View source for Category:Sex hormones

A '''sex hormone''' is a steroid hormone produced principally by the gonads, the ovary and the testis, with significant secondary production by the adrenal cortex. The category covers the [[:Category:Estrogens|estrogens]] and [[:Category:Progestins|progestins]] of the ovarian cycle and of pregnancy, the testosterone and dihydrotestosterone of the male reproductive system, and the synthetic analogues and receptor modulators developed across the twentieth century for contraception, for replacement at menopause and at andropause, for assisted reproduction, and for the treatment of hormone-responsive cancers, [[wikipedia:Endometriosis|endometriosis]], [[wikipedia:Polycystic ovary syndrome|polycystic ovary syndrome]], and the [[wikipedia:Gender dysphoria|gender-related medical care]] of transgender adults.

The pharmacological history begins, oddly, with a self-experiment by an eminent physiologist nearing the end of his career. On 1 June 1889 [[wikipedia:Charles-Édouard Brown-Séquard|Charles-Édouard Brown-Séquard]], aged seventy-two and Professor at the [[wikipedia:Collège de France|Collège de France]], presented to the [[wikipedia:Société de Biologie|Société de Biologie]] in Paris an account of self-injection with an emulsion of macerated dog and guinea-pig testes; he reported substantially improved strength, mental clarity, urinary stream, and conjugal performance.<ref name="brownsequard1889">Brown-Séquard CE. The effects produced on man by subcutaneous injections of a liquid obtained from the testicles of animals. ''Lancet''. 1889 Jul 20;134(3438):105-107.</ref> The improvements were largely placebo, but the report excited the public imagination, organotherapy preparations were marketed across Europe and North America for the next thirty years, and the modern endocrine pharmacology of the gonads dates from that lecture.

The chemical isolation of the ovarian hormones occupied the next half-century. In 1923 the American gynecologist [[wikipedia:Edgar Allen (anatomist)|Edgar Allen]] and the biochemist [[wikipedia:Edward Doisy|Edward Doisy]] at the [[wikipedia:Washington University in St. Louis|Washington University]] in St Louis identified, in the follicular fluid of sow ovaries, a fat-soluble substance that produced cornification of the vaginal epithelium of ovariectomised mice; the assay became standard for estrogen activity and remained so for thirty years.<ref name="allen1923">Allen E, Doisy EA. An ovarian hormone: preliminary report on its localization, extraction, partial purification, and action in test animals. ''JAMA''. 1923 Sep 8;81(10):819-821.</ref> Doisy crystallised the principal ovarian estrogen, [[wikipedia:Estrone|estrone]], in 1929; he received the Nobel Prize in 1943, though chiefly for the parallel isolation of vitamin K. The progestational hormone was isolated independently in 1929-1934 by four groups (Corner and Allen in the United States, Slotta in Germany, Butenandt in Berlin, and Hartmann and Wettstein at Ciba), and named [[Progesterone|progesterone]] in 1935. [[wikipedia:Adolf Butenandt|Adolf Butenandt]] at the [[wikipedia:Kaiser Wilhelm Institute|Kaiser Wilhelm Institute]] in Berlin and [[wikipedia:Leopold Ružička|Leopold Ružička]] at the ETH in Zürich worked out the four-ring steroid skeleton common to all the sex and adrenal hormones, sharing the 1939 Nobel Prize in Chemistry (Butenandt was forced by the Nazi regime to decline).

The synthesis problem was the same one that constrained the corticosteroid story. Progesterone, harvested from animal ovaries, cost two hundred dollars a gram in 1939. The Pennsylvania chemist [[wikipedia:Russell Earl Marker|Russell Marker]], later working in Mexico, identified ''[[wikipedia:Dioscorea mexicana|Dioscorea mexicana]]'' (the Mexican wild yam, locally called ''cabeza de negro'') as a source of diosgenin in industrial quantity, and developed a five-step degradation to progesterone that dropped the price to a dollar by 1947. Marker founded [[wikipedia:Syntex|Syntex]] on the discovery, then quarrelled with his partners and left abruptly, taking his synthesis routes with him; the Austrian chemist [[wikipedia:Carl Djerassi|Carl Djerassi]] joined Syntex in 1949 and, with [[wikipedia:Luis E. Miramontes|Luis Miramontes]] and [[wikipedia:George Rosenkranz|George Rosenkranz]], synthesised on 15 October 1951 the first orally active progestational steroid, [[Norethindrone|norethindrone]] (norethisterone).<ref name="djerassi1951sex">Djerassi C, Miramontes L, Rosenkranz G, Sondheimer F. Steroids. LIV. Synthesis of 19-nor-17α-ethynyltestosterone and 19-nor-17α-methyltestosterone. ''Journal of the American Chemical Society''. 1954;76(16):4092-4094.</ref> Within a decade norethindrone, combined with the synthetic estrogen mestranol, was approved by the U.S. Food and Drug Administration as Enovid in 1960 as the first oral contraceptive. The contraceptive pill is generally considered the most consequential medicine of the twentieth century in its social as much as in its medical effects.

Testosterone followed a similar arc. Crystalline testosterone was isolated in 1935 by [[wikipedia:Karoly Gyula David|Karoly David]] in Amsterdam, named, and synthesised within months by Butenandt and by Ružička independently. The first clinical use, for hypogonadism and for postmenopausal libido restoration, dates from the late 1930s; the medicine was administered first as an oily intramuscular injection and later as transdermal gel and patch, transbuccal preparation, intranasal spray, and short-acting and long-acting injectable esters (testosterone enanthate, cypionate, undecanoate). The selective androgen-receptor modulators (SARMs), pursued since the 1990s as potential prostate-sparing alternatives, have not yet produced an approved medicine in the United States.

The receptor pharmacology was elucidated only in the 1960s and after. [[wikipedia:Elwood V. Jensen|Elwood Jensen]] at the University of Chicago demonstrated in 1958 the presence of a specific intracellular estrogen-binding protein in target tissues and developed the receptor concept that has since shaped the entire field of nuclear-receptor biology; the cloning of the estrogen, progesterone, androgen, and glucocorticoid receptors in the 1980s by [[wikipedia:Pierre Chambon|Pierre Chambon]] and others completed the molecular picture. The selective estrogen-receptor modulators ([[Tamoxifen|tamoxifen]], originally a failed contraceptive that proved to be an effective treatment for hormone-receptor-positive breast cancer; raloxifene, used in osteoporosis prevention) and the [[:Category:Aromatase_inhibitors|aromatase inhibitors]] (anastrozole, letrozole, exemestane, which block peripheral conversion of androgen to estrogen) extended the pharmacology in the oncologic direction. The selective progesterone-receptor modulator [[wikipedia:Mifepristone|mifepristone]] (Roussel-Uclaf, 1980) is used in early pregnancy termination and in the management of Cushing's syndrome. The [[:Category:Antiandrogens|antiandrogens]] [[wikipedia:Bicalutamide|bicalutamide]], [[wikipedia:Enzalutamide|enzalutamide]], and abiraterone, and the gonadotropin-releasing hormone agonists and antagonists, treat prostate cancer by ablation of the androgen signal at every accessible step of its production and recognition.

The contemporary clinical use of the sex hormones is dominated by a handful of large indications: combined oral contraception (estrogen plus progestin) and progestin-only contraception (the mini-pill, depot medroxyprogesterone, the levonorgestrel intrauterine system, the etonogestrel subdermal implant), menopausal hormone therapy (transdermal estradiol with a progestin if the uterus is intact, since the [[wikipedia:Women's Health Initiative|Women's Health Initiative]] trial in 2002 substantially redefined the risk-benefit balance of long-term combined oral hormone replacement), male hypogonadism (testosterone replacement of various routes), gender-affirming hormonal therapy for transgender adults, treatment of endometriosis (combined contraceptives, GnRH agonists with add-back, dienogest, the GnRH antagonist [[wikipedia:Elagolix|elagolix]]), polycystic ovary syndrome (combined contraceptives, antiandrogens including [[wikipedia:Spironolactone|spironolactone]]), and the breast and prostate cancer chemotherapies above.

== Classes indexed ==

By category:

* [[:Category:Estrogens|Estrogens]]: [[Estradiol|estradiol]] (the principal endogenous and most-prescribed bioidentical estrogen), conjugated equine estrogens, [[wikipedia:Ethinylestradiol|ethinylestradiol]] (the synthetic estrogen of most combined oral contraceptives), [[wikipedia:Mestranol|mestranol]]
* [[:Category:Progestins|Progestins]] and [[:Category:Progestogens|progestogens]] (the natural hormone and its synthetic analogues): [[Progesterone|progesterone]] (bioidentical), [[Norethindrone|norethindrone]], [[Medroxyprogesterone|medroxyprogesterone]] (also as the depot intramuscular contraceptive), levonorgestrel, desogestrel, drospirenone, dienogest
* Androgens and androgen modulators: [[wikipedia:Testosterone|testosterone]] and its esters; [[Finasteride|finasteride]] and [[Dutasteride|dutasteride]] (5α-reductase inhibitors, also indexed under [[:Category:5-alpha-reductase_inhibitors|5α-reductase inhibitors]]); selective androgen-receptor modulators (research, no approved agents)
* [[:Category:Antiandrogens|Antiandrogens]]: [[wikipedia:Bicalutamide|bicalutamide]], [[wikipedia:Enzalutamide|enzalutamide]], [[wikipedia:Abiraterone|abiraterone]], [[wikipedia:Cyproterone|cyproterone acetate]], [[wikipedia:Spironolactone|spironolactone]] (the mineralocorticoid antagonist's secondary antiandrogen activity is used in polycystic ovary syndrome and gender-affirming care)
* Selective estrogen-receptor modulators: [[Tamoxifen|tamoxifen]], [[wikipedia:Raloxifene|raloxifene]], [[wikipedia:Ospemifene|ospemifene]], [[wikipedia:Bazedoxifene|bazedoxifene]]
* [[:Category:Aromatase_inhibitors|Aromatase inhibitors]] (peripheral estrogen-biosynthesis blockade): [[wikipedia:Anastrozole|anastrozole]], [[wikipedia:Letrozole|letrozole]], [[wikipedia:Exemestane|exemestane]]
* Gonadotropin-releasing hormone agonists and antagonists (centrally acting on the hypothalamic-pituitary axis): [[wikipedia:Leuprolide|leuprolide]], [[wikipedia:Goserelin|goserelin]], [[wikipedia:Triptorelin|triptorelin]] (agonists); [[wikipedia:Degarelix|degarelix]], [[wikipedia:Elagolix|elagolix]], relugolix (antagonists)
* Progesterone-receptor antagonists and modulators: [[wikipedia:Mifepristone|mifepristone]], [[wikipedia:Ulipristal|ulipristal acetate]]
* [[:Category:Hormonal_contraceptives|Hormonal contraceptives]] (collected separately): combined oral, progestin-only oral, depot medroxyprogesterone, the levonorgestrel intrauterine system, the etonogestrel subdermal implant, the combined transdermal patch and vaginal ring

== Notes on scope ==

The boundary of this category is "medicine consisting of, or derived from, an endogenous gonadal steroid hormone or its receptor-modulating analogue." The adrenal corticosteroids are collected separately under [[:Category:Corticosteroids|corticosteroids]] despite their common steroid skeleton. The peptide hormones of the hypothalamic-pituitary-gonadal axis (gonadotropin-releasing hormone, the gonadotropins follicle-stimulating hormone and luteinising hormone, prolactin) are listed under [[:Category:Hormones|hormones]] in the broader sense and are indexed here when their indication involves sex-hormone-pathway modulation. The thyroid hormones and the parathyroid hormone, although hormones, are not sex hormones and are collected under [[:Category:Thyroid_hormones|thyroid hormones]] and elsewhere. The anabolic-androgenic steroids of athletic doping are mentioned briefly on the testosterone-derivative pages for their safety implications but are not collected here as a clinical category.

== About these pages ==

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.

== References ==

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[[Category:Medicines]]
[[Category:Hormones]]
[[Category:Endocrine_therapy]]
[[Category:CuratedCategoryPage]]