5α-Reductase inhibitors are inhibitors of the enzyme 5α-reductase, and are a type of specific androgen synthesis inhibitor.[184][185] 5α-Reductase is an enzyme that is responsible for the conversion of testosterone into the more potent androgen dihydrotestosterone (DHT).[184][185] There are three different isoforms of 5α-reductase, types 1, 2, and 3, and these three isoforms show different patterns of expression in the body.[184] Relative to testosterone, DHT is about 2.5- to 10-fold more potent as an agonist of the androgen receptor.[184][185][186] As such, 5α-reductase serves to considerably potentiate the effects of testosterone.[184][185] However, 5α-reductase is expressed only in specific tissues, such as skin, hair follicles, and the prostate gland, and for this reason, conversion of testosterone into DHT happens only in certain parts of the body.[184][185][187] Furthermore, circulating levels of total and free DHT in men are very low at about one-tenth and one-twentieth those of testosterone, respectively,[185][188][184] and DHT is efficiently inactivated into weak androgens in various tissues such as muscle, fat, and liver.[184][166][189] As such, it is thought that DHT plays little role as a systemic androgen hormone and serves more as a means of locally potentiating the androgenic effects of testosterone in a tissue-specific manner.[184][190][191] Conversion of testosterone into DHT by 5α-reductase plays an important role in male reproductive system development and maintenance (specifically of the penis, scrotum, prostate gland, and seminal vesicles), male-pattern facial/body hair growth, and scalp hair loss, but has little role in other aspects of masculinization.[184][185][187][192][193] Besides the involvement of 5α-reductase in androgen signaling, it is also required for the conversion of steroid hormones such as progesterone and testosterone into neurosteroids like allopregnanolone and 3α-androstanediol, respectively.[194][195]
One of the first transgender health clinics was opened in the mid-1960s at the Johns Hopkins School of Medicine.[379][90] By 1981, there were almost 40 such centers.[380] A review of the hormonal regimens of 20 of the centers was published that year.[369][380] The first International Symposium on Gender Identity, chaired by Christopher John Dewhurst, was held in London in 1969,[381] and the first medical textbook on transgenderism, titled Transsexualism and Sex Reassignment and edited by Richard Green and John Money, was published by Johns Hopkins University Press in 1969.[382][383] This textbook included a chapter on hormone therapy written by Christian Hamburger and Harry Benjamin.[374] The Harry Benjamin International Gender Dysphoria Association (HBIGDA), now known as the World Professional Association for Transgender Health (WPATH), was formed in 1979, with the first version of the Standards of Care published the same year.[365] The Endocrine Society published guidelines for the hormonal care of transgender people in 2009, with a revised version in 2017.[369][384][1]
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