The purpose of the therapy is to cause the development of the secondary sex characteristics of the desired sex, such as breasts and a feminine pattern of hair, fat, and muscle distribution. It cannot undo many of the changes produced by naturally occurring puberty, which may necessitate surgery and other treatments to reverse (see below). The medications used for feminizing hormone therapy include estrogens, antiandrogens, progestogens, and gonadotropin-releasing hormone modulators (GnRH modulators).
Feminizing hormone therapy has been empirically shown to reduce the distress and discomfort associated with gender dysphoria in transfeminine individuals.[7][8][9]
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.[10][11] 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.[10][11]
The accessibility of transgender hormone therapy differs throughout the world and throughout individual countries.[2]
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.[23] 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.[24][25][26] 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.[27][28]
In addition to producing feminization, estrogens have antigonadotropic effects, suppressing testosterone and other gonadalsex hormones.[15][29][30] Levels of estradiol of 200pg/mL and above suppress testosterone levels by about 90%, while estradiol levels of 500pg/mL and above suppress testosterone levels by about 95%, or to an equivalent extent as surgical castration and GnRH modulators.[31][32] Lower levels of estradiol can also considerably but incompletely suppress testosterone production.[29] When testosterone levels are insufficiently suppressed by estradiol alone, antiandrogens can be used to suppress or block the effects of residual testosterone.[15] Oral estradiol often has difficulty adequately suppressing testosterone levels, due to the relatively low estradiol levels achieved with it.[29][33][34]
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.[68][69][70] This is to help suppress testosterone levels.[69] The Endocrine Society (2017) recommends maintaining estradiol levels roughly within the normal average range for premenopausal women of about 100 to 200pg/mL.[1] However, it notes that these physiological levels of estradiol are usually unable to suppress testosterone levels into the female range.[1] 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.[71] The review proposal noted that high-dose parenteral estradiol is known to be safe.[71] 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 10mg per week estradiol valerate by intramuscular injection.[1] A single such injection results in estradiol levels of about 1,250pg/mL at peak and levels of around 200pg/mL after 7days.[27][28] Dosages of estrogens can be reduced after an orchiectomy or sex reassignment surgery, when gonadal testosterone suppression is no longer needed.[5]
Testosterone levels in relation to estradiol levels (and corresponding estradiol dosages) during therapy with oral estradiol alone or in combination with an antiandrogen in transgender women. The dashed purple line is the upper limit for the female/castrate range (~50ng/dL) and the dashed grey line is the testosterone level in a comparison group of post-operative transgender women (21.7ng/dL).Estradiol and testosterone levels over 12weeks after a single intramuscular injection of 320mg polyestradiol phosphate, a polymeric estradiol ester and prodrug, in men with prostate cancer. Demonstrates the suppression of testosterone levels by parenteral estradiol.
Antiandrogens that directly block the androgen receptor are known as androgen receptor antagonists or blockers, while antiandrogens that inhibit the enzymaticbiosynthesis of androgens are known as androgen synthesis inhibitors and antiandrogens that suppress androgen production in the gonads are known as antigonadotropins.[74]Estrogens and progestogens are antigonadotropins and hence are functional antiandrogens.[15][82][83][84] The purpose of the use of antiandrogens in transgender women is to block or suppress residual testosterone that is not suppressed by estrogens alone.[15][73][30] Additional antiandrogen therapy is not necessarily required if testosterone levels are in the normal female range or if the person has undergone orchiectomy.[15][73][30] 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.[85][86][87]
Testosterone levels with estradiol (E2) alone or in combination with an antiandrogen (AA) in the form of spironolactone (SPL) or cyproterone acetate (CPA) in transfeminine people. Estradiol was used in the form of oral estradiol valerate (EV) in almost all cases. The dashed horizontal line is the upper limit of the female/castrate range (~50ng/dL).
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.[95] Spironolactone is an antiandrogen as a secondary and originally unintended action.[95] It works as an antiandrogen mainly by acting as an androgen receptor antagonist.[96] The medication is also a weak steroidogenesis inhibitor, and inhibits the enzymaticsynthesis of androgens.[97][96][98] However, this action is of low potency, and spironolactone has mixed and inconsistent effects on hormone levels.[97][96][98][99][100] In any case, testosterone levels are usually unchanged by spironolactone.[97][96][98][99][100] Studies in transgender women have found testosterone levels to be unaltered with spironolactone[29] or to be decreased.[94] Spironolactone is described as a relatively weak antiandrogen.[101][102][103] It is widely used in the treatment of acne, excessive hair growth, and hyperandrogenism in women, who have much lower testosterone levels than men.[99][100] Because of its antimineralocorticoid activity, spironolactone has antimineralocorticoid side effects[104] and can cause high potassium levels.[105][106] Hospitalization and/or death can potentially result from high potassium levels due to spironolactone,[105][106][107] but the risk of high potassium levels in people taking spironolactone appears to be minimal in those without risk factors for it.[100][108][109] As such, monitoring of potassium levels may not be necessary in most cases.[100][108][109] Spironolactone has been found to decrease the bioavailability of high doses of oral estradiol.[29] 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.[29]
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.[110][111] It works primarily as an antigonadotropin, secondarily to its potent progestogenic activity, and strongly suppresses gonadal androgen production.[110][30] Cyproterone acetate at a dosage of 5 to 10mg/day has been found to lower testosterone levels in men by about 50 to 70%,[112][113][114][115] while a dosage of 100mg/day has been found to lower testosterone levels in men by about 75%.[116][117] The combination of 25mg/day cyproterone acetate and a moderate dosage of estradiol has been found to suppress testosterone levels in transgender women by about 95%.[118] In combination with estrogen, 10, 25, and 50mg/day cyproterone acetate have all shown the same degree of testosterone suppression.[119] In addition to its actions as an antigonadotropin, cyproterone acetate is an androgen receptor antagonist.[110][73] 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 (100–300mg/day).[120][121] Cyproterone acetate can cause elevated liver enzymes and liver damage, including liver failure.[73][122] 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.[73] Cyproterone acetate also has a variety of other adverse effects, such as fatigue and weight gain, and risks, such as blood clots and benignbrain tumors, among others.[30][73][123] High dosages of cyproterone-based medication have been linked with meningioma.[124] 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.[92][93] 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.[92][93] Medroxyprogesterone acetate suppresses testosterone levels in transgender women similarly to cyproterone acetate.[93][29] Oral medroxyprogesterone acetate has been found to suppress testosterone levels in men by about 30 to 75% across a dosage range of 20 to 100mg/day.[125][126][127][128][129] In contrast to cyproterone acetate however, medroxyprogesterone acetate is not also an androgen receptor antagonist.[14][130] Medroxyprogesterone acetate has similar side effects and risks as cyproterone acetate, but is not associated with liver problems.[131][104]
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.[132][133][134][135][136][137][138] Progestogens alone are in general able to suppress testosterone levels in men by a maximum of about 70 to 80%, or to just above female/castrate levels when used at sufficiently high doses.[139][140][141] The combination of a sufficient dosage of a progestogen with very small doses of an estrogen (e.g., as little as 0.5–1.5mg/day oral estradiol) is synergistic in terms of antigonadotropic effect and is able to fully suppress gonadal testosterone production, reducing testosterone levels to the female/castrate range.[142][143]
Nonsteroidal antiandrogens are antiandrogens which are nonsteroidal and hence unrelated to steroid hormones in terms of chemical structure.[88][144] These medications are primarily used in the treatment of prostate cancer,[144] but are also used for other purposes such as the treatment of acne, excessive facial/body hair growth, and high androgen levels in women.[39][145][146][147] Unlike steroidal antiandrogens, nonsteroidal antiandrogens are highly selective for the androgen receptor and act as pure androgen receptor antagonists.[144][148] Similarly to spironolactone however, they do not lower androgen levels, and instead work exclusively by preventing androgens from activating the androgen receptor.[144][148] Nonsteroidal antiandrogens are more efficacious androgen receptor antagonists than are steroidal antiandrogens,[88][149] and for this reason, in conjunction with GnRH modulators, have largely replaced steroidal antiandrogens in the treatment of prostate cancer.[144][150]
The nonsteroidal antiandrogens that have been used in transgender women include the first-generation medications flutamide (Eulexin), nilutamide (Anandron, Nilandron), and bicalutamide (Casodex).[39][151][5][3][152]:477 Newer and even more efficacious second-generation nonsteroidal antiandrogens like enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa) also exist, but are very expensive due to generics being unavailable and have not been used in transgender women.[153][154] Flutamide and nilutamide have relatively high toxicity, including considerable risks of liver damage and lung disease.[155][145] Due to its risks, the use of flutamide in cisgender and transgender women is now limited and discouraged.[39][145][5] Flutamide and nilutamide have largely been superseded by bicalutamide in clinical practice,[156][157] with bicalutamide accounting for almost 90% of nonsteroidal antiandrogen prescriptions in the United States by the mid-2000s.[158][148] Bicalutamide is said to have excellent tolerability and safety relative to flutamide and nilutamide, as well as in comparison to cyproterone acetate.[159][160][161] It has few to no side effects in women.[146][147] Despite its greatly improved tolerability and safety profile however, bicalutamide does still have a small risk of elevated liver enzymes and association with rare cases of serious liver damage and lung disease.[39][155][162]
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.[163][164][165] However, estrogens suppress testosterone levels and at high doses can markedly disrupt sex drive and function and fertility on their own.[166][167][168][169] Moreover, disruption of gonadal function and fertility by estrogens may be permanent after extended exposure.[168][169]
There are two types of GnRH modulators: GnRH agonists and GnRH antagonists.[170] These medications have the opposite action on the GnRH receptor but paradoxically have the same therapeutic effects.[170] 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.[170][171] 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.[174][175][170] At the initiation of treatment, GnRH agonists are associated with a "flare" effect on hormone levels due to acute overstimulation of the GnRH receptor.[170][176] In men, LH levels increase by up to 800%, while testosterone levels increase to about 140 to 200% of baseline.[177][176] Gradually however, the GnRH receptor desensitizes; testosterone levels peak after about 2 to 4days, return to baseline after about 7 to 8days, and are reduced to castrate levels within 2 to 4weeks.[176] 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.[178][177][179][180][15][181] In contrast to GnRH agonists, GnRH antagonists, such as degarelix (Firmagon) and elagolix (Orilissa), work by binding to the GnRH receptor without activating it, thereby displacing GnRH from the receptor and preventing its activation.[170] Unlike with GnRH agonists, there is no initial surge effect with GnRH antagonists; the therapeutic effects are immediate, with sex hormone levels being reduced to castrate levels within a few days.[170][171]
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.[1][182] However, GnRH modulators tend to be very expensive (typically US$10,000 to US$15,000 per year in the United States), and are often denied by medical insurance.[1][183][184][185] GnRH modulator therapy is much less economical than surgical castration, and is less convenient than surgical castration in the long-term as well.[186] Because of their costs, many transgender women cannot afford GnRH modulators and must use other, often less effective options for testosterone suppression.[1][183] GnRH agonists are prescribed as standard practice for transgender women in the United Kingdom however, where the National Health Service (NHS) covers them.[183][187] This is in contrast to the rest of Europe and to the United States.[187] Another drawback of GnRH modulators is that most of them are peptides and are not orally active, requiring administration by injection, implant, or nasal spray.[179] However, non-peptide and orally active GnRH antagonists, elagolix (Orilissa) and relugolix (Relumina), were introduced for medical use in 2018 and 2019, respectively. But they are under patent protection and, as with other GnRH modulators, are very expensive at present.[188]
5α-Reductase inhibitors include finasteride and dutasteride.[190][191] Finasteride is a selective inhibitor of 5α-reductase types 2 and 3, while dutasteride is an inhibitor of all three isoforms of 5α-reductase.[190][202][203] Finasteride can decrease circulating DHT levels by up to 70%, whereas dutasteride can decrease circulating DHT levels by up to 99%.[202][203] Conversely, 5α-reductase inhibitors do not decrease testosterone levels, and may actually increase them slightly.[1][29][30][204] 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.[202][205] They are also used in the treatment of androgen-dependent scalp hair loss in men and women.[206][207][208] The medications are able to prevent further scalp hair loss in men and can restore some scalp hair density.[206][207][209] Conversely, the effectiveness of 5α-reductase inhibitors in the treatment of scalp hair loss in women is less clear.[208][191] 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.[208][191] 5α-Reductase inhibitors are also used to treat hirsutism (excessive body/facial hair growth) in women, and are very effective for this indication.[210] 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.[211][212][144] In addition to their antiandrogenic uses, 5α-reductase inhibitors have been found to reduce adverse affective symptoms in premenstrual dysphoric disorder in women.[213][214] 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.[213][214]
5α-Reductase inhibitors are sometimes used as a component of feminizing hormone therapy for transgender women in combination with estrogens and/or other antiandrogens.[4][215][70] They may have beneficial effects limited to improvement of scalp hair loss, body hair growth, and possibly skin symptoms such as acne.[216][2][217][70] 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.[215][218] Moreover, 5α-reductase inhibitors have only mild and specific antiandrogenic activity, and are not recommended as general antiandrogens.[218]
5α-Reductase inhibitors have minimal side effects and are well tolerated in both men and women.[219][220] 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.[219][220][221][222][223] Another side effect in men is breast changes, such as breast tenderness and gynecomastia (2.8% incidence).[220] Due to decreased levels of androgens and/or neurosteroids, 5α-reductase inhibitors may slightly increase the risk of depression (~2.0% incidence).[222][224][225][219][201] 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.[223][226][224][227][222][221][201] Some of the possible side effects of 5α-reductase inhibitors in men, such as gynecomastia and sexual dysfunction, are actually welcome changes for many transgender women.[39] In any case, caution may be warranted in using 5α-reductase inhibitors in transgender women, as this group is already at a high risk for depression and suicidality.[228][30]
There are two types of progestogens: progesterone, which is the natural and bioidentical hormone in the body; and progestins, which are synthetic progestogens.[14] There are dozens of clinically used progestins.[14][234][235] 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.[92][93] Aside from the specific use of testosterone suppression however, there are no other indications of progestogens in transgender women at present.[2] In relation to this, the use of progestogens in transgender women is controversial, and they are not otherwise routinely prescribed or recommended.[2][5][6][216][218][236] 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.[237][238][218][239][5][240] Progestins in general largely have the same progestogenic effects however, and in theory, any progestin could be used in transgender women.[14]
Clinical research on the use of progestogens in transgender women is very limited.[2][232] 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.[4][3][232] There are no clinical studies to support such reports at present.[2][4][232] 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.[232][241][182] These studies, albeit limited in the quality of their findings, reported no benefit of progestogens on breast development in transgender women.[232][182][216] This has also been the case in limited clinical experience.[242]
Progestogens have some antiestrogenic effects in the breasts, for instance decreasing expression of the estrogen receptor and increasing expression of estrogen-metabolizingenzymes,[243][244][245][246] and for this reason, have been used to treat breast pain and benign breast disorders.[247][248][249][250] Progesterone levels during female puberty do not normally increase importantly until near the end of puberty in cisgender girls, a point by which most breast development has already been completed.[251] In addition, concern has been expressed that premature exposure to progestogens during the process of breast development is unphysiological and might compromise final breast growth outcome, although this notion presently remains theoretical.[39][232][252] Though the role of progestogens in pubertal breast development is uncertain, progesterone is essential for lobuloalveolar maturation of the mammary glands during pregnancy.[230] Hence, progestogens are required for any transgender woman who wishes to lactate or breastfeed.[65][253][232] A study found full lobuloalveolar maturation of the mammary glands on histological examination in transgender women treated with an estrogen and high-dose cyproterone acetate.[254][255][256] However, lobuloalveolar development reversed with discontinuation of cyproterone acetate, indicating that continued progestogen exposure is necessary to maintain the tissue.[254]
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.[239] Another study likewise found that oral progesterone did not improve sexual function in cisgender women.[257]
Progestogens can have adverse effects.[216][218][14][234][258][17] Oral progesterone has inhibitoryneurosteroid effects and can produce side effects such as sedation, mood changes, and alcohol-like effects.[14][259][260] Many progestins have off-target activity, such as androgenic, antiandrogenic, glucocorticoid, and antimineralocorticoid activity, and these activities likewise can contribute unwanted side effects.[14][234] 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.[261][218][216][262] Although it is unknown if these health risks of progestins occur in transgender women similarly, it cannot be ruled out that they do.[261][218][216] High-dose progestogens increase the risk of benignbrain tumors including prolactinomas and meningiomas as well.[263][264] 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., 2–3years).[261][216][5][6][236] 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.[3] In general, some transgender women respond favorably to the effects of progestogens, while others respond negatively.[3]
Progesterone is most commonly taken orally.[14][262] However, oral progesterone has very low bioavailability, and produces relatively weak progestogenic effects even at high doses.[265][266][262][267][268] In accordance, and in contrast to progestins, oral progesterone has no antigonadotropic effects in men even at high doses.[259][269] Progesterone can also be taken by various parenteral (non-oral) routes, including sublingually, rectally, and by intramuscular or subcutaneous injection.[14][249][270] These routes do not have the bioavailability and efficacy issues of oral progesterone, and accordingly, can produce considerable antigonadotropic and other progestogenic effects.[14][267][271] Transdermal progesterone is poorly effective, owing to absorption issues.[14][249][268] Progestins are usually taken orally.[14] In contrast to progesterone, most progestins have high oral bioavailability, and can produce full progestogenic effects with oral administration.[14] Some progestins, such as medroxyprogesterone acetate and hydroxyprogesterone caproate, are or can be used by intramuscular or subcutaneous injection instead.[272][249] Almost all progestins, with the exception of dydrogesterone, have antigonadotropic effects.[14]
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:
Effects of feminizing hormone therapy in transfeminine people
1 2 Estimates represent published and unpublished clinical observations.
↑ Time at which further changes are unlikely at maximum maintained dose. Maximum effects vary widely depending on genetics, body habitus, age, and status of gonad removal. Generally, older individuals with intact gonads may have less feminization overall.
↑ Additional research is needed to determine permanency, but a permanent impact of estrogen therapy on sperm quality is likely and sperm preservation options should be counseled on and considered before initiation of therapy.
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.[291]
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.[292] Some transgender women report a significant reduction in libido, depending on the dosage of antiandrogens.[293] 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.[261] One study found that sex drive returned to baseline after three years of hormone therapy.[281] It is possible to approximate outcomes of these therapies on transgender people based on their observed effect in cisgender men and women.[292] 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.[292] 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.[292] Typically, the estrogens given for feminizing gender transition are 2 to 3 times higher than the recommended dose for HRT in postmenopausal women.[261] 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.[261]
Several studies have found that hormone therapy in transgender women causes the structure of the brain to change in the direction of female proportions.[294][295][296][297][298] In addition, studies have found that hormone therapy in transgender women causes performance in cognitive tasks, including visuospatial, verbal memory, and verbal fluency, to shift in a more female direction.[294][291]
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.[299] 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.
Well-developed breasts of transgender woman induced by hormone therapy.
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.[300][217] Breast development seems to be better in transgender women who have a higher body mass index.[300][217] This indicates that weight gain in the early phases of hormone therapy may be beneficial not only for fat distribution, but for breast development.[300][217] Different estrogens, such as estradiol valerate, conjugated estrogens, and ethinylestradiol, appear to produce equivalent results in terms of breast sizes in transgender women.[300][241][182] The sudden discontinuation of estrogen therapy has been associated with onset of galactorrhea (lactation).[300][217]
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.[299]
Fertility
The effect of feminizing hormone therapy on fertility is not clear, but it is known that testosterone suppression can prevent sperm production.[301] 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.[302][303]
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.[304] His study also includes an in-depth description of other methods for fertility restoration.[304]
Skin
Estrogens cause the accumulation of subcutaneous fat and an increased epidermal thickness, softening the skin.[299][305] Some skin conditions, including melasma, are found in trans women at the same rate at cisgender women.[306]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.[299][307]
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.[308] Bone density continue to grow and change over time.
Significant changes to bone structure have been observed,[309][310][311] and transgender women have statistically poorer bone health even before beginning the transition process, possibly due to a lack of physical exercise[312] or other risk factors such as low vitamin D, eating disorders, and substance abuse.[313]
Approximately 14% of transgender women suffer from osteoporosis.[313] 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.[314] Current clinical guidelines are for bone health to be monitored regularly throughout the transition process, particularly if risk factors are present.[308] 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.[315]
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,[316] and poor compliance with prescribed hormone therapy after gonadectomy may account in part for the observed fracture risk.[317]
Hair
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.[306] In patients in their teens or early twenties, antiandrogens prevent new facial hair from developing if testosterone levels are within the normal female range.[299][307]
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.[299][307]Eyebrows do not change because they are not androgenic hair.[318]
Occasionally, hormones can have effects on scalp hair texture, depending on various genetic factors.
Eye morphology
The lens of the eye changes in curvature.[319][320][321][305] Because of decreased androgen levels, the meibomian glands (the sebaceous glands on the upper and lower eyelids that open up at the edges) produce less oil. Because oil prevents the tear film from evaporating, this change may cause dry eyes.[322][323][324][325][326]
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.[327][169][21] 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.[14] Non-bioidentical estrogens such as conjugated estrogens and especially ethinylestradiol have markedly disproportionate effects on liver protein synthesis relative to estradiol.[14] 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.[14][328]
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.[217]
A 2018 cohort study of 2842transfeminine individuals in the United States treated with a mean follow-up of 4.0years observed an increased risk of VTE, stroke, and heart attack relative to a cisgender reference population.[329][330][39][20] The estrogens used included oral estradiol (1 to 10mg/day) and other estrogen formulations.[20] Other medications such as antiandrogens like spironolactone were also used.[20]
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.[331] 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.[331][332] 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.[331] 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.[331]
In a 2016 study that specifically assessed oral estradiol, the incidence of VTE in 676transgender women who were treated for an average of 1.9years each was only one individual, or 0.15% of the group, with an incidence of 7.8events per 10,000person-years.[333][334] The dosage of oral estradiol used was 2 to 8mg/day.[334] 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).[334] The findings of this study suggest that the incidence of VTE is low in transgender women taking oral estradiol.[333][334]
Cardiovascular health in transgender women has been reviewed in recent publications.[335][19]
Gastrointestinal
Estrogens may increase the risk of gallbladder disease, especially in older and obese people.[305]
Cancer risk
Studies are mixed on whether the risk of breast cancer is increased with hormone therapy in transgender women.[336][337][338][339] Two cohort studies found no increase in risk relative to cisgender men,[337][338] 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.[339][336] There is no evidence that breast cancer risk in transgender women is greater than in cisgender women.[340] Twenty cases of breast cancer in transgender women have been reported as of 2019.[336][341]
Cisgender men with gynecomastia have not been found to have an increased risk of breast cancer.[342] 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).[342] 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).[342][343][344] The incidences of breast cancer in karyotypical men, men with Klinefelter's syndrome, and karyotypical women are approximately 0.1%,[345] 3%,[343] and 12.5%,[346] 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,[347] yet have not been reported to develop breast cancer.[75][348] 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.[349]
Prostate cancer is extremely rare in gonadectomized transgender women who have been treated with estrogens for a prolonged period of time.[1][350][351] Whereas as many as 70% of men show prostate cancer by their 80s,[157] only a handful of cases of prostate cancer in transgender women have been reported in the literature.[1][350][351] 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.[1][350][351]
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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.[353]
Facial hair develops during puberty and is only slightly affected by HRT.[307]
A person's voice is unaffected by feminizing hormone therapy. Transgender individuals who have undergone male puberty often opt for vocal training, though this may take many years of practice to achieve the desired results. Some may also opt for vocal surgery, though this is to be done in addition to vocal training, not instead of.[354][355][356]
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 threemonths in the first year.[1] Recommended ranges for total estradiol and total testosterone levels include but are not limited to the following:
"[T]estosterone levels [...] below the upper limit of the normal female range and estradiol levels within a premenopausal female range but well below supraphysiologic levels." "[M]aintain levels within physiologic ranges for a patient's desired gender expression (based on goals of full feminization/masculinization)."
"The interpretation of hormone levels for transgender individuals is not yet evidence based; physiologic hormone levels in non-transgender people are used as reference ranges." "Providers are encouraged to consult with their local lab(s) to obtain hormone level reference ranges for both 'male' and 'female' norms, [which can vary,] and then apply the correct range when interpreting results based on the current hormonal sex, rather than the sex of registration."
"Some guidelines recommend checking estradiol and testosterone levels at baseline and throughout the monitoring of estrogen therapy. We have not found a clinical use for routine hormone levels that justifies the expense. However, we recognize that individual providers may adjust their prescribing and monitoring practices as needed to comply with guidelines or when guided by patient need."
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).[1]
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.[1][357]
If prolactin levels are greater than 100ng/mL, estrogen therapy should be stopped and prolactin levels should be rechecked after 6 to 8weeks.[357] If prolactin levels remain high, an MRI scan of the pituitary gland to check for the presence of a prolactinoma should be ordered.[357] Otherwise, estrogen therapy may be restarted at a lower dosage.[357] Cyproterone acetate is particularly associated with elevated prolactin levels, and discontinuation of cyproterone acetate lowers prolactin levels.[352][264][358] In contrast to cyproterone acetate, estrogen and spironolactone therapy is not associated with increased prolactin levels.[358][359]
History
Effective pharmaceutical female sex-hormonal medications, including androgens, estrogens, and progestogens, first became available in the 1920s and 1930s.[360] One of the earliest reports of hormone therapy in transgender women was published by DanishendocrinologistChristian Hamburger in 1953.[361] One of his patients was Christine Jorgensen, who he had treated starting in 1950.[362][363][364][365] 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.[366][367][368][369][370][371] However, Benjamin had several hundred transgender patients under his care by the late 1950s,[93] and had treated transgender women with hormone therapy as early as the late 1940s or early 1950s.[372][373][374][362] In any case, Hamburger is said to be the first to treat transgender women with hormone therapy.[375]
In modern times, hormone therapy in transgender women is usually done with the combination of an estrogen and an antiandrogen.[391] 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.[392]
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.
A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.
Norethisterone, also known as norethindrone and sold under the brand name Norlutin among others, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in both low-dose and high-dose formulations and both alone and in combination with an estrogen. It is used by mouth or, as norethisterone enanthate, by injection into muscle.
Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women. It is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like France and Japan, at low, moderate, and high doses alone for various indications. It is taken by mouth.
Allylestrenol, sold under the brand names Gestanin and Turinal among others, is a progestin medication which is used to treat recurrent and threatened miscarriage and to prevent premature labor in pregnant women. However, except in the case of proven progesterone deficiency, its use for such purposes is no longer recommended. It is also used in Japan to treat benign prostatic hyperplasia (BPH) in men. The medication is used alone and is not formulated in combination with an estrogen. It is taken by mouth.
Sexual motivation is influenced by hormones such as testosterone, estrogen, progesterone, oxytocin, and vasopressin. In most mammalian species, sex hormones control the ability and motivation to engage in sexual behaviours.
Estradiol undecylate, also known as estradiol undecanoate and formerly sold under the brand names Delestrec and Progynon Depot 100 among others, is an estrogen medication which has been used in the treatment of prostate cancer in men. It has also been used as a part of hormone therapy for transgender women. Although estradiol undecylate has been used in the past, it was discontinued. The medication has been given by injection into muscle usually once a month.
Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender individuals, and in birth control pills. It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.
Cyproterone, also known by its developmental code name SH-80881, is a steroidal antiandrogen which was studied in the 1960s and 1970s but was never introduced for medical use. It is a precursor of cyproterone acetate (CPA), an antiandrogen, progestin, and antigonadotropin which was introduced instead of cyproterone and is widely used as a medication. Cyproterone and CPA were among the first antiandrogens to be developed.
Benorterone, also known by its developmental code name SKF-7690 and as 17α-methyl-B-nortestosterone, is a steroidal antiandrogen which was studied for potential medical use but was never marketed. It was the first known antiandrogen to be studied in humans. It is taken by mouth or by application to skin.
A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure. They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like testosterone and dihydrotestosterone (DHT) and by suppressing gonadal androgen production. SAAs lower concentrations of testosterone through simulation of the negative feedback inhibition of the hypothalamus. SAAs are used in the treatment of androgen-dependent conditions in men and women, and are also used in veterinary medicine for the same purpose. They are the converse of nonsteroidal antiandrogens (NSAAs), which are antiandrogens that are not steroids and are structurally unrelated to testosterone.
High-dose estrogen therapy (HDE) is a type of hormone therapy in which high doses of estrogens are given. When given in combination with a high dose of progestogen, it has been referred to as pseudopregnancy. It is called this because the estrogen and progestogen levels achieved are in the range of the very high levels of these hormones that occur during pregnancy. HDE and pseudopregnancy have been used in medicine for a number of hormone-dependent indications, such as breast cancer, prostate cancer, and endometriosis, among others. Both natural or bioidentical estrogens and synthetic estrogens have been used and both oral and parenteral routes may be used.
The medical uses of bicalutamide, a nonsteroidal antiandrogen (NSAA), include the treatment of androgen-dependent conditions and hormone therapy to block the effects of androgens. Indications for bicalutamide include the treatment of prostate cancer in men, skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, high testosterone levels in women, hormone therapy in transgender women, as a puberty blocker to prevent puberty in transgender girls and to treat early puberty in boys, and the treatment of long-lasting erections in men. It may also have some value in the treatment of paraphilias and hypersexuality in men.
An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.
The pharmacology of estradiol, an estrogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration.
The pharmacology of progesterone, a progestogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration.
The pharmacodynamics of spironolactone, an antimineralocorticoid and antiandrogen medication, concern its mechanisms of action, including its biological targets and activities, as well as its physiological effects. The pharmacodynamics of spironolactone are characterized by high antimineralocorticoid activity, moderate antiandrogenic activity, and weak steroidogenesis inhibition. In addition, spironolactone has sometimes been found to increase estradiol and cortisol levels and hence could have slight indirect estrogenic and glucocorticoid effects. The medication has also been found to interact very weakly with the estrogen and progesterone receptors, and to act as an agonist of the pregnane X receptor. Likely due to increased activation of the estrogen and/or progesterone receptors, spironolactone has very weak but significant antigonadotropic effects.
The pharmacology of cyproterone acetate (CPA) concerns the pharmacology of the steroidal antiandrogen and progestin medication cyproterone acetate.
The side effects of cyproterone acetate (CPA), a steroidal antiandrogen and progestin, including its frequent and rare side effects, have been studied and characterized. It is generally well-tolerated and has a mild side-effect profile, regardless of dosage, when it used as a progestin or antiandrogen in combination with an estrogen such as ethinylestradiol or estradiol valerate in women. Side effects of CPA include hypogonadism and associated symptoms such as demasculinization, sexual dysfunction, infertility, and osteoporosis; breast changes such as breast tenderness, enlargement, and gynecomastia; emotional changes such as fatigue and depression; and other side effects such as vitamin B12 deficiency, weak glucocorticoid effects, and elevated liver enzymes. Weight gain can occur with CPA when it is used at high doses. Some of the side effects of CPA can be improved or fully prevented if it is combined with an estrogen to prevent estrogen deficiency. Few quantitative data are available on many of the potential side effects of CPA. Pooled tolerability data for CPA is not available in the literature.
Ethinylestradiol/cyproterone acetate (EE/CPA), also known as co-cyprindiol and sold under the brand names Diane and Diane-35 among others, is a combination of ethinylestradiol (EE), an estrogen, and cyproterone acetate (CPA), a progestin and antiandrogen, which is used as a birth control pill to prevent pregnancy in women. It is also used to treat androgen-dependent conditions in women such as acne, seborrhea, excessive facial/body hair growth, scalp hair loss, and high androgen levels associated with ovaries with cysts. The medication is taken by mouth once daily for 21 days, followed by a 7-day free interval.
↑ Murad MH, Elamin MB, Garcia MZ, Mullan RJ, Murad A, Erwin PJ, etal. (February 2010). "Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes". Clinical Endocrinology. 72 (2): 214–231. doi:10.1111/j.1365-2265.2009.03625.x. PMID19473181. S2CID19590739.
↑ Steever J, Francis J, Gordon LP, Lee J (21 August 2014). "Sexual Minority Youth". In Shore WB (ed.). Adolescent Medicine, An Issue of Primary Care: Clinics in Office Practice, E-Book. Elsevier Health Sciences. pp.663–. ISBN978-0-323-32340-6.
↑ Lauritzen C (December 1986). "[Treatment of disorders of the climacteric by vaginal, rectal and transdermal estrogen substitution]" [Treatment of disorders of the climacteric by vaginal, rectal and transdermal estrogen substitution]. Der Gynakologe (in German). 19 (4): 248–253. PMID3817597.
1 2 Ockrim J, Lalani EN, Abel P (October 2006). "Therapy Insight: parenteral estrogen treatment for prostate cancer--a new dawn for an old therapy". Nature Clinical Practice. Oncology. 3 (10): 552–563. doi:10.1038/ncponc0602. PMID17019433. S2CID6847203.
↑ Lycette JL, Bland LB, Garzotto M, Beer TM (December 2006). "Parenteral estrogens for prostate cancer: can a new route of administration overcome old toxicities?". Clinical Genitourinary Cancer. 5 (3): 198–205. doi:10.3816/CGC.2006.n.037. PMID17239273.
↑ Kariyawasam NM, Ahmad T, Sarma S, Fung R (2024-03-05). "Comparison of Estrone/Estradiol Ratio and Levels in Transfeminine Individuals on Different Routes of Estradiol". Transgender Health. doi:10.1089/trgh.2023.0138. ISSN2688-4887.
↑ Stege R, Carlström K, Collste L, Eriksson A, Henriksson P, Pousette A (1988). "Single drug polyestradiol phosphate therapy in prostatic cancer". American Journal of Clinical Oncology. 11 (Suppl 2): S101–S103. doi:10.1097/00000421-198801102-00024. PMID3242384. S2CID32650111.
↑ Ockrim JL, Lalani EN, Laniado ME, Carter SS, Abel PD (May 2003). "Transdermal estradiol therapy for advanced prostate cancer--forward to the past?". The Journal of Urology. 169 (5): 1735–1737. doi:10.1097/01.ju.0000061024.75334.40. PMID12686820.
↑ Wesp LM, Deutsch MB (March 2017). "Hormonal and Surgical Treatment Options for Transgender Women and Transfeminine Spectrum Persons". The Psychiatric Clinics of North America. 40 (1): 99–111. doi:10.1016/j.psc.2016.10.006. PMID28159148.
↑ Gooren LJ (March 2011). "Clinical practice. Care of transsexual persons". The New England Journal of Medicine. 364 (13): 1251–1257. doi:10.1056/NEJMcp1008161. PMID21449788.
↑ Gooren LJ, Giltay EJ, Bunck MC (January 2008). "Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience". The Journal of Clinical Endocrinology and Metabolism. 93 (1): 19–25. doi:10.1210/jc.2007-1809. PMID17986639.
↑ Athanasoulia-Kaspar AP, Stalla GK (2019). "Endokrinologische Betreuung von Patienten mit Transsexualität" [Endocrinological care of patients with transsexuality]. Geburtshilfe und Frauenheilkunde. 79 (7): 672–675. doi:10.1055/a-0801-3319. ISSN0016-5751. S2CID199033008.
↑ Meriggiola MC, Gava G (November 2015). "Endocrine care of transpeople part II. A review of cross-sex hormonal treatments, outcomes and adverse effects in transwomen". Clinical Endocrinology. 83 (5): 607–615. doi:10.1111/cen.12754. PMID25692882. S2CID39706760.
↑ Costa EM, Mendonca BB (March 2014). "Clinical management of transsexual subjects". Arquivos Brasileiros de Endocrinologia e Metabologia. 58 (2): 188–196. doi:10.1590/0004-2730000003091. PMID24830596.
↑ Moore E, Wisniewski A, Dobs A (August 2003). "Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects". The Journal of Clinical Endocrinology and Metabolism. 88 (8): 3467–3473. doi:10.1210/jc.2002-021967. PMID12915619.
↑ Rosenthal SM (December 2014). "Approach to the patient: transgender youth: endocrine considerations". The Journal of Clinical Endocrinology and Metabolism. 99 (12): 4379–4389. doi:10.1210/jc.2014-1919. PMID25140398.
↑ Bourgeois AL, Auriche P, Palmaro A, Montastruc JL, Bagheri H (February 2016). "Risk of hormonotherapy in transgender people: Literature review and data from the French Database of Pharmacovigilance". Annales d'Endocrinologie. 77 (1): 14–21. doi:10.1016/j.ando.2015.12.001. PMID26830952.
↑ Gooren LJ, Giltay EJ, Bunck MC (January 2008). "Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience". The Journal of Clinical Endocrinology and Metabolism. 93 (1): 19–25. doi:10.1210/jc.2007-1809. PMID17986639.
1 2 Wylie KR, Fung Jr R, Boshier C, Rotchell M (2009). "Recommendations of endocrine treatment for patients with gender dysphoria". Sexual and Relationship Therapy. 24 (2): 175–187. doi:10.1080/14681990903023306. ISSN1468-1994. S2CID20471537.
↑ Dimitrakakis C (September 2011). "Androgens and breast cancer in men and women". Endocrinology and Metabolism Clinics of North America. 40 (3): 533–47, viii. doi:10.1016/j.ecl.2011.05.007. PMID21889719.
↑ Neumann F (1978). "The physiological action of progesterone and the pharmacological effects of progestogens--a short review". Postgraduate Medical Journal. 54 (Suppl 2): 11–24. PMID368741.
↑ Schmidt TH, Shinkai K (October 2015). "Evidence-based approach to cutaneous hyperandrogenism in women". Journal of the American Academy of Dermatology. 73 (4): 672–690. doi:10.1016/j.jaad.2015.05.026. PMID26138647.
1 2 3 4 McMullen GR, Van Herle AJ (December 1993). "Hirsutism and the effectiveness of spironolactone in its management". Journal of Endocrinological Investigation. 16 (11): 925–932. doi:10.1007/BF03348960. PMID8144871. S2CID42231952.
1 2 Pavone-Macaluso M, de Voogt HJ, Viggiano G, Barasolo E, Lardennois B, de Pauw M, etal. (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. 136 (3): 624–631. doi:10.1016/S0022-5347(17)44996-2. PMID2942707.
↑ Wang C, Yeung KK (March 1980). "Use of low-dosage oral cyproterone acetate as a male contraceptive". Contraception. 21 (3): 245–272. doi:10.1016/0010-7824(80)90005-0. PMID6771091.
↑ Moltz L, Römmler A, Post K, Schwartz U, Hammerstein J (April 1980). "Medium dose cyproterone acetate (CPA): effects on hormone secretion and on spermatogenesis in men". Contraception. 21 (4): 393–413. doi:10.1016/s0010-7824(80)80017-5. PMID6771095.
↑ Knuth UA, Hano R, Nieschlag E (November 1984). "Effect of flutamide or cyproterone acetate on pituitary and testicular hormones in normal men". The Journal of Clinical Endocrinology and Metabolism. 59 (5): 963–969. doi:10.1210/jcem-59-5-963. PMID6237116.
↑ Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R (June 1980). "Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial". British Journal of Urology. 52 (3): 208–215. doi:10.1111/j.1464-410x.1980.tb02961.x. PMID7000222.
↑ Fung R, Hellstern-Layefsky M, Lega I (2017). "Is a lower dose of cyproterone acetate as effective at testosterone suppression in transgender women as higher doses?". International Journal of Transgenderism. 18 (2): 123–128. doi:10.1080/15532739.2017.1290566. ISSN1553-2739. S2CID79095497.
↑ Pucci E, Petraglia F (December 1997). "Treatment of androgen excess in females: yesterday, today and tomorrow". Gynecological Endocrinology. 11 (6): 411–433. doi:10.3109/09513599709152569. PMID9476091.
↑ Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A (2004). "Hepatotoxicity induced by antiandrogens: a review of the literature". Urologia Internationalis. 73 (4): 289–295. doi:10.1159/000081585. PMID15604569. S2CID24799765.
↑ Gava G, Mancini I, Cerpolini S, Baldassarre M, Seracchioli R, Meriggiola MC (December 2018). "Testosterone undecanoate and testosterone enanthate injections are both effective and safe in transmen over 5 years of administration". Clinical Endocrinology. 89 (6): 878–886. doi:10.1111/cen.13821. PMID30025172. S2CID51701184.
↑ Lothstein LM (1996). "Antiandrogen treatment for sexual disorders: Guidelines for establishing a standard of care". Sexual Addiction & Compulsivity. 3 (4): 313–331. doi:10.1080/10720169608400122. ISSN1072-0162.
↑ Novak E, Hendrix JW, Chen TT, Seckman CE, Royer GL, Pochi PE (October 1980). "Sebum production and plasma testosterone levels in man after high-dose medroxyprogesterone acetate treatment and androgen administration". Acta Endocrinologica. 95 (2): 265–270. doi:10.1530/acta.0.0950265. PMID6449127.
↑ Kirschner MA, Schneider G (February 1972). "Suppression of the pituitary-Leydig cell axis and sebum production in normal men by medroxyprogesterone acetate (provera)". Acta Endocrinologica. 69 (2): 385–393. doi:10.1530/acta.0.0690385. PMID5066846.
↑ Kumamoto Y, Yamaguchi Y, Sato Y, Suzuki R, Tanda H, Kato S, etal. (February 1990). "[Effects of anti-androgens on sexual function. Double-blind comparative studies on allylestrenol and chlormadinone acetate Part I: Nocturnal penile tumescence monitoring]". Hinyokika Kiyo. Acta Urologica Japonica (in Japanese). 36 (2): 213–226. PMID1693037.
↑ Geller J, Albert J, Geller S (1982). "Acute therapy with megestrol acetate decreases nuclear and cytosol androgen receptors in human BPH tissue". The Prostate. 3 (1): 11–15. doi:10.1002/pros.2990030103. PMID6176985. S2CID23541558.
↑ Sander S, Nissen-Meyer R, Aakvaag A (1978). "On gestagen treatment of advanced prostatic carcinoma". Scandinavian Journal of Urology and Nephrology. 12 (2): 119–121. doi:10.3109/00365597809179977. PMID694436.
↑ Wenderoth UK, Jacobi GH (1983). "Gonadotropin-releasing hormone analogues for palliation of carcinoma of the prostate". World Journal of Urology. 1 (1): 40–48. doi:10.1007/BF00326861. ISSN0724-4983. S2CID23447326.
↑ Schröder FH, Radlmaier A (2009). "Steroidal Antiandrogens". In Jordan VC, Furr BJ (eds.). Hormone Therapy in Breast and Prostate Cancer. Humana Press. pp.325–346. doi:10.1007/978-1-59259-152-7_15. ISBN978-1-60761-471-5. CPA, as mentioned earlier, leads to an incomplete suppression of plasma testosterone levels, which decrease by about 70% and remain at about three times castration values. [Rennie et al.] found that the combination of CPA with an extremely low dose (0.1 mg/d) of DES led to a very effective withdrawal of androgens in terms of plasma testosterone and tissue dihydrotestosterone. [...] this regimen combines the testosterone-reducing effects of two compounds, therefore, only small amounts of estrogen are required to bring down plasma testosterone to approximately castrate levels.
↑ Melamed AJ (March 1987). "Current concepts in the treatment of prostate cancer". Drug Intelligence & Clinical Pharmacy. 21 (3): 247–254. doi:10.1177/106002808702100302. PMID3552544. S2CID7482144. [Megestrol acetate] produces a transient reduction in plasma testosterone to levels somewhat higher than those in castrated men. When used in a dose of 40 mg tid, in combination with estradiol 0.5–1.5 mg/d, it acts synergistically to suppress pituitary gonadotropins and maintain plasma testosterone at castration levels for periods up to one year.
↑ Gooren LJ (March 2011). "Clinical practice. Care of transsexual persons". The New England Journal of Medicine. 364 (13): 1251–1257. doi:10.1056/NEJMcp1008161. PMID21449788.
↑ Kolvenbag GJ, Blackledge GR (January 1996). "Worldwide activity and safety of bicalutamide: a summary review". Urology. 47 (1A Suppl): 70–9, discussion 80–4. doi:10.1016/S0090-4295(96)80012-4. PMID8560681.
↑ Vogelzang NJ (September 2012). "Enzalutamide--a major advance in the treatment of metastatic prostate cancer". The New England Journal of Medicine. 367 (13): 1256–1257. doi:10.1056/NEJMe1209041. PMID23013078.
↑ Gao Y, Maurer T, Mirmirani P (August 2018). "Understanding and Addressing Hair Disorders in Transgender Individuals". American Journal of Clinical Dermatology. 19 (4): 517–527. doi:10.1007/s40257-018-0343-z. PMID29352423. S2CID6467968. Non-steroidal antiandrogens include flutamide, nilutamide, and bicalutamide, which do not lower androgen levels and may be favorable for individuals who want to preserve sex drive and fertility [9].
↑ Morgante E, Gradini R, Realacci M, Sale P, D'Eramo G, Perrone GA, etal. (March 2001). "Effects of long-term treatment with the anti-androgen bicalutamide on human testis: an ultrastructural and morphometric study". Histopathology. 38 (3): 195–201. doi:10.1046/j.1365-2559.2001.01077.x. hdl:11573/387981. PMID11260298. S2CID36892099.
↑ Jones CA, Reiter L, Greenblatt E (2016). "Fertility preservation in transgender patients". International Journal of Transgenderism. 17 (2): 76–82. doi:10.1080/15532739.2016.1153992. ISSN1553-2739. S2CID58849546. Traditionally, patients have been advised to cryopreserve sperm prior to starting cross-sex hormone therapy as there is a potential for a decline in sperm motility with high-dose estrogen therapy over time (Lubbert et al., 1992). However, this decline in fertility due to estrogen therapy is controversial due to limited studies.
↑ Payne AH, Hardy MP (28 October 2007). The Leydig Cell in Health and Disease. Springer Science & Business Media. pp.422–431. ISBN978-1-59745-453-7. Estrogens are highly efficient inhibitors of the hypothalamic-hypophyseal-testicular axis (212–214). Aside from their negative feedback action at the level of the hypothalamus and pituitary, direct inhibitory effects on the testis are likely (215,216). [...] The histology of the testes [with estrogen treatment] showed disorganization of the seminiferous tubules, vacuolization and absence of lumen, and compartmentalization of spermatogenesis.
1 2 Salam MA (2003). Principles & Practice of Urology: A Comprehensive Text. Universal-Publishers. pp.684–. ISBN978-1-58112-412-5. Estrogens act primarily through negative feedback at the hypothalamic-pituitary level to reduce LH secretion and testicular androgen synthesis. [...] Interestingly, if the treatment with estrogens is discontinued after 3 yr. of uninterrupted exposure, serum testosterone may remain at castration levels for up to another 3 yr. This prolonged suppression is thought to result from a direct effect of estrogens on the Leydig cells.
↑ Conn PM, Crowley WF (January 1991). "Gonadotropin-releasing hormone and its analogues". The New England Journal of Medicine. 324 (2): 93–103. doi:10.1056/NEJM199101103240205. PMID1984190.
1 2 3 Krakowsky Y, Morgentaler A (January 2019). "Risk of Testosterone Flare in the Era of the Saturation Model: One More Historical Myth". European Urology Focus. 5 (1): 81–89. doi:10.1016/j.euf.2017.06.008. PMID28753828. S2CID10011200.
↑ Emans SJ, Laufer MR (5 January 2012). Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology. Lippincott Williams & Wilkins. pp.365–. ISBN978-1-4511-5406-1. Archived from the original on 16 May 2016. Therapy with GnRH analogs is expensive and requires intramuscular injections of depot formulations, the insert of a subcutaneous implant yearly, or, much less commonly, daily subcutaneous injections.
↑ Jin Y, Penning TM (March 2001). "Steroid 5alpha-reductases and 3alpha-hydroxysteroid dehydrogenases: key enzymes in androgen metabolism". Best Practice & Research. Clinical Endocrinology & Metabolism. 15 (1): 79–94. doi:10.1053/beem.2001.0120. PMID11469812.
↑ Okeigwe I, Kuohung W (December 2014). "5-Alpha reductase deficiency: a 40-year retrospective review". Current Opinion in Endocrinology, Diabetes, and Obesity. 21 (6): 483–487. doi:10.1097/MED.0000000000000116. PMID25321150. S2CID1093345.
↑ Imperato-McGinley J, Zhu YS (December 2002). "Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency". Molecular and Cellular Endocrinology. 198 (1–2): 51–59. doi:10.1016/S0303-7207(02)00368-4. PMID12573814. S2CID54356569.
1 2 3 Bartsch G, Rittmaster RS, Klocker H (April 2000). "Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia". European Urology. 37 (4): 367–380. doi:10.1159/000020181. PMID10765065. S2CID25793400.
1 2 Yamana K, Labrie F, Luu-The V (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. 2 (3): 293–299. doi:10.1515/HMBCI.2010.035. PMID25961201. S2CID28841145.
↑ Traish AM, Krakowsky Y, Doros G, Morgentaler A (January 2019). "Do 5α-Reductase Inhibitors Raise Circulating Serum Testosterone Levels? A Comprehensive Review and Meta-Analysis to Explaining Paradoxical Results". Sexual Medicine Reviews. 7 (1): 95–114. doi:10.1016/j.sxmr.2018.06.002. PMID30098986. S2CID51968365.
↑ Azzouni F, Mohler J (September 2012). "Role of 5α-reductase inhibitors in benign prostatic diseases". Prostate Cancer and Prostatic Diseases. 15 (3): 222–230. doi:10.1038/pcan.2012.1. PMID22333687. S2CID205537645.
1 2 3 Trost L, Saitz TR, Hellstrom WJ (May 2013). "Side Effects of 5-Alpha Reductase Inhibitors: A Comprehensive Review". Sexual Medicine Reviews. 1 (1): 24–41. doi:10.1002/smrj.3. PMID27784557.
1 2 Liu L, Zhao S, Li F, Li E, Kang R, Luo L, etal. (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. 13 (9): 1297–1310. doi:10.1016/j.jsxm.2016.07.006. PMID27475241.
1 2 Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML (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. 8 (3): 872–884. doi:10.1111/j.1743-6109.2010.02157.x. PMID21176115.
1 2 Traish AM (2018). "The Post-finasteride Syndrome: Clinical Manifestation of Drug-Induced Epigenetics Due to Endocrine Disruption". Current Sexual Health Reports. 10 (3): 88–103. doi:10.1007/s11930-018-0161-6. ISSN1548-3584. S2CID81560714.
↑ Traish AM, Melcangi RC, Bortolato M, Garcia-Segura LM, Zitzmann M (September 2015). "Adverse effects of 5α-reductase inhibitors: What do we know, don't know, and need to know?". Reviews in Endocrine & Metabolic Disorders. 16 (3): 177–198. doi:10.1007/s11154-015-9319-y. PMID26296373. S2CID25002351.
1 2 3 4 5 6 7 8 Wierckx K, Gooren L, T'Sjoen G (May 2014). "Clinical review: Breast development in trans women receiving cross-sex hormones". The Journal of Sexual Medicine. 11 (5): 1240–1247. doi:10.1111/jsm.12487. PMID24618412.
↑ Cox DB, Kent JC, Casey TM, Owens RA, Hartmann PE (March 1999). "Breast growth and the urinary excretion of lactose during human pregnancy and early lactation: endocrine relationships". Experimental Physiology. 84 (2): 421–434. doi:10.1017/S0958067099018072. PMID10226182.
1 2 Kronawitter D, Gooren LJ, Zollver H, Oppelt PG, Beckmann MW, Dittrich R, etal. (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. 161 (2): 363–368. doi:10.1530/EJE-09-0265. PMID19497984. S2CID207122869.
1 2 Meyer WJ, Webb A, Stuart CA, Finkelstein JW, Lawrence B, Walker PA (April 1986). "Physical and hormonal evaluation of transsexual patients: a longitudinal study". Archives of Sexual Behavior. 15 (2): 121–138. doi:10.1007/bf01542220. PMID3013122. S2CID42786642.
↑ Mishell DR, Davajan V (1979). Reproductive endocrinology, infertility, and contraception. F. A. Davis Co. p.224. ISBN978-0-8036-6235-3. It has been suggested that progestins be added during the last week of each cycle of estrogen therapy in order to develop more rounded breasts rather than the conical breasts many of these patients develop, but we have been unable to detect any difference in breast contour with or without progestins.
↑ Pasqualini JR (December 2009). "Breast cancer and steroid metabolizing enzymes: the role of progestogens". Maturitas. 65 (Suppl 1): S17–S21. doi:10.1016/j.maturitas.2009.11.006. PMID19962254.
↑ Schindler AE (February 2011). "Dydrogesterone and other progestins in benign breast disease: an overview". Archives of Gynecology and Obstetrics. 283 (2): 369–371. doi:10.1007/s00404-010-1456-7. PMID20383772. S2CID9125889.
↑ Winkler UH, Schindler AE, Brinkmann US, Ebert C, Oberhoff C (December 2001). "Cyclic progestin therapy for the management of mastopathy and mastodynia". Gynecological Endocrinology. 15 (Suppl 6): 37–43. doi:10.1080/gye.15.s6.37.43. PMID12227885. S2CID27589741.
1 2 3 Foss GL (March 1958). "Disturbances of lactation". Clinical Obstetrics and Gynecology. 1 (1): 245–254. doi:10.1097/00003081-195803000-00021. PMID13573669. S2CID42825519. Experimentally I have been able to induce lactogenesis in a male transvestite whose testes had been removed some years before and whose breasts had been well developed over a long period with stilbestrol and ethisterone.9 In July, 1955, 600 mg. of estradiol was implanted subcutaneously and weekly injections of 50 mg. of progesterone were given for four months. For the next month daily injections of 10 mg. estradiol dipropionate and 50 mg. progesterone were given. These injections were continued for another month, increasing progesterone to 100 mg. daily. Both hormones were then withdrawn, and daily injections of increasing doses of prolactin and somatotropin were given for four days; at the same time, the patient used a breast bump four times daily for 5 minutes on both sides. During this time the mammary veins were visibly enlarged and on the sixth and seventh days 1 to 2 cc. of milky fluid was collected.
↑ Worsley R, Santoro N, Miller KK, Parish SJ, Davis SR (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. 13 (3): 283–290. doi:10.1016/j.jsxm.2015.12.014. PMID26944460.
↑ Kuhl H (2011). "Pharmacology of Progestogens"(PDF). Journal für Reproduktionsmedizin und Endokrinologie-Journal of Reproductive Medicine and Endocrinology. 8 (1): 157–177.
1 2 Hermann AC, Nafziger AN, Victory J, Kulawy R, Rocci ML, Bertino JS (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. 45 (6): 614–619. doi:10.1177/0091270005276621. PMID15901742. S2CID28399314.
↑ Tollan A, Oian P, Kjeldsen SE, Eide I, Maltau JM (1993). "Progesterone reduces sympathetic tone without changing blood pressure or fluid balance in men". Gynecologic and Obstetric Investigation. 36 (4): 234–238. doi:10.1159/000292636. PMID8300009.
↑ Unfer V, di Renzo GC, Gerli S, Casini ML (2006). "The Use of Progesterone in Clinical Practice: Evaluation of its Efficacy in Diverse Indications Using Different Routes of Administration". Current Drug Therapy. 1 (2): 211–219. doi:10.2174/157488506776930923. ISSN1574-8855.
1 2 Kozlov GI, Mel'nichenko GA, Golubeva IV (1985). "[Case of galactorrhea in a transsexual male patient]"[Case of galactorrhea in a transsexual male patient]. Problemy Endokrinologii (in Russian). 31 (1): 37–38. PMID4039061. [...] castration and feminizing plastic surgery of the external genitalia was performed [...] Some time after the operation, the patient developed a renewed interest in life. After the surgical and hormonal correction, the patient irresistibly developed maternal instincts. Unmarried, the patient obtained permission for the adoption of a child, simulated pregnancy, and was discharged from the maternity hospital with a son. From the first days after the "birth", galactorrhea sharply increased, and spontaneous outflow of milk appeared, with galactorrhea (+++). The baby was breastfed up to 6 months of age. [...] Our message is the second in the world literature describing galactorrhea in a male patient with transsexualism. The first description of this kind was made in 1983 by R. [Flückiger] et al. (6). This observation demonstrates the independence of the mechanism of lactation development from one's genetic sex and is alarming with regard to the possibility of drug-induced galactorrhea development in men.
↑ Foss GL (January 1956). "Abnormalities of form and function of the human breast". Journal of Endocrinology. 14 (1): R6–R9. Based on the theories of lactogenesis and stimulated by the success of Lyons, Li, Johnson & Cole [1955], who succeeded in producing lactation in male rats, an attempt was made to initiate lactogenesis in a male transvestist. Six years ago this patient had been given oestrogens. Both testes and penis were then removed and an artificial vagina was constructed by plastic surgery. The patient was implanted with 500 mg oestradiol in September 1954, and 600 mg in July 1955. The breasts were then developed more intensively with daily injections of oestradiol dipropionate and progesterone for 6 weeks. Immediately following withdrawal of this treatment, prolactin 22·9 mg was injected daily for 3 days without effect. After a second month on oestradiol and progesterone daily, combined injections of prolactin and somatotrophin were given for 4 days and suction was applied by a breast pump-four times daily. On the 4th and 5th days a few drops of colostrum were expressed from the right nipple.
↑ Gardiner-Hill H (1958). Modern Trends in Endocrinology. Butterworth. p.192. Recently, an attempt has been made by Foss (1956) to initiate lactation in a castrated male transvestist. He was given an implant of 500 milligrams of oestradiol, and 10 months later, a further 600 milligrams of oestradiol, followed by daily injections of oestradiol dipropionate and progesterone for 6 weeks. Immediately after withdrawal of this treatment, 22·9 milligrams of prolactin were injected daily for 3 days but without effect. After a second month of treatment with oestradiol and progesterone daily, he was given combined injections of prolactin and somatotrophin for 4 days, suction with a breast-pump being employed 4 times daily. On the fourth and fifth days a few drops of colostrum were expressed from the right nipple. There is a possible application here of modern hormone knowledge to man, and further trials would be of interest.
↑ Pfeffer CA (2017). Queering Families: The Postmodern Partnerships of Cisgender Women and Transgender Men. Oxford University Press. pp.19–. ISBN978-0-19-990805-9. Just 2 years later, Winfrey would feature another interview that elicited many of the same audience reactions. In this 2010 episode, lesbian partners Dr. Christine McGinn and Lisa Bortz beamed with joy as they held their infant twins. Again, audience members' jaws dropped when it was revealed that beautiful Christine was a male-to-female transsexual who used to be a handsome military officer Chris, and that Lisa had given birth to the couple's biological children using sperm Chris banked prior to gender confirmation surgeries.10 And it was Winfrey's chin that nearly hit the floor as she watched video of Christine breastfeeding the couples' children (the episode is referred to online as "The Mom Who Fathered Her Own Children"). [...]
↑ de Blok C, Klaver M, Nota N, Dekker M, den Heijer M (2016). "Breast development in male-to-female transgender patients after one year cross-sex hormonal treatment". Endocrine Abstracts. 41. doi:10.1530/endoabs.41.GP146. ISSN1479-6848.
1 2 3 4 Klein C, Gorzalka BB (November 2009). "Sexual functioning in transsexuals following hormone therapy and genital surgery: a review". The Journal of Sexual Medicine. 6 (11): 2922–2939. doi:10.1111/j.1743-6109.2009.01370.x. PMID20092545.
1 2 Smith ES, Junger J, Derntl B, Habel U (December 2015). "The transsexual brain--A review of findings on the neural basis of transsexualism". Neuroscience and Biobehavioral Reviews. 59: 251–266. doi:10.1016/j.neubiorev.2015.09.008. PMID26429593. S2CID23913935.
1 2 3 4 Giltay EJ, Gooren LJ (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. 85 (8): 2913–2921. doi:10.1210/jcem.85.8.6710. PMID10946903.
↑ Van Caenegem E, Wierckx K, Taes Y, Schreiner T, Vandewalle S, Toye K, etal. (January 2015). "Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study". Osteoporosis International. 26 (1): 35–47. doi:10.1007/s00198-014-2805-3. PMID25377496. S2CID32758960.
↑ Van Caenegem E, Taes Y, Wierckx K, Vandewalle S, Toye K, Kaufman JM, etal. (May 2013). "Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy". Bone. 54 (1): 92–97. doi:10.1016/j.bone.2013.01.039. PMID23369987.
↑ Motta G, Marinelli L, Barale M, Brustio PR, Manieri C, Ghigo E, etal. (November 2020). "Fracture risk assessment in an Italian group of transgender women after gender-confirming surgery". Journal of Bone and Mineral Metabolism. 38 (6): 885–893. doi:10.1007/s00774-020-01127-9. PMID32691168. S2CID220656777.
↑ Randall VA, Hibberts NA, Thornton MJ, Hamada K, Merrick AE, Kato S, etal. (2000). "The hair follicle: a paradoxical androgen target organ". Hormone Research. 54 (5–6): 243–250. doi:10.1159/000053266 (inactive 1 November 2024). PMID11595812. S2CID42826314.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
↑ Leach NE, Wallis NE, Lothringer LL, Olson JA (May 1971). "Corneal hydration changes during the normal menstrual cycle--a preliminary study". The Journal of Reproductive Medicine. 6 (5): 201–204. PMID5094729.
Henriksson P, Eriksson A, Stege R, Collste L, Pousette A, von Schoultz B, etal. (1988). "Cardiovascular follow-up of patients with prostatic cancer treated with single-drug polyestradiol phosphate". The Prostate. 13 (3): 257–261. doi:10.1002/pros.2990130308. PMID3211807. S2CID20686808.
von Schoultz B, Carlström K, Collste L, Eriksson A, Henriksson P, Pousette A, etal. (1989). "Estrogen therapy and liver function--metabolic effects of oral and parenteral administration". The Prostate. 14 (4): 389–395. doi:10.1002/pros.2990140410. PMID2664738. S2CID21510744.
Asscheman H, Gooren LJ, Eklund PL (September 1989). "Mortality and morbidity in transsexual patients with cross-gender hormone treatment". Metabolism. 38 (9): 869–873. doi:10.1016/0026-0495(89)90233-3. PMID2528051.
Aro J, Haapiainen R, Rasi V, Rannikko S, Alfthan O (1990). "The effect of parenteral estrogen versus orchiectomy on blood coagulation and fibrinolysis in prostatic cancer patients". European Urology. 17 (2): 161–165. doi:10.1159/000464026. PMID2178941.
Henriksson P, Blombäck M, Eriksson A, Stege R, Carlström K (March 1990). "Effect of parenteral oestrogen on the coagulation system in patients with prostatic carcinoma". British Journal of Urology. 65 (3): 282–285. doi:10.1111/j.1464-410X.1990.tb14728.x. PMID2110842.
Aro J (1991). "Cardiovascular and all-cause mortality in prostatic cancer patients treated with estrogens or orchiectomy as compared to the standard population". The Prostate. 18 (2): 131–137. doi:10.1002/pros.2990180205. PMID2006119. S2CID27915767.
Henriksson P, Stege R (1991). "Cost comparison of parenteral estrogen and conventional hormonal treatment in patients with prostatic cancer". International Journal of Technology Assessment in Health Care. 7 (2): 220–225. doi:10.1017/S0266462300005110. PMID1907600. S2CID21957827.
Caine YG, Bauer KA, Barzegar S, ten Cate H, Sacks FM, Walsh BW, etal. (October 1992). "Coagulation activation following estrogen administration to postmenopausal women". Thrombosis and Haemostasis. 68 (4): 392–395. doi:10.1055/s-0038-1646283. PMID1333098. S2CID31885899.
Stege R, Sander S (March 1993). "[Endocrine treatment of prostatic cancer. A renaissance for parenteral estrogen]" [Endocrine treatment of prostatic cancer. A renaissance for parenteral estrogen]. Tidsskrift for den Norske Laegeforening (in Norwegian). 113 (7): 833–835. PMID8480286.
Stege R, Carlström K, Hedlund PO, Pousette A, von Schoultz B, Henriksson P (September 1995). "[Intramuscular depot estrogens (Estradurin) in treatment of patients with prostate carcinoma. Historical aspects, mechanism of action, results and current clinical status]" [Intramuscular depot estrogens (Estradurin) in treatment of patients with prostate carcinoma. Historical aspects, mechanism of action, results and current clinical status]. Der Urologe. Ausg. A (in German). 34 (5): 398–403. PMID7483157.
Henriksson P, Carlström K, Pousette A, Gunnarsson PO, Johansson CJ, Eriksson B, etal. (July 1999). "Time for revival of estrogens in the treatment of advanced prostatic carcinoma? Pharmacokinetics, and endocrine and clinical effects, of a parenteral estrogen regimen". The Prostate. 40 (2): 76–82. doi:10.1002/(SICI)1097-0045(19990701)40:2<76::AID-PROS2>3.0.CO;2-Q. PMID10386467. S2CID12240276.
Hedlund PO, Henriksson P (March 2000). "Parenteral estrogen versus total androgen ablation in the treatment of advanced prostate carcinoma: effects on overall survival and cardiovascular mortality. The Scandinavian Prostatic Cancer Group (SPCG)-5 Trial Study". Urology. 55 (3): 328–333. doi:10.1016/S0090-4295(99)00580-4. PMID10699602.
Hedlund PO, Ala-Opas M, Brekkan E, Damber JE, Damber L, Hagerman I, etal. (2002). "Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer -- Scandinavian Prostatic Cancer Group (SPCG) Study No. 5". Scandinavian Journal of Urology and Nephrology. 36 (6): 405–413. doi:10.1080/003655902762467549. PMID12623503. S2CID2799580.
Scarabin PY, Oger E, Plu-Bureau G (August 2003). "Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk". Lancet. 362 (9382): 428–432. doi:10.1016/S0140-6736(03)14066-4. PMID12927428. S2CID45789951.
Basurto L, Saucedo R, Zárate A, Martínez C, Gaminio E, Reyes E, etal. (2006). "Effect of pulsed estrogen therapy on hemostatic markers in comparison with oral estrogen regimen in postmenopausal women". Gynecologic and Obstetric Investigation. 61 (2): 61–64. doi:10.1159/000088603. PMID16192735. S2CID38375159.
Hedlund PO, Damber JE, Hagerman I, Haukaas S, Henriksson P, Iversen P, etal. (2008). "Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5". Scandinavian Journal of Urology and Nephrology. 42 (3): 220–229. doi:10.1080/00365590801943274. PMID18432528. S2CID38638336.
1 2 3 4 Arnold JD, Sarkodie EP, Coleman ME, Goldstein DA (November 2016). "Incidence of Venous Thromboembolism in Transgender Women Receiving Oral Estradiol". The Journal of Sexual Medicine. 13 (11): 1773–1777. doi:10.1016/j.jsxm.2016.09.001. PMID27671969.
1 2 Streed CG, Harfouch O, Marvel F, Blumenthal RS, Martin SS, Mukherjee M (August 2017). "Cardiovascular Disease Among Transgender Adults Receiving Hormone Therapy: A Narrative Review". Annals of Internal Medicine. 167 (4): 256–267. doi:10.7326/M17-0577. PMID28738421. S2CID207538881.
1 2 Gooren LJ, van Trotsenburg MA, Giltay EJ, van Diest PJ (December 2013). "Breast cancer development in transsexual subjects receiving cross-sex hormone treatment". The Journal of Sexual Medicine. 10 (12): 3129–3134. doi:10.1111/jsm.12319. PMID24010586.
↑ Hartley RL, Stone JP, Temple-Oberle C (October 2018). "Breast cancer in transgender patients: A systematic review. Part 1: Male to female". European Journal of Surgical Oncology. 44 (10): 1455–1462. doi:10.1016/j.ejso.2018.06.035. PMID30087072. S2CID51936024.
↑ Schoemaker MJ, Swerdlow AJ, Higgins CD, Wright AF, Jacobs PA (March 2008). "Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study". The Lancet. Oncology. 9 (3): 239–246. doi:10.1016/S1470-2045(08)70033-0. PMID18282803.
↑ Casado JC, Rodríguez-Parra MJ, Adrián JA (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. 274 (4): 2049–2058. doi:10.1007/s00405-016-4420-8. PMID27942897. S2CID24231820.
↑ Nolan IT, Morrison SD, Arowojolu O, Crowe CS, Massie JP, Adler RK, etal. (July 2019). "The Role of Voice Therapy and Phonosurgery in Transgender Vocal Feminization". The Journal of Craniofacial Surgery. 30 (5): 1368–1375. doi:10.1097/SCS.0000000000005132. PMID31299724. S2CID59303952.
1 2 Mahfouda S, Moore JK, Siafarikas A, Hewitt T, Ganti U, Lin A, etal. (June 2019). "Gender-affirming hormones and surgery in transgender children and adolescents". The Lancet. Diabetes & Endocrinology. 7 (6): 484–498. doi:10.1016/S2213-8587(18)30305-X. PMID30528161. S2CID54478571.
↑ Bisson JR, Chan KJ, Safer JD (July 2018). "Prolactin Levels do Not Rise Among Transgender Women Treated with Estradiol and Spironolactone". Endocrine Practice. 24 (7): 646–651. doi:10.4158/EP-2018-0101. PMID29708436. S2CID14022275.
1 2 Hamburger C, Sturup GK, Dahl-Iversen E (May 1953). "Transvestism; hormonal, psychiatric, and surgical treatment". Journal of the American Medical Association. 152 (5): 391–396. doi:10.1001/jama.1953.03690050015006. PMID13044539.
1 2 3 Gooren L, Asscheman H (2014). "Sex Reassignment: Endocrinological Interventions in Adults with Gender Dysphoria". Gender Dysphoria and Disorders of Sex Development. Focus on Sexuality Research. Springer. pp.277–297. doi:10.1007/978-1-4614-7441-8_14. ISBN978-1-4614-7440-1. ISSN2195-2264.
1 2 3 Hamburger C, Benjamin H (1969). "Endocrine Treatment of Male and Female Transsexualism / Appendix for the Practicing Physician: Suggestions and Guidelines for the Management of Transsexuals". In Money J, Green R (eds.). Transsexualism and Sex Reassignment. Johns Hopkins Press. pp.291–307. ISBN9780801810381. OCLC6866559.
↑ Schaefer LC, Wheeler CC (February 1995). "Harry Benjamin's first ten cases (1938-1953): a clinical historical note". Archives of Sexual Behavior. 24 (1): 73–93. doi:10.1007/bf01541990. PMID7733806. S2CID31571764.
↑ Benjamin H, Ihlenfeld CL (November 1970). "The nature and treatment of transsexualism". Medical Opinion and Review. 6 (11): 24–35. Fortunately, the first medical textbook in this field, Transsexualism and Sex Reassignment, edited by Richard Green and John Money (Johns Hopkins Press, Baltimore, 1969), is now available
1 2 3 4 Prior JC, Vigna YM, Watson D (February 1989). "Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism". Archives of Sexual Behavior. 18 (1): 49–57. doi:10.1007/BF01579291. PMID2540730. S2CID22802329.
1 2 3 Prior JC, Vigna YM, Watson D, Diewold P, Robinow O. "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 (1): 1–7.
↑ Zingg E, König MP, Cornu F, Wildholz A, Blaser A (1980). "Transsexualismus: Erfahrungen mit der operativen Korrektur bei männlichen Transsexuellen" [Transsexualism: Experience with surgical correction in male transsexuals]. Aktuelle Urologie. 11 (2): 67–77. doi:10.1055/s-2008-1062961. ISSN0001-7868. S2CID56512058.
1 2 Jequier AM, Bullimore NJ, Bishop MJ (1989). "Cyproterone acetate and a small dose of oestrogen in the pre-operative management of male transsexuals. A report of three cases". Andrologia. 21 (5): 456–461. doi:10.1111/j.1439-0272.1989.tb02447.x. PMID2530920. S2CID30370123.
↑ Kuiper AJ, Cohen-Kettenis PT, Van der Reyt F (1985). "Transsexuality in The Netherlands. Some medical and legal aspects". Medicine and Law. 4 (4): 373–378. PMID3900616.
↑ Dahl M, Feldman JL, Goldberg JM, Jaberi A (2006). "Physical Aspects of Transgender Endocrine Therapy". International Journal of Transgenderism. 9 (3–4): 111–134. doi:10.1300/J485v09n03_06. ISSN1553-2739. S2CID146232471.
↑ 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.
↑ Chekir C, Emi Y, Arai F, Kikuchi Y, Sasaki A, Matsuda M, etal. (June 2012). "Altered arterial stiffness in male-to-female transsexuals undergoing hormonal treatment". The Journal of Obstetrics and Gynaecology Research. 38 (6): 932–940. doi:10.1111/j.1447-0756.2011.01815.x. PMID22487218. S2CID39877004. Estrogen is given to MTF transsexuals orally as conjugated estrogens, or 17b-estradiol, as transdermal estrogen, or as parenteral estrogen esters to feminize the body.5 There is no evidence that progestin has beneficial effects on treatment with estrogen in MTF transsexuals; however, progestins were administered to some of MTF transsexuals. Because administration of antiandrogen to MTF transsexuals is not common in Japan, we could exclude the modification with antiandrogen in the present study.
Gooren LJ (March 2011). "Clinical practice. Care of transsexual persons". The New England Journal of Medicine. 364 (13): 1251–1257. doi:10.1056/NEJMcp1008161. PMID21449788.
Gooren LJ, Giltay EJ, Bunck MC (January 2008). "Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience". The Journal of Clinical Endocrinology and Metabolism. 93 (1): 19–25. doi:10.1210/jc.2007-1809. PMID17986639.
Wesp LM, Deutsch MB (March 2017). "Hormonal and Surgical Treatment Options for Transgender Women and Transfeminine Spectrum Persons". The Psychiatric Clinics of North America. 40 (1): 99–111. doi:10.1016/j.psc.2016.10.006. PMID28159148.
Wierckx K, Gooren L, T'Sjoen G (May 2014). "Clinical review: Breast development in trans women receiving cross-sex hormones". The Journal of Sexual Medicine. 11 (5): 1240–1247. doi:10.1111/jsm.12487. PMID24618412.
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