{{Short description|Medication and naturally occurring steroid hormone}}{{About|testosterone as a medication|the natural hormone|Testosterone}}{{Redirect|Testavan|the wine-tasting accessory|Tastevin}}{{Use mdy dates|date=February 2024}}{{cs1 config|name-list-style=vanc|display-authors=6}}{{Drugbox| Watchedfields = changed| verifiedrevid = 649778658| drug_name = Testosterone| image = Testosteron.svg| width = 225| alt =| image2 = Testosterone molecule ball.png| width2 = 225| alt2 =| caption =

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weblink" title="web.archive.org/web/20171201080834weblink">Testosterone. Oxford Dictionaries (website)>Oxford Dictionaries.

#Brand names>others

monograph|testosterone}}| MedlinePlus = a619028| DailyMedID = Testosterone| pregnancy_AU = D

DATE=AUGUST 20, 2019

ACCESS-DATE=JANUARY 8, 2020

ARCHIVE-URL=HTTPS://WEB.ARCHIVE.ORG/WEB/20140201201902/HTTP://WWW.DRUGS.COM/PREGNANCY/TESTOSTERONE.HTML, live,

Contraindication>Contraindicated due to teratogenic effects

Oral administration>By mouth, buccal administration

, sublingual administration>sublingual, intranasal administration

, transdermal administration>transdermal (gel, cream, transdermal patch

, Solution (chemistry)>solution), vaginal administration

(cream, gel, suppository), rectal administration>rectal (suppository), intramuscular injection

date=August 2023}}| legal_AU_comment =| legal_BR = C5

DATE=MARCH 31, 2023

TRANS-TITLE=COLLEGIATE BOARD RESOLUTION NO. 784 - LISTS OF NARCOTIC, PSYCHOTROPIC, PRECURSOR, AND OTHER SUBSTANCES UNDER SPECIAL CONTROL

URL-STATUS=LIVE

ARCHIVE-DATE=AUGUST 3, 2023

PUBLISHER=DIÃ¡RIO OFICIAL DA UNIÃ£O

PUBLICATION-DATE=APRIL 4, 2023,

date=August 2023}}| legal_CA_comment =

date=August 2023}}| legal_DE_comment =

date=August 2023}}| legal_NZ_comment =

date=August 2023}}| legal_UK_comment =

date=August 2023}}| legal_US_comment =| legal_EU = Rx-only

URL = HTTPS://WWW.EMA.EUROPA.EU/DOCUMENTS/PSUSA/TESTOSTERONE-ALL-FORMULATIONS-APART-TOPICAL-USE-LIST-NATIONALLY-AUTHORISED-MEDICINAL-PRODUCTS-PSUSA/00010631/202112_EN.PDF

PUBLISHER = EUROPEAN MEDICINES AGENCY

ACCESS-DATE = SEPTEMBER 6, 2022

ARCHIVE-URL = HTTPS://WEB.ARCHIVE.ORG/WEB/20220906054434/HTTPS://WWW.EMA.EUROPA.EU/EN/DOCUMENTS/PSUSA/TESTOSTERONE-ALL-FORMULATIONS-APART-TOPICAL-USE-LIST-NATIONALLY-AUTHORISED-MEDICINAL-PRODUCTS-PSUSA/00010631/202112_EN.PDF

URL = HTTPS://WWW.EMA.EUROPA.EU/DOCUMENTS/PSUSA/TESTOSTERONE-TOPICAL-USE-LIST-NATIONALLY-AUTHORISED-MEDICINAL-PRODUCTS-PSUSA/00002908/202112_EN.PDF

PUBLISHER = EUROPEAN MEDICINES AGENCY

ACCESS-DATE = SEPTEMBER 6, 2022

ARCHIVE-URL = HTTPS://WEB.ARCHIVE.ORG/WEB/20220906054434/HTTPS://WWW.EMA.EUROPA.EU/EN/DOCUMENTS/PSUSA/TESTOSTERONE-TOPICAL-USE-LIST-NATIONALLY-AUTHORISED-MEDICINAL-PRODUCTS-PSUSA/00002908/202112_EN.PDF, live,

date=August 2023}}| legal_UN_comment =| legal_status = Rx-only{{citation needed|date=August 2023}}

first pass effect>first pass metabolism)

SHBG

human serum albumin>albumin)MELMED S, POLONSKY KS, LARSEN PR>TITLE=WILLIAMS TEXTBOOK OF ENDOCRINOLOGY

DATE=NOVEMBER 11, 2015

ISBN=978-0-323-34157-8

ACCESS-DATE=NOVEMBER 18, 2016

ARCHIVE-URL=HTTPS://WEB.ARCHIVE.ORG/WEB/20190414214954/HTTPS://BOOKS.GOOGLE.COM/BOOKS?ID=IPIACWAAQBAJ&PG=PA709, live,

Liver (mainly redox>reduction and conjugation)| metabolites =| onset =

date=October 2016}}| duration_of_action =| excretion = Urine (90%), feces (6%)

correct|CAS}}| CAS_number = 58-22-0

57-85-2}} (propionate){{CAS

enanthate){{CAS>58-20-8}} (cypionate){{CAS|5949-44-0}} (undecanoate)| PubChem = 6013| IUPHAR_ligand = 2858

correct|drugbank}}| DrugBank = DB00624

correct|chemspider}}| ChemSpiderID = 5791

correct|FDA}}| UNII = 3XMK78S47O

correct|kegg}}| KEGG = D00075

correct|EBI}}| ChEBI = 17347

correct|EBI}}| ChEMBL = 386630| NIAID_ChemDB =| PDB_ligand =| synonyms = Androst-4-en-17Î²-ol-3-one| IUPAC_name = (8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one| C = 19| H = 28| O = 2| SMILES = O=C4C=C2/[C@]([C@H]1CC[C@@]3([C@@H](O)CC[C@H]3[C@@H]1CC2)C)(C)CC4

correct|chemspider}}| StdInChI = 1S/C19H28O2/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/h11,14-17,21H,3-10H2,1-2H3/t14-,15-,16-,17-,18-,19-/m0/s1| StdInChI_comment =

correct|chemspider}}| StdInChIKey = MUMGGOZAMZWBJJ-DYKIIFRCSA-N| density =| density_notes =| melting_point = 155| melting_high =| melting_notes =| boiling_point =| boiling_notes =| solubility =| sol_units =| specific_rotation = +110.2Â°}}Testosterone (T) is a medication and naturally occurring steroid hormone. It is used to treat male hypogonadism, gender dysphoria, and certain types of breast cancer.WEB, List of Gender Dysphoria Medications (6 Compared),weblink Drugs.com, May 6, 2020, en, April 26, 2020,weblink live, It may also be used to increase athletic ability in the form of doping. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful.WEB, Staff, Testosterone Products: Drug Safety Communication â€“ FDA Cautions About Using Testosterone Products for Low Testosterone Due to Aging; Requires Labeling Change to Inform of Possible Increased Risk of Heart Attack And Stroke,weblink March 3, 2015, FDA, March 5, 2015, live,weblink March 5, 2015, Testosterone can be used as a gel or patch that is applied to the skin, injection into a muscle, tablet that is placed in the cheek, or tablet that is taken by mouth.Common side effects of testosterone include acne, swelling, and breast enlargement in men. Serious side effects may include liver toxicity, heart disease, and behavioral changes. Women and children who are exposed may develop masculinization. It is recommended that individuals with prostate cancer should not use the medication. It can cause harm to the baby if used during pregnancy or breastfeeding. Testosterone is in the androgen family of medications.Testosterone was first isolated in 1935, and approved for medical use in 1939.BOOK, Taylor WN, Anabolic Steroids and the Athlete, 2002, McFarland, 978-0-7864-1128-3, 180, 2nd,weblink live,weblink September 14, 2016, BOOK, Fischer J, Ganellin CR, Analogue-based Drug Discovery, 2006, John Wiley & Sons, 9783527607495, 481,weblink en, August 18, 2020, August 23, 2022,weblink live, Rates of use have increased three times in the United States between 2001 and 2011.JOURNAL, Desroches B, Kohn TP, Welliver C, Pastuszak AW, Testosterone therapy in the new era of Food and Drug Administration oversight, Translational Andrology and Urology, 5, 2, 207â€“12, April 2016, 27141448, 4837303, 10.21037/tau.2016.03.13, free, It is on the World Health Organization's List of Essential Medicines.BOOK, ((World Health Organization)), World Health Organization model list of essential medicines: 21st list 2019, 2019, 10665/325771, World Health Organization, World Health Organization, Geneva, WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO, It is available as a generic medication.WEB, Testosterone,weblink Drugs.com, American Society of Health-System Pharmacists, September 3, 2016, December 4, 2015,weblink August 20, 2016, live, In 2021, it was the 143rd most commonly prescribed medication in the United States, with more than 4{{nbsp}}million prescriptions.WEB, The Top 300 of 2021,weblink ClinCalc, January 14, 2024, January 15, 2024,weblink live, WEB, Testosterone - Drug Usage Statistics, ClinCalc,weblink January 14, 2024, July 8, 2020,weblink live, {{TOC limit}}

Medical uses

{{See also|Androgen replacement therapy#Medical uses|Anabolic steroid#Medical}}The primary use of testosterone is the treatment of males with too little or no natural testosterone production, also termed male hypogonadism or hypoandrogenism (androgen deficiency).JOURNAL, Margo K, Winn R, Testosterone treatments: why, when, and how?, American Family Physician, 73, 9, 1591â€“8, May 2006, 16719252,weblink October 3, 2016, live,weblink" title="web.archive.org/web/20161003184639weblink">weblink October 3, 2016, This treatment is referred to as hormone replacement therapy (HRT), or alternatively, and more specifically, as testosterone replacement therapy (TRT) or androgen replacement therapy (ART). It is used to maintain serum testosterone levels in the normal male range. Decline of testosterone production with age has led to interest in testosterone supplementation.JOURNAL, Myers JB, Meacham RB, Androgen replacement therapy in the aging male, Reviews in Urology, 5, 4, 216â€“26, 2003, 16985841, 1508369, A 2020 guideline from the American College of Physicians supports the discussion of testosterone in adult men with age-related low levels of testosterone who have sexual dysfunction. They recommend yearly evaluation regarding possible improvement and, if none, to discontinue testosterone; physicians should consider intramuscular treatments, rather than transdermal treatments, due to costs and since the effectiveness and harm of either method is similar. Testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended.JOURNAL, Qaseem A, Horwitch CA, Vijan S, Etxeandia-Ikobaltzeta I, Kansagara D, Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians, Annals of Internal Medicine, January 2020, 172, 2, 126â€“133, 31905405, 10.7326/M19-0882, free, NEWS, Parry NM, New Guideline for Testosterone Treatment in Men With 'Low T',weblink January 7, 2020, Medscape.com, January 7, 2020, live, January 8, 2020,weblink

Deficiency

{{Further|Hypogonadism#Treatment|Androgen deficiency#Treatment}}Testosterone deficiency (also termed hypotestosteronism or hypotestosteronemia) is an abnormally low testosterone production. It may occur because of testicular dysfunction (primary hypogonadism) or hypothalamicâ€“pituitary dysfunction (secondary hypogonadism) and may be congenital or acquired.JOURNAL, Gould DC, Petty R, The male menopause: does it exist?: for: some men need investigation and testosterone treatment, The Western Journal of Medicine, 173, 2, 76â€“8, Aug 2000, 10924412, 1070997, 10.1136/ewjm.173.2.76, {{medcn|date=June 2016}}{{Androgen replacement therapy formulations and dosages used in men}}

Low levels due to aging

Testosterone levels may decline gradually with age.BOOK,weblink Testosterone and Aging: Clinical Research Directions., Introduction, Liverman CT, Blazer DG, ((Institute of Medicine (US) Committee on Assessing the Need for Clinical Trials of Testosterone Replacement Therapy)), January 1, 2004, National Academies Press (US), www.ncbi.nlm.nih.gov, 978-0-309-09063-6, 10.17226/10852, 25009850, November 11, 2016, January 10, 2016,weblink" title="web.archive.org/web/20160110170928weblink">weblink live, JOURNAL, Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K, Flicker L, In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study, European Journal of Endocrinology, 156, 5, 585â€“94, May 2007, 17468195, 10.1530/EJE-06-0714, free, The United States Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone supplement have been established for low testosterone levels due to aging. The FDA has required that labels on testosterone include warnings about increased risk of heart attacks and stroke.

Transgender men

{{Further|Transgender hormone therapy (female-to-male)}}To take advantage of its virilizing effects, testosterone is administered to transgender men and other transmasculine individuals as part of masculinizing hormone therapy,WEB,weblink Gender dysphoria â€“ Treatment, NHS Gov.uk, May 21, 2012, October 31, 2013, live,weblink" title="web.archive.org/web/20131102135038weblink">weblink November 2, 2013, titrated to clinical effect with a "target level" of the average male's testosterone level.WEB, Gorton RN, Buth J, Spade D, Medical Therapy and Health Maintenance for Transgender Men: A Guide For Health Care Providers,weblink Lyon-Martin Women's Health Services, December 11, 2016, live,weblink" title="web.archive.org/web/20161130005122weblink">weblink November 30, 2016, {{Medications and dosages used in hormone therapy for transgender men}}{{clear}}

Women

Testosterone therapy is effective in the short-term for the treatment of hypoactive sexual desire disorder (HSDD) in women. However, its long-term safety is unclear.JOURNAL, Wierman ME, Arlt W, Basson R, Davis SR, Miller KK, Murad MH, Rosner W, Santoro N, Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline, The Journal of Clinical Endocrinology and Metabolism, 99, 10, 3489â€“510, Oct 2014, 25279570, 10.1210/jc.2014-2260, free, Because of a lack data to support its efficacy and safety, the Endocrine Society recommends against the routine use of testosterone in women to treat low androgen levels due to hypopituitarism, adrenal insufficiency, surgical removal of the ovaries, high-dose corticosteroid therapy, or other causes. Similarly, because of a lack of data to support its efficacy and safety, the Endocrine Society recommends against the use of testosterone in women to improve general well-being, to treat infertility, sexual dysfunction due to causes other than HSDD, or to improve cognitive, cardiovascular, metabolic, and/or bone health.A 2014 systematic review and meta-analysis of 35 studies consisting of over 5,000 postmenopausal women with normal adrenal gland function found that testosterone therapy was associated with significant improvement in a variety of domains of sexual function.JOURNAL, Elraiyah T, Sonbol MB, Wang Z, Khairalseed T, Asi N, Undavalli C, Nabhan M, Firwana B, Altayar O, Prokop L, Montori VM, Murad MH, Clinical review: The benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis, J. Clin. Endocrinol. Metab., 99, 10, 3543â€“50, 2014, 25279572, 5393495, 10.1210/jc.2014-2262, These domains included frequency of sexual activity, orgasm, arousal, and sexual satisfaction, among others. Women who were menopausal due to ovariectomy showed significantly greater improvement in sexual function with testosterone relative to those who had normal menopause. In addition to beneficial effects on sexual function, testosterone was associated with unfavorable changes in blood lipids. These included decreased levels of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol, and increased levels of low-density lipoprotein (LDL) cholesterol. However, the changes were small in magnitude, and the long-term significance in relation to cardiovascular outcomes is uncertain. The changes were more pronounced with oral testosterone undecanoate than with parenteral routes, such as transdermal testosterone. Testosterone showed no significant effect on depressed mood anxiety, bone mineral density (BMD), or anthropomorphic measures like body weight or body mass index. Conversely, it was associated with a significant incidence of androgenic side effects, including acne and hirsutism (excessive facial/body hair growth). Other androgenic side effects, such as weight gain, pattern hair loss, and voice deepening, were also reported in some trials, but were excluded from analyses due to insufficient data. The overall quality of the evidence was rated as low and was considered to be inconclusive in certain areas, for instance on long-term safety.A subsequent 2017 systematic review and meta-analysis of studies including over 3,000 postmenopausal women with HSDD similarly found that short-term transdermal testosterone therapy was effective in improving multiple domains of sexual function.JOURNAL, Achilli C, Pundir J, Ramanathan P, Sabatini L, Hamoda H, Panay N, Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis, Fertil. Steril., 107, 2, 475â€“482.e15, 2017, 27916205, 10.1016/j.fertnstert.2016.10.028, free, Androgenic adverse effects such as acne and hirsutism were significantly greater in incidence with testosterone therapy, whereas no significant differences in "increase in facial hair, alopecia, voice deepening, urinary symptoms, breast pain, headache, site reaction to the patch, total adverse events, serious adverse events, reasons for withdrawal from the study, and the number of women who completed the study" were seen relative to controls.Although testosterone has been found to be effective at improving sexual function in postmenopausal women, the doses employed have been supraphysiological.JOURNAL, Cappelletti M, Wallen K, Increasing women's sexual desire: The comparative effectiveness of estrogens and androgens, Horm Behav, 78, 178â€“93, February 2016, 26589379, 4720522, 10.1016/j.yhbeh.2015.11.003, JOURNAL, Reed BG, Bou Nemer L, Carr BR, Has testosterone passed the test in premenopausal women with low libido? A systematic review, Int J Women's Health, 8, 599â€“607, 2016, 27785108, 5066846, 10.2147/IJWH.S116212, free, In contrast to these high doses, there is little support for the notion that testosterone is a critical hormone for sexual desire and function in women under normal physiological circumstances. Low doses of testosterone resulting in physiological levels of testosterone (50 ng/dL) significantly increase sexual desire in women, with levels of testosterone of 80 to 150 ng/dL "slightly" increasing sex drive. In accordance, men experience sexual dysfunction at testosterone levels of below 300 ng/dL, and men that have levels of testosterone of approximately 200 ng/dL frequently experience such problems. The high doses of testosterone required to increase sexual desire in women may have a significant risk of masculinization with long-term therapy. For this reason, and due to the unknown health effects and safety of testosterone therapy, its use may be inappropriate. In 2003, the FDA rejected Intrinsa, a 300 Âµg/day testosterone patch for the treatment of sexual dysfunction in postmenopausal women. The reasons cited were limited efficacy (about one additional sexually satisfying event per month), concerns about safety and potential adverse effects with long-term therapy, and concerns about inappropriate off-label use. It appears that in women, rather than testosterone, estradiol may be the most important hormone involved in sexual desire, although data on the clinical use of estradiol to increase sexual desire in women is limited.JOURNAL, Santoro N, Worsley R, Miller KK, Parish SJ, Davis SR, Role of Estrogens and Estrogen-Like Compounds in Female Sexual Function and Dysfunction, J Sex Med, 13, 3, 305â€“16, March 2016, 26944462, 10.1016/j.jsxm.2015.11.015, JOURNAL, Stone L, 7140458, Sexual medicine: Transdermal oestrogen is effective, Nat Rev Urol, 14, 11, 638, November 2017, 28895561, 10.1038/nrurol.2017.152, free, There are no testosterone products approved for use in women in the United States and many other countries.BOOK, Pal L, Sayegh RA, Essentials of Menopause Management: A Case-Based Approach,weblink January 21, 2017, Springer, 978-3-319-42451-4, 180â€“, July 31, 2018, April 14, 2019,weblink live, There are approved testosterone products for women in Australia, where it is considered a drug of dependence, medicines that are subject to misuse and trafficking, WEB, Drugs of dependence and drug-dependent persons,weblink Department of Health, Victorian Government, May 24, 2022, March 8, 2022,weblink live, and some European countries. Testosterone pellet implants are approved for use in postmenopausal women in the United Kingdom.BOOK, Lobo RA, Kelsey J, Marcus R, Menopause: Biology and Pathobiology,weblink May 22, 2000, Academic Press, 978-0-08-053620-0, 454â€“, September 27, 2018, April 14, 2019,weblink live, BOOK, Bagatell C, Bremner WJ, Androgens in Health and Disease,weblink May 27, 2003, Springer Science & Business Media, 978-1-59259-388-0, 374â€“, September 27, 2018, December 20, 2019,weblink live, Testosterone products for men can be used off-label in women in the United States. Alternatively, testosterone products for women are available from compounding pharmacies in the United States, although such products are unregulated and manufacturing quality is not ensured.JOURNAL, L'Hermite M, 26079596, Custom-compounded bioidentical hormone therapy: why so popular despite potential harm? The case against routine use, Climacteric, 20, 3, 205â€“211, June 2017, 28509626, 10.1080/13697137.2017.1285277, {{Androgen replacement therapy formulations and dosages used in women}}{{Androgen/anabolic steroid dosages for breast cancer}}

Available forms

(File:Androderm testosterone skin patch.jpg|thumb|172x172px|Androderm testosterone skin patch)Testosterone has been marketed for use by oral, sublingual, buccal, intranasal, transdermal (patches), topical (gels), intramuscular (injection), and subcutaneous (implant) administration.BOOK, Nieschlag E, Behre MH, Testosterone: Action - Deficiency - Substitution,weblink December 6, 2012, Springer Science & Business Media, 978-3-642-72185-4, 1â€“,9,298,309â€“331,349â€“353,366â€“367, November 18, 2016, April 14, 2019,weblink live, It is provided unmodified and as a testosterone ester such as testosterone cypionate, testosterone enanthate, testosterone propionate, or testosterone undecanoate, which act as prodrugs of testosterone. The most common route of administration for testosterone is by intramuscular injection. However, it has been reported that AndroGel, a transdermal gel formulation of testosterone, has become the most popular form of testosterone in androgen replacement therapy for hypogonadism in the United States.{{Available forms of testosterone}}

Non-medical use

Athletics

{{See also|Ergogenic use of anabolic steroids|Anabolicâ€“androgenic steroids abuse}}Testosterone is used as a form of doping among athletes in order to improve performance.WEB,weblink S1. Anabolic Agents {{!, List of Prohibited Substances and Methods|website=list.wada-ama.org|access-date=June 6, 2016|url-status=dead|archive-url=https://web.archive.org/web/20160527144701weblink|archive-date=May 27, 2016}} Testosterone is classified as an anabolic agent and is on the World Anti-Doping Agency (WADA) List of Prohibited Substances and Methods. Hormone supplements cause the endocrine system to adjust its production and lower the natural production of the hormone, so when supplements are discontinued, natural hormone production is lower than it was originally.{{citation needed|date=November 2016}}Anabolicâ€“androgenic steroids (AAS), including testosterone and its esters, have also been taken to enhance muscle development, strength, or endurance. They do so directly by increasing the muscles' protein synthesis. As a result, muscle fibers become larger and repair faster than the average person's.{{citation needed|date=November 2016}}After a series of scandals and publicity in the 1980s (such as Ben Johnson's improved performance at the 1988 Summer Olympics), prohibitions of AAS use were renewed or strengthened by many sports organizations. Testosterone and other AAS were designated a "controlled substance" by the United States Congress in 1990, with the Anabolic Steroid Control Act.WEB, Anabolic Steroid Control Act,weblink United States Sentencing Commission, 1990, November 11, 2016, dead, August 30, 2016,weblink" title="web.archive.org/web/20160830201115weblink">weblink Their use is seen as an issue in modern sport, particularly given the lengths to which athletes and professional laboratories go to in trying to conceal such use from sports regulators. Steroid use once again came into the spotlight as a result of Canadian professional wrestler Chris Benoit's double murder-suicide in 2007; however, there is no evidence implicating steroid use as a factor in the incident.{{citation needed|date=February 2014}}Some female athletes may have naturally higher levels of testosterone than others, and may be asked to consent to sex verification and either surgery or drugs to decrease testosterone levels.NEWS, Karkazis K, Jordan-Young R, The Trouble With Too Much T,weblink April 11, 2014, The New York Times, April 12, 2014,weblink" title="web.archive.org/web/20140412011234weblink">weblink April 12, 2014, live, This has proven contentious, with the Court of Arbitration for Sport suspending the IAAF policy due to insufficient evidence of a link between high androgen levels and improved athletic performance.WEB, Fagan K, Kate Fagan (sportswriter), Katie Ledecky is crushing records, so why are we still worried about Caster Semenya?, ESPN, August 27, 2016, August 13, 2016,weblink live,weblink" title="web.archive.org/web/20160818073128weblink">weblink August 18, 2016, NEWS, 0362-4331, Padawer R, The Humiliating Practice of Sex-Testing Female Athletes, The New York Times, August 27, 2016, June 28, 2016,weblink live,weblink" title="web.archive.org/web/20160628124045weblink">weblink June 28, 2016,

Detection of abuse

A number of methods for detecting testosterone use by athletes have been employed, most based on a urine test. These include the testosterone/epitestosterone ratio (normally less than 6), the testosterone/luteinizing hormone ratio and the carbon-13/carbon-12 ratio (pharmaceutical testosterone contains less carbon-13 than endogenous testosterone). In some testing programs, an individual's own historical results may serve as a reference interval for interpretation of a suspicious finding. Another approach being investigated is the detection of the administered form of testosterone, usually an ester, in hair.JOURNAL, Strahm E, Emery C, Saugy M, Dvorak J, Saudan C, Detection of testosterone administration based on the carbon isotope ratio profiling of endogenous steroids: international reference populations of professional soccer players, British Journal of Sports Medicine, 43, 13, 1041â€“44, Dec 2009, 19549614, 2784500, 10.1136/bjsm.2009.058669, JOURNAL, Kicman AT, Cowan DA, Subject-based profiling for the detection of testosterone administration in sport, Drug Testing and Analysis, 1, 1, 22â€“4, Jan 2009, 20355155, 10.1002/dta.14, free, JOURNAL, Pozo OJ, Deventer K, Van Eenoo P, Rubens R, Delbeke FT, Quantification of testosterone undecanoate in human hair by liquid chromatography-tandem mass spectrometry, Biomedical Chromatography, 23, 8, 873â€“80, Aug 2009, 19353724, 10.1002/bmc.1199, BOOK, Baselt RC, Disposition of Toxic Drugs & Chemicals in Man, 8th, Biomedical Publications, Foster City, Calif, 2008, 1501â€“04, 978-0-9626523-7-0,

Contraindications

Absolute contraindications of testosterone include prostate cancer, elevated hematocrit (>54%), uncontrolled congestive heart failure, various other cardiovascular diseases, and uncontrolled obstructive sleep apnea.BOOK, Kavoussi P, Costabile RA, Salonia A, Clinical Urologic Endocrinology: Principles for Men's Health,weblink October 19, 2012, Springer Science & Business Media, 978-1-4471-4405-2, 65â€“, November 13, 2016, April 14, 2019,weblink live, Breast cancer is said by some sources to be an absolute contraindication of testosterone therapy, but androgens including testosterone have also actually been used to treat breast cancer.BOOK, Perry MC, The Chemotherapy Source Book,weblink 2008, Lippincott Williams & Wilkins, 978-0-7817-7328-7, 368â€“,weblink September 8, 2017, live, Relative contraindications of testosterone include elevated prostate-specific antigen (PSA) in men with a high risk of prostate cancer due to ethnicity or family history, severe lower urinary tract symptoms, and elevated hematocrit (>50%).

Side effects

{{See also|Anabolic steroid#Adverse effects|Androgen replacement therapy#Adverse effects}}Adverse effects may also include minor side effects such as oily skin, acne, and seborrhea, as well as loss of scalp hair, which may be prevented or reduced with 5Î±-reductase inhibitors. In women, testosterone can produce hirsutism (excessive facial/body hair growth), deepening of the voice, and other signs of virilization. Exogenous testosterone may cause suppression of spermatogenesis in men, leading to, in some cases, reversible infertility.JOURNAL, 25825354, Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility, Lancet, 336, 8721, 955â€“9, October 1990, 1977002, 10.1016/0140-6736(90)92416-F, Gynecomastia and breast tenderness may occur with high dosages of testosterone due to peripheral conversion of testosterone by aromatase into excessive amounts of the estrogen estradiol.JOURNAL, Rhoden EL, Morgentaler A, Treatment of testosterone-induced gynecomastia with the aromatase inhibitor, anastrozole, International Journal of Impotence Research, 16, 1, 95â€“7, February 2004, 14963480, 10.1038/sj.ijir.3901154, free, Testosterone treatment, particularly in high dosages, can also be associated with mood changes, increased aggression, increased sex drive, spontaneous erections, and nocturnal emissions.JOURNAL, Yates WR, Testosterone in Psychiatry, Archives of General Psychiatry, 57, 2, 2000, 155, 0003-990X, 10.1001/archpsyc.57.2.155, JOURNAL, Johnson JM, Nachtigall LB, Stern TA, The effect of testosterone levels on mood in men: a review, Psychosomatics, 54, 6, 509â€“514, 2013, 24016385, 10.1016/j.psym.2013.06.018, JOURNAL, Davidson JM, Kwan M, Greenleaf WJ, Hormonal replacement and sexuality in men, Clinics in Endocrinology and Metabolism, 11, 3, 599â€“623, November 1982, 6814798, 10.1016/s0300-595x(82)80003-0, BOOK, Bagatell C, Bremner WJ, Androgens in Health and Disease,weblink May 27, 2003, Springer Science & Business Media, 978-1-59259-388-0, 144, 259â€“261, 351, November 18, 2016, April 14, 2019,weblink live, Other side effects include increased hematocrit, which can require venipuncture in order to treat, and exacerbation of sleep apnea.JOURNAL, Pastuszak AW, Pearlman AM, Lai WS, Godoy G, Sathyamoorthy K, Liu JS, Miles BJ, Lipshultz LI, Khera M, Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy, The Journal of Urology, 190, 2, 639â€“44, Aug 2013, 23395803, 4544840, 10.1016/j.juro.2013.02.002, The FDA stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging. The FDA has required that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke. They have also required the label include concerns about abuse and dependence.WEB, Testosterone and Other Anabolic Androgenic Steroids (AAS): FDA Statement - Risks Associated With Abuse and Dependence,weblink FDA, October 26, 2016, October 25, 2016, live,weblink October 27, 2016, Injectable forms of testosterone can cause a lung problem called pulmonary oil microembolism (POME). Symptoms of POME include cough, shortness of breath, tightening of the throat, chest pain, sweating, dizziness, and fainting.WEB, August 2, 2020, Testosterone Injection, Drugs.com,weblink January 4, 2021, January 8, 2021,weblink live, WEB, March 15, 2019, Testosterone Injection, MedlinePlus,weblink January 4, 2021,weblink December 23, 2019, live, A postmarketing analysis by the manufacturer of Aveed (testosterone undeconate injection) found that POME occurred at a rate of less than 1% per injection per year for Aveed.JOURNAL, Pastuszak AW, Hu Y, Freid JD, Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis, Sexual Medicine, 8, 2, 237â€“242, June 2020, 32184081, 7261689, 10.1016/j.esxm.2020.01.009,

Long-term adverse effects

Cardiovascular disease

{{See also|Testosterone and the cardiovascular system}}Adverse effects of testosterone supplementation may include increased cardiovascular events (including strokes and heart attacks) and deaths based on three peer-reviewed studies involving men taking testosterone replacement.JOURNAL, Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF, Hoover RN, Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men, PLOS ONE, 9, 1, e85805, January 2014, 24489673, 3905977, 10.1371/journal.pone.0085805, 2014PLoSO...985805F, free, In addition, an increase of 30% in deaths and heart attacks in older men has been reported.JOURNAL, Vigen R, O'Donnell CI, BarÃ³n AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM, Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels, JAMA, 310, 17, 1829â€“36, Nov 2013, 24193080, 10.1001/jama.2013.280386, free, Due to an increased incidence of adverse cardiovascular events compared to a placebo group, a Testosterone in Older Men with Mobility Limitations (TOM) trial (a National Institute of Aging randomized trial) was halted early by the Data Safety and Monitoring Committee.JOURNAL, Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S, Adverse events associated with testosterone administration, The New England Journal of Medicine, 363, 2, 109â€“22, July 8, 2010, 20592293, 3440621, 10.1056/NEJMoa1000485, On January 31, 2014, reports of strokes, heart attacks, and deaths in men taking FDA-approved testosterone-replacement led the FDA to announce that it would be investigating the issue.WEB, Staff, FDA evaluating risk of stroke, heart attack and death with FDA-approved testosterone products,weblink U.S. Food and Drug Administration, January 31, 2014, September 17, 2014, live,weblink February 19, 2014, Later, in September 2014, the FDA announced, as a result of the "potential for adverse cardiovascular outcomes", a review of the appropriateness and safety of Testosterone Replacement Therapy (TRT).NEWS, Tavernise S, F.D.A. Panel Backs Limits on Testosterone Drugs,weblink September 17, 2014, The New York Times, September 18, 2014, live,weblink" title="web.archive.org/web/20140917201336weblink">weblink September 17, 2014, NEWS, Staff, FDA Panel To Review Testosterone Therapy Appropriateness and Safety,weblink September 5, 2014, CNN News, September 14, 2014, dead,weblink" title="web.archive.org/web/20140911081501weblink">weblink September 11, 2014, WEB, Staff, Joint Meeting for Bone, Reproductive and Urologic Drugs Advisory Committee (BRUDAC) and the Drug Safety And Risk Management Advisory Committee (DSARM AC) â€“ FDA background documents for the discussion of two major issues in testosterone replacement therapy (TRT): 1. The appropriate indicated population for TRT, and 2. The potential for adverse cardiovascular outcomes associated with use of TRT,weblink September 17, 2014, Food and Drug Administration, September 14, 2014, live,weblink September 6, 2014, The FDA now requires warnings in the drug labeling of all approved testosterone products regarding deep vein thrombosis and pulmonary embolism.WEB, Staff, FDA adding general warning to testosterone products about potential for venous blood clots,weblink FDA, October 9, 2014, June 19, 2014, live, October 6, 2014,weblink Up to the year 2010, studies had not shown any effect on the risk of death, prostate cancer or cardiovascular disease;JOURNAL, Haddad RM, Kennedy CC, Caples SM, Tracz MJ, BoloÃ±a ER, Sideras K, Uraga MV, Erwin PJ, Montori VM, Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials, Mayo Clinic Proceedings, 82, 1, 29â€“39, Jan 2007, 17285783, 10.4065/82.1.29, JOURNAL, FernÃ¡ndez-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos-Orozco JF, Wang AT, Erwin PJ, Bhasin S, Montori VM, Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis, The Journal of Clinical Endocrinology and Metabolism, 95, 6, 2560â€“75, Jun 2010, 20525906, 10.1210/jc.2009-2575, free, more recent{{when|date=January 2020}} studies, however, do raise concerns.WEB, Testosterone Products: Drug Safety Communication â€“ FDA Investigating Risk of Cardiovascular Events, FDA, January 31, 2014,weblink February 3, 2014, live, February 14, 2014,weblink A 2013 study, published in the Journal of the American Medical Association, reported "the use of testosterone therapy was significantly associated with increased risk of adverse outcomes." The study began after a previous, randomized, clinical trial of testosterone therapy in men was stopped prematurely "due to adverse cardiovascular events raising concerns about testosterone therapy safety."However, when given to men with hypogonadism in the short- and medium-term, testosterone replacement therapy does not increase the risk of cardiovascular events (including strokes and heart attacks and other heart diseases). The long-term safety of the therapy is not known yet.JOURNAL, February 6, 2023, Research provides reassurance about the safety of testosterone treatment,weblink NIHR Evidence, Plain English summary, National Institute for Health and Care Research, 10.3310/nihrevidence_56696, 257851823, February 28, 2023, February 28, 2023,weblink live, JOURNAL, Hudson J, Cruickshank M, Quinton R, Aucott L, Aceves-Martins M, Gillies K, Bhasin S, Snyder PJ, Ellenberg SS, Grossmann M, Travison TG, Gianatti EJ, van der Schouw YT, Emmelot-Vonk MH, Giltay EJ, Hackett G, Ramachandran S, Svartberg J, Hildreth KL, Groti Antonic K, Brock GB, Tenover JL, Tan HM, Kong CH, Tan WS, Marks LS, Ross RJ, Schwartz RS, Manson P, Roberts S, Andersen MS, Magnussen LV, HernÃ¡ndez R, Oliver N, Wu F, Dhillo WS, Bhattacharya S, Brazzelli M, Jayasena CN, Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis, The Lancet. Healthy Longevity, 3, 6, e381â€“e393, June 2022, 35711614, 9184259, 10.1016/S2666-7568(22)00096-4,

Benign prostatic hyperplasia

Testosterone therapy for patients with late-onset hypogonadism, in addition to increasing risk of cardiovascular disease and prostate cancer, may exacerbate the risk factors associated with benign prostatic hyperplasia, a condition that involves the noncancerous enlargement of the prostate gland, which can lead to urinary symptoms.JOURNAL, Snyder P, Testosterone treatment of late-onset hypogonadism - benefits and risks, Rev Endocr Metab Disord, 23, 6, 1151â€“1157, December 2022, 35266057, 10.1007/s11154-022-09712-1,

Prostate cancer

Testosterone in the presence of a slow-growing prostate cancer is assumed to increase its growth rate. However, the association between testosterone supplementation and the development of prostate cancer is unproven.JOURNAL, Rhoden EL, Averbeck MA, 20250546, Testosterone therapy and prostate carcinoma, Current Urology Reports, 10, 6, 453â€“59, Nov 2009, 19863857, 10.1007/s11934-009-0072-1, Nevertheless, physicians are cautioned about the cancer risk associated with testosterone supplementation.JOURNAL, Gaylis FD, Lin DW, Ignatoff JM, Amling CL, Tutrone RF, Cosgrove DJ, Prostate cancer in men using testosterone supplementation, The Journal of Urology, 174, 2, 534â€“38; discussion 538, Aug 2005, 16006887, 10.1097/01.ju.0000165166.36280.60, Testosterone may accelerate pre-existing prostate cancer growth in individuals who have undergone androgen deprivation. It is recommended that physicians screen for prostate cancer with a digital rectal exam and prostate-specific antigen (PSA) level before starting therapy, and monitor PSA and hematocrit levels closely during therapy.Ethnic groups have different rates of prostate cancer. Differences in sex hormones, including testosterone, have been suggested as an explanation for these differences.JOURNAL, Calistro Alvarado L, Population differences in the testosterone levels of young men are associated with prostate cancer disparities in older men, American Journal of Human Biology, 22, 4, 449â€“455, 2010, 20087895, 10.1002/ajhb.21016, 21117845, This apparent paradox can be resolved by noting that prostate cancer is very common. In autopsies, 80% of 80-year-old men have prostate cancer.JOURNAL, Bostwick DG, Burke HB, Djakiew D, Euling S, Ho SM, Landolph J, Morrison H, Sonawane B, Shifflett T, Waters DJ, Timms B, Human prostate cancer risk factors, Cancer, 101, 10 Suppl, 2371â€“2490, Nov 2004, 15495199, 10.1002/cncr.20408, 24807561,

Pregnancy and breastfeeding

Testosterone is contraindicated in pregnancy and not recommended during breastfeeding.WEB, Testosterone Pregnancy and Breastfeeding Warnings,weblink February 1, 2014, live,weblink" title="web.archive.org/web/20140201201902weblink">weblink February 1, 2014, Androgens like testosterone are teratogens and are known to cause fetal harm, such as producing virilization and ambiguous genitalia.

Interactions

5Î±-Reductase inhibitors

5Î±-Reductase inhibitors like finasteride and dutasteride can slightly increase circulating levels of testosterone by inhibiting its metabolism.BOOK, Jameson JL, de Kretser DM, Marshall JC, De Groot JL, Endocrinology Adult and Pediatric: Reproductive Endocrinology,weblink May 7, 2013, Elsevier Health Sciences, 978-0-323-22152-8, 1â€“, live,weblink September 8, 2017, However, these drugs do this via prevention of the conversion of testosterone into its more potent metabolite dihydrotestosterone (DHT), and this results in dramatically reduced circulating levels of DHT (which circulates at much lower relative concentrations).BOOK, Blume-Peytavi U, Whiting DA, TrÃ¼eb RM, Hair Growth and Disorders,weblink June 26, 2008, Springer Science & Business Media, 978-3-540-46911-7, 182â€“, live,weblink September 8, 2017, In addition, local levels of DHT in so-called androgenic (5Î±-reductase-expressing) tissues are also markedly reduced, and this can have a strong impact on certain effects of testosterone.BOOK, Bagatelle C, Bremner WJ, Androgens in Health and Disease,weblink May 27, 2003, Springer Science & Business Media, 978-1-59259-388-0, 78â€“, December 6, 2016, April 14, 2019,weblink live, For instance, growth of body and facial hair and penile growth induced by testosterone may be inhibited by 5Î±-reductase inhibitors, and this could be considered undesirable in the context of, for instance, puberty induction.BOOK, Baskin LS, Hypospadias and Genital Development,weblink December 6, 2012, Springer Science & Business Media, 978-1-4419-8995-6, 37â€“, December 6, 2016, April 14, 2019,weblink live, On the other hand, 5Î±-reductase inhibitors may prevent or reduce adverse androgenic side effects of testosterone like scalp hair loss, oily skin, acne, and seborrhea. In addition to the prevention of testosterone conversion into DHT, 5Î±-reductase inhibitors also prevent the formation of neurosteroids like 3Î±-androstanediol from testosterone, and this may have neuropsychiatric consequences in some men.BOOK, Neurosteroids,weblink Frontiers E-books, 978-2-88919-078-2, 357â€“358, December 6, 2016, April 14, 2019,weblink live,

Aromatase inhibitors

Aromatase inhibitors like anastrozole prevent the conversion of testosterone into estradiol by aromatase. As only a very small fraction of testosterone is converted into estradiol, this does not affect testosterone levels, but it can prevent estrogenic side effects like gynecomastia that can occur when testosterone is administered at relatively high dosages. However, estradiol exerts negative feedback on the hypothalamicâ€“pituitaryâ€“gonadal axis and, for this reason, prevention of its formation can reduce this feedback and disinhibit gonadal production of testosterone, which in turn can increase levels of endogenous testosterone.JOURNAL, Simpson ER, 11210435, Sources of estrogen and their importance, J. Steroid Biochem. Mol. Biol., 86, 3â€“5, 225â€“30, September 2003, 14623515, 10.1016/S0960-0760(03)00360-1, Testosterone therapy is sometimes combined with an aromatase inhibitor for men with secondary hypogonadism who wish to conceive children with their partners.BOOK, Nieschlag E, Behre HM, Nieschlag S, Andrology: Male Reproductive Health and Dysfunction, 2009, Springer, Berlin, 978-3-540-78354-1, 459, 3rd,

Cytochrome P450 inhibitors

Inhibitors and inducers of cytochrome P450 enzymes like CYP3A4 have been associated with little or no effect on circulating testosterone levels.{{Citation needed|date=December 2016}}

Antiandrogens and estrogens

Antiandrogens like cyproterone acetate, spironolactone, and bicalutamide can block the androgenic and anabolic effects of testosterone.BOOK, Wecker L, Crespo L, Dunaway G, Faingold C, Watts S, Brody's Human Pharmacology,weblink April 1, 2009, Elsevier Health Sciences, 978-0-323-07575-6, 468â€“469, November 13, 2016, April 14, 2019,weblink live, Estrogens can reduce the effects of testosterone by increasing the hepatic production and in turn circulating levels of sex hormone-binding globulin (SHBG), a carrier protein that binds to and occupies androgens like testosterone and DHT, and thereby reducing free concentrations of these androgens.BOOK, Partin AW, Wein AJ, Kavoussi LR, Peters CA, Campbell-Walsh Urology,weblink October 23, 2015, Elsevier Health Sciences, 978-0-323-26374-0, 7207â€“, December 6, 2016, live, April 14, 2019,weblink

Pharmacology

Pharmacodynamics

{{See also|Testosterone#Mechanism of action|Anabolic steroid#Pharmacology}}{{Relative androgenic to anabolic activity in animals}}Testosterone is a high affinity ligand for and agonist of the nuclear androgen receptor (AR). In addition, testosterone binds to and activates membrane androgen receptors (mARs) such as GPRC6A and ZIP9. Testosterone is also potentiated via transformation by 5Î±-reductase into the more potent androgen DHT in so-called androgenic tissues such as the prostate gland, seminal vesicles, skin, and hair follicles. In contrast to the case of testosterone, such potentiation occurs to a reduced extent or not at all with most synthetic AAS (as well as with DHT), and this is primarily responsible for the dissociation of anabolic and androgenic effects with these agents.JOURNAL, Kicman AT, Pharmacology of anabolic steroids, British Journal of Pharmacology, 154, 3, 502â€“21, June 2008, 18500378, 2439524, 10.1038/bjp.2008.165, In addition to DHT, testosterone is converted at a rate of approximately 0.3% into the estrogen estradiol via aromatase.BOOK, Burtis CA, Ashwood ER, Bruns DE, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics,weblink October 14, 2012, Elsevier Health Sciences, 978-1-4557-5942-2, 1947â€“, live,weblink May 22, 2016, This occurs in many tissues, especially adipose tissue, the liver, and the brain, but primarily in adipose tissue. Testosterone, after conversion into DHT, is also metabolized into 3Î±-androstanediol, a neurosteroid and potent positive allosteric modulator of the GABAA receptor, and 3Î²-androstanediol, a potent and preferential agonist of the ERÎ².BOOK, Kohtz AS, Frye CA, Dissociating Behavioral, Autonomic, and Neuroendocrine Effects of Androgen Steroids in Animal Models, Psychiatric Disorders, Methods in Molecular Biology, 829, 397â€“431, 2012, Springer, 22231829, 10.1007/978-1-61779-458-2_26, 978-1-61779-457-5, These metabolites, along with estradiol, may be involved in a number of the effects of testosterone in the brain, including its antidepressant, anxiolytic, stress-relieving, rewarding, and pro-sexual effects. Whereas testosterone produced both anabolic and androgenic effects, despite the lack of clear boundaries between these effects, as there is a great deal of mutual overlap between them,BOOK, Androgen Physiology, Pharmacology and Abuse,weblink Handelsman DJ, Endotext [Internet], MDText.com, Inc, January 2013, 25905231, November 11, 2016, March 9, 2021,weblink live, the relative potency of these effects exerted by testosterone can depend on various factors and is a topic of ongoing research.BOOK,weblink 10.1007/978-3-319-29456-8_11-1, Anabolic and Metabolic Effects of Testosterone and Other Androgens: Direct Effects and Role of Testosterone Metabolic Products, Thyroid Diseases, Endocrinology, 2017, ÄŒeponis J, Wang C, Swerdloff S, Liu PY, 1â€“22, 978-3-319-29195-6, April 6, 2024, April 7, 2024,weblink live, JOURNAL, Kuhn CM, Anabolic steroids, Recent Prog Horm Res, 57, 411â€“34, 2002, 12017555, 10.1210/rp.57.1.411, free,

Effects in the body and brain

The ARs are expressed widely throughout the body, including in the penis, testicles, epididymides, prostate gland, seminal vesicles, fat, skin, bone, bone marrow, muscle, larynx, heart, liver, kidneys, pituitary gland, hypothalamus, and elsewhere throughout the brain.BOOK, Nieschlag E, Behre HM, Nieschlag S, Andrology: Male Reproductive Health and Dysfunction,weblink January 13, 2010, Springer Science & Business Media, 978-3-540-78355-8, 49â€“54,441â€“446, live,weblink June 23, 2016, BOOK, Strauss JF, Barbieri RL, Gargiulo AR, Yen & Jaffe's Reproductive Endocrinology E-Book: Physiology, Pathophysiology, and Clinical Management,weblink December 23, 2017, Elsevier Health Sciences, 978-0-323-58232-2, 292â€“, March 31, 2018, April 14, 2019,weblink live, Through activation of the ARs (as well as the mARs), testosterone has many effects, including the following:{{Additional citation needed|date=April 2018}}

Promotes growth, function, and maintenance of the prostate gland, seminal vesicles, and penis during puberty and thereafter
Promotes growth and maintenance of muscles, particularly of the upper body
Causes subcutaneous fat to be deposited in a masculine pattern and decreases overall body fat
Suppresses breast development induced by estrogens, but can also still produce gynecomastia via excessive conversion into estradiol if levels are too high
Maintains skin health, integrity, appearance, and hydration and slows the rate of aging of the skin, but can also cause oily skin, acne, and seborrhea
Promotes the growth of facial and body hair, but can also cause scalp hair loss and hirsutism
Contributes to bone growth and causes broadening of the shoulders at puberty
Modulates liver protein synthesis, such as the production of sex hormone-binding globulin and many other proteins
Increases production of erythropoietin in the kidneys and thereby stimulates red blood cell production in bone marrow and elevates hematocrit
Exerts negative feedback on the hypothalamicâ€“pituitaryâ€“gonadal axis by suppressing the secretion of the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland, thereby inhibiting gonadal sex hormone production as well as spermatogenesis and fertility
Regulates the vasomotor system and body temperature via the hypothalamus, thereby preventing hot flashes
Modulates brain function, with effects on mood, emotionality, aggression, and sexuality, as well as cognition and memory
Increases sex drive and erectile capacity and causes spontaneous erections and nocturnal emissions
Increases the risk of benign prostatic hyperplasia and accelerates the progression of prostate cancer
Decreases breast proliferation and the risk of breast cancer

Pharmacokinetics

{{See also|Testosterone (patch)|Androgen ester#Testosterone esters}}Testosterone can be taken by a variety of different routes of administration.BOOK, Behre HM, Nieschlag E, Testosterone preparations for clinical use in males, Nieschlag E, Behre HM, Nieschlag S, 309â€“335, 10.1017/CBO9781139003353.016, Testosterone: Action, Deficiency, Substitution, July 26, 2012, Cambridge University Press, 978-1-107-01290-5, These include oral, buccal, sublingual, intranasal, transdermal (gels, creams, patches), rectal suppositories), by intramuscular or subcutaneous injection (in oil or aqueous), and as a subcutaneous implant. The pharmacokinetics of testosterone, including its bioavailability, circulating testosterone levels, metabolism, biological half-life, and other parameters, differ by route of administration.

Chemistry

Testosterone is a naturally occurring androstane steroid and is also known by the chemical name androst-4-en-17Î²-ol-3-one.BOOK, Elks J, The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies,weblink November 14, 2014, Springer, 978-1-4757-2085-3, 641â€“642, live,weblink February 15, 2017, It has a double bond between the C4 and C5 positions (making it an androstene), a ketone group at the C3 position, and a hydroxyl (alcohol) group at the C17Î² position.

Derivatives

{{See also|Androgen ester#Testosterone esters|List of androgens/anabolic steroids}}Testosterone esters are substituted at the C17Î² position with a lipophilic fatty acid ester moiety of varying chain length.BOOK, Jameson JL, De Groot LJ, Endocrinology: Adult and Pediatric,weblink February 25, 2015, Elsevier Health Sciences, 978-0-323-32195-2, 2387â€“, November 18, 2016, April 14, 2019,weblink live, Major testosterone esters include testosterone cypionate, testosterone enanthate, testosterone propionate, and testosterone undecanoate.BOOK, Chapple CR, Steers WD, Practical Urology: Essential Principles and Practice: Essential Principles and Practice,weblink May 10, 2011, Springer Science & Business Media, 978-1-84882-034-0, 228â€“, November 18, 2016, April 14, 2019,weblink live, A C17Î² ether prodrug of testosterone, cloxotestosterone acetate, has also been marketed, although it is little known and is used very rarely or no longer. Another C17Î² ether prodrug of testosterone, silandrone, also exists but was never marketed, and is notable in that it is orally active. In addition to ester and ether prodrugs, androgen prohormones or precursors of testosterone, such as dehydroepiandrosterone (DHEA), androstenediol, and androstenedione, exist as well, and convert into testosterone to variable extents upon oral ingestion.BOOK, Gregory HM, Travis TN, Essentials of Strength Training and Conditioning, 4th,weblink September 23, 2015, Human Kinetics, 978-1-4925-0162-6, 229, 233, November 18, 2016, February 17, 2018,weblink live, Unlike testosterone ester and ether prodrugs however, these prohormones are only weakly androgenic/anabolic.All synthetic AAS are derivatives of testosterone. Prominent examples include nandrolone (19-nortestosterone), metandienone (17Î±-methyl-Î´1-testosterone), and stanozolol (a 17Î±-alkylated derivative of DHT). Unlike testosterone, AAS that are 17Î±-alkylated, like metandienone and stanozolol, are orally active. This is due to steric hindrance of C17Î²-position metabolism during the first-pass through the liver. In contrast, most AAS that are not 17Î±-alkylated, like nandrolone, are not active orally, and must instead be administered via intramuscular injection. This is almost always in ester form; for instance, in the case of nandrolone, as nandrolone decanoate or nandrolone phenylpropionate.{{Structural properties of major testosterone esters}}

History

{{See also|Testosterone#History|Anabolic steroid#History}}Testosterone was first isolated and synthesized in 1935.BOOK, Taylor WN, Anabolic Steroids and the Athlete, 2nd,weblink January 16, 2002, McFarland, 978-0-7864-1128-3, 180â€“, November 13, 2016, July 29, 2018,weblink live, Shortly thereafter, in 1937, testosterone first became commercially available as a pharmaceutical drug in the form of pellets and then in ester form for intramuscular injection as the relatively short-acting testosterone propionate.BOOK, Llewellyn W, Anabolics,weblink 2011, Molecular Nutrition Llc, 978-0-9828280-1-4, 385â€“394, 413, 426, 607, 666, December 18, 2017, April 14, 2019,weblink live, BOOK, Hoberman J, Testosterone Dreams: Rejuvenation, Aphrodisia, Doping,weblink registration, February 21, 2005, University of California Press, 978-0-520-93978-3, 134â€“, Methyltestosterone, one of the first synthetic AAS and orally active androgens, was introduced in 1935, but was associated with hepatotoxicity and eventually became largely medically obsolete. In the mid-1950s, the longer-acting testosterone esters testosterone enanthate and testosterone cypionate were introduced. They largely superseded testosterone propionate and became the major testosterone esters used medically for over half a century. In the 1970s, testosterone undecanoate was introduced for oral use in Europe, although intramuscular testosterone undecanoate had already been in use in China for several years.BOOK, Mundy AR, Fitzpatrick J, Neal DE, George NJ, The Scientific Basis of Urology,weblink July 26, 2010, CRC Press, 978-1-84184-749-8, 294â€“, November 18, 2016, April 14, 2019,weblink live, Intramuscular testosterone undecanoate was not introduced in Europe and the United States until much later (in the early to mid 2000s and 2014, respectively).JOURNAL, ((Adis R&D Profile)), 43349541, 2004, Testosterone Undecanoateâ€”Schering AG, Drugs, 5, 6, 368â€“369, 10.2165/00126839-200405060-00012, 15563244, The history of testosterone as a medication has been reviewed.BOOK, Nieschlag E, Nieschlag S, The History of Testosterone and the Testes: From Antiquity to Modern Times, Testosterone, 2017, 1â€“19, Springer, 10.1007/978-3-319-46086-4_1, 978-3-319-46084-0, JOURNAL, Nieschlag E, Nieschlag S, ENDOCRINE HISTORY: The history of discovery, synthesis and development of testosterone for clinical use, European Journal of Endocrinology, 180, 6, R201â€“R212, June 2019, 30959485, 10.1530/EJE-19-0071, free, JOURNAL, Nieschlag E, Nieschlag S, Testosterone deficiency: a historical perspective, Asian Journal of Andrology, 16, 2, 161â€“8, 2014, 24435052, 3955324, 10.4103/1008-682X.122358, free, JOURNAL, Morgentaler A, Traish A, The History of Testosterone and the Evolution of its Therapeutic Potential, Sexual Medicine Reviews, 8, 2, 286â€“296, April 2020, 29661690, 10.1016/j.sxmr.2018.03.002, 4903551,

Society and culture

{{See also|Androgen replacement therapy#Society and culture|Anabolic steroid#Society and culture}}

Usage

In the US in the 2000s, companies and figures in the popular media have heavily marketed notions of "andropause" as something parallel to menopause; these notions have been rejected by the medical community.WEB, Male Menopause,weblink www.nhs.uk, NHS Choices, April 8, 2016, October 7, 2016, live,weblink" title="web.archive.org/web/20161009181414weblink">weblink October 9, 2016, WEB, Gorski D, "Low T": The triumph of marketing over science Â« Science-Based Medicine,weblink Science-Based Medicine, November 25, 2013, live,weblink September 11, 2016, Additionally, advertising from drug companies selling testosterone and human growth hormone, as well as dietary supplement companies selling all kinds of "boosters" for aging men, have emphasized the "need" of middle-aged or ageing men for testosterone. There is a medical condition called late-onset hypogonadism; according to Thomas Perls and David J. Handelsman, writing in a 2015 editorial in the Journal of the American Geriatrics Society, it appears that this condition is overdiagnosed and overtreated.JOURNAL, Perls T, Handelsman DJ, Disease mongering of age-associated declines in testosterone and growth hormone levels, Journal of the American Geriatrics Society, 63, 4, 809â€“11, April 2015, 25809947, 10.1111/jgs.13391, 328558, free, Perls and Handelsman note that in the US, "sales of testosterone increased from $324 million in 2002 to $2 billion in 2012, and the number of testosterone doses prescribed climbed from 100 million in 2007 to half a billion in 2012, not including the additional contributions from compounding pharmacies, Internet, and direct-to-patient clinic sales."

Generic names

Testosterone is the generic name of testosterone in English and Italian and the {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BAN|British Approved Name|BAN}}, and {{abbrlink|DCIT|Denominazione Comune Italiana}} of the drug, while testostÃ©rone is its French name and the {{abbrlink|DCF|DÃ©nomination Commune FranÃ§aise}}.BOOK, Index Nominum 2000: International Drug Directory,weblink January 2000, Taylor & Francis, 978-3-88763-075-1, December 2, 2016, October 21, 2021,weblink live, It is also referred to in Latin as testosteronum, in Spanish and Portuguese as testosterona, and in German, Dutch, and Russian and other Slavic languages as testosteron. The Cyrillic script of testosterone is Ñ‚ÐµÑÑ‚Ð¾ÑÑ‚ÐµÑ€Ð¾Ð½.BOOK, Ð’Ð»Ð°Ð´Ð¸Ð¼Ð¸Ñ€ ÐœÑŽÐ»Ð»ÐµÑ€, ÐÐ½Ð³Ð»Ð¾-Ñ€ÑƒÑÑÐºÐ¸Ð¹ ÑÐ»Ð¾Ð²Ð°Ñ€ÑŒ. Ð ÑƒÑÑÐºÐ¾-Ð°Ð½Ð³Ð»Ð¸Ð¹ÑÐºÐ¸Ð¹ ÑÐ»Ð¾Ð²Ð°Ñ€ÑŒ. 250 000 ÑÐ»Ð¾Ð²,weblink April 15, 2016, Ð›Ð¸Ñ‚Ð ÐµÑ, 978-5-457-98308-3, 643â€“, December 2, 2016, April 14, 2019,weblink live,

Brand names

(File:Depo-testosterone 200 mg ml crop.jpg|thumb|upright=0.8|A vial of Depo-Testosterone (testosterone cypionate in oil) for intramuscular injection)Testosterone is marketed under a large number of brand names throughout the world.WEB, Testosterone - International,weblink Drugs.com, November 12, 2016, live,weblink November 13, 2016, Major brand names of testosterone and/or its esters include Andriol, Androderm, AndroGel, Axiron, Delatestryl, Depo-Testosterone, Intrinsa, Nebido, Omnadren, Primoteston, Sustanon, Testim, TestoGel, TestoPatch, Testoviron, and Tostran.

Availability

United States

{{See also|List of androgens/anabolic steroids available in the United States#Testosterone and esters}}{{As of|2016|11}}, unmodified (non-esterified) testosterone is available in the United States in the following formulations:

Topical gels: AndroGel, Fortesta, Testim, Testosterone (generic)
Topical solutions: Axiron, Testosterone (generic)
Transdermal patches: Androderm, Testoderm (discontinued), Testoderm TTS (discontinued), Testosterone (generic)
Intranasal gels: Natesto
Buccal tablets: Striant
Pellet implants: Testopel

And the following ester prodrugs of testosterone are available in the United States in oil solutions for intramuscular injection:

Testosterone cypionate: Depo-Testosterone, Testosterone Cypionate (generic)
Testosterone enanthate: Delatestryl, Xyosted (auto-injector), Testosterone Enanthate (generic)
Testosterone propionate: Testosterone Propionate (generic)
Testosterone undecanoate: Aveed

Unmodified testosterone was also formerly available for intramuscular injection but was discontinued.Testosterone cypionate and testosterone enanthate were formerly available in combination with estradiol cypionate and estradiol valerate, respectively, under the brand names Depo-Testadiol and Ditate-DS, respectively, as oil solutions for intramuscular injection, but these formulations have been discontinued.Unlike in Europe, Canada, and much of the rest of the world, oral testosterone undecanoate is not available in the United States.BOOK, Morley JE, Testosterone, Morley JE, van den Berg L, Endocrinology of Aging, Disease-a-Month,weblink November 5, 1999, 34, 7, Springer Science & Business Media, 978-1-59259-715-4, 141â€“, 10.1016/s0011-5029(98)90024-4, 3044718, November 15, 2016, April 14, 2019,weblink live, BOOK, Bagatell C, Bremner WJ, Androgens in Health and Disease,weblink May 27, 2003, Springer Science & Business Media, 978-1-59259-388-0, November 18, 2016, April 14, 2019,weblink live,

Canada

{{as of|2016|11}}, testosterone is available in Canada in the form of topical gels (AndroGel, Testim), topical solutions (Axiron), transdermal patches (Androderm), and intranasal gels (Natesto).WEB, Drug Product Database - Health Canada, Health Canada,weblink November 13, 2016, live,weblink" title="web.archive.org/web/20161119200516weblink">weblink November 19, 2016, March 18, 2010, Testosterone cypionate (Depo-Testosterone, Testosterone Cypionate (generic)), testosterone enanthate (Delatestryl, PMS-Testosterone Enanthate), and testosterone propionate (Testosterone Propionate (generic)) are available as oil solutions for intramuscular injection and testosterone undecanoate (Andriol, PMS-Testosterone, Taro-Testosterone) is available in the form of oral capsules. Testosterone buccal tablets and pellet implants do not appear to be available in Canada.

Other countries

Testosterone and/or its esters are widely available in countries throughout the world in a variety of formulations.

Legal status

{{See also|Anabolic steroid#Legal status}}Testosterone and its esters, along with other AAS, are prescription-only controlled substances in many countries throughout the world. In the United States, they are Schedule III drugs under the Controlled Substances Act, in Canada, they are Schedule IV drugs under the Controlled Drugs and Substances Act, and in the United Kingdom, they are Class C drugs under the Misuse of Drugs Act.BOOK, Karch SB, Drug Abuse Handbook, Second Edition,weblink December 21, 2006, CRC Press, 978-1-4200-0346-8, 30â€“, November 11, 2017, April 14, 2019,weblink live, BOOK, Lilley LL, Snyder JS, Collins SR, Pharmacology for Canadian Health Care Practice,weblink August 5, 2016, Elsevier Health Sciences, 978-1-77172-066-3, 50â€“, November 11, 2017, April 14, 2019,weblink live,

Litigation

{{As of|2014}}, a number of lawsuits are underway against manufacturers of testosterone, alleging a significantly increased rate of stroke and heart attack in elderly men who use testosterone supplementation.NEWS, Harris A, Abbott Labs Sued by Five Men Claiming Androgel Injuries,weblink Bloomberg.com, February 5, 2014, Bloomberg, L.P., June 16, 2014, live,weblink" title="web.archive.org/web/20140714195657weblink">weblink July 14, 2014, {{update inline|date=January 2020}}

Doping in sports

{{See also|List of doping in sport cases#Testosterone and esters}}There are many known cases of doping in sports with testosterone and its esters by professional athletes.

Research

Depression

Testosterone has been used to treat depression in men who are of middle age with low testosterone. However, a 2014 review showed no benefit on the mood of the men with normal levels of testosterone or on the mood of the older men with low testosterone.JOURNAL, Amanatkar HR, Chibnall JT, Seo BW, Manepalli JN, Grossberg GT, Impact of exogenous testosterone on mood: a systematic review and meta-analysis of randomized placebo-controlled trials, Annals of Clinical Psychiatry, 26, 1, 19â€“32, Feb 2014, 24501728,weblink {{Dead link|date=July 2020 |bot=InternetArchiveBot |fix-attempted=yes }} Conversely, a 2009 review found that testosterone had an antidepressant effect in men with depression, especially those with hypogonadism, HIV/AIDS, and in the elderly.JOURNAL, Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M, 205423837, Testosterone and depression: systematic review and meta-analysis, J Psychiatr Pract, 15, 4, 289â€“305, July 2009, 19625884, 10.1097/01.pra.0000358315.88931.fc,

Heart failure

Testosterone replacement can significantly improve exercise capacity, muscle strength and reduce QT intervals in men with chronic heart failure (CHF). Over the 3 to 6-month course of the studies reviewed, testosterone therapy appeared safe and generally effective, and (ruling out prostate cancer) the authors found no justification to absolutely restrict its use in men with CHF.JOURNAL, Wang W, Jiang T, Li C, Chen J, Cao K, Qi LW, Li P, Zhu W, Zhu B, Chen Y, Will testosterone replacement therapy become a new treatment of chronic heart failure? A review based on 8 clinical trials, Journal of Thoracic Disease, 8, 5, E269â€“77, May 2016, 27162680, 4842839, 10.21037/jtd.2016.03.39, free, A similar 2012 review also found increased exercise capacity and reasoned the benefits generlizable to women.JOURNAL, Toma M, McAlister FA, Coglianese EE, Vidi V, Vasaiwala S, Bakal JA, Armstrong PW, Ezekowitz JA, Testosterone Supplementation in Heart Failure: A Meta-Analysis, Circulation: Heart Failure, 5, 3, 315â€“21, May 2012, 22511747, 10.1161/CIRCHEARTFAILURE.111.965632, free, However, both reviews advocate larger, longer term, randomized controlled trials.

Male contraception

Testosterone, as esters such as testosterone undecanoate or testosterone buciclate, has been studied and promoted as a male contraceptive analogous to estrogen-based contraceptives in women. Otherwise considered an adverse effect of testosterone, reduced spermatogenesis can be further suppressed with the addition of a progestin such as norethisterone enanthate or levonorgestrel butanoate, improving the contraceptive effect.JOURNAL, Wang C, Festin MP, Swerdloff RS, Male Hormonal Contraception: Where Are We Now?, Current Obstetrics and Gynecology Reports, 5, 38â€“47, 2016, 26949570, 4762912, 10.1007/s13669-016-0140-8, JOURNAL, Chao JH, Page ST, The current state of male hormonal contraception, Pharmacology & Therapeutics, 163, 109â€“17, July 2016, 27016468, 10.1016/j.pharmthera.2016.03.012,

Anorgasmia

{{See also|List of investigational sexual dysfunction drugs}}Testosterone is under development in a low-dose intranasal formulation for the treatment of anorgasmia in women.WEB,weblink Testosterone intranasal (low-dose), September 5, 2017, live,weblink" title="web.archive.org/web/20170906035736weblink">weblink September 6, 2017,

Miscellaneous

Testosterone therapy may improve the management of type 2 diabetes.JOURNAL, Traish AM, Saad F, Guay A, The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance, Journal of Andrology, 30, 1, 23â€“32, 2009, 18772488, 10.2164/jandrol.108.005751, Low testosterone has been associated with the development of Alzheimer's disease.JOURNAL, Pike CJ, Rosario ER, Nguyen TV, 13852805, Androgens, aging, and Alzheimer's disease, Endocrine, 29, 2, 233â€“41, Apr 2006, 16785599, 10.1385/ENDO:29:2:233, JOURNAL, Rosario ER, Chang L, Stanczyk FZ, Pike CJ, Age-related testosterone depletion and the development of Alzheimer disease, JAMA, 292, 12, 1431â€“32, Sep 2004, 15383512, 10.1001/jama.292.12.1431-b, Topical androgens like testosterone have been used and studied in the treatment of cellulite in women.JOURNAL, Gruber CJ, Wieser F, Gruber IM, Ferlitsch K, Gruber DM, Huber JC, 37424524, Current concepts in aesthetic endocrinology, Gynecol. Endocrinol., 16, 6, 431â€“41, December 2002, 12626029, 10.1080/gye.16.6.431.441,

References

External links

WEB, Testosterone Transdermal Patch, MedlinePlus,weblink
WEB, Testosterone Buccal, MedlinePlus,weblink
WEB, Testosterone Topical, MedlinePlus,weblink
WEB, Testosterone Injection, MedlinePlus,weblink
WEB, Testosterone Nasal Gel, MedlinePlus,weblink

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Testosterone (medication)

Medical uses

Deficiency

Low levels due to aging

Transgender men

Women

Available forms

Non-medical use

Athletics

Detection of abuse

Contraindications

Side effects

Long-term adverse effects

Cardiovascular disease

Benign prostatic hyperplasia

Prostate cancer

Pregnancy and breastfeeding

Interactions

5Î±-Reductase inhibitors

Aromatase inhibitors

Cytochrome P450 inhibitors

Antiandrogens and estrogens

Pharmacology

Pharmacodynamics

Effects in the body and brain

Pharmacokinetics

Chemistry

Derivatives

History

Society and culture

Usage

Generic names

Brand names

Availability

United States

Canada

Other countries

Legal status

Litigation

Doping in sports

Research

Depression

Heart failure

Male contraception

Anorgasmia

Miscellaneous

References

Further reading

External links