Editing Testosterone (section)

==Biochemistry==
[[File:Steroidogenesis.svg|thumb|upright=2|{{vanchor|Figure 1}}: Human [[steroidogenesis]], showing testosterone near bottom<ref name="HäggströmRichfield2014">{{cite journal | vauthors = Häggström M, Richfield D |year=2014|title=Diagram of the pathways of human steroidogenesis|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.005|doi-access=free}}</ref>]]

===Biosynthesis===
Like other [[steroid]] hormones, testosterone is derived from [[cholesterol]] {{Crossreference|([[#Figure 1|Figure 1]])}}.<ref name="pmid1307739">{{cite journal | vauthors = Waterman MR, Keeney DS | title = Genes involved in androgen biosynthesis and the male phenotype | journal = Hormone Research | volume = 38 | issue = 5–6 | pages = 217–21 | year = 1992 | pmid = 1307739 | doi = 10.1159/000182546 }}</ref> The first step in the [[biosynthesis]] involves the oxidative cleavage of the side-chain of cholesterol by [[cholesterol side-chain cleavage enzyme]] (P450scc, CYP11A1), a [[mitochondrion|mitochondrial]] [[cytochrome P450]] oxidase with the loss of six carbon atoms to give [[pregnenolone]]. In the next step, two additional carbon atoms are removed by the [[CYP17A1]] (17α-hydroxylase/17,20-lyase) enzyme in the [[endoplasmic reticulum]] to yield a variety of C<sub>19</sub> steroids.<ref name="pmid3535074">{{cite journal | vauthors = Zuber MX, Simpson ER, Waterman MR | title = Expression of bovine 17 alpha-hydroxylase cytochrome P-450 cDNA in nonsteroidogenic (COS 1) cells | journal = Science | volume = 234 | issue = 4781 | pages = 1258–61 | date = Dec 1986 | pmid = 3535074 | doi = 10.1126/science.3535074 | bibcode = 1986Sci...234.1258Z }}</ref> In addition, the 3β-hydroxyl group is oxidized by [[3β-hydroxysteroid dehydrogenase]] to produce [[androstenedione]]. In the final and rate limiting step, the C17 keto group androstenedione is reduced by [[17β-hydroxysteroid dehydrogenase]] to yield testosterone.

The largest amounts of testosterone (>95%) are produced by the [[testis|testes]] in men,<ref name="pmid3549275"/> while the [[adrenal gland]]s account for most of the remainder. Testosterone is also synthesized in far smaller total quantities in women by the adrenal glands, [[theca of follicle|thecal cells]] of the [[ovary|ovaries]], and, during [[pregnancy]], by the [[placenta]].<ref name="pmid15507105">{{cite journal | vauthors = Zouboulis CC, Degitz K | title = Androgen action on human skin – from basic research to clinical significance | journal = Experimental Dermatology | volume = 13 | issue = Suppl 4 | pages = 5–10 | year = 2004 | pmid = 15507105 | doi = 10.1111/j.1600-0625.2004.00255.x | s2cid = 34863608 }}</ref> In the testes, testosterone is produced by the [[Leydig cell]]s.<ref name="pmid58744">{{cite journal | vauthors = Brooks RV | title = Androgens | journal = Clinics in Endocrinology and Metabolism | volume = 4 | issue = 3 | pages = 503–20 | date = Nov 1975 | pmid = 58744 | doi = 10.1016/S0300-595X(75)80045-4 }}</ref> The male generative glands also contain [[Sertoli cell]]s, which require testosterone for [[spermatogenesis]]. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific [[plasma protein]], [[sex hormone-binding globulin]] (SHBG).

{{Production rates, secretion rates, clearance rates, and blood levels of major sex hormones}}

====Regulation====
[[File:Hypothalamus pituitary testicles axis.png|thumb|right|{{vanchor|Figure 2}}. Hypothalamic–pituitary–testicular axis]]

In males, testosterone is synthesized primarily in [[Leydig cells]]. The number of Leydig cells in turn is regulated by [[luteinizing hormone]] (LH) and [[follicle-stimulating hormone]] (FSH). In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH, which regulates the expression of [[17β-hydroxysteroid dehydrogenase]].<ref name="isbn0-9627422-7-9">{{cite book | vauthors =  Payne AH, O'Shaughnessy P |veditors=Payne AH, Hardy MP, Russell LD | title = Leydig Cell | publisher = Cache River Press | location = Vienna [Il] | year = 1996 | pages = 260–85 | isbn = 978-0-9627422-7-9 | chapter = Structure, function, and regulation of steroidogenic enzymes in the Leydig cell }}</ref>

The amount of testosterone synthesized is regulated by the [[hypothalamic–pituitary–gonadal axis|hypothalamic–pituitary–testicular axis]] {{crossreference|([[#Figure 2|Figure 2]])}}.<ref name="pmid1377467">{{cite journal | vauthors = Swerdloff RS, Wang C, Bhasin S | title = Developments in the control of testicular function | journal = Baillière's Clinical Endocrinology and Metabolism | volume = 6 | issue = 2 | pages = 451–83 | date = Apr 1992 | pmid = 1377467 | doi = 10.1016/S0950-351X(05)80158-2 }}</ref> When testosterone levels are low, gonadotropin-releasing hormone ([[gonadotropin-releasing hormone|GnRH]]) is released by the [[hypothalamus]], which in turn stimulates the [[pituitary gland]] to release FSH and LH. These latter two hormones stimulate the testis to synthesize testosterone.  Finally, increasing levels of testosterone through a negative [[feedback]] loop act on the hypothalamus and pituitary to inhibit the release of GnRH and FSH/LH, respectively.

Factors affecting testosterone levels may include:
* Age: Testosterone levels gradually reduce as men age.<ref name="pmid25009850">{{cite book | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK216164/ | title = Testosterone and Aging: Clinical Research Directions. | chapter = Introduction | collaboration = Institute of Medicine (US) Committee on Assessing the Need for Clinical Trials of Testosterone Replacement Therapy | vauthors = Liverman CT, Blazer DG | date = January 1, 2004 | publisher = National Academies Press (US) | via = www.ncbi.nlm.nih.gov | isbn = 978-0-309-09063-6 | doi = 10.17226/10852 | pmid = 25009850 | access-date = September 26, 2016 | archive-date = January 10, 2016 | archive-url = https://web.archive.org/web/20160110170928/http://www.ncbi.nlm.nih.gov/books/NBK216164/ | url-status = live }}</ref><ref name="pmid24407185">{{cite journal | vauthors = Huhtaniemi I | title = Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment | journal = Asian Journal of Andrology | volume = 16 | issue = 2 | pages = 192–202 | year = 2014 | pmid = 24407185 | pmc = 3955328 | doi = 10.4103/1008-682X.122336 | doi-access = free }}</ref> This effect is sometimes referred to as [[andropause]] or [[late-onset hypogonadism]].<ref name="pmid24793989">{{cite journal | vauthors = Huhtaniemi IT | title = Andropause--lessons from the European Male Ageing Study | journal = Annales d'Endocrinologie | volume = 75 | issue = 2 | pages = 128–31 | year = 2014 | pmid = 24793989 | doi = 10.1016/j.ando.2014.03.005 }}</ref>
* Exercise: [[Strength training|Resistance training]] increases testosterone levels acutely,<ref name="Vingren_2010">{{cite journal | vauthors = Vingren JL, Kraemer WJ, Ratamess NA, Anderson JM, Volek JS, Maresh CM | s2cid = 11683565 | title = Testosterone physiology in resistance exercise and training: the up-stream regulatory elements | journal = Sports Medicine | volume = 40 | issue = 12 | pages = 1037–53 | year = 2010 | pmid = 21058750 | doi = 10.2165/11536910-000000000-00000 }}</ref>  however, in older men, that increase can be avoided by protein ingestion.<ref name="pmid18455389">{{cite journal | vauthors = Hulmi JJ, Ahtiainen JP, Selänne H, Volek JS, Häkkinen K, Kovanen V, Mero AA | s2cid = 26280370 | title = Androgen receptors and testosterone in men—effects of protein ingestion, resistance exercise and fiber type | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 110 | issue = 1–2 | pages = 130–37 | date = May 2008 | pmid = 18455389 | doi = 10.1016/j.jsbmb.2008.03.030 }}</ref> [[Endurance training]] in men may lead to lower testosterone levels.<ref name="pmid16268050">{{cite journal | vauthors = Hackney AC, Moore AW, Brownlee KK | title = Testosterone and endurance exercise: development of the "exercise-hypogonadal male condition" | journal = Acta Physiologica Hungarica | volume = 92 | issue = 2 | pages = 121–37 | year = 2005 | pmid = 16268050 | doi = 10.1556/APhysiol.92.2005.2.3 }}</ref>
* Nutrients: [[Vitamin A deficiency]] may lead to sub-optimal plasma testosterone levels.<ref name="pmid12141930">{{cite journal | vauthors = Livera G, Rouiller-Fabre V, Pairault C, Levacher C, Habert R | title = Regulation and perturbation of testicular functions by vitamin A | journal = Reproduction | volume = 124 | issue = 2 | pages = 173–180 | date = August 2002 | pmid = 12141930 | doi = 10.1530/rep.0.1240173 | doi-access = free }}</ref> The secosteroid [[vitamin D]] in levels of 400–1000&nbsp;[[international unit|IU]]/d (10–25&nbsp;μg/d) raises testosterone levels.<ref name="pmid21154195">{{cite journal | vauthors = Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J, Obermayer-Pietsch B, Wehr E, Zittermann A | title = Effect of vitamin D supplementation on testosterone levels in men | journal = Hormone and Metabolic Research | volume = 43 | issue = 3 | pages = 223–225 | date = March 2011 | pmid = 21154195 | doi = 10.1055/s-0030-1269854 | s2cid = 206315145 | doi-access = free }}</ref> [[Zinc deficiency]] lowers testosterone levels<ref name="pmid8875519">{{cite journal | vauthors = Prasad AS, Mantzoros CS, Beck FW, Hess JW, Brewer GJ | title = Zinc status and serum testosterone levels of healthy adults | journal = Nutrition | volume = 12 | issue = 5 | pages = 344–348 | date = May 1996 | pmid = 8875519 | doi = 10.1016/S0899-9007(96)80058-X | citeseerx = 10.1.1.551.4971 }}</ref> but over-supplementation has no effect on serum testosterone.<ref name="pmid17882141">{{cite journal | vauthors = Koehler K, Parr MK, Geyer H, Mester J, Schänzer W | title = Serum testosterone and urinary excretion of steroid hormone metabolites after administration of a high-dose zinc supplement | journal = European Journal of Clinical Nutrition | volume = 63 | issue = 1 | pages = 65–70 | date = January 2009 | pmid = 17882141 | doi = 10.1038/sj.ejcn.1602899 | doi-access = free }}</ref> There is limited evidence that [[low-fat diet]]s may reduce total and [[#Free testosterone|free testosterone]] levels in men.<ref>{{cite journal | vauthors = Whittaker J, Wu K | title = Low-fat diets and testosterone in men: Systematic review and meta-analysis of intervention studies | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 210 | pages = 105878 | date = June 2021 | pmid = 33741447 | doi = 10.1016/j.jsbmb.2021.105878 | arxiv = 2204.00007 | s2cid = 232246357 }}</ref>
* Weight loss: Reduction in weight may result in an increase in testosterone levels. Fat cells synthesize the enzyme aromatase, which converts testosterone, the male sex hormone, into estradiol, the female sex hormone.<ref name="pmid21849026">{{cite journal | vauthors = Håkonsen LB, Thulstrup AM, Aggerholm AS, Olsen J, Bonde JP, Andersen CY, Bungum M, Ernst EH, Hansen ML, Ernst EH, Ramlau-Hansen CH | title = Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men | journal = Reproductive Health | volume = 8 | issue = 1 | page = 24 | year = 2011 | pmid = 21849026 | pmc = 3177768 | doi = 10.1186/1742-4755-8-24 | doi-access = free }}</ref>  However no clear association between [[body mass index]] and testosterone levels has been found.<ref name="pmid19889752">{{cite journal | vauthors = MacDonald AA, Herbison GP, Showell M, Farquhar CM | title = The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis | journal = Human Reproduction Update | volume = 16 | issue = 3 | pages = 293–311 | year = 2010 | pmid = 19889752 | doi = 10.1093/humupd/dmp047 | doi-access = free }}</ref>
* Miscellaneous: ''Sleep'': ([[REM sleep]]) increases nocturnal testosterone levels.<ref name="pmid18519168">{{cite journal | vauthors = Andersen ML, Tufik S | title = The effects of testosterone on sleep and sleep-disordered breathing in men: its bidirectional interaction with erectile function | journal = Sleep Medicine Reviews | volume = 12 | issue = 5 | pages = 365–79 | date = Oct 2008 | pmid = 18519168 | doi = 10.1016/j.smrv.2007.12.003 }}</ref> 
* Behavior:  Dominance challenges can, in some cases, stimulate increased testosterone release in men.<ref name="pmid10603287">{{cite journal | vauthors = Schultheiss OC, Campbell KL, McClelland DC | s2cid = 6002474 | title = Implicit power motivation moderates men's testosterone responses to imagined and real dominance success | journal = Hormones and Behavior | volume = 36 | issue = 3 | pages = 234–41 | date = Dec 1999 | pmid = 10603287 | doi = 10.1006/hbeh.1999.1542 | citeseerx = 10.1.1.326.9322 }}</ref> 
* Foods: Natural or man-made [[antiandrogens]] including [[spearmint]] tea reduce testosterone levels.<ref name="pmid17310494">{{cite journal | vauthors = Akdoğan M, Tamer MN, Cüre E, Cüre MC, Köroğlu BK, Delibaş N | title = Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism | journal = Phytotherapy Research | volume = 21 | issue = 5 | pages = 444–47 | date = May 2007 | pmid = 17310494 | doi = 10.1002/ptr.2074 | s2cid = 21961390 }}</ref><ref name="pmid18804513">{{cite journal | vauthors = Kumar V, Kural MR, Pereira BM, Roy P | title = Spearmint induced hypothalamic oxidative stress and testicular anti-androgenicity in male rats - altered levels of gene expression, enzymes and hormones | journal = Food and Chemical Toxicology | volume = 46 | issue = 12 | pages = 3563–70 | date = Dec 2008 | pmid = 18804513 | doi = 10.1016/j.fct.2008.08.027 }}</ref><ref name="pmid19585478">{{cite journal | vauthors = Grant P | title = Spearmint herbal tea has significant anti-androgen effects in polycystic ovarian syndrome. A randomized controlled trial | journal = Phytotherapy Research | volume = 24 | issue = 2 | pages = 186–88 | date = Feb 2010 | pmid = 19585478 | doi = 10.1002/ptr.2900 | s2cid = 206425734 }}</ref> [[Licorice]] can decrease the production of testosterone and this effect is greater in females.<ref>{{cite journal | vauthors = Armanini D, Fiore C, Mattarello MJ, Bielenberg J, Palermo M | title = History of the endocrine effects of licorice | journal = Experimental and Clinical Endocrinology & Diabetes | volume = 110 | issue = 6 | pages = 257–61 | date = Sep 2002 | pmid = 12373628 | doi = 10.1055/s-2002-34587 }}</ref>

===Distribution===
The [[plasma protein binding]] of testosterone is 98.0 to 98.5%, with 1.5 to 2.0% free or unbound.<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=26 July 2012 |publisher=Cambridge University Press |isbn=978-1-107-01290-5 |pages=61– |access-date=March 23, 2018 |archive-date=January 11, 2023 |archive-url=https://web.archive.org/web/20230111143032/https://books.google.com/books?id=MkrAPaQ4wJkC&pg=PA61 |url-status=live }}</ref> It is bound 65% to [[sex hormone-binding globulin]] (SHBG) and 33% bound weakly to [[human serum albumin|albumin]].<ref name="pmid4044776">{{cite journal | vauthors = Cumming DC, Wall SR | title = Non-sex hormone-binding globulin-bound testosterone as a marker for hyperandrogenism | journal = The Journal of Clinical Endocrinology & Metabolism| volume = 61 | issue = 5 | pages = 873–6 | date = November 1985 | pmid = 4044776 | doi = 10.1210/jcem-61-5-873 }}</ref>

{{Plasma protein binding of testosterone and dihydrotestosterone}}

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

Both testosterone and 5α-DHT are [[metabolism|metabolized]] mainly in the [[liver]].<ref name="MelmedPolonsky2015">{{cite book | vauthors = Melmed S, Polonsky KD, Larsen PR, Kronenberg HM | title = Williams Textbook of Endocrinology | url = https://books.google.com/books?id=YZ8_CwAAQBAJ&pg=PA711 | date = 30 November 2015 | publisher = Elsevier Health Sciences|isbn=978-0-323-29738-7 | pages = 711– }}</ref><ref name="Becker2001">{{cite book | vauthors = Becker KL | title = Principles and Practice of Endocrinology and Metabolism | url = https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1116 | year = 2001 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-1750-2 | pages = 1116, 1119, 1183 | access-date = November 3, 2016 | archive-date = January 11, 2023 | archive-url = https://web.archive.org/web/20230111143043/https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1116 | url-status = live }}</ref> Approximately 50% of testosterone is metabolized via [[conjugation (biochemistry)|conjugation]] into [[testosterone glucuronide]] and to a lesser extent [[testosterone sulfate]] by [[glucuronosyltransferase]]s and [[sulfotransferase]]s, respectively.<ref name="MelmedPolonsky2015" /> An additional 40% of testosterone is metabolized in equal proportions into the [[17-ketosteroid]]s [[androsterone]] and [[etiocholanolone]] via the combined actions of [[5α-reductase|5α-]] and [[5β-reductase]]s, [[3α-hydroxysteroid dehydrogenase]], and 17β-HSD, in that order.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /><ref name="WeckerWatts2009">{{cite book | vauthors = Wecker L, Watts S, Faingold C, Dunaway G, Crespo L | title = Brody's Human Pharmacology | url = https://books.google.com/books?id=kfsrz_-OrMQC&pg=PA468 | date = 1 April 2009 | publisher = Elsevier Health Sciences | isbn = 978-0-323-07575-6 | pages = 468–469 | access-date = November 3, 2016 | archive-date = January 11, 2023 | archive-url = https://web.archive.org/web/20230111143031/https://books.google.com/books?id=kfsrz_-OrMQC&pg=PA468 | url-status = live }}</ref> Androsterone and etiocholanolone are then [[glucuronidation|glucuronidated]] and to a lesser extent [[sulfation|sulfated]] similarly to testosterone.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /> The conjugates of testosterone and its hepatic metabolites are released from the liver into [[circulatory system|circulation]] and [[excretion|excreted]] in the [[urine]] and [[bile]].<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /><ref name="WeckerWatts2009" /> Only a small fraction (2%) of testosterone is excreted unchanged in the urine.<ref name="Becker2001" />

In the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive [[5β-Dihydrotestosterone|5β-DHT]], respectively.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /> Then, 5α-DHT and 5β-DHT are converted by 3α-HSD into [[3α-androstanediol]] and [[3α-etiocholanediol]], respectively.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /> Subsequently, 3α-androstanediol and 3α-etiocholanediol are converted by 17β-HSD into androsterone and etiocholanolone, which is followed by their conjugation and excretion.<ref name="MelmedPolonsky2015" /><ref name="Becker2001" /> [[3β-Androstanediol]] and [[3β-etiocholanediol]] can also be formed in this pathway when 5α-DHT and 5β-DHT are acted upon by 3β-HSD instead of 3α-HSD, respectively, and they can then be transformed into [[epiandrosterone]] and [[epietiocholanolone]], respectively.<ref name="pmid20186052">{{cite journal | vauthors = Penning TM | title = New frontiers in androgen biosynthesis and metabolism | journal = Curr Opin Endocrinol Diabetes Obes | volume = 17 | issue = 3 | pages = 233–9 | year = 2010 | pmid = 20186052 | pmc = 3206266 | doi = 10.1097/MED.0b013e3283381a31 }}</ref><ref name="HorskyPresl2012">{{cite book | vauthors = Horsky J, Presl J | title = Ovarian Function and its Disorders: Diagnosis and Therapy | url = https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA107 | date = 6 December 2012 | publisher = Springer Science & Business Media | isbn = 978-94-009-8195-9 | pages = 107– | access-date = November 5, 2016 | archive-date = January 11, 2023 | archive-url = https://web.archive.org/web/20230111143033/https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA107 | url-status = live }}</ref> A small portion of approximately 3% of testosterone is [[reversible reaction|reversibly]] converted in the liver into [[androstenedione]] by 17β-HSD.<ref name="WeckerWatts2009" />

In addition to conjugation and the 17-ketosteroid pathway, testosterone can also be [[hydroxylation|hydroxylated]] and [[oxidation|oxidized]] in the liver by [[cytochrome P450]] [[enzyme]]s, including [[CYP3A4]], [[CYP3A5]], [[CYP2C9]], [[CYP2C19]], and [[CYP2D6]].<ref name="Zhou2016">{{cite book | vauthors = Zhou S | title=Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism | url = https://books.google.com/books?id=UJqmCwAAQBAJ&pg=PA242|date=6 April 2016 | publisher = CRC Press | isbn = 978-1-4665-9788-4 | pages = 242– }}</ref> 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations.<ref name="Zhou2016" /> The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism.<ref name="Zhou2016" /> In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites.<ref name="Zhou2016" /><ref name="isbn0-3870-8012-0">{{cite book | vauthors = Trager L | title = Steroidhormone: Biosynthese, Stoffwechsel, Wirkung | language = de | publisher = Springer-Verlag  | year = 1977 | page = 349  | isbn = 978-0-387-08012-3  }}</ref> Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.<ref name="Zhou2016" />

Two of the immediate metabolites of testosterone, 5α-DHT and [[estradiol]], are biologically important and can be formed both in the liver and in extrahepatic tissues.<ref name="Becker2001" /> Approximately 5 to 7% of testosterone is converted by 5α-reductase into 5α-DHT, with circulating levels of 5α-DHT about 10% of those of testosterone, and approximately 0.3% of testosterone is converted into estradiol by [[aromatase]].<ref name="pmid3549275"/><ref name="Becker2001" /><ref name="pmid8092979">{{cite journal | vauthors = Randall VA | title = Role of 5 alpha-reductase in health and disease | journal = Baillière's Clinical Endocrinology and Metabolism | volume = 8 | issue = 2 | pages = 405–31 | date = Apr 1994 | pmid = 8092979 | doi = 10.1016/S0950-351X(05)80259-9 }}</ref><ref name="pmid12428207">{{cite journal | vauthors = Meinhardt U, Mullis PE | title = The essential role of the aromatase/p450arom | journal = Seminars in Reproductive Medicine | volume = 20 | issue = 3 | pages = 277–84 | date = August 2002 | pmid = 12428207 | doi = 10.1055/s-2002-35374 | s2cid = 25407830 }}</ref> 5α-Reductase is highly expressed in the [[male reproductive system|male reproductive organ]]s (including the [[prostate gland]], [[seminal vesicle]]s, and [[epididymides]]),<ref name="Noakes2009">{{cite book | vauthors = Noakes DE | title=Arthur's Veterinary Reproduction and Obstetrics | url = https://books.google.com/books?id=W5TdAwAAQBAJ&pg=PA695 | date = 23 April 2009 | publisher = Elsevier Health Sciences UK | isbn = 978-0-7020-3990-4 | pages = 695– }}</ref> [[skin]], [[hair follicle]]s, and [[brain]]<ref name="NieschlagBehre2004">{{cite book | vauthors  = Nieschlag E, Behre HM | title = Testosterone: Action, Deficiency, Substitution | url = https://books.google.com/books?id=ZiZ7MWDqo5oC&pg=PA626 | date = 1 April 2004 | publisher = Cambridge University Press | isbn = 978-1-139-45221-2 | pages = 626– }}</ref> and aromatase is highly expressed in adipose tissue, [[bone]], and the brain.<ref name="Parl2000">{{cite book | vauthors = Parl FF | title = Estrogens, Estrogen Receptor and Breast Cancer | url = https://books.google.com/books?id=v7ai5Mz9TZQC&pg=PA25 | year = 2000 | publisher = IOS Press | isbn = 978-0-9673355-4-4 | pages = 25– }}</ref><ref name="NormanHenry2014">{{cite book | vauthors = Norman AW, Henry HL | title = Hormones|url=https://books.google.com/books?id=_renonjXq68C&pg=PA261 | date=30 July 2014 | publisher = Academic Press | isbn = 978-0-08-091906-5 | pages = 261– }}</ref> As much as 90% of testosterone is converted into 5α-DHT in so-called androgenic tissues with high 5α-reductase expression,<ref name="WeckerWatts2009" /> and due to the several-fold greater potency of 5α-DHT as an AR agonist relative to testosterone,<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 | date = 18 September 2011 | publisher = Springer Science & Business Media | isbn = 978-1-61779-222-9 | pages = 656– }}</ref> it has been estimated that the effects of testosterone are potentiated 2- to 3-fold in such tissues.<ref name="pmid7626464">{{cite journal | vauthors = Sundaram K, Kumar N, Monder C, Bardin CW | s2cid = 32619627 | title = Different patterns of metabolism determine the relative anabolic activity of 19-norandrogens | journal = J. Steroid Biochem. Mol. Biol. | volume = 53 | issue = 1–6 | pages = 253–7 | year = 1995 | pmid = 7626464 | doi = 10.1016/0960-0760(95)00056-6}}</ref>

===Levels===
Total levels of testosterone in the body have been reported as 264 to 916&nbsp;ng/dL (nanograms per deciliter) in non-obese European and American men age 19 to 39&nbsp;years,<ref name="pmid28324103">{{cite journal | vauthors = Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, Lapauw B, Fiers T, Matsumoto AM, Bhasin S | title = Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 102 | issue = 4 | pages = 1161–1173 | date = April 2017 | pmid = 28324103 | pmc = 5460736 | doi = 10.1210/jc.2016-2935 }}</ref> while mean testosterone levels in adult men have been reported as 630&nbsp;ng/dL.<ref name="Sperling2014" /> Although commonly used as a [[reference range]],<ref>{{cite web |title=Testosterone, total |url=https://www.labcorp.com/tests/004226/testosterone-total |website=LabCorp |access-date=20 December 2021 |archive-date=December 20, 2021 |archive-url=https://web.archive.org/web/20211220171446/https://www.labcorp.com/tests/004226/testosterone-total |url-status=live }}</ref> some physicians have disputed the use of this range to determine [[hypogonadism]].<ref>{{cite journal | vauthors = Morgentaler A | title = Andrology: Testosterone reference ranges and diagnosis of testosterone deficiency | journal = Nature Reviews. Urology | volume = 14 | issue = 5 | pages = 263–264 | date = May 2017 | pmid = 28266512 | doi = 10.1038/nrurol.2017.35 | s2cid = 29122481 }}</ref><ref>{{cite journal | vauthors = Morgentaler A, Khera M, Maggi M, Zitzmann M | title = Commentary: Who is a candidate for testosterone therapy? A synthesis of international expert opinions | journal = The Journal of Sexual Medicine | volume = 11 | issue = 7 | pages = 1636–1645 | date = July 2014 | pmid = 24797325 | doi = 10.1111/jsm.12546 }}</ref> Several professional medical groups have recommended that 350&nbsp;ng/dL generally be considered the minimum normal level,<ref>{{cite journal | vauthors = Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC | title = ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males | journal = International Journal of Impotence Research | volume = 21 | issue = 1 | pages = 1–8 | date = 16 October 208 | pmid = 18923415 | doi = 10.1038/ijir.2008.41 | s2cid = 30430279 | url = https://biblio.ugent.be/publication/631584/file/741306 | url-access = subscription }}</ref> which is consistent with previous findings.<ref>{{cite journal | vauthors = Bhasin S, Pencina M, Jasuja GK, Travison TG, Coviello A, Orwoll E, Wang PY, Nielson C, Wu F, Tajar A, Labrie F, Vesper H, Zhang A, Ulloor J, Singh R, D'Agostino R, Vasan RS | title = Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 96 | issue = 8 | pages = 2430–2439 | date = August 2011 | pmid = 21697255 | pmc = 3146796 | doi = 10.1210/jc.2010-3012 }}</ref>{{primary source inline|date=December 2021}}{{medical citation needed|date=December 2021}} Levels of testosterone in men decline with age.<ref name="pmid28324103" /> In women, mean levels of total testosterone have been reported to be 32.6&nbsp;ng/dL.<ref name="Camacho2012">{{cite book|vauthors=Camacho PM|title=Evidence-Based Endocrinology|url=https://books.google.com/books?id=s06wXkPAnfcC&pg=PA217|date=26 September 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-7146-4|pages=217–|access-date=May 19, 2018|archive-date=January 11, 2023|archive-url=https://web.archive.org/web/20230111143033/https://books.google.com/books?id=s06wXkPAnfcC&pg=PA217|url-status=live}}</ref><ref name="pmid15251757">{{cite journal | vauthors = Steinberger E, Ayala C, Hsi B, Smith KD, Rodriguez-Rigau LJ, Weidman ER, Reimondo GG | title = Utilization of commercial laboratory results in management of hyperandrogenism in women | journal = Endocrine Practice | volume = 4 | issue = 1 | pages = 1–10 | date = 1998 | pmid = 15251757 | doi = 10.4158/EP.4.1.1 }}</ref> In women with [[hyperandrogenism]], mean levels of total testosterone have been reported to be 62.1&nbsp;ng/dL.<ref name="Camacho2012" /><ref name="pmid15251757" />

{{Testosterone levels in males and females}}

{| class="wikitable mw-collapsible mw-collapsed" style="text-align:left; margin-left:auto; margin-right:auto; border:none;"
|+ class="nowrap" | Total testosterone levels in males throughout life
|-
! Life stage !! Tanner stage !! Age range !! Mean age !! Levels range !! Mean levels
|-
| Child || Stage I || <10 years || – || <30&nbsp;ng/dL || 5.8&nbsp;ng/dL
|-
| rowspan="4" | Puberty || Stage II || 10–14 years || 12 years || <167&nbsp;ng/dL || 40&nbsp;ng/dL
|-
| Stage III || 12–16 years || 13–14 years || 21–719&nbsp;ng/dL || 190&nbsp;ng/dL
|-
| Stage IV || 13–17 years || 14–15 years || 25–912&nbsp;ng/dL || 370&nbsp;ng/dL
|-
| Stage V || 13–17 years || 15 years || 110–975&nbsp;ng/dL || 550&nbsp;ng/dL
|-
| Adult || – || ≥18 years || – || 250–1,100&nbsp;ng/dL || 630&nbsp;ng/dL
|- class="sortbottom"
| colspan="6" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Sources:''' <ref name="BajajBerman2011">{{cite book|vauthors=Bajaj L, Berman S|title=Berman's Pediatric Decision Making|url=https://books.google.com/books?id=NPhnHrDQ1_kC&pg=PA160|date=1 January 2011|publisher=Elsevier Health Sciences|isbn=978-0-323-05405-8|pages=160–|access-date=March 25, 2018|archive-date=January 11, 2023|archive-url=https://web.archive.org/web/20230111143033/https://books.google.com/books?id=NPhnHrDQ1_kC&pg=PA160|url-status=live}}</ref><ref name="Styne2016">{{cite book|vauthors=Styne DM|title=Pediatric Endocrinology: A Clinical Handbook|url=https://books.google.com/books?id=akMWDAAAQBAJ&pg=PA191|date=25 April 2016|publisher=Springer|isbn=978-3-319-18371-8|pages=191–|access-date=March 25, 2018|archive-date=January 11, 2023|archive-url=https://web.archive.org/web/20230111143038/https://books.google.com/books?id=akMWDAAAQBAJ&pg=PA191|url-status=live}}</ref><ref name="Sperling2014">{{cite book|vauthors=Sperling MA|title=Pediatric Endocrinology E-Book|url=https://books.google.com/books?id=GgXnAgAAQBAJ&pg=PA488|date=10 April 2014|publisher=Elsevier Health Sciences|isbn=978-1-4557-5973-6|pages=488–|access-date=March 25, 2018|archive-date=January 11, 2023|archive-url=https://web.archive.org/web/20230111143036/https://books.google.com/books?id=GgXnAgAAQBAJ&pg=PA488|url-status=live}}</ref><ref name="PaganaPagana2014">{{cite book |vauthors=Pagana KD, Pagana TJ, Pagana TN |title=Mosby's Diagnostic and Laboratory Test Reference – E-Book |url=https://books.google.com/books?id=J7eXBAAAQBAJ&pg=PA879 |date=19 September 2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-22592-2 |pages=879– |access-date=March 25, 2018 |archive-date=January 11, 2023 |archive-url=https://web.archive.org/web/20230111143038/https://books.google.com/books?id=J7eXBAAAQBAJ&pg=PA879 |url-status=live }}</ref><ref name="HospitalEngorn2014">{{cite book |vauthors=Engorn B, Flerlage J |title=The Harriet Lane Handbook E-Book |url=https://books.google.com/books?id=6cSLAwAAQBAJ&pg=PA240 |date=1 May 2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-11246-8 |pages=240– |access-date=March 25, 2018 |archive-date=January 11, 2023 |archive-url=https://web.archive.org/web/20230111143039/https://books.google.com/books?id=6cSLAwAAQBAJ&pg=PA240 |url-status=live }}</ref>
|}

{{wide image|Blood values sorted by mass and molar concentration.png|1200px|[[Reference ranges for blood tests]], showing adult male testosterone levels in light blue at center-left}}