.
260. (11 November 2009). "Breast Cancer Epidemiology". Springer Science & Business Media.
261. (13 March 2013). "The Molecular Biology of Cancer: A Bridge from Bench to Bedside". John Wiley & Sons.
262. (2004). "Breast Imaging". Lippincott Williams & Wilkins.
263. (13 September 2013). "Yen and Jaffe's Reproductive Endocrinology". Elsevier Health Sciences.
264. (October 2012). "Androgen insensitivity syndrome". Seminars in Reproductive Medicine.
265. (March 2008). "Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study". The Lancet. Oncology.
266. (December 2014). "Prostate cancer incidence in orchidectomised male-to-female transsexual persons treated with oestrogens". Andrologia.
267. (2013). "Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy". Canadian Urological Association Journal.
268. (December 2018). "Gender-affirming hormone therapy and the risk of sex hormone-dependent tumours in transgender individuals-A systematic review". Clinical Endocrinology.
269. (2012). "Peterson's Principles of Oral and Maxillofacial Surgery". PMPH-USA.
270. (August 2019). "Transgender Voice and Communication". Otolaryngologic Clinics of North America.
271. (April 2017). "Voice feminization in male-to-female transgendered clients after Wendler's glottoplasty with vs. without voice therapy support". European Archives of Oto-Rhino-Laryngology.
272. (July 2019). "The Role of Voice Therapy and Phonosurgery in Transgender Vocal Feminization". The Journal of Craniofacial Surgery.
273. "Protocols for the Provision of Hormone Therapy". Callen-Lorde Community Health Center.
274. (June 2019). "Gender-affirming hormones and surgery in transgender children and adolescents". The Lancet. Diabetes & Endocrinology.
275. (July 2018). "Prolactin Levels do Not Rise Among Transgender Women Treated with Estradiol and Spironolactone". Endocrine Practice.
276. (16 April 2007). "The Estrogen Elixir: A History of Hormone Replacement Therapy in America". JHU Press.
277. (May 1953). "Transvestism; hormonal, psychiatric, and surgical treatment". Journal of the American Medical Association.
278. (24 June 2011). "The Health of Lesbian, Gay, Bisexual, and Transgender People: Building a Foundation for Better Understanding". National Academies Press.
279. (September 1975). "Transsexualism in history". Archives of Sexual Behavior.
280. (13 May 2013). "Current Concepts in Transgender Identity". Routledge.
281. (2006). "The Transgender Studies Reader". Taylor & Francis.
282. (1 July 2013). "Gender Dysphoria and Disorders of Sex Development: Progress in Care and Knowledge". Springer Science & Business Media.
283. (July 1964). "Clinical aspects of transsexualism in the male and female". American Journal of Psychotherapy.
284. (1966). "The Transsexual Phenomenon". Ace Publishing Company.
285. (1967). "Transvestism and Transsexualism in the male and female1". Journal of Sex Research.
286. (1969). "Transsexualism and Sex Reassignment". Johns Hopkins Press.
287. (February 1995). "Harry Benjamin's first ten cases (1938-1953): a clinical historical note". Archives of Sexual Behavior.
288. (13 April 2016). "The SAGE Encyclopedia of LGBTQ Studies". SAGE Publications.
289. (18 October 2013). "The Transgender Studies Reader". Routledge.
290. (January 1970). "The surgical treatment of transsexual patients. Limitations and indications". Plastic and Reconstructive Surgery.
291. (2016). "Science, Politics and Clinical Intervention: Harry Benjamin, Transsexualism and the Problem of Heteronormativity". Sexualities.
292. (2014). "Gender Dysphoria and Disorders of Sex Development". Springer.
293. "International Symposia - WPATH World Professional Association for Transgender Health".
294. Green, R., & Money, J. (1969). ''Transsexualism and Sex Reassignment.'' Johns Hopkins University Press. https://scholar.google.com/scholar?cluster=8048451400842332421 https://books.google.com/books?id=pdBrAAAAMAAJ
295. (November 1970). "The nature and treatment of transsexualism.". Medical Opinion and Review.
296. (September 2009). "Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline". The Journal of Clinical Endocrinology and Metabolism.
297. (1981). "A survey of transsexual hormonal treatment in twenty gender-treatment centers". The Journal of Sex Research.
298. (1977). "Of Homosexuality: The Current State of Knowledge". Journal of Christian Education.
299. (1980). "Transsexualismus: Erfahrungen mit der operativen Korrektur bei männlichen Transsexuellen". Aktuelle Urologie.
300. (1989). "Cyproterone acetate and a small dose of oestrogen in the pre-operative management of male transsexuals. A report of three cases". Andrologia.
301. (1985). "Transsexuality in The Netherlands. Some medical and legal aspects". Medicine and Law.
302. (2006). "Physical Aspects of Transgender Endocrine Therapy". International Journal of Transgenderism.
303. "Spironolactone in the presurgical therapy of male to female transsexuals: Philosophy and experience of the Vancouver Gender Dysphoria Clinic". Journal of Sex Information & Education Council of Canada.
304. (February 1989). "Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism". Archives of Sexual Behavior.
305. (2015). "Management of Gender Dysphoria". Springer.
306. (1984). "Androgens in the feedback regulation of gonadotropin secretion in men: effects of administration of dihydrotestosterone to eugonadal and agonadal subjects and of spironolactone to eugonadal subjects". Andrologia.
307. Schaefer, L. C., Wheeler, C. C., & Futterweit, W. (1995). Gender identity disorders (transsexualism). In Rosenthal, N. E., & Gabbard, G. O. Treatment of Psychiatric Disorders, 2nd Edition, Volume 2 (pp. ). Washington, D.C.: American Psychiatric Press.
308. (2016). "Lesbian, Gay, Bisexual, and Transgender Healthcare". Springer.
309. (30 November 2021). "Trends in Feminizing Hormone Therapy for Transgender Patients, 2006–2017". Transgender Health.
310. (June 2012). "Altered arterial stiffness in male-to-female transsexuals undergoing hormonal treatment". The Journal of Obstetrics and Gynaecology Research.