Dihydrotestosterone: Difference between revisions

{{Short description|Human hormone}}

{{About|dihydrotestosterone as a hormone|its use as a medication|Androstanolone}}

{{About|5α-dihydrotestosterone, an androgen|the inactive 5β isomer|5β-Dihydrotestosterone}}

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{{Use dmy dates|date=December 2023}}

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<!-- Images -->

| ImageFile1 = Androstanolone.svg

| ImageSize1 = 225px

| ImageAlt1 = The chemical structure of dihydrotestosterone.

| ImageFile2 = Dihydrotestosterone molecule ball.png

| ImageSize2 = 225px

| ImageAlt2 = A ball-and-stick model of dihydrotestosterone.

<!-- Names -->

| IUPACName = 17β-Hydroxy-5α-androstan-3-one

| SystematicName = (1''S'',3a''S'',3b''R'',5a''S'',9a''S'',9b''S'',11a''S'')-1-Hydroxy-9a,11a-dimethylhexadecahydro-7''H''-cyclopenta[''a'']phenanthren-7-one

| OtherNames = DHT; 5α-Dihydrotestosterone; 5α-DHT; Androstanolone; Stanolone; 5α-Androstan-17β-ol-3-one

| verifiedrevid = 459443200

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| Section1 = {{Chembox Identifiers

| CASNo_Ref = {{cascite|correct|??}}

| CASNo = 521-18-6

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 16330

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 27769

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 10189

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB02901

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = C03917

| PubChem = 10635

| SMILES = O=C4C[C@@H]3CC[C@@H]2[C@H](CC[C@]1(C)[C@@H](O)CC[C@H]12)[C@@]3(C)CC4

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C19H30O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h12,14-17,21H,3-11H2,1-2H3/t12-,14-,15-,16-,17-,18-,19-/m0/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = NVKAWKQGWWIWPM-ABEVXSGRSA-N

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 08J2K08A3Y

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| Section2 = {{Chembox Properties

| C=19 | H=30 | O=2

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| Section6 = {{Chembox Pharmacology

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| ATCCode_prefix = A14

| ATCCode_suffix = AA01

| ATC_Supplemental =

| AdminRoutes = [[Transdermal]] ([[gel]]), [[buccal administration|in the cheek]], [[sublingual administration|under the tongue]], [[intramuscular injection]] (as [[Androgen ester#Dihydrotestosterone esters|ester]]s)

| Bioavail = [[Oral administration|Oral]]: very low (due to extensive [[first pass effect|first pass metabolism]])<ref name="pmid9365393">{{cite journal | vauthors = Coutts SB, Kicman AT, Hurst DT, Cowan DA | title = Intramuscular administration of 5 alpha-dihydrotestosterone heptanoate: changes in urinary hormone profile | journal = Clinical Chemistry | volume = 43 | issue = 11 | pages = 2091–2098 | date = November 1997 | pmid = 9365393 | doi = 10.1093/clinchem/43.11.2091 | doi-access = free }}</ref>

| Excretion =

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'''Dihydrotestosterone''' ('''DHT''', '''5α-dihydrotestosterone''', '''5α-DHT''', '''androstanolone''' or '''stanolone''') is an [[endogenous]] [[androgen]] [[sex steroid]] and [[steroid hormone|hormone]] primarily involved in the growth and repair of the [[prostate]] and the [[penis]], as well as the production of [[sebum]] and [[body hair]] composition.

The [[enzyme]] [[5α-reductase]] catalyzes the [[biosynthesis|formation]] of DHT from [[testosterone]] in certain [[tissue (biology)|tissue]]s including the [[prostate gland]], [[seminal vesicles]], [[epididymis|epididymides]], [[skin]], [[hair follicle]]s, [[liver]], and [[brain]]. This enzyme mediates reduction of the C4-5 [[double bond]] of testosterone. DHT may also be synthesized from [[progesterone]] and [[17α-hydroxyprogesterone]] via the [[androgen backdoor pathway]] in the absence of testosterone. Relative to testosterone, DHT is considerably more potent as an [[agonist]] of the [[androgen receptor]] (AR).

In addition to its role as a natural hormone, DHT has been used as a [[medication]], for instance in the treatment of [[hypogonadism|low testosterone levels in men]]; for information on DHT as a medication, see the [[androstanolone]] article.

{{TOC limit|3}}

==Biological function==

DHT is biologically important for [[sexual differentiation]] of the [[male genitalia]] during [[embryogenesis]], maturation of the penis and scrotum at [[puberty]], [[hair growth|growth]] of [[facial hair|facial]], [[body hair|body]], and [[pubic hair]], and development and maintenance of the [[Prostate|prostate gland]] and [[seminal vesicles]]. It is produced from the less potent [[testosterone]] by the [[enzyme]] [[5α-reductase]] in select tissues, and is the primary androgen in the genitals, [[Prostate|prostate gland]], [[seminal vesicles]], [[skin]], and [[hair follicle]]s.<ref name="pmid16985920" />

DHT signals act mainly in an [[intracrine]] and [[paracrine]] manner in the tissues in which it is produced, playing only a minor role, if any, as a circulating [[endocrine]] hormone.<ref name="pmid1551803">{{cite journal | vauthors = Horton R | title = Dihydrotestosterone is a peripheral paracrine hormone | journal = Journal of Andrology | volume = 13 | issue = 1 | pages = 23–27 | year = 1992 | pmid = 1551803 | doi = 10.1002/j.1939-4640.1992.tb01621.x | doi-access = free }}</ref><ref name="pmid8630237">{{cite journal | vauthors = Wilson JD | title = Role of dihydrotestosterone in androgen action | journal = The Prostate. Supplement | volume = 6 | issue = S6 | pages = 88–92 | year = 1996 | pmid = 8630237 | doi = 10.1002/(SICI)1097-0045(1996)6+<88::AID-PROS17>3.0.CO;2-N | s2cid = 41352599 }}</ref><ref name="pmid28472278">{{cite journal | vauthors = Swerdloff RS, Dudley RE, Page ST, Wang C, Salameh WA | title = Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels | journal = Endocrine Reviews | volume = 38 | issue = 3 | pages = 220–254 | date = June 2017 | pmid = 28472278 | pmc = 6459338 | doi = 10.1210/er.2016-1067 }}</ref> Circulating levels of DHT are one-tenth and one-twentieth those of testosterone in terms of total and free concentrations, respectively,<ref name="Bhasin1996">{{cite book | vauthors = Bhasin S |title=Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects|url=https://books.google.com/books?id=hurRyWje4DMC&pg=PA72|year=1996|publisher=John Wiley & Sons|isbn=978-0-471-13320-9|pages=72–}}</ref> whereas local DHT levels may be up to 10&nbsp;times those of testosterone in tissues with high 5α-reductase expression such as the prostate gland.<ref name="HayWass2009" /> In addition, unlike testosterone, DHT is inactivated by [[3α-Hydroxysteroid dehydrogenase|3α-hydroxysteroid dehydrogenase]] (3α-HSD) into the very weak androgen [[3α-Androstanediol|3α-androstanediol]] in various [[tissue (biology)|tissue]]s such as [[muscle]], [[adipose tissue|adipose]], and [[liver]] among others,<ref name="pmid28472278" /><ref name="Melmed2016" /><ref name="pmid11469812">{{cite journal | vauthors = Jin Y, Penning TM | title = Steroid 5alpha-reductases and 3alpha-hydroxysteroid dehydrogenases: key enzymes in androgen metabolism | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 15 | issue = 1 | pages = 79–94 | date = March 2001 | pmid = 11469812 | doi = 10.1053/beem.2001.0120 }}</ref> and in relation to this, DHT has been reported to be a very poor [[anabolic]] agent when administered exogenously as a medication.<ref name="Llewellyn2009">{{cite book|vauthors=Llewellyn W|title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC|year=2009|publisher=Molecular Nutrition Llc|isbn=978-0-9679304-7-3|pages=19, 163|access-date=6 November 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110191245/https://books.google.com/books?id=afKLA-6wW0oC|url-status=live}}</ref>

{| class="wikitable"

|+ Selective biological functions of testosterone versus DHT in male puberty<ref name="Chang2002">{{cite book | vauthors = Chang C |title=Androgens and Androgen Receptor: Mechanisms, Functions, and Clinical Applications|url=https://books.google.com/books?id=ODBLQc2BdDIC&pg=PA451|date=2002|publisher=Springer Science & Business Media|isbn=978-1-4020-7188-1|pages=451–}}</ref><ref name="pmid23431485">{{cite journal | vauthors = Marchetti PM, Barth JH | title = Clinical biochemistry of dihydrotestosterone | journal = Annals of Clinical Biochemistry | volume = 50 | issue = Pt 2 | pages = 95–107 | date = March 2013 | pmid = 23431485 | doi = 10.1258/acb.2012.012159 | s2cid = 8325257 | doi-access = free }}</ref>

|-

! Testosterone !! DHT

|-

| Spermatogenesis and fertility || Prostate enlargement and prostate cancer risk

|-

| Male musculoskeletal development || Facial, axillary, pubic, and body hair growth

|-

| Voice deepening || Scalp temporal recession and pattern hair loss

|-

| Increased sebum production and acne ||

|-

| Increased sex drive and erections ||

|}

In addition to normal biological functions, DHT also plays an important causative role in a number of [[androgen-dependent condition]]s including hair conditions like [[hirsutism]] (excessive facial/body hair growth) and [[pattern hair loss]] (androgenic alopecia or pattern baldness) and [[prostate disease]]s such as [[benign prostatic hyperplasia]] (BPH) and [[prostate cancer]].<ref name="pmid16985920" /> [[5α-Reductase inhibitor]]s, which prevent DHT synthesis, are effective in the prevention and treatment of these conditions.<ref name="Blume-PeytaviWhiting2008" /><ref name="pmid22333687">{{cite journal | vauthors = Azzouni F, Mohler J | title = Role of 5α-reductase inhibitors in benign prostatic diseases | journal = Prostate Cancer and Prostatic Diseases | volume = 15 | issue = 3 | pages = 222–230 | date = September 2012 | pmid = 22333687 | doi = 10.1038/pcan.2012.1 | s2cid = 205537645 | doi-access = free }}</ref><ref name="pmid22446342" /><ref name="KatsambasLotti2015" /> Androgen deprivation is a therapeutic approach to prostate cancer that can be implemented by castration to eliminate gonadal testosterone as a precursor to DHT, but metastatic tumors may then develop into castration-resistant prostate cancer (CRPC). Although castration results in 90-95% decrease of serum testosterone, DHT in the prostate is only decreased by 50%, supporting the notion that the prostate expresses necessary enzymes (including 5α-reductase) to produce DHT without testicular testosterone,<ref name=wj/> that outline the importance of 5α-reductase inhibitors.<ref name="pmid22333687"/>

DHT may play a function in skeletal muscle amino acid transporter recruitment and function.<ref name="pmid27239418">{{cite journal | vauthors = Wendowski O, Redshaw Z, Mutungi G | title = Dihydrotestosterone treatment rescues the decline in protein synthesis as a result of sarcopenia in isolated mouse skeletal muscle fibres | journal = Journal of Cachexia, Sarcopenia and Muscle | volume = 8 | issue = 1 | pages = 48–56 | date = February 2017 | pmid = 27239418 | pmc = 4863930 | doi = 10.1002/jcsm.12122 }}</ref>

[[Metabolite]]s of DHT have been found to act as [[neurosteroid]]s with their own AR-independent biological activity.<ref name="pmid22231829">{{cite book | vauthors = Kohtz AS, Frye CA | chapter = Dissociating Behavioral, Autonomic, and Neuroendocrine Effects of Androgen Steroids in Animal Models | title = Psychiatric Disorders | volume = 829 | pages = 397–431 | year = 2012 | pmid = 22231829 | doi = 10.1007/978-1-61779-458-2_26 | series = Methods in Molecular Biology | publisher = Springer | isbn = 978-1-61779-457-5 }}</ref> [[3α-Androstanediol]] is a potent [[positive allosteric modulator]] of the [[GABAA receptor|GABA_A receptor]], while [[3β-androstanediol]] is a potent and [[binding selectivity|selective]] agonist of the [[estrogen receptor]] (ER) subtype [[ERβ]].<ref name="pmid22231829" /> These metabolites may play important roles in the [[central nervous system|central]] effects of DHT and by extension testosterone, including their [[antidepressant]], [[anxiolytic]], [[reward system|rewarding]]/[[hedonism|hedonic]], [[anti-stress]], and [[nootropic|pro-cognitive]] effects.<ref name="pmid22231829" /><ref name="pmid26259885">{{cite journal | vauthors = Brunton PJ | title = Neuroactive steroids and stress axis regulation: Pregnancy and beyond | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 160 | pages = 160–168 | date = June 2016 | pmid = 26259885 | doi = 10.1016/j.jsbmb.2015.08.003 | s2cid = 43499796 }}</ref>

===5α-Reductase 2 deficiency===

{{See also|5α-Reductase 2 deficiency}}

Much of the biological role of DHT has been elucidated in studies of individuals with [[congenital]] [[5α-reductase deficiency|5α-reductase type 2 deficiency]], an [[intersex condition]] caused by a [[loss-of-function mutation]] in the [[gene]] encoding [[5α-reductase type 2]], the major enzyme responsible for the production of DHT in the body.<ref name="Blume-PeytaviWhiting2008">{{cite book|vauthors=Blume-Peytavi U, Whiting DA, Trüeb RM|title=Hair Growth and Disorders|url=https://books.google.com/books?id=pHrX2-huQCoC&pg=PA161|date=2008|publisher=Springer Science & Business Media|isbn=978-3-540-46911-7|pages=161–62|access-date=27 September 2016|archive-date=11 January 2023|archive-url=https://web.archive.org/web/20230111121853/https://books.google.com/books?id=pHrX2-huQCoC&pg=PA161|url-status=live}}</ref><ref name="pmid25321150">{{cite journal | vauthors = Okeigwe I, Kuohung W | title = 5-Alpha reductase deficiency: a 40-year retrospective review | journal = Current Opinion in Endocrinology, Diabetes, and Obesity | volume = 21 | issue = 6 | pages = 483–487 | date = December 2014 | pmid = 25321150 | doi = 10.1097/MED.0000000000000116 | s2cid = 1093345 }}</ref><ref name="pmid16985920">{{cite journal | vauthors = Marks LS | title = 5alpha-reductase: history and clinical importance | journal = Reviews in Urology | volume = 6 | issue = Suppl 9 | pages = S11–S21 | year = 2004 | pmid = 16985920 | pmc = 1472916 }}</ref> It is characterized by a defective and non-functional 5α-reductase type 2 enzyme and a partial but majority loss of DHT production in the body.<ref name="Blume-PeytaviWhiting2008" /><ref name="pmid25321150" /> In the condition, circulating testosterone levels are within or slightly above the normal male range, but DHT levels are low (around 30% of normal),<ref name="HeesakkersChapple2016" />{{Better source needed|date=July 2017}} and the ratio of circulating testosterone to DHT is greatly elevated (at about 3.5 to 5&nbsp;times higher than normal).<ref name="Blume-PeytaviWhiting2008" />

Genetic males (46,XY) with 5α-reductase type 2 deficiency are born with [[undervirilization]] including [[pseudohermaphroditism]] (ambiguous genitalia), [[pseudovaginal perineoscrotal hypospadias]], and usually [[cryptorchidism|undescended testes]]. Their external genitalia are female-like, with [[micropenis]] (a small, [[clitoris]]-like [[phallus]]), a partially unfused, [[labia]]-like [[scrotum]], and a blind-ending, shallow [[vagina|vaginal pouch]].<ref name="Blume-PeytaviWhiting2008" /> Due to their lack of conspicuous [[male genitalia]], genetic males with the condition are typically raised as girls.<ref name="pmid25321150" /> At the time of [[puberty]] however, they develop striking phenotypically masculine [[secondary sexual characteristic]]s including partial virilization of the genitals (enlargement of the phallus into a near-functional penis and [[testicular descent|descent of the testes]]), [[voice deepening]], typical male [[human musculoskeletal system|musculoskeletal]] development,<ref name="pmid23431485" /> and no [[menstruation]], [[breast development]], or other signs of [[feminization (biology)|feminization]] that occur during female puberty.<ref name="Blume-PeytaviWhiting2008" /><ref name="pmid25321150" /><ref name="pmid16985920" /> In addition, normal [[libido]] and [[spontaneous erection]]s develop,<ref name="pmid12573814" /> they usually show a [[sexual orientation|sexual preference]] for females, and almost all develop a male [[gender identity]].<ref name="Blume-PeytaviWhiting2008" /><ref name="pmid431680">{{cite journal | vauthors = Imperato-McGinley J, Peterson RE, Gautier T, Sturla E | title = Androgens and the evolution of male-gender identity among male pseudohermaphrodites with 5alpha-reductase deficiency | journal = The New England Journal of Medicine | volume = 300 | issue = 22 | pages = 1233–1237 | date = May 1979 | pmid = 431680 | doi = 10.1056/NEJM197905313002201 }}</ref>

Nonetheless, males with 5α-reductase type 2 deficiency exhibit signs of continued undervirilization in a number of domains. [[Facial hair]] was absent or sparse in a relatively large group of [[People of the Dominican Republic|Dominican]] males with the condition, known as the [[Güevedoce]]s. However, more facial hair has been observed in patients with the disorder from other parts of the world, although facial hair was still reduced relative to that of other men in the same communities. The divergent findings may reflect racial differences in androgen-dependent hair growth. A female pattern of [[androgenic hair]] [[hair growth|growth]], with [[terminal hair]] largely restricted to the [[axilla]]e and lower [[pubic area|pubic triangle]], is observed in males with the condition. No temporal recession of the hairline or [[androgenic alopecia]] (pattern hair loss or baldness) has been observed in any of the cases of 5α-reductase type 2 deficiency that have been reported, whereas this is normally seen to some degree in almost all Caucasian males in their teenage years.<ref name="Blume-PeytaviWhiting2008" /> Individuals with 5α-reductase type 2 deficiency were initially reported to have no incidence of [[acne]],<ref name="Melmed2016" /><ref name="pmid16985920" /> but subsequent research indicated normal [[sebum]] [[secretion]] and acne incidence.<ref name="pmid23431485"/>

In genetic males with 5α-reductase type 2 deficiency, the [[prostate gland]] is rudimentary or absent, and if present, remains small, underdeveloped, and unpalpable throughout life.<ref name="Melmed2016" /><ref name="pmid8630237" /> In addition, neither BPH nor prostate cancer have been reported in these individuals.<ref name="pmid22333687" /> Genetic males with the condition generally show [[oligozoospermia]] due to undescended testes, but [[spermatogenesis]] is reported to be normal in those with testes that have descended, and there are case instances of men with the condition successfully fathering children.<ref name="pmid12573814">{{cite journal | vauthors = Imperato-McGinley J, Zhu YS | title = Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency | journal = Molecular and Cellular Endocrinology | volume = 198 | issue = 1–2 | pages = 51–59 | date = December 2002 | pmid = 12573814 | doi = 10.1016/s0303-7207(02)00368-4 | s2cid = 54356569 }}</ref><ref name="pmid24412121">{{cite journal | vauthors = Kang HJ, Imperato-McGinley J, Zhu YS, Rosenwaks Z | title = The effect of 5α-reductase-2 deficiency on human fertility | journal = Fertility and Sterility | volume = 101 | issue = 2 | pages = 310–316 | date = February 2014 | pmid = 24412121 | pmc = 4031759 | doi = 10.1016/j.fertnstert.2013.11.128 }}</ref>

Unlike males, genetic females with 5α-reductase type 2 deficiency are phenotypically normal. However, similarly to genetic males with the condition, they show reduced body hair growth, including an absence of hair on the arms and legs, slightly decreased axillary hair, and moderately decreased pubic hair.<ref name="pmid7593420">{{cite journal | vauthors = Katz MD, Cai LQ, Zhu YS, Herrera C, DeFillo-Ricart M, Shackleton CH, Imperato-McGinley J | title = The biochemical and phenotypic characterization of females homozygous for 5 alpha-reductase-2 deficiency | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 80 | issue = 11 | pages = 3160–3167 | date = November 1995 | pmid = 7593420 | doi = 10.1210/jcem.80.11.7593420 }}</ref><ref name="pmid12573814" /> On the other hand, [[sebum]] production is normal.<ref name="pmid7593420" /><ref name="pmid11314752">{{cite journal | vauthors = Cilotti A, Danza G, Serio M | title = Clinical application of 5alpha-reductase inhibitors | journal = Journal of Endocrinological Investigation | volume = 24 | issue = 3 | pages = 199–203 | date = March 2001 | pmid = 11314752 | doi = 10.1007/bf03343844 | s2cid = 73167928 }}</ref> This is in accordance with the fact that sebum secretion appears to be entirely under the control of 5α-reductase type 1.<ref name="pmid11314752" />

===5α-Reductase inhibitors===

{{See also|5α-Reductase inhibitor|Finasteride|Dutasteride|MK-386}}

[[5α-Reductase inhibitor]]s like [[finasteride]] and [[dutasteride]] inhibit 5α-reductase type 2 and/or other isoforms and are able to decrease circulating DHT levels by 65 to 98% depending on the 5α-reductase inhibitor in question.<ref name="Bradbury2007">{{cite book | vauthors = Bradbury R |title= Cancer|url=https://books.google.com/books?id=fdtDAAAAQBAJ&pg=PA49|year=2007|publisher=Springer Science & Business Media|isbn=978-3-540-33120-9|pages=49–}}</ref><ref name="BurchumRosenthal2014">{{cite book|vauthors=Burchum J, Rosenthal L|title=Lehne's Pharmacology for Nursing Care|url=https://books.google.com/books?id=C7_NBQAAQBAJ&pg=PA803|date=2014|publisher=Elsevier Health Sciences|isbn=978-0-323-34026-7|pages=803–|access-date=16 July 2017|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112145742/https://books.google.com/books?id=C7_NBQAAQBAJ&pg=PA803|url-status=live}}</ref><ref name="BostwickCheng2014">{{cite book | vauthors = Bostwick DG, Cheng L |title=Urologic Surgical Pathology|url=https://books.google.com/books?id=wrHQAgAAQBAJ&pg=PA492|date=2014|publisher=Elsevier Health Sciences|isbn=978-0-323-08619-6|pages=492–}}</ref><ref name="HeesakkersChapple2016">{{cite book | vauthors = Heesakkers J, Chapple C, Ridder DD, Farag F |title=Practical Functional Urology|url=https://books.google.com/books?id=aWKhCwAAQBAJ&pg=PA280|year= 2016|publisher=Springer|isbn=978-3-319-25430-2|pages=280–}}</ref> As such, similarly to the case of 5α-reductase type 2 deficiency, they provide useful insights in the elucidation of the biological functions of DHT.<ref name="pmid9667860">{{cite journal | vauthors = Harris GS, Kozarich JW | title = Steroid 5alpha-reductase inhibitors in androgen-dependent disorders | journal = Current Opinion in Chemical Biology | volume = 1 | issue = 2 | pages = 254–259 | date = August 1997 | pmid = 9667860 | doi = 10.1016/s1367-5931(97)80017-8 }}</ref> 5α-Reductase inhibitors were developed and are used primarily for the treatment of BPH. The drugs are able to significantly reduce the size of the prostate gland and to alleviate symptoms of the condition.<ref name="pmid22333687" /><ref name="pmid21756226">{{cite journal | vauthors = Sun J, Xiang H, Yang LL, Chen JB | title = A review on steroidal 5α-reductase inhibitors for treatment of benign prostatic hyperplasia | journal = Current Medicinal Chemistry | volume = 18 | issue = 23 | pages = 3576–3589 | year = 2011 | pmid = 21756226 | doi = 10.2174/092986711796642517 }}</ref> Long-term treatment with 5α-reductase inhibitors is also able to significantly reduce the overall risk of prostate cancer, although a simultaneous small increase in the risk of certain high-grade tumors has been observed.<ref name="pmid22446342">{{cite journal | vauthors = Azzouni F, Mohler J | title = Role of 5α-reductase inhibitors in prostate cancer prevention and treatment | journal = Urology | volume = 79 | issue = 6 | pages = 1197–1205 | date = June 2012 | pmid = 22446342 | doi = 10.1016/j.urology.2012.01.024 }}</ref> In addition to prostate diseases, 5α-reductase inhibitors have subsequently been developed and introduced for the treatment of [[pattern hair loss]] in men.<ref name="pmid26370642">{{cite journal | vauthors = Torres F | title = Androgenetic, diffuse and senescent alopecia in men: practical evaluation and management | journal = Current Problems in Dermatology | volume = 47 | pages = 33–44 | year = 2015 | pmid = 26370642 | doi = 10.1159/000369403 | isbn = 978-3-318-02774-7 }}</ref> They are able to prevent further progression of hair loss in most men with the condition and to produce some recovery of hair in about two-thirds of men.<ref name="Blume-PeytaviWhiting2008" /> 5α-Reductase inhibitors seem to be less effective for pattern hair loss in women on the other hand, although they do still show some effectiveness.<ref name="pmid26411201">{{cite journal | vauthors = Check JH, Cohen R | title = An update on the treatment of female alopecia and the introduction of a potential novel therapy | journal = Clinical and Experimental Obstetrics & Gynecology | volume = 42 | issue = 4 | pages = 411–415 | year = 2015 | pmid = 26411201 | doi = 10.12891/ceog1960.2015 | s2cid = 32583007 | doi-access = free }}</ref> Aside from pattern hair loss, the drugs are also useful in the treatment of hirsutism and can greatly reduce facial and body hair growth in women with the condition.<ref name="Blume-Peytavi-2008-Hair-Growth">{{cite book|vauthors=Blume-Peytavi U, Whiting DA, Trüeb RM|title=Hair Growth and Disorders|url=https://books.google.com/books?id=pHrX2-huQCoC&pg=PA369|date=2008|publisher=Springer Science & Business Media|isbn=978-3-540-46911-7|pages=182, 369|access-date=16 December 2017|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031700/https://books.google.com/books?id=pHrX2-huQCoC&pg=PA369|url-status=live}}</ref><ref name="KatsambasLotti2015">{{cite book | vauthors = Lotti F, Maggi M | veditors = Katsambas A, Lotti T, Dessinioti C, D'Erme AM | chapter = Hormonal Treatment for Skin Androgen-Related Disorders | title = European Handbook of Dermatological Treatments |chapter-url= https://books.google.com/books?id=fHi6CAAAQBAJ&pg=PA1451|year=2015|publisher=Springer|isbn=978-3-662-45139-7|pages=1451–64}}</ref>

5α-Reductase inhibitors are overall [[tolerability|well tolerated]] and show a low incidence of [[adverse effect]]s.<ref name="pmid27672412">{{cite journal | vauthors = Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS | title = Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review | journal = The Journal of Clinical and Aesthetic Dermatology | volume = 9 | issue = 7 | pages = 56–62 | date = July 2016 | pmid = 27672412 | pmc = 5023004 }}</ref> [[Sexual dysfunction]], including [[erectile dysfunction]], [[loss of libido]], and [[hypospermia|reduced ejaculate volume]], may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride.<ref name="pmid27672412" /><ref name="pmid27475241">{{cite journal | vauthors = Liu L, Zhao S, Li F, Li E, Kang R, Luo L, Luo J, Wan S, Zhao Z | display-authors = 6 | title = Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials | journal = The Journal of Sexual Medicine | volume = 13 | issue = 9 | pages = 1297–1310 | date = September 2016 | pmid = 27475241 | doi = 10.1016/j.jsxm.2016.07.006 }}</ref> A small increase in the risk of [[affective disorder|affective symptom]]s including [[depression (mood)|depression]], [[anxiety]], and [[self-harm]] may be seen.<ref name="pmid24955220" /><ref name="pmid28319231">{{cite journal | vauthors = Welk B, McArthur E, Ordon M, Anderson KK, Hayward J, Dixon S | title = Association of Suicidality and Depression With 5α-Reductase Inhibitors | journal = JAMA Internal Medicine | volume = 177 | issue = 5 | pages = 683–691 | date = May 2017 | pmid = 28319231 | pmc = 5818776 | doi = 10.1001/jamainternmed.2017.0089 }}</ref><ref name="pmid28319227">{{cite journal | vauthors = Thielke S | title = The Risk of Suicidality and Depression From 5-α Reductase Inhibitors | journal = JAMA Internal Medicine | volume = 177 | issue = 5 | pages = 691–692 | date = May 2017 | pmid = 28319227 | doi = 10.1001/jamainternmed.2017.0096 }}</ref> Both the sexual dysfunction and affective symptoms may be due partially or fully to prevention of the synthesis of [[neurosteroid]]s like [[allopregnanolone]] rather necessarily than due to inhibition of DHT production.<ref name="pmid24955220">{{cite journal | vauthors = Traish AM, Mulgaonkar A, Giordano N | title = The dark side of 5α-reductase inhibitors' therapy: sexual dysfunction, high Gleason grade prostate cancer and depression | journal = Korean Journal of Urology | volume = 55 | issue = 6 | pages = 367–379 | date = June 2014 | pmid = 24955220 | pmc = 4064044 | doi = 10.4111/kju.2014.55.6.367 }}</ref> A small risk of [[gynecomastia]] has been associated with 5α-reductase inhibitors (1.2–3.5%).<ref name="pmid27672412" /><ref name="pmid28232919">{{cite journal | vauthors = Fertig R, Shapiro J, Bergfeld W, Tosti A | title = Investigation of the Plausibility of 5-Alpha-Reductase Inhibitor Syndrome | journal = Skin Appendage Disorders | volume = 2 | issue = 3–4 | pages = 120–129 | date = January 2017 | pmid = 28232919 | pmc = 5264352 | doi = 10.1159/000450617 }}</ref> Based on reports of 5α-reductase type 2 deficiency in males and the effectiveness of 5α-reductase inhibitors for hirsutism in women, reduced body and/or facial hair growth is a likely potential side effect of these drugs in men.<ref name="Blume-PeytaviWhiting2008" /><ref name="KatsambasLotti2015" /> There are far fewer studies evaluating the side effects of 5α-reductase inhibitors in women. However, due to the known role of DHT in male sexual differentiation, 5α-reductase inhibitors may cause [[birth defect]]s such as ambiguous genitalia in the male [[fetus]]es of [[pregnancy|pregnant]] women. As such, they are not used in women during pregnancy.<ref name="pmid27672412" />

[[MK-386]] is a selective 5α-reductase type 1 inhibitor which was never marketed.<ref name="MachettiGuarna2005">{{cite journal | vauthors = Machetti F, Guarna A| title = Novel inhibitors of 5α-reductase|journal=Expert Opinion on Therapeutic Patents|volume=12|issue=2|year=2005|pages=201–15|issn=1354-3776|doi=10.1517/13543776.12.2.201| s2cid = 85073794 }}</ref> Whereas 5α-reductase type 2 inhibitors achieve much higher reductions in circulating DHT production, MK-386 decreases circulating DHT levels by 20 to 30%.<ref name="pmid8768856">{{cite journal | vauthors = Schwartz JI, Van Hecken A, De Schepper PJ, De Lepeleire I, Lasseter KC, Shamblen EC, Winchell GA, Constanzer ML, Chavez CM, Wang DZ, Ebel DL, Justice SJ, Gertz BJ | display-authors = 6 | title = Effect of MK-386, a novel inhibitor of type 1 5 alpha-reductase, alone and in combination with finasteride, on serum dihydrotestosterone concentrations in men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 81 | issue = 8 | pages = 2942–2947 | date = August 1996 | pmid = 8768856 | doi = 10.1210/jcem.81.8.8768856 | doi-access = free }}</ref> Conversely, it was found to decrease sebum DHT levels by 55% in men versus a modest reduction of only 15% for finasteride.<ref name="pmid9141518">{{cite journal | vauthors = Schwartz JI, Tanaka WK, Wang DZ, Ebel DL, Geissler LA, Dallob A, Hafkin B, Gertz BJ | display-authors = 6 | title = MK-386, an inhibitor of 5alpha-reductase type 1, reduces dihydrotestosterone concentrations in serum and sebum without affecting dihydrotestosterone concentrations in semen | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 82 | issue = 5 | pages = 1373–1377 | date = May 1997 | pmid = 9141518 | doi = 10.1210/jcem.82.5.3912 | doi-access = free }}</ref><ref name="Kaufman2001">{{cite journal| vauthors = Kaufman KD |title=5α-Reductase Inhibitors in the Treatment of Androgenetic Alopecia|journal=International Journal of Cosmetic Surgery and Aesthetic Dermatology|volume=3|issue=2|year=2001|pages=107–19|issn=1530-8200|doi=10.1089/153082001753231036}}</ref> However, MK-386 failed to show significant effectiveness in a subsequent clinical study for the treatment of acne.<ref name="pmid22235201">{{cite journal | vauthors = Azzouni F, Godoy A, Li Y, Mohler J | title = The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases | journal = Advances in Urology | volume = 2012 | pages = 530121 | year = 2012 | pmid = 22235201 | pmc = 3253436 | doi = 10.1155/2012/530121 | doi-access = free }}</ref>

==Biological activity==

DHT is a [[potency (pharmacology)|potent]] [[agonist]] of the AR, and is in fact the most potent known [[endogenous]] [[ligand (biochemistry)|ligand]] of the receptor. It has an [[affinity (pharmacology)|affinity]] (K_d) of 0.25 to 0.5&nbsp;nM for the human AR, which is about 2- to 3-fold higher than that of [[testosterone]] (K_d = 0.4 to 1.0&nbsp;nM)<ref name="MozayaniRaymon2011">{{cite book | vauthors = Mozayani A, Raymon L | title = Handbook of Drug Interactions: A Clinical and Forensic Guide | url = https://books.google.com/books?id=NhBJ6kg_uP0C&pg=PA656 | year= 2011 | publisher = Springer Science & Business Media|isbn=978-1-61779-222-9|pages=656–}}</ref> and 15–30&nbsp;times higher than that of [[adrenal androgen]]s.<ref name="isbn1-903737-05-2">{{cite book | vauthors = Hemat RA | title = Principles Of Orthomolecularism | publisher = Urotext | year = 2004 | isbn = 978-1-903737-05-7 | url = https://books.google.com/books?id=ED_xI-CEzFYC&q=DHT+is+3+times+more+potent+than+testosterone%3B+testosterone+is+5-10+times+more+potent+than+adrenal+androgens | page = 426 | access-date = 8 October 2020 | archive-date = 24 February 2024 | archive-url = https://web.archive.org/web/20240224205541/https://books.google.com/books?id=ED_xI-CEzFYC&q=DHT+is+3+times+more+potent+than+testosterone%3B+testosterone+is+5-10+times+more+potent+than+adrenal+androgens#v=snippet&q=DHT%20is%203%20times%20more%20potent%20than%20testosterone%3B%20testosterone%20is%205-10%20times%20more%20potent%20than%20adrenal%20androgens&f=false | url-status = live }}</ref> In addition, the [[dissociation rate]] of DHT from the AR is 5-fold slower than that of testosterone.<ref name="pmid2298157">{{cite journal | vauthors = Grino PB, Griffin JE, Wilson JD | title = Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone | journal = Endocrinology | volume = 126 | issue = 2 | pages = 1165–1172 | date = February 1990 | pmid = 2298157 | doi = 10.1210/endo-126-2-1165 }}</ref> The [[EC50|EC₅₀]] of DHT for activation of the AR is 0.13&nbsp;nM, which is about 5-fold stronger than that of testosterone (EC₅₀ = 0.66&nbsp;nM).<ref name="Wilderer-2010">{{cite book | vauthors = Wilderer PA | title = Treatise on Water Science, Four-Volume Set | chapter = Bioassays for Estrogenic and Androgenic Effects of Water Constituents | chapter-url = https://books.google.com/books?id=HSPtBDpRSXMC&pg=PT1805 | date = 2010 | publisher = Newnes | isbn = 978-0-444-53199-5 | pages = 1805– }}</ref> In [[bioassay]]s, DHT has been found to be 2.5- to 10-fold more potent than testosterone.<ref name="MozayaniRaymon2011" />

The [[elimination half-life]] of DHT in the body (53&nbsp;minutes) is longer than that of testosterone (34&nbsp;minutes), and this may account for some of the difference in their potency.<ref name="pmid10495361">{{cite journal | vauthors = Diamanti-Kandarakis E | title = Current aspects of antiandrogen therapy in women | journal = Current Pharmaceutical Design | volume = 5 | issue = 9 | pages = 707–723 | date = September 1999 | pmid = 10495361 | doi = 10.2174/1381612805666230111201150 }}</ref> A study of transdermal (patches) DHT and testosterone treatment reported terminal half-lives of 2.83&nbsp;hours and 1.29&nbsp;hours, respectively.<ref name="MozayaniRaymon2003">{{cite book |title=Handbook of Drug Interactions |vauthors=von Deutsch DA, Abukhalaf IK, Lapu-Bula R |date=2012 |publisher=Springer Science & Business Media |isbn=978-1-59259-654-6 |veditors=Mozayani A, Raymon L |pages=647– |chapter=Anabolic Doping Agents |doi=10.1007/978-1-61779-222-9_15 |chapter-url=https://books.google.com/books?id=dwMyBwAAQBAJ&pg=PA510}}</ref>

Unlike other androgens such as testosterone, DHT cannot be converted by the enzyme [[aromatase]] into an [[estrogen]] like [[estradiol]]. Therefore, it is frequently used in research settings to distinguish between the effects of testosterone caused by binding to the AR and those caused by testosterone's conversion to estradiol and subsequent binding to and activation of ERs.<ref name="pmid10332569">{{cite journal | vauthors = Swerdloff RS, Wang C | title = Dihydrotestosterone: a rationale for its use as a non-aromatizable androgen replacement therapeutic agent | journal = Bailliere's Clinical Endocrinology and Metabolism | volume = 12 | issue = 3 | pages = 501–506 | date = October 1998 | pmid = 10332569 | doi = 10.1016/s0950-351x(98)80267-x }}</ref> Although DHT cannot be aromatized, it is still transformed into metabolites with significant ER affinity and activity. These are 3α-androstanediol and 3β-androstanediol, which are predominant agonists of the ERβ.<ref name="pmid22231829" />

==Biochemistry==

[[File:Steroidogenesis.svg|thumb|450px|right|Comprehensive overview of [[steroidogenesis]], showing DHT around the bottom middle among the androgens<ref name="HäggströmRichfield2014">{{cite journal | vauthors = Häggström M, Richfield D | title = Diagram of the pathways of human steroidogenesis | journal=WikiJournal of Medicine|volume=1|issue=1|year=2014|issn=2002-4436|doi=10.15347/wjm/2014.005| doi-access=free}}</ref>]]

===Biosynthesis===

DHT is synthesized [[irreversible reaction|irreversibly]] from [[testosterone]] by the enzyme [[5α-reductase]].<ref name="Melmed2016">{{cite book | vauthors = Melmed S | title = Williams Textbook of Endocrinology|url=https://books.google.com/books?id=YZ8_CwAAQBAJ&pg=PA621|year=2016|publisher=Elsevier Health Sciences|isbn=978-0-323-29738-7|pages=621, 711}}</ref><ref name="Blume-PeytaviWhiting2008" /> This occurs in various [[tissue (biology)|tissue]]s including the [[genital]]s ([[penis]], [[scrotum]], [[clitoris]], [[labia majora]]),<ref name="RhoadesBell2012">{{cite book | vauthors = Rhoades RA, Bell DR | title = Medical Physiology: Principles for Clinical Medicine|url=https://books.google.com/books?id=1kGcFOKCUzkC&pg=PA690|date= 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-427-3|pages=690–}}</ref> [[prostate gland]], [[skin]], [[hair follicle]]s, [[liver]], and [[brain]].<ref name="Melmed2016" /> Around 5 to 7% of testosterone undergoes 5α-reduction into DHT,<ref name="Rakel2012">{{cite book | vauthors = Rakel D |title=Integrative Medicine E-Book|url=https://books.google.com/books?id=BMNeorjr8aEC&pg=PA321|year=2012|publisher=Elsevier Health Sciences|isbn=978-1-4557-2503-8|pages=321–}}</ref><ref name="Morrison2000">{{cite book | vauthors = Morrison MF |title=Hormones, Gender and the Aging Brain: The Endocrine Basis of Geriatric Psychiatry|url=https://books.google.com/books?id=DzDZE4ZpvQEC&pg=PA17|date=2000|publisher=Cambridge University Press|isbn=978-1-139-42645-9|pages=17–}}</ref> and approximately 200 to 300&nbsp;μg of DHT is synthesized in the body per day. Most DHT is produced in peripheral tissues like the skin and liver, whereas most ''circulating'' DHT originates specifically from the liver. The testes and prostate gland contribute relatively little to concentrations of DHT in circulation.<ref name="Melmed2016" />

There are two major [[isoform]]s of 5α-reductase, [[SRD5A1]] (type 1) and [[SRD5A2]] (type 2), with the latter being the most biologically important isoenzyme.<ref name="Melmed2016" /> There is also third 5α-reductase: [[SRD5A3]].<ref name="pmid22235201"/> SRD5A2 is most highly expressed in the genitals, [[prostate gland]], [[epididymis|epididymides]], [[seminal vesicle]]s, [[genital skin]], [[facial hair|facial]] and [[chest hair|chest]] hair follicles,<ref name="pmid17326004">{{cite journal | vauthors = Zouboulis CC, Chen WC, Thornton MJ, Qin K, Rosenfield R | title = Sexual hormones in human skin | journal = Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Métabolisme | volume = 39 | issue = 2 | pages = 85–95 | date = February 2007 | pmid = 17326004 | doi = 10.1055/s-2007-961807 | doi-access = free }}</ref><ref name="BologniaJorizzo2012">{{cite book | vauthors = Bolognia JL, Jorizzo JL, Schaffer JV | title = Dermatology E-Book|url=https://books.google.com/books?id=A78BaiEKnzIC&pg=PA1094|year=2012|publisher=Elsevier Health Sciences|isbn=978-0-7020-5182-1|pages=1094–}}</ref> and [[liver]], while lower expression is observed in certain [[brain]] areas, non-genital skin/hair follicles, [[testicle|testes]], and [[kidney]]s. SRD5A1 is most highly expressed in non-genital skin/hair follicles, the liver, and certain brain areas, while lower levels are present in the prostate, epididymides, seminal vesicles, genital skin, testes, [[adrenal gland]]s, and kidneys.<ref name="Melmed2016" /> In the skin, 5α-reductase is expressed in [[sebaceous gland]]s, [[sweat gland]]s, [[epidermal cell]]s, and hair follicles.<ref name="pmid17326004" /><ref name="BologniaJorizzo2012" /> Both isoenzymes are expressed in [[scalp hair]] follicles,<ref name="Murphy2011">{{cite book | vauthors = Murphy MJ | title = Molecular Diagnostics in Dermatology and Dermatopathology|url=https://books.google.com/books?id=cyDyIqkmJAMC&pg=PA373|year=2011|publisher=Springer Science & Business Media|isbn=978-1-60761-171-4|pages=373–}}</ref> although SRD5A2 predominates in these cells.<ref name="BologniaJorizzo2012" /> The SRD5A2 subtype is the almost exclusive isoform expressed in the prostate gland.<ref name="pmid18318566">{{cite journal | vauthors = Keam SJ, Scott LJ | title = Dutasteride: a review of its use in the management of prostate disorders | journal = Drugs | volume = 68 | issue = 4 | pages = 463–485 | year = 2008 | pmid = 18318566 | doi = 10.2165/00003495-200868040-00008 | s2cid = 242987808 }}</ref><ref name="HeesakkersChapple2016" />

====Backdoor pathway====

[[File:Androgen backdoor pathway.svg|thumb|right|The androgen backdoor pathway (red arrows) roundabout testosterone embedded in within conventional androgen synthesis that lead to 5α-dihydrotestosterone through testosterone.<ref name=wj/><ref name="pmid30763313">{{cite journal | vauthors = O'Shaughnessy PJ, Antignac JP, Le Bizec B, Morvan ML, Svechnikov K, Söder O, Savchuk I, Monteiro A, Soffientini U, Johnston ZC, Bellingham M, Hough D, Walker N, Filis P, Fowler PA | display-authors = 6 | title = Alternative (backdoor) androgen production and masculinization in the human fetus | journal = PLOS Biology | volume = 17 | issue = 2 | pages = e3000002 | date = February 2019 | pmid = 30763313 | pmc = 6375548 | doi = 10.1371/journal.pbio.3000002 | doi-access = free }}</ref><ref name="pmid30943210"/>]]{{Main article|Androgen backdoor pathway}}DHT under certain normal and pathological conditions can additionally be produced via a route that does not involve testosterone as an [[metabolic intermediate|intermediate]] but instead goes through other intermediates.<ref name=wj>{{cite journal|doi=10.15347/WJM/2023.003 |doi-access=free |title=Alternative androgen pathways |year=2023 | vauthors = Masiutin M, Yadav M |journal=WikiJournal of Medicine |volume=10 |pages=X |s2cid=257943362}}</ref> This route is called the "backdoor pathway".<ref name="pmid15519890">{{cite journal | vauthors = Auchus RJ | title = The backdoor pathway to dihydrotestosterone | journal = Trends in Endocrinology and Metabolism | volume = 15 | issue = 9 | pages = 432–438 | date = November 2004 | pmid = 15519890 | doi = 10.1016/j.tem.2004.09.004 | s2cid = 10631647 }}</ref>

The pathway can start from [[17α-hydroxyprogesterone]] or from [[progesterone]] and can be outlined as follows (depending on the initial substrate):

* [[17α-hydroxyprogesterone]] → [[5α-pregnan-17α-ol-3,20-dione]] → [[5α-Pregnane-3α,17α-diol-20-one|5α-pregnane-3α,17α-diol-20-one]] → [[androsterone]] → [[5α-androstane-3α,17β-diol]] → DHT.<ref name="pmid12538619">{{cite journal | vauthors = Wilson JD, Auchus RJ, Leihy MW, Guryev OL, Estabrook RW, Osborn SM, Shaw G, Renfree MB | display-authors = 6 | title = 5alpha-androstane-3alpha,17beta-diol is formed in tammar wallaby pouch young testes by a pathway involving 5alpha-pregnane-3alpha,17alpha-diol-20-one as a key intermediate | journal = Endocrinology | volume = 144 | issue = 2 | pages = 575–580 | date = February 2003 | pmid = 12538619 | doi = 10.1210/en.2002-220721 | doi-access = free }}</ref>

* [[progesterone]] → [[5α-dihydroprogesterone]] → [[allopregnanolone]] → [[5α-pregnane-3α,17α-diol-20-one]] → [[androsterone]] → [[5α-androstane-3α,17β-diol]] → DHT.<ref name=wj/>

This pathway is not always considered in the clinical evaluation of patients with [[hyperandrogenism]], for instance due to rare [[disorders of sex development]] like [[21α-hydroxylase deficiency]]. Ignoring this pathway in such instances may lead to diagnostic pitfalls and confusion,<ref name="pmid32610579">{{cite journal | vauthors = Sumińska M, Bogusz-Górna K, Wegner D, Fichna M | title = Non-Classic Disorder of Adrenal Steroidogenesis and Clinical Dilemmas in 21-Hydroxylase Deficiency Combined with Backdoor Androgen Pathway. Mini-Review and Case Report | journal = International Journal of Molecular Sciences | volume = 21 | issue = 13 | pages = 4622 | date = June 2020 | pmid = 32610579 | pmc = 7369945 | doi = 10.3390/ijms21134622 | doi-access = free }}</ref> when the conventional androgen biosynthetic pathway cannot fully explain the observed consequences.<ref name="pmid15519890"/>

As with the conventional pathway of DHT synthesis, the backdoor pathway similarly requires [[5α-reductase]].<ref name="pmid30943210">{{cite journal | vauthors = Miller WL, Auchus RJ | title = The "backdoor pathway" of androgen synthesis in human male sexual development | journal = PLOS Biology | volume = 17 | issue = 4 | pages = e3000198 | date = April 2019 | pmid = 30943210 | pmc = 6464227 | doi = 10.1371/journal.pbio.3000198 | doi-access = free }}</ref> Whereas 5α-reduction is the last transformation in the classical androgen pathway, it is the first step in the backdoor pathway.<ref name=wj/>

===Distribution===

The [[plasma protein binding]] of DHT is more than 99%. In men, approximately 0.88% of DHT is unbound and hence free, while in premenopausal women, about 0.47–0.48% is unbound. In men, DHT is bound 49.7% to [[sex hormone-binding globulin]] (SHBG), 39.2% to [[human serum albumin|albumin]], and 0.22% to [[corticosteroid-binding globulin]] (CBG), while in premenopausal women, DHT is bound 78.1–78.4% to SHBG, 21.0–21.3% to albumin, and 0.12% to CBG. In late pregnancy, only 0.07% of DHT is unbound in women; 97.8% is bound to SHBG while 2.15% is bound to albumin and 0.04% is bound to CBG.<ref name="NieschlagBehre2012">{{cite book|vauthors=Nieschlag E, Behre HM, Nieschlag S|title=Testosterone: Action, Deficiency, Substitution|url=https://books.google.com/books?id=MkrAPaQ4wJkC&pg=PA61|date=2012|publisher=Cambridge University Press|isbn=978-1-107-01290-5|pages=61–|access-date=8 March 2018|archive-date=11 January 2023|archive-url=https://web.archive.org/web/20230111143032/https://books.google.com/books?id=MkrAPaQ4wJkC&pg=PA61|url-status=live}}</ref><ref name="pmid7195404">{{cite journal | vauthors = Dunn JF, Nisula BC, Rodbard D | title = Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 53 | issue = 1 | pages = 58–68 | date = July 1981 | pmid = 7195404 | doi = 10.1210/jcem-53-1-58 }}</ref> DHT has higher [[affinity (pharmacology)|affinity]] for SHBG than does testosterone, estradiol, or any other steroid hormone.<ref name="WilliamsFoye2002">{{cite book | vauthors = Williams DA, Foye WO, Lemke TL |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=qLJ6Bs1Qml4C&pg=PA707|year=2002|publisher=Lippincott Williams & Wilkins|isbn=978-0-683-30737-5|pages=707–}}</ref><ref name="pmid7195404" />

{{Plasma protein binding of testosterone and dihydrotestosterone}}

===Metabolism===

{{See also|Testosterone#Metabolism}}

{{Testosterone metabolism mini|align=right|caption=This diagram illustrates the [[metabolic pathway]]s involved in the [[metabolism]] of DHT in humans. In addition to the [[biotransformation|transformation]]s shown in the diagram, [[conjugation (biochemistry)|conjugation]] (e.g., [[sulfation]] and [[glucuronidation]]) occurs with DHT and [[metabolite]]s that have one or more available [[hydroxyl group|hydroxyl]] (–OH) [[functional group|group]]s.}}

DHT is inactivated in the liver and extrahepatic tissues like the skin into [[3α-androstanediol]] and [[3β-androstanediol]] by the enzymes [[3α-hydroxysteroid dehydrogenase]] and [[3β-hydroxysteroid dehydrogenase]], respectively.<ref name="Melmed2016" /><ref name="pmid12810547">{{cite journal | vauthors = Rizner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR, Penning TM | title = Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells | journal = Endocrinology | volume = 144 | issue = 7 | pages = 2922–2932 | date = July 2003 | pmid = 12810547 | doi = 10.1210/en.2002-0032 | doi-access = free }}</ref> These [[metabolite]]s are in turn converted, respectively, into [[androsterone]] and [[epiandrosterone]], then [[conjugation (biochemistry)|conjugated]] (via [[glucuronidation]] and/or [[sulfation]]), released into [[circulatory system|circulation]], and [[excretion|excreted]] in [[urine]].<ref name="Melmed2016" />

Unlike testosterone, DHT cannot be [[aromatized]] into an [[estrogen]] like estradiol, and for this reason, has no propensity for estrogenic effects.<ref name="WeinerGallagher2003">{{cite book | vauthors = Weiner IB, Gallagher M | title=Handbook of Psychology, Biological Psychology|url=https://books.google.com/books?id=07UXE4gG3PcC&pg=PA333|year=2003|publisher=John Wiley & Sons|isbn=978-0-471-38403-8|pages=333–}}</ref>

===Excretion===

DHT is [[excretion|excreted]] in the [[urine]] as [[metabolite]]s, such as [[conjugation (biochemistry)|conjugate]]s of [[3α-androstanediol]] and [[androsterone]].<ref name="SchillComhaire2006">{{cite book | vauthors = Schill W, Comhaire FH, Hargreave TB | title = Andrology for the Clinician|url=https://books.google.com/books?id=5Ts_AAAAQBAJ&pg=PA243|year= 2006|publisher=Springer Science & Business Media|isbn=978-3-540-33713-3|pages=243–}}</ref><ref name="Melmed2016" />

===Levels===

Ranges for circulating total DHT levels tested with [[HPLC–MS/MS]] and reported by [[LabCorp]] are as follows:<ref name="LabCorp2020">{{cite web |url=https://www.esoterix.com/sites/default/files/L5167-0320-17.pdf |title=Endocrinology: Expected Values | publisher = LabCorp | work = www.esoterix.com |access-date=3 October 2022 |archive-url=https://web.archive.org/web/20200330030510/https://www.esoterix.com/sites/default/files/L5167-0320-17.pdf |archive-date=30 March 2020 |url-status=dead}}</ref>

* Men: 30–85{{nbsp}}ng/dL

* Women: 4–22{{nbsp}}ng/dL

* Prepubertal children: <3{{nbsp}}ng/dL

* Pubertal boys: 3–65{{nbsp}}ng/dL (mean at [[Tanner stage 5]]: 43{{nbsp}}ng/dL)

* Pubertal girls: 3–19{{nbsp}}ng/dL (mean at Tanner stage 5: 9{{nbsp}}ng/dL)

Ranges for circulating free DHT levels tested with HPLC–MS/MS and [[equilibrium dialysis]] and reported by LabCorp are as follows:<ref name="LabCorp2020" />

* <18 years of age: not established

* Adult males: 2.30–11.60{{nbsp}}pg/mL (0.54–2.58% free)

* Adult females: 0.09–1.02{{nbsp}}pg/mL (<1.27% free)

Other studies and labs assessing circulating total DHT levels with [[LC–MS/MS]] have reported ranges of 11–95{{nbsp}}ng/dL (0.38–3.27{{nbsp}}nmol/L) in adult men, 14–77{{nbsp}}ng/dL (0.47–2.65{{nbsp}}nmol/L) for healthy adult men (age 18–59{{nbsp}}years), 23–102&nbsp;ng/dL (0.8–3.5 nmol/L) for community-dwelling adult men (age <65{{nbsp}}years), and 14–92{{nbsp}}ng/dL (0.49–3.2{{nbsp}}nmol/L) for healthy older men (age 71–87{{nbsp}}years).<ref name="pmid28472278" /> In the case of women, mean circulating DHT levels have been found to be about 9{{nbsp}}ng/dL (0.3{{nbsp}}nmol/L) in [[premenopausal]] women and 3{{nbsp}}ng/dL (0.1{{nbsp}}nmol/L) in [[postmenopausal]] women.<ref name="pmid28472278" /> There was no variation in DHT levels across the [[menstrual cycle]] in premenopausal women, which is in contrast to testosterone (which shows a peak at [[mid-cycle]]).<ref name="pmid28472278" /> With [[immunoassay]]-based techniques, testosterone levels in premenopausal women have been found to be about 40{{nbsp}}ng/dL (1.4{{nbsp}}nmol/L) and DHT levels about 10{{nbsp}}ng/dL (0.34{{nbsp}}nmol/L).<ref name="pmid28472278" /><ref name="pmid16772150">{{cite journal | vauthors = Stanczyk FZ | title = Diagnosis of hyperandrogenism: biochemical criteria | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 20 | issue = 2 | pages = 177–191 | date = June 2006 | pmid = 16772150 | doi = 10.1016/j.beem.2006.03.007 }}</ref> With [[radioimmunoassay]]s, the ranges for testosterone and DHT levels in women have been found to be 20 to 70{{nbsp}}ng/dL and 5 to 30{{nbsp}}ng/dL, respectively.<ref name="pmid16772150" />

Levels of total testosterone, free testosterone, and free DHT, but not total DHT, all measured with [[LC–MS/MS]], are higher in women with [[polycystic ovary syndrome]] (PCOS) than in women without this condition.<ref name="pmid28472278" /><ref name="pmid25387259">{{cite journal | vauthors = Münzker J, Hofer D, Trummer C, Ulbing M, Harger A, Pieber T, Owen L, Keevil B, Brabant G, Lerchbaum E, Obermayer-Pietsch B | display-authors = 6 | title = Testosterone to dihydrotestosterone ratio as a new biomarker for an adverse metabolic phenotype in the polycystic ovary syndrome | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 100 | issue = 2 | pages = 653–660 | date = February 2015 | pmid = 25387259 | doi = 10.1210/jc.2014-2523 | doi-access = free }}</ref>

Circulating DHT levels in eugonadal men are about 7- to 10-fold lower than those of testosterone, and plasma levels of testosterone and DHT are highly correlated ([[correlation coefficient]] of 0.7).<ref name="pmid28472278" /><ref name="HayWass2009" /> In contrast to the circulation however, levels of DHT in the prostate gland are approximately 5- to 10-fold higher than those of testosterone.<ref name="HayWass2009">{{cite book | vauthors = Hay ID, Wass JA | title = Clinical Endocrine Oncology|url=https://books.google.com/books?id=fGio-5vtqqkC&pg=PA37|date=2009|publisher=John Wiley & Sons|isbn=978-1-4443-0023-9|pages=37–}}</ref> This is due to a more than 90% conversion of testosterone into DHT in the prostate via locally expressed [[5α-reductase]].<ref name="HayWass2009" /> Because of this, and because DHT is much more potent as an androgen receptor agonist than testosterone,<ref name="MozayaniRaymon2011" /> DHT is the major androgen in the prostate gland.<ref name="HayWass2009" />

==Medical use==

{{Main|Androstanolone}}

DHT is available in [[pharmaceutical drug|pharmaceutical]] [[drug form|formulation]]s for [[medicine|medical use]] as an [[androgen]] or [[anabolic–androgenic steroid]] (AAS).<ref name="HydeGengenbach2007">{{cite book | vauthors = Hyde TE, Gengenbach MS | title = Conservative Management of Sports Injuries|url=https://books.google.com/books?id=uzPwfNYyjjUC&pg=PA1100|year=2007|publisher=Jones & Bartlett Learning|isbn=978-0-7637-3252-3|pages=1100–}}</ref> It is used mainly in the treatment of male [[hypogonadism]].<ref name="AdisInsight" /> When used as a medication, dihydrotestosterone is referred to as ''androstanolone'' ({{abbrlink|INN|International Nonproprietary Name}}) or as ''stanolone'' ({{abbrlink|BAN|British Approved Name}}),<ref name="HydeGengenbach2007" /><ref name="Elks2014">{{cite book | vauthors = Elks J | title = The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA640|year=2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=640–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA63|date=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=63–}}</ref> and is sold under brand names such as ''Andractim'' among others.<ref name="HydeGengenbach2007" /><ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="AdisInsight" /><ref name="ListHörhammer2013">{{cite book | vauthors = List PH, Hörhammer L | title = Chemikalien und Drogen: Teil B: R, S|url=https://books.google.com/books?id=VXutBgAAQBAJ&pg=PA523|date=2013|publisher=Springer-Verlag|isbn=978-3-642-66377-2|pages=523–}}</ref> The availability of pharmaceutical DHT is limited; it is not available in the [[United States]] or [[Canada]],<ref name="Drugs@FDA">{{cite web |title=Drugs@FDA: FDA Approved Drug Products |publisher=United States Food and Drug Administration |access-date=16 November 2016 |url=http://www.accessdata.fda.gov/scripts/cder/daf/ |archive-date=16 November 2016 |archive-url=https://web.archive.org/web/20161116164727/http://www.accessdata.fda.gov/scripts/cder/daf/ |url-status=live }}</ref><ref name="DPD@HealthCanada">{{cite web |title=Drug Product Database |date=18 March 2010 |publisher=Health Canada |url=http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php |access-date=13 November 2016 |archive-date=19 November 2016 |archive-url=https://web.archive.org/web/20161119200516/http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php |url-status=live }}</ref> but is available in certain [[Europe]]an countries.<ref name="IndexNominum2000" /><ref name="AdisInsight">{{cite web | url = https://adisinsight.springer.com/drugs/800011409 | title = Androstanolone Drug Profile | work = Adis Insight | date = 4 December 2006 | access-date = 13 December 2016 | archive-date = 15 February 2021 | archive-url = https://web.archive.org/web/20210215182303/https://adisinsight.springer.com/drugs/800011409 | url-status = live }}</ref> The available formulations of DHT include [[buccal administration|buccal]] or [[sublingual administration|sublingual]] [[tablet (pharmacy)|tablet]]s, [[topical gels]], and, as [[ester]]s in [[oil]], [[injectable]]s like [[androstanolone propionate]] and [[androstanolone valerate]].<ref name="HydeGengenbach2007" /><ref name="AdisInsight" /><ref name="ListHörhammer2013" />

==Performance enhancement==

DHT has been used as a [[performance enhancing drug]], specifically as an alternative to [[testosterone]], as it was once known to be capable of falsifying drug tests.{{sfn|Mottram|2003}}

==Chemistry==

DHT, also known as 5α-androstan-17β-ol-3-one, is a [[natural product|naturally occurring]] [[androstane]] [[steroid]] with a [[ketone group]] at the C3 position and a [[hydroxyl group]] at the C17β position. It is the [[chemical derivative|derivative]] of testosterone in which the [[double bond]] between the C4 and C5 positions has been [[redox|reduced]] or [[hydrogenation|hydrogenated]].

==History==

DHT was first [[chemical synthesis|synthesized]] by [[Adolf Butenandt]] and his colleagues in 1935.<ref name="Schnitzer1967">{{cite book | vauthors = Schnitzer R | title = Experimental Chemotherapy|url=https://books.google.com/books?id=elAJWRnKqDEC&pg=PA156|year= 1967|publisher=Elsevier Science|isbn=978-0-323-14611-1|pages=156–}}</ref><ref name="Krüskemper2013">{{cite book | vauthors = Krüskemper HL | title = Anabolic Steroids|url=https://books.google.com/books?id=4xIlBQAAQBAJ&pg=PA12|year=2013|publisher=Elsevier|isbn=978-1-4832-6504-9|pages=12–}}</ref> It was prepared via [[hydrogenation]] of testosterone,<ref name="Krüskemper2013" /> which had been discovered earlier that year.<ref name="M.D.2002">{{cite book | vauthors = Taylor WN | title = Anabolic Steroids and the Athlete|edition=2d|url=https://books.google.com/books?id=OGcQ0Tp2AFcC&pg=PA178|year=2002|publisher=McFarland|isbn=978-0-7864-1128-3|pages=178–}}</ref> DHT was introduced for medical use as an AAS in 1953, and was noted to be more potent than testosterone but with reduced androgenicity.<ref name="Publishing2007">{{cite book|title=Pharmaceutical Manufacturing Encyclopedia|url=https://books.google.com/books?id=dXpUAAAAMAAJ|year=2007|publisher=William Andrew Pub.|isbn=978-0-8155-1526-5}}</ref><ref name="Newsweek1953">{{cite book|title=Newsweek|url=https://books.google.com/books?id=tsALAQAAIAAJ|year=1953|publisher=Newsweek}}</ref><ref name="Lippincott1958">{{cite book|title=New and Nonofficial Drugs|url=https://books.google.com/books?id=eY4wAAAAIAAJ|year=1958|publisher=Lippincott}}</ref> It was not elucidated to be an endogenous substance until 1956, when it was shown to be formed from testosterone in rat liver homogenates.<ref name="Krüskemper2013" /><ref name="pmid13323010">{{cite journal | vauthors = Rubin BL, Dorfman RI | title = In vitro conversion of testosterone to 17beta-hydroxyandrostan-3-one | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 91 | issue = 4 | pages = 585–586 | date = April 1956 | pmid = 13323010 | doi = 10.3181/00379727-91-22337 | s2cid = 36534106 }}</ref> In addition, the biological importance of DHT was not realized until the early 1960s, when it was found to be produced by 5α-reductase from circulating testosterone in target tissues like the prostate gland and seminal vesicles and was found to be more potent than testosterone in bioassays.<ref name="Agmo2011">{{cite book | vauthors = Agmo A | title = Functional and Dysfunctional Sexual Behavior: A Synthesis of Neuroscience and Comparative Psychology|url=https://books.google.com/books?id=mmJjj6UvB9YC&pg=PA196|date=2011|publisher=Academic Press|isbn=978-0-08-054938-5|pages=196–}}</ref><ref name="OreopoulosMichelis2012">{{cite book | vauthors = Oreopoulos DG, Michelis M, Herschorn S | title = Nephrology and Urology in the Aged Patient|url=https://books.google.com/books?id=8BioBgAAQBAJ&pg=PA495|date= 2012|publisher=Springer Science & Business Media|isbn=978-94-011-1822-4|pages=495–}}</ref><ref name="WebsterRawlings2007">{{cite book | vauthors = Webster GF, Rawlings AV | title = Acne and Its Therapy|url=https://books.google.com/books?id=sx_cua_GYS4C&pg=PA168|year=2007|publisher=CRC Press|isbn=978-1-4200-1841-7|pages=168–}}</ref><ref name="SmithMitchell2013">{{cite book | vauthors = Smith LB, Mitchell RT, McEwan IJ | title=Testosterone: From Basic Research to Clinical Applications|url=https://books.google.com/books?id=wH69BAAAQBAJ&pg=PA5|date= 2013|publisher=Springer Science & Business Media|isbn=978-1-4614-8978-8|pages=5–}}</ref> The biological functions of DHT in humans became much more clearly defined upon the discovery and characterization of 5α-reductase type 2 deficiency in 1974.<ref name="pmid22333687" /> DHT was the last major sex hormone, the others being testosterone, [[estradiol]], and [[progesterone]], to be discovered, and is unique in that it is the only major sex hormone that functions principally as an intracrine and paracrine hormone rather than as an endocrine hormone.<ref name="pmid28582536">{{cite journal | vauthors = Anawalt BD | title = Is Dihydrotestosterone a Classic Hormone? | journal = Endocrine Reviews | volume = 38 | issue = 3 | pages = 170–172 | date = June 2017 | pmid = 28582536 | doi = 10.1210/er.2017-00091 | doi-access = free }}</ref>

DHT was{{when|date=May 2023}} one of the original "underground" methods used to falsify drug testing in sport, as DHT does not alter the ratio of testosterone to [[Epitestosterone|epistestosterone]] in an athlete's urinary steroid profile, a measurement that was once the basis of drug tests used to detect steroid use. However, DHT use can still be detected by other means which are now universal in athletic drug tests, such as metabolite analysis.<ref name="Mottram-2003">{{cite book |vauthors=Mottram D |title=Drugs in Sport |date=2003 |publisher=Routledge |isbn=978-1-134-53575-0 |page=165 |url=https://books.google.com/books?id=x4uBAgAAQBAJ&pg=PA165 |language=en |access-date=21 January 2023 |archive-date=21 January 2023 |archive-url=https://web.archive.org/web/20230121014451/https://books.google.com/books?id=x4uBAgAAQBAJ&pg=PA165 |url-status=live }}</ref>

In 2004, Richard Auchus, in a review published in [[Trends in Endocrinology and Metabolism]] coined the term "backdoor pathway" as a [[metabolic route]] to DHT that: 1) bypasses conventional intermediates [[androstenedione]] and testosterone; 2) involves [[5α-Reductase|5α-reduction]] of 21-carbon (C21) [[Pregnane#Pregnanes|pregnanes]] to 19-carbon (C19) [[Androstane#Androstanes|androstanes]]; and 3) involves the 3α-oxidation of [[5α-androstane-3α,17β-diol]] to DHT. This newly discovered pathway explained how DHT is produced under certain normal and pathological conditions in humans when the classical androgen pathway (via testosterone) cannot fully explain the observed consequences.<ref name="pmid15519890"/> This review was based on earlier works (published in 2000–2004) by Shaw et al., Wilson et al., and Mahendroo et al., who studied DHT biosynthesis in tammar wallaby pouch young and mice.<ref name=wj/>

In 2011, Chang et al.<ref name="pmid21795608">{{cite journal | vauthors = Chang KH, Li R, Papari-Zareei M, Watumull L, Zhao YD, Auchus RJ, Sharifi N | title = Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 33 | pages = 13728–13733 | date = August 2011 | pmid = 21795608 | pmc = 3158152 | doi = 10.1073/pnas.1107898108 | publisher = Proceedings of the National Academy of Sciences | bibcode = 2011PNAS..10813728C | doi-access = free }}</ref> demonstrated that yet another metabolic pathway to DHT was dominant and possibly essential in castration-resistant prostate cancer (CRPC). This pathway can be outlined as [[androstenedione]] → [[5α-androstanedione|5α-androstane-3,17-dione]] → DHT. While this pathway was described as the "5α-dione pathway" in a 2012 review,<ref name="pmid22064602">{{cite journal | vauthors = Sharifi N | title = The 5α-androstanedione pathway to dihydrotestosterone in castration-resistant prostate cancer | journal = Journal of Investigative Medicine | volume = 60 | issue = 2 | pages = 504–507 | date = February 2012 | pmid = 22064602 | pmc = 3262939 | doi = 10.2310/JIM.0b013e31823874a4 }}</ref> the existence of such a pathway in the prostate was hypothesized in a 2008 review by Luu-The et al.<ref name="pmid18471780">{{cite journal | vauthors = Luu-The V, Bélanger A, Labrie F | title = Androgen biosynthetic pathways in the human prostate | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 22 | issue = 2 | pages = 207–221 | date = April 2008 | pmid = 18471780 | doi = 10.1016/j.beem.2008.01.008 | publisher = Elsevier BV }}</ref><ref name=wj/>

== References ==

* {{Creative Commons text attribution notice|cc=by4|url=https://en.wikiversity.org/wiki?curid=269289}}

{{Reflist}}

{{Endogenous steroids}}

{{Androgens and antiandrogens}}

{{Navboxes

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{{Androgen receptor modulators}}

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[[Category:5α-Reduced steroid metabolites]]

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[[Category:Animal reproductive system]]

[[Category:Cyclopentanols]]

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[[Category:Hormones of the hypothalamus-pituitary-gonad axis]]

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[[Category:Human hormones]]

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[[Category:Selective ERβ agonists]]

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[[Category:Testosterone]]