testosterone (medication)

{{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).{{cite journal | vauthors = Margo K, Winn R | title = Testosterone treatments: why, when, and how? | journal = American Family Physician | volume = 73 | issue = 9 | pages = 1591–8 | date = May 2006 | pmid = 16719252 | url = http://www.aafp.org/afp/2006/0501/p1591.html | access-date = October 3, 2016 | url-status = live | archive-url = https://web.archive.org/web/20161003184639/http://www.aafp.org/afp/2006/0501/p1591.html | archive-date = 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.{{cite journal | vauthors = Myers JB, Meacham RB | title = Androgen replacement therapy in the aging male | journal = Reviews in Urology | volume = 5 | issue = 4 | pages = 216–26 | year = 2003 | pmid = 16985841 | pmc = 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.{{cite journal | vauthors = Qaseem A, Horwitch CA, Vijan S, Etxeandia-Ikobaltzeta I, Kansagara D | title = Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians | journal = Annals of Internal Medicine | date = January 2020 | volume = 172 | issue = 2 | pages = 126–133 | pmid = 31905405 | doi = 10.7326/M19-0882 | doi-access = free }}{{cite news |vauthors=Parry NM |title=New Guideline for Testosterone Treatment in Men With 'Low T' |url=https://www.medscape.com/viewarticle/923449 |date=January 7, 2020 |work=Medscape.com |access-date=January 7, 2020 |url-status=live |archive-date=January 8, 2020 |archive-url=https://web.archive.org/web/20200108011908/https://www.medscape.com/viewarticle/923449}}

{{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 hypothalamic–pituitary dysfunction (secondary hypogonadism) and may be congenital or acquired.{{cite book | vauthors = Sizar O, Leslie SW, Schwartz J | chapter = Male Hypogonadism | title = StatPearls | publisher=StatPearls Publishing | date=February 25, 2024 | pmid=30422528 | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK532933/ | access-date=August 30, 2024}}

{{Androgen replacement therapy formulations and dosages used in men}}

{{Main|Late-onset hypogonadism#Management}}

Testosterone levels may decline gradually with age.{{cite book | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK216164/ | title = Testosterone and Aging: Clinical Research Directions | chapter = Introduction | veditors = Liverman CT, Blazer DG | date = January 1, 2004 | publisher = National Academies Press (US) | isbn = 978-0-309-09063-6 | doi = 10.17226/10852 | pmid = 25009850 | access-date = November 11, 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 }}{{cite journal | vauthors = Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K, Flicker L | title = In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study | journal = European Journal of Endocrinology| volume = 156 | issue = 5 | pages = 585–94 | date = May 2007 | pmid = 17468195 | doi = 10.1530/EJE-06-0714 | doi-access = 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.

{{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,{{cite web | url=http://www.nhs.uk/Conditions/Gender-dysphoria/Pages/Treatment.aspx | title=Gender dysphoria – Treatment | publisher=NHS Gov.uk | date=May 21, 2012 | access-date=October 31, 2013 | url-status=live | archive-url=https://web.archive.org/web/20131102135038/http://www.nhs.uk/Conditions/Gender-dysphoria/Pages/Treatment.aspx | archive-date=November 2, 2013}} titrated to clinical effect with a "target level" of the average male's testosterone level.{{cite web | vauthors = Gorton RN, Buth J, Spade D | title = Medical Therapy and Health Maintenance for Transgender Men: A Guide For Health Care Providers | url = http://www.nickgorton.org/Medical%20Therapy%20and%20HM%20for%20Transgender%20Men_2005.pdf | publisher = Lyon-Martin Women's Health Services | access-date = December 11, 2016 | url-status = live | archive-url = https://web.archive.org/web/20161130005122/http://www.nickgorton.org/Medical%20Therapy%20and%20HM%20for%20Transgender%20Men_2005.pdf | archive-date = November 30, 2016}}

{{Medications and dosages used in hormone therapy for transgender men}}

{{clear}}

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.{{cite journal | vauthors = Wierman ME, Arlt W, Basson R, Davis SR, Miller KK, Murad MH, Rosner W, Santoro N | title = Androgen therapy in women: a reappraisal: an Endocrine Society clinical practice guideline | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 99 | issue = 10 | pages = 3489–510 | date = Oct 2014 | pmid = 25279570 | doi = 10.1210/jc.2014-2260 | doi-access = 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.{{cite journal | vauthors = Elraiyah T, Sonbol MB, Wang Z, Khairalseed T, Asi N, Undavalli C, Nabhan M, Firwana B, Altayar O, Prokop L, Montori VM, Murad MH | title = Clinical review: The benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis | journal = J. Clin. Endocrinol. Metab. | volume = 99 | issue = 10 | pages = 3543–50 | year = 2014 | pmid = 25279572 | pmc = 5393495 | doi = 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.{{cite journal | vauthors = Achilli C, Pundir J, Ramanathan P, Sabatini L, Hamoda H, Panay N | title = Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis | journal = Fertil. Steril. | volume = 107 | issue = 2 | pages = 475–482.e15 | year = 2017 | pmid = 27916205 | doi = 10.1016/j.fertnstert.2016.10.028 | doi-access = 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.{{cite journal | vauthors = Cappelletti M, Wallen K | title = Increasing women's sexual desire: The comparative effectiveness of estrogens and androgens | journal = Horm Behav | volume = 78 | pages = 178–93 | date = February 2016 | pmid = 26589379 | pmc = 4720522 | doi = 10.1016/j.yhbeh.2015.11.003 }}{{cite journal | vauthors = Reed BG, Bou Nemer L, Carr BR | title = Has testosterone passed the test in premenopausal women with low libido? A systematic review | journal = Int J Women's Health | volume = 8 | pages = 599–607 | year = 2016 | pmid = 27785108 | pmc = 5066846 | doi = 10.2147/IJWH.S116212 | doi-access = 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) have not been found to significantly increase sexual desire or function in women in most studies. Similarly, there appears to be little or no relationship between total or free testosterone levels in the normal physiological range and sexual desire in premenopausal women. Only high doses of testosterone resulting in supraphysiological 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 μg/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.{{cite journal | vauthors = Santoro N, Worsley R, Miller KK, Parish SJ, Davis SR | title = Role of Estrogens and Estrogen-Like Compounds in Female Sexual Function and Dysfunction | journal = J Sex Med | volume = 13 | issue = 3 | pages = 305–16 | date = March 2016 | pmid = 26944462 | doi = 10.1016/j.jsxm.2015.11.015 }}{{cite journal | vauthors = Stone L | s2cid = 7140458 | title = Sexual medicine: Transdermal oestrogen is effective | journal = Nat Rev Urol | volume = 14 | issue = 11 | pages = 638 | date = November 2017 | pmid = 28895561 | doi = 10.1038/nrurol.2017.152 | doi-access = free }}

There are no testosterone products approved for use in women in the United States and many other countries.{{cite book|vauthors=Pal L, Sayegh RA|title=Essentials of Menopause Management: A Case-Based Approach|url=https://books.google.com/books?id=HVkLDgAAQBAJ&pg=PA180|date=January 21, 2017|publisher=Springer|isbn=978-3-319-42451-4|pages=180–|access-date=July 31, 2018|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414214953/https://books.google.com/books?id=HVkLDgAAQBAJ&pg=PA180|url-status=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, {{cite web | title = Drugs of dependence and drug-dependent persons | url = http://www.health.vic.gov.au/drugs-and-poisons/drugs-of-dependence-and-drug-dependent-persons | work= Department of Health | publisher = Victorian Government | access-date = May 24, 2022 | archive-date = March 8, 2022 | archive-url = https://web.archive.org/web/20220308145610/https://www.health.vic.gov.au/drugs-and-poisons/drugs-of-dependence-and-drug-dependent-persons | url-status = live }} and some European countries. Testosterone pellet implants are approved for use in postmenopausal women in the United Kingdom.{{cite book|vauthors=Lobo RA, Kelsey J, Marcus R|title=Menopause: Biology and Pathobiology|url=https://books.google.com/books?id=i9HXKhjvNVAC&pg=PA454|date=May 22, 2000|publisher=Academic Press|isbn=978-0-08-053620-0|pages=454–|access-date=September 27, 2018|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215015/https://books.google.com/books?id=i9HXKhjvNVAC&pg=PA454|url-status=live}}{{cite book|vauthors=Bagatell C, Bremner WJ|title=Androgens in Health and Disease|url=https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA374|date=May 27, 2003|publisher=Springer Science & Business Media|isbn=978-1-59259-388-0|pages=374–|access-date=September 27, 2018|archive-date=December 20, 2019|archive-url=https://web.archive.org/web/20191220150236/https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA374|url-status=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.{{cite journal | vauthors = L'Hermite M | s2cid = 26079596 | title = Custom-compounded bioidentical hormone therapy: why so popular despite potential harm? The case against routine use | journal = Climacteric | volume = 20 | issue = 3 | pages = 205–211 | date = June 2017 | pmid = 28509626 | doi = 10.1080/13697137.2017.1285277 }}

{{Androgen replacement therapy formulations and dosages used in women}}

{{Androgen/anabolic steroid dosages for breast cancer}}

File:Androderm testosterone skin patch.jpg

Testosterone has been marketed for use by oral, sublingual, buccal, intranasal, transdermal (patches), topical (gels), intramuscular (injection), and subcutaneous (implant) administration.{{cite book|vauthors=Nieschlag E, Behre MH|title=Testosterone: Action - Deficiency - Substitution|url=https://books.google.com/books?id=jn3nCAAAQBAJ&pg=PA350|date=December 6, 2012|publisher=Springer Science & Business Media|isbn=978-3-642-72185-4|pages=1–,9,298,309–331,349–353,366–367|access-date=November 18, 2016 |archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215012/https://books.google.com/books?id=jn3nCAAAQBAJ&pg=PA350|url-status=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}}

{{See also|Ergogenic use of anabolic steroids|Anabolic–androgenic steroids abuse}}

Testosterone is used as a form of doping among athletes in order to improve performance.{{Cite web|url=http://list.wada-ama.org/list/s1-anabolic-agents|title=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/20160527144701/http://list.wada-ama.org/list/s1-anabolic-agents/|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}}

Anabolic–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.{{cite web| title=Anabolic Steroid Control Act| url=http://www.ussc.gov/USSCsteroidsreport-0306.pdf#search=%22Anabolic%20Steroid%20Control%20Act%20of%201990%22| publisher=United States Sentencing Commission| year=1990| access-date=November 11, 2016| url-status=dead| archive-date=August 30, 2016| archive-url=https://web.archive.org/web/20160830201115/http://www.ussc.gov/USSCsteroidsreport-0306.pdf#search=%22Anabolic%20Steroid%20Control%20Act%20of%201990%22}} 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.{{cite news | vauthors = Karkazis K, Jordan-Young R | title = The Trouble With Too Much T | url = https://www.nytimes.com/2014/04/11/opinion/the-trouble-with-too-much-t.html | date = April 11, 2014 | work=The New York Times | access-date = April 12, 2014 | archive-url = https://web.archive.org/web/20140412011234/http://www.nytimes.com/2014/04/11/opinion/the-trouble-with-too-much-t.html | archive-date = April 12, 2014 | url-status = 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.{{cite web| vauthors = Fagan K | author-link = Kate Fagan (sportswriter) | title = Katie Ledecky is crushing records, so why are we still worried about Caster Semenya?| work= ESPN| access-date = August 27, 2016| date = August 13, 2016| url = http://www.espn.com/espnw/voices/article/17275159/| url-status = live| archive-url = https://web.archive.org/web/20160818073128/http://www.espn.com/espnw/voices/article/17275159/| archive-date = August 18, 2016}}{{Cite news| issn = 0362-4331| vauthors = Padawer R | title = The Humiliating Practice of Sex-Testing Female Athletes| work= The New York Times| access-date = August 27, 2016| date = June 28, 2016| url = https://www.nytimes.com/2016/07/03/magazine/the-humiliating-practice-of-sex-testing-female-athletes.html| url-status = live| archive-url = https://web.archive.org/web/20160628124045/http://www.nytimes.com/2016/07/03/magazine/the-humiliating-practice-of-sex-testing-female-athletes.html| archive-date = June 28, 2016}}

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.{{cite journal | vauthors = Strahm E, Emery C, Saugy M, Dvorak J, Saudan C | title = Detection of testosterone administration based on the carbon isotope ratio profiling of endogenous steroids: international reference populations of professional soccer players | journal = British Journal of Sports Medicine | volume = 43 | issue = 13 | pages = 1041–44 | date = Dec 2009 | pmid = 19549614 | pmc = 2784500 | doi = 10.1136/bjsm.2009.058669 }}{{cite journal | vauthors = Kicman AT, Cowan DA | title = Subject-based profiling for the detection of testosterone administration in sport | journal = Drug Testing and Analysis | volume = 1 | issue = 1 | pages = 22–4 | date = Jan 2009 | pmid = 20355155 | doi = 10.1002/dta.14 | doi-access = free }}{{cite journal | vauthors = Pozo OJ, Deventer K, Van Eenoo P, Rubens R, Delbeke FT | title = Quantification of testosterone undecanoate in human hair by liquid chromatography-tandem mass spectrometry | journal = Biomedical Chromatography | volume = 23 | issue = 8 | pages = 873–80 | date = Aug 2009 | pmid = 19353724 | doi = 10.1002/bmc.1199 }}{{cite book | vauthors = Baselt RC | title = Disposition of Toxic Drugs & Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, Calif | year = 2008 | pages = 1501–04 | isbn = 978-0-9626523-7-0 }}

Absolute contraindications of testosterone include prostate cancer, elevated hematocrit (>54%), uncontrolled congestive heart failure, various other cardiovascular diseases, and uncontrolled obstructive sleep apnea.{{cite book |veditors=Kavoussi P, Costabile RA, Salonia A|title=Clinical Urologic Endocrinology: Principles for Men's Health|url=https://books.google.com/books?id=Eko5nLSINv8C&pg=PA65|date=October 19, 2012|publisher=Springer Science & Business Media|isbn=978-1-4471-4405-2|pages=65–|access-date=November 13, 2016|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215026/https://books.google.com/books?id=Eko5nLSINv8C&pg=PA65|url-status=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.{{cite book| vauthors = Perry MC |title=The Chemotherapy Source Book |url=https://books.google.com/books?id=CDADMzS0TKUC&pg=PA368|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-7328-7 |pages=368–|archive-url=https://web.archive.org/web/20170908214106/https://books.google.com/books?id=CDADMzS0TKUC&pg=PA368|archive-date=September 8, 2017|url-status=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%).

{{See also|Anabolic steroid#Adverse effects|Androgen replacement therapy#Adverse effects}}

In February 2025, the US Food and Drug Administration (FDA) specified label changes for products containing testosterone. The changes include removing language from the boxed warning related to an increased risk of adverse cardiovascular outcomes and adding a new warning about increased blood pressure.{{cite web | title=FDA issues class-wide labeling changes for testosterone products | website=U.S. Food and Drug Administration (FDA) | date=February 28, 2025 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-issues-class-wide-labeling-changes-testosterone-products | access-date=March 6, 2025}} {{PD-notice}}

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 5α-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.{{cite journal | s2cid = 25825354 | title = Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility | journal = Lancet | volume = 336 | issue = 8721 | pages = 955–9 | date = October 1990 | pmid = 1977002 | doi = 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.{{cite journal | vauthors = Rhoden EL, Morgentaler A | title = Treatment of testosterone-induced gynecomastia with the aromatase inhibitor, anastrozole | journal = International Journal of Impotence Research | volume = 16 | issue = 1 | pages = 95–7 | date = February 2004 | pmid = 14963480 | doi = 10.1038/sj.ijir.3901154 | doi-access = free }} Testosterone treatment, particularly in high dosages, can also be associated with mood changes, increased aggression, increased sex drive, spontaneous erections, and nocturnal emissions.{{cite journal| vauthors=Yates WR |title=Testosterone in Psychiatry |journal=Archives of General Psychiatry |volume=57 |issue=2 |year=2000 |pages=155 |issn=0003-990X |doi=10.1001/archpsyc.57.2.155}}{{cite journal |vauthors=Johnson JM, Nachtigall LB, Stern TA |title=The effect of testosterone levels on mood in men: a review |journal=Psychosomatics |volume=54 |issue=6 |pages=509–514 |year=2013 |pmid=24016385 |doi=10.1016/j.psym.2013.06.018}}{{cite journal |vauthors=Davidson JM, Kwan M, Greenleaf WJ |title=Hormonal replacement and sexuality in men |journal= Clinics in Endocrinology and Metabolism |volume=11 |issue=3 |pages=599–623 |date=November 1982 |pmid=6814798 |doi=10.1016/s0300-595x(82)80003-0}}{{cite book |vauthors=Bagatell C, Bremner WJ |title=Androgens in Health and Disease |url=https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA259|date=May 27, 2003|publisher=Springer Science & Business Media|isbn=978-1-59259-388-0|pages=144, 259–261, 351|access-date=November 18, 2016|archive-date=April 14, 2019 |archive-url=https://web.archive.org/web/20190414215125/https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA259|url-status=live}}

Other side effects include increased hematocrit, which can require venipuncture in order to treat, and exacerbation of sleep apnea.{{cite journal | vauthors = Pastuszak AW, Pearlman AM, Lai WS, Godoy G, Sathyamoorthy K, Liu JS, Miles BJ, Lipshultz LI, Khera M | title = Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy | journal = The Journal of Urology | volume = 190 | issue = 2 | pages = 639–44 | date = Aug 2013 | pmid = 23395803 | pmc = 4544840 | doi = 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.{{cite web|title=Testosterone and Other Anabolic Androgenic Steroids (AAS): FDA Statement - Risks Associated With Abuse and Dependence |url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm526151.htm |website=FDA|access-date=October 26, 2016|date=October 25, 2016|url-status=dead|archive-url=https://web.archive.org/web/20161027052404/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm526151.htm |archive-date=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.{{Cite web|date=August 2, 2020|title=Testosterone Injection|website=Drugs.com |url=https://www.drugs.com/testosterone.html|access-date=January 4, 2021|archive-date=January 8, 2021|archive-url=https://web.archive.org/web/20210108041736/https://www.drugs.com/testosterone.html|url-status=live}}{{Cite web|date=March 15, 2019|title=Testosterone Injection|website=MedlinePlus |url=https://medlineplus.gov/druginfo/meds/a614041.html|access-date=January 4, 2021|archive-url=https://web.archive.org/web/20191223210513/https://medlineplus.gov/druginfo/meds/a614041.html|archive-date=December 23, 2019|url-status=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.{{cite journal |vauthors=Pastuszak AW, Hu Y, Freid JD |title=Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis |journal=Sexual Medicine |volume=8 |issue=2 |pages=237–242 |date=June 2020 |pmid=32184081 |pmc=7261689 |doi=10.1016/j.esxm.2020.01.009}}

{{See also|Testosterone and the cardiovascular system}}

Results from the TRAVERSE trial were submitted in 2023, concluding that there was no increase in the risk of adverse cardiovascular outcomes in men using testosterone for hypogonadism.{{cite journal | vauthors = Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, Cunningham GR, Granger CB, Khera M, Thompson IM, Wang Q, Wolski K, Davey D, Kalahasti V, Khan N, Miller MG, Snabes MC, Chan A, Dubcenco E, Li X, Yi T, Huang B, Pencina KM, Travison TG, Nissen SE | title = Cardiovascular Safety of Testosterone-Replacement Therapy | journal = The New England Journal of Medicine | volume = 389 | issue = 2 | pages = 107–117 | date = July 2023 | pmid = 37326322 | doi = 10.1056/NEJMoa2215025 }}

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.{{cite journal | vauthors = Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF, Hoover RN | title = Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men | journal = PLOS ONE | volume = 9 | issue = 1 | page = e85805 | date = January 2014 | pmid = 24489673 | pmc = 3905977 | doi = 10.1371/journal.pone.0085805 | bibcode = 2014PLoSO...985805F | doi-access = free }} In addition, an increase of 30% in deaths and heart attacks in older men has been reported.{{cite journal | vauthors = Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM | title = Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels | journal = JAMA | volume = 310 | issue = 17 | pages = 1829–36 | date = Nov 2013 | pmid = 24193080 | doi = 10.1001/jama.2013.280386 | doi-access = 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.{{cite journal | vauthors = 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 | title = Adverse events associated with testosterone administration | journal = The New England Journal of Medicine | volume = 363 | issue = 2 | pages = 109–22 | date = July 8, 2010 | pmid = 20592293 | pmc = 3440621 | doi = 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.{{cite web |author=Staff |title=FDA evaluating risk of stroke, heart attack and death with FDA-approved testosterone products |url=https://www.fda.gov/downloads/Drugs/DrugSafety/UCM383909.pdf |publisher=U.S. Food and Drug Administration |date=January 31, 2014 |access-date=September 17, 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140219213907/https://www.fda.gov/downloads/Drugs/DrugSafety/UCM383909.pdf |archive-date=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).{{cite news | vauthors = Tavernise S | title = F.D.A. Panel Backs Limits on Testosterone Drugs | url = https://www.nytimes.com/2014/09/18/health/testosterone-drugs-fda.html | date = September 17, 2014 | work=The New York Times | access-date = September 18, 2014 | url-status = live | archive-url = https://web.archive.org/web/20140917201336/http://www.nytimes.com/2014/09/18/health/testosterone-drugs-fda.html | archive-date = September 17, 2014}}{{cite news |author=Staff |title=FDA Panel To Review Testosterone Therapy Appropriateness and Safety |url=http://ireport.cnn.com/docs/DOC-1167887 |date=September 5, 2014 |work=CNN News |access-date=September 14, 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140911081501/http://ireport.cnn.com/docs/DOC-1167887 |archive-date=September 11, 2014}}{{cite web |author=Staff |title=Joint Meeting for Bone, Reproductive and Urologic Drugs Advisory Committee (BRUDAC) and the Drug Safety And Risk Management Advisory Committee (DSARM AC) – 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 |url=https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM412536.pdf |date=September 17, 2014 |work=Food and Drug Administration |access-date=September 14, 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140906043632/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM412536.pdf |archive-date=September 6, 2014}} The FDA now requires warnings in the drug labeling of all approved testosterone products regarding deep vein thrombosis and pulmonary embolism.{{cite web|author=Staff|title=FDA adding general warning to testosterone products about potential for venous blood clots|url=https://www.fda.gov/Drugs/DrugSafety/ucm401746.htm|website=FDA|access-date=October 9, 2014|date=June 19, 2014|url-status=dead|archive-date=October 6, 2014|archive-url=https://web.archive.org/web/20141006074106/https://www.fda.gov/Drugs/DrugSafety/ucm401746.htm}}

Up to the year 2010, studies had not shown any effect on the risk of death, prostate cancer or cardiovascular disease;{{cite journal | vauthors = Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Boloña ER, Sideras K, Uraga MV, Erwin PJ, Montori VM | title = Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials | journal = Mayo Clinic Proceedings | volume = 82 | issue = 1 | pages = 29–39 | date = Jan 2007 | pmid = 17285783 | doi = 10.4065/82.1.29 }}{{cite journal | vauthors = Fernández-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 | title = Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 95 | issue = 6 | pages = 2560–75 | date = Jun 2010 | pmid = 20525906 | doi = 10.1210/jc.2009-2575 | doi-access = free }} more recent{{when|date=January 2020}} studies, however, do raise concerns.{{cite web|title=Testosterone Products: Drug Safety Communication – FDA Investigating Risk of Cardiovascular Events|work=FDA|date=January 31, 2014 |url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm384225.htm |access-date=February 3, 2014|url-status=dead|archive-date=February 14, 2014|archive-url=https://web.archive.org/web/20140214183006/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm384225.htm}} 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.{{Cite journal |date=February 6, 2023 |title=Research provides reassurance about the safety of testosterone treatment |url=https://evidence.nihr.ac.uk/alert/research-provides-reassurance-about-safety-testosterone-treatment/ |journal=NIHR Evidence |type=Plain English summary |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_56696 |s2cid=257851823 |access-date=February 28, 2023 |archive-date=February 28, 2023 |archive-url=https://web.archive.org/web/20230228091540/https://evidence.nihr.ac.uk/alert/research-provides-reassurance-about-safety-testosterone-treatment/ |url-status=live |url-access=subscription }}{{cite journal | vauthors = 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, Hernández R, Oliver N, Wu F, Dhillo WS, Bhattacharya S, Brazzelli M, Jayasena CN | title = Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis | journal = The Lancet. Healthy Longevity | volume = 3 | issue = 6 | pages = e381–e393 | date = June 2022 | pmid = 35711614 | pmc = 9184259 | doi = 10.1016/S2666-7568(22)00096-4 }}

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.{{cite journal |vauthors=Snyder P |title=Testosterone treatment of late-onset hypogonadism - benefits and risks |journal=Rev Endocr Metab Disord |volume=23 |issue=6 |pages=1151–1157 |date=December 2022 |pmid=35266057 |doi=10.1007/s11154-022-09712-1}}

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.{{cite journal | vauthors = Rhoden EL, Averbeck MA | s2cid = 20250546 | title = Testosterone therapy and prostate carcinoma | journal = Current Urology Reports | volume = 10 | issue = 6 | pages = 453–59 | date = Nov 2009 | pmid = 19863857 | doi = 10.1007/s11934-009-0072-1 }} Nevertheless, physicians are cautioned about the cancer risk associated with testosterone supplementation.{{cite journal | vauthors = Gaylis FD, Lin DW, Ignatoff JM, Amling CL, Tutrone RF, Cosgrove DJ | title = Prostate cancer in men using testosterone supplementation | journal = The Journal of Urology | volume = 174 | issue = 2 | pages = 534–38; discussion 538 | date = Aug 2005 | pmid = 16006887 | doi = 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.{{cite journal |vauthors=Calistro Alvarado L |title=Population differences in the testosterone levels of young men are associated with prostate cancer disparities in older men |journal=American Journal of Human Biology |volume=22 |issue=4 |pages=449–455 |year=2010 |pmid=20087895 |doi=10.1002/ajhb.21016 |s2cid=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.{{cite journal |vauthors=Bostwick DG, Burke HB, Djakiew D, Euling S, Ho SM, Landolph J, Morrison H, Sonawane B, Shifflett T, Waters DJ, Timms B |title=Human prostate cancer risk factors |journal=Cancer |volume=101 |issue=10 Suppl |pages=2371–2490 |date=Nov 2004 |pmid=15495199 |doi=10.1002/cncr.20408 |s2cid=24807561}}

Testosterone is contraindicated in pregnancy and not recommended during breastfeeding.{{cite web|title=Testosterone Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/testosterone.html|access-date=February 1, 2014|url-status=live|archive-url=https://web.archive.org/web/20140201201902/http://www.drugs.com/pregnancy/testosterone.html|archive-date=February 1, 2014}} Androgens like testosterone are teratogens and are known to cause fetal harm, such as producing virilization and ambiguous genitalia.

5α-Reductase inhibitors like finasteride and dutasteride can slightly increase circulating levels of testosterone by inhibiting its metabolism.{{cite book | vauthors = Jameson JL, de Kretser DM, Marshall JC, De Groot JL | title = Endocrinology Adult and Pediatric: Reproductive Endocrinology | url = https://books.google.com/books?id=Np8xxP6pcdUC&pg=RA1-PT1157 | date = May 7, 2013 | publisher = Elsevier Health Sciences | isbn = 978-0-323-22152-8 | pages = 1– | url-status = live | archive-url = https://web.archive.org/web/20170908214106/https://books.google.com/books?id=Np8xxP6pcdUC&pg=RA1-PT1157 | archive-date = 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).{{cite book | vauthors = Blume-Peytavi U, Whiting DA, Trüeb RM | title = Hair Growth and Disorders | url = https://books.google.com/books?id=pHrX2-huQCoC&pg=PA182 | date = June 26, 2008 | publisher = Springer Science & Business Media | isbn = 978-3-540-46911-7 | pages = 182– | url-status = live | archive-url = https://web.archive.org/web/20170908214106/https://books.google.com/books?id=pHrX2-huQCoC&pg=PA182 | archive-date = September 8, 2017}} In addition, local levels of DHT in so-called androgenic (5α-reductase-expressing) tissues are also markedly reduced, and this can have a strong impact on certain effects of testosterone.{{cite book | vauthors = Bagatelle C, Bremner WJ | title = Androgens in Health and Disease | url = https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA78 | date = May 27, 2003 | publisher = Springer Science & Business Media | isbn = 978-1-59259-388-0 | pages = 78– | access-date = December 6, 2016 | archive-date = April 14, 2019 | archive-url = https://web.archive.org/web/20190414215015/https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA78 | url-status = live }} For instance, growth of body and facial hair and penile growth induced by testosterone may be inhibited by 5α-reductase inhibitors, and this could be considered undesirable in the context of, for instance, puberty induction.{{cite book|vauthors=Baskin LS|title=Hypospadias and Genital Development|url=https://books.google.com/books?id=8zfaBwAAQBAJ&pg=PA37|date=December 6, 2012|publisher=Springer Science & Business Media|isbn=978-1-4419-8995-6|pages=37–|access-date=December 6, 2016|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215056/https://books.google.com/books?id=8zfaBwAAQBAJ&pg=PA37|url-status=live}} On the other hand, 5α-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, 5α-reductase inhibitors also prevent the formation of neurosteroids like 3α-androstanediol from testosterone, and this may have neuropsychiatric consequences in some men.{{cite book|title=Neurosteroids|url=https://books.google.com/books?id=fSgNRlZUwt0C&pg=PA358|publisher=Frontiers E-books|isbn=978-2-88919-078-2|pages=357–358|access-date=December 6, 2016|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414214952/https://books.google.com/books?id=fSgNRlZUwt0C&pg=PA358|url-status=live}}

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 hypothalamic–pituitary–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.{{cite journal | vauthors = Simpson ER | s2cid = 11210435 | title = Sources of estrogen and their importance | journal = J. Steroid Biochem. Mol. Biol. | volume = 86 | issue = 3–5 | pages = 225–30 |date=September 2003 | pmid = 14623515 | doi = 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.{{cite book |veditors=Nieschlag E, Behre HM, Nieschlag S |title=Andrology: Male Reproductive Health and Dysfunction |date=2009 |publisher=Springer |location=Berlin |isbn=978-3-540-78354-1 |page=459 |edition=3rd}}

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 like cyproterone acetate, spironolactone, and bicalutamide can block the androgenic and anabolic effects of testosterone.{{cite book | vauthors = Wecker L, Crespo L, Dunaway G, Faingold C, Watts S | title = Brody's Human Pharmacology | url = https://books.google.com/books?id=kfsrz_-OrMQC&pg=PA468 | date = April 1, 2009 | publisher = Elsevier Health Sciences | isbn = 978-0-323-07575-6 | pages = 468–469 | access-date = November 13, 2016 | archive-date = April 14, 2019 | archive-url = https://web.archive.org/web/20190414215026/https://books.google.com/books?id=kfsrz_-OrMQC&pg=PA468 | url-status = 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.{{cite book | vauthors = Partin AW, Wein AJ, Kavoussi LR, Peters CA | title = Campbell-Walsh Urology | url = https://books.google.com/books?id=OH_OCgAAQBAJ&pg=PT7207 | date = October 23, 2015 | publisher = Elsevier Health Sciences | isbn = 978-0-323-26374-0 | pages = 7207– | access-date = December 6, 2016 | url-status = live | archive-date = April 14, 2019 | archive-url = https://web.archive.org/web/20190414215011/https://books.google.com/books?id=OH_OCgAAQBAJ&pg=PT7207}}

{{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 5α-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.{{cite journal | vauthors = Kicman AT | title = Pharmacology of anabolic steroids | journal = British Journal of Pharmacology | volume = 154 | issue = 3 | pages = 502–21 | date = June 2008 | pmid = 18500378 | pmc = 2439524 | doi = 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.{{cite book | vauthors = Burtis CA, Ashwood ER, Bruns DE | title = Tietz Textbook of Clinical Chemistry and Molecular Diagnostics | url = https://books.google.com/books?id=BBLRUI4aHhkC&pg=PA1947 | date = October 14, 2012 | publisher = Elsevier Health Sciences | isbn = 978-1-4557-5942-2 | pages = 1947– | url-status = live | archive-url = https://web.archive.org/web/20160522142447/https://books.google.com/books?id=BBLRUI4aHhkC | archive-date = 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 3α-androstanediol, a neurosteroid and potent positive allosteric modulator of the GABA_A receptor, and 3β-androstanediol, a potent and preferential agonist of the ERβ.{{cite book | vauthors = Kohtz AS, Frye CA | chapter = Dissociating Behavioral, Autonomic, and Neuroendocrine Effects of Androgen Steroids in Animal Models | title = Psychiatric Disorders | series = Methods in Molecular Biology | volume = 829 | pages = 397–431 | year = 2012 | publisher = Springer | pmid = 22231829 | doi = 10.1007/978-1-61779-458-2_26 | isbn = 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,{{cite book | chapter = Androgen Physiology, Pharmacology and Abuse | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK279000/ | vauthors = Handelsman DJ | title = Endotext [Internet] | publisher = MDText.com, Inc | date = January 2013 | pmid = 25905231 | access-date = November 11, 2016 | archive-date = March 9, 2021 | archive-url = https://web.archive.org/web/20210309030923/https://www.ncbi.nlm.nih.gov/books/NBK279000/ | url-status = live }} the relative potency of these effects exerted by testosterone can depend on various factors and is a topic of ongoing research.{{cite book | chapter-url=https://link.springer.com/referenceworkentry/10.1007/978-3-319-29456-8_11-1 | doi=10.1007/978-3-319-29456-8_11-1 | chapter=Anabolic and Metabolic Effects of Testosterone and Other Androgens: Direct Effects and Role of Testosterone Metabolic Products | title=Thyroid Diseases | series=Endocrinology | date=2017 | vauthors = Čeponis J, Wang C, Swerdloff S, Liu PY | pages=1–22 | isbn=978-3-319-29195-6 | access-date=April 6, 2024 | archive-date=April 7, 2024 | archive-url=https://web.archive.org/web/20240407084734/https://link.springer.com/referenceworkentry/10.1007/978-3-319-29456-8_11-1 | url-status=live }}{{cite journal |vauthors=Kuhn CM |title=Anabolic steroids |journal=Recent Prog Horm Res |volume=57 |issue= |pages=411–34 |date=2002 |pmid=12017555 |doi=10.1210/rp.57.1.411|doi-access=free }}

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.{{cite book | vauthors = Nieschlag E, Behre HM, Nieschlag S | title = Andrology: Male Reproductive Health and Dysfunction | url = https://books.google.com/books?id=mEgckDNkonUC&pg=PA442 | date = January 13, 2010 | publisher = Springer Science & Business Media | isbn = 978-3-540-78355-8 | pages = 49–54,441–446 | url-status = live | archive-url = https://web.archive.org/web/20160623203518/https://books.google.com/books?id=mEgckDNkonUC | archive-date = June 23, 2016}}{{cite book |vauthors=Strauss JF, Barbieri RL, Gargiulo AR|title=Yen & Jaffe's Reproductive Endocrinology E-Book: Physiology, Pathophysiology, and Clinical Management |url=https://books.google.com/books?id=67ZEDwAAQBAJ&pg=PA292 |date=December 23, 2017|publisher=Elsevier Health Sciences|isbn=978-0-323-58232-2|pages=292–|access-date=March 31, 2018|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215014/https://books.google.com/books?id=67ZEDwAAQBAJ&pg=PA292|url-status=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 hypothalamic–pituitary–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

{{Main|Pharmacokinetics of testosterone}}

{{See also|Testosterone (patch)|Androgen ester#Testosterone esters}}

Testosterone can be taken by a variety of different routes of administration.{{cite book| vauthors = Behre HM, Nieschlag E |chapter=Testosterone preparations for clinical use in males| veditors = Nieschlag E, Behre HM, Nieschlag S |pages=309–335|doi=10.1017/CBO9781139003353.016|title=Testosterone: Action, Deficiency, Substitution|date=July 26, 2012|publisher=Cambridge University Press|isbn=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.

Testosterone is a naturally occurring androstane steroid and is also known by the chemical name androst-4-en-17β-ol-3-one.{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA641|date=November 14, 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=641–642|url-status=live|archive-url=https://web.archive.org/web/20170215024945/https://books.google.com/books?id=0vXTBwAAQBAJ|archive-date=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 C17β position.

{{See also|Androgen ester#Testosterone esters|List of androgens/anabolic steroids}}

Testosterone esters are substituted at the C17β position with a lipophilic fatty acid ester moiety of varying chain length.{{cite book|vauthors=Jameson JL, De Groot LJ|title=Endocrinology: Adult and Pediatric|url=https://books.google.com/books?id=xmLeBgAAQBAJ&pg=PA2387|date=February 25, 2015|publisher=Elsevier Health Sciences|isbn=978-0-323-32195-2|pages=2387–|access-date=November 18, 2016|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414214952/https://books.google.com/books?id=xmLeBgAAQBAJ&pg=PA2387|url-status=live}} Major testosterone esters include testosterone cypionate, testosterone enanthate, testosterone propionate, and testosterone undecanoate.{{cite book|vauthors=Chapple CR, Steers WD|title=Practical Urology: Essential Principles and Practice: Essential Principles and Practice|url=https://books.google.com/books?id=A9m8TkdCUqEC&pg=PA228|date=May 10, 2011|publisher=Springer Science & Business Media|isbn=978-1-84882-034-0|pages=228–|access-date=November 18, 2016|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215041/https://books.google.com/books?id=A9m8TkdCUqEC&pg=PA228|url-status=live}} A C17β ether prodrug of testosterone, cloxotestosterone acetate, has also been marketed, although it is little known and is used very rarely or no longer. Another C17β 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.{{cite book|vauthors=Gregory HM, Travis TN|title=Essentials of Strength Training and Conditioning|edition=4th|url=https://books.google.com/books?id=bfuXCgAAQBAJ&pg=PA233|date=September 23, 2015|publisher=Human Kinetics|isbn=978-1-4925-0162-6|pages=229, 233|access-date=November 18, 2016|archive-date=February 17, 2018|archive-url=https://web.archive.org/web/20180217202709/https://books.google.com/books?id=bfuXCgAAQBAJ&pg=PA233|url-status=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 (17α-methyl-δ¹-testosterone), and stanozolol (a 17α-alkylated derivative of DHT). Unlike testosterone, AAS that are 17α-alkylated, like metandienone and stanozolol, are orally active. This is due to steric hindrance of C17β-position metabolism during the first-pass through the liver. In contrast, most AAS that are not 17α-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}}

{{See also|Testosterone#History|Anabolic steroid#History}}

Testosterone was first isolated and synthesized in 1935.{{cite book | vauthors = Taylor WN | title = Anabolic Steroids and the Athlete | edition = 2nd | url = https://books.google.com/books?id=OGcQ0Tp2AFcC&pg=PA180 | date = January 16, 2002 | publisher = McFarland | isbn = 978-0-7864-1128-3 | pages = 180– | access-date = November 13, 2016 | archive-date = July 29, 2018 | archive-url = https://web.archive.org/web/20180729102024/https://books.google.com/books?id=OGcQ0Tp2AFcC&pg=PA180 | url-status = 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.{{cite book|vauthors=Llewellyn W|title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC&pg=PT385|year=2011|publisher=Molecular Nutrition Llc|isbn=978-0-9828280-1-4|pages=385–394, 413, 426, 607, 666|access-date=December 18, 2017|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215102/https://books.google.com/books?id=afKLA-6wW0oC|url-status=live}}{{cite book | vauthors = Hoberman J | title = Testosterone Dreams: Rejuvenation, Aphrodisia, Doping | url = https://archive.org/details/testosteronedrea00hobe | url-access = registration | date = February 21, 2005 |publisher=University of California Press|isbn=978-0-520-93978-3|pages=[https://archive.org/details/testosteronedrea00hobe/page/134 134]–}} 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.{{cite book|vauthors=Mundy AR, Fitzpatrick J, Neal DE, George NJ|title=The Scientific Basis of Urology|url=https://books.google.com/books?id=h6HSBQAAQBAJ&pg=PA294|date=July 26, 2010|publisher=CRC Press|isbn=978-1-84184-749-8|pages=294–|access-date=November 18, 2016|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215011/https://books.google.com/books?id=h6HSBQAAQBAJ&pg=PA294|url-status=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).{{cite journal | vauthors = ((Adis R&D Profile)) | s2cid = 43349541 | year = 2004 | title = Testosterone Undecanoate—Schering AG | journal = Drugs | volume = 5 | issue = 6| pages = 368–369 | doi=10.2165/00126839-200405060-00012| pmid = 15563244 }}

The history of testosterone as a medication has been reviewed.{{cite book| vauthors = Nieschlag E, Nieschlag S |chapter=The History of Testosterone and the Testes: From Antiquity to Modern Times |title=Testosterone|year=2017|pages=1–19|publisher=Springer |doi=10.1007/978-3-319-46086-4_1|isbn=978-3-319-46084-0}}{{cite journal | vauthors = Nieschlag E, Nieschlag S | title = ENDOCRINE HISTORY: The history of discovery, synthesis and development of testosterone for clinical use | journal = European Journal of Endocrinology | volume = 180 | issue = 6 | pages = R201–R212 | date = June 2019 | pmid = 30959485 | doi = 10.1530/EJE-19-0071 | doi-access = free }}{{cite journal | vauthors = Nieschlag E, Nieschlag S | title = Testosterone deficiency: a historical perspective | journal = Asian Journal of Andrology | volume = 16 | issue = 2 | pages = 161–8 | year = 2014 | pmid = 24435052 | pmc = 3955324 | doi = 10.4103/1008-682X.122358 | doi-access = free }}{{cite journal | vauthors = Morgentaler A, Traish A | title = The History of Testosterone and the Evolution of its Therapeutic Potential | journal = Sexual Medicine Reviews | volume = 8 | issue = 2 | pages = 286–296 | date = April 2020 | pmid = 29661690 | doi = 10.1016/j.sxmr.2018.03.002 | s2cid = 4903551 }}

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

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.{{cite web|title=Male Menopause|url=http://www.nhs.uk/conditions/Male-menopause/Pages/Introduction.aspx|website=www.nhs.uk|publisher=NHS Choices|date=April 8, 2016|access-date=October 7, 2016|url-status=live |archive-url=https://web.archive.org/web/20161009181414/http://www.nhs.uk/conditions/Male-menopause/Pages/Introduction.aspx|archive-date=October 9, 2016}}{{cite web | vauthors = Gorski D | title = "Low T": The triumph of marketing over science « Science-Based Medicine | url = https://www.sciencebasedmedicine.org/low-t-the-triumph-of-marketing-over-science/ | publisher = Science-Based Medicine | date = November 25, 2013 | url-status = live | archive-url = https://web.archive.org/web/20160911022624/https://www.sciencebasedmedicine.org/low-t-the-triumph-of-marketing-over-science/ | archive-date = 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.{{cite journal | vauthors = Perls T, Handelsman DJ | title = Disease mongering of age-associated declines in testosterone and growth hormone levels | journal = Journal of the American Geriatrics Society | volume = 63 | issue = 4 | pages = 809–11 | date = April 2015 | pmid = 25809947 | doi = 10.1111/jgs.13391 | s2cid = 328558 | doi-access = 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."

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 testostérone is its French name and the {{abbrlink|DCF|Dénomination Commune Française}}.{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|access-date=December 2, 2016|archive-date=October 21, 2021|archive-url=https://web.archive.org/web/20211021002502/https://books.google.com/books?id=5GpcTQD_L2oC|url-status=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 тестостерон.{{cite book|author=Владимир Мюллер|title=Англо-русский словарь. Русско-английский словарь. 250 000 слов|url=https://books.google.com/books?id=rOP6CwAAQBAJ&pg=PA643|date=April 15, 2016|publisher=ЛитРес|isbn=978-5-457-98308-3|pages=643–|access-date=December 2, 2016|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414214954/https://books.google.com/books?id=rOP6CwAAQBAJ&pg=PA643|url-status=live}}

File:Depo-testosterone 200 mg ml crop.jpg

Testosterone is marketed under a large number of brand names throughout the world.{{cite web |title=Testosterone - International |url=https://www.drugs.com/international/testosterone.html |publisher=Drugs.com |access-date=November 12, 2016 |url-status=live |archive-url=https://web.archive.org/web/20161113175707/https://www.drugs.com/international/testosterone.html |archive-date=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.

{{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.

{{cite book | vauthors = Morley JE | chapter = Testosterone | veditors = Morley JE, van den Berg L | title = Endocrinology of Aging | series = Disease-a-Month | chapter-url = https://books.google.com/books?id=hGD0BwAAQBAJ&pg=PA141 | date = November 5, 1999 | volume = 34 | issue = 7 | publisher = Springer Science & Business Media | isbn = 978-1-59259-715-4 | pages = 141– | doi = 10.1016/s0011-5029(98)90024-4 | pmid = 3044718 | access-date = November 15, 2016 | archive-date = April 14, 2019 | archive-url = https://web.archive.org/web/20190414215126/https://books.google.com/books?id=hGD0BwAAQBAJ&pg=PA141 | url-status = live }}{{cite book|vauthors=Bagatell C, Bremner WJ|title=Androgens in Health and Disease|url=https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA259|date=May 27, 2003|publisher=Springer Science & Business Media|isbn=978-1-59259-388-0|access-date=November 18, 2016|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215125/https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA259|url-status=live}}

{{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).{{cite web |title=Drug Product Database - Health Canada |publisher=Health Canada |url=http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php |access-date=November 13, 2016 |url-status=live |archive-url=https://web.archive.org/web/20161119200516/http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php |archive-date=November 19, 2016 |date=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.

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

{{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.{{cite book|vauthors=Karch SB|title=Drug Abuse Handbook, Second Edition|url=https://books.google.com/books?id=ZjrMBQAAQBAJ&pg=PA30|date=December 21, 2006|publisher=CRC Press|isbn=978-1-4200-0346-8|pages=30–|access-date=November 11, 2017|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215105/https://books.google.com/books?id=ZjrMBQAAQBAJ&pg=PA30|url-status=live}}{{cite book |vauthors=Lilley LL, Snyder JS, Collins SR |title=Pharmacology for Canadian Health Care Practice |url=https://books.google.com/books?id=dNgoDwAAQBAJ&pg=PA50 |date=August 5, 2016 |publisher=Elsevier Health Sciences |isbn=978-1-77172-066-3 |pages=50– |access-date=November 11, 2017 |archive-date=April 14, 2019 |archive-url=https://web.archive.org/web/20190414214954/https://books.google.com/books?id=dNgoDwAAQBAJ&pg=PA50 |url-status=live }}

{{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.{{cite news | vauthors = Harris A | title = Abbott Labs Sued by Five Men Claiming Androgel Injuries | url = https://www.bloomberg.com/news/2014-02-05/abbott-labs-sued-by-five-men-claiming-androgel-injuries.html | website = Bloomberg.com | date = February 5, 2014 | publisher = Bloomberg, L.P. | access-date = June 16, 2014 | url-status = live | archive-url = https://web.archive.org/web/20140714195657/http://www.bloomberg.com/news/2014-02-05/abbott-labs-sued-by-five-men-claiming-androgel-injuries.html | archive-date = July 14, 2014}}{{update inline|date=January 2020}}

{{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.

A 2018 meta-analysis concluded that testosterone treatment is associated with a modest reduction in depressive symptoms in men, especially at higher doses and in carefully selected populations.{{Cite journal | vauthors = Breidenstein J, Miller R, Walther A | title = Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis | journal = JAMA Psychiatry | volume = 76 | issue = 1 | pages = 31–40 | date = 2019-01-01 | pmid = 30427999 | pmc = 6583468 | doi = 10.1001/jamapsychiatry.2018.2734 | issn = 2168-6238 }} A 2014 meta-analysis found that testosterone improves mood, especially in middle-aged hypogonadal men with subthreshold depression, but shows limited effect in older or eugonadal men.{{Cite journal | vauthors = Chibnall JT, Seo BW, Manepalli JN, Grossberg GT, Amanatkar HR | title = Impact of exogenous testosterone on mood: a systematic review and meta-analysis of randomized placebo-controlled trials | journal = Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists | volume = 26 | issue = 1 | pages = 19–32 | date = 2014 | pmid = 24501728 | issn = 1547-3325 }} A 2009 review found that testosterone had an antidepressant effect in men with depression, especially those with hypogonadism, HIV/AIDS, and in the elderly.{{cite journal | vauthors = Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M | title = Testosterone and depression: systematic review and meta-analysis | journal = Journal of Psychiatric Practice | volume = 15 | issue = 4 | pages = 289–305 | date = July 2009 | pmid = 19625884 | doi = 10.1097/01.pra.0000358315.88931.fc | s2cid = 205423837 }}

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.{{cite journal | vauthors = Wang W, Jiang T, Li C, Chen J, Cao K, Qi LW, Li P, Zhu W, Zhu B, Chen Y | title = Will testosterone replacement therapy become a new treatment of chronic heart failure? A review based on 8 clinical trials | journal = Journal of Thoracic Disease | volume = 8 | issue = 5 | pages = E269–77 | date = May 2016 | pmid = 27162680 | pmc = 4842839 | doi = 10.21037/jtd.2016.03.39 | doi-access = free }} A similar 2012 review also found increased exercise capacity and reasoned the benefits generlizable to women.{{cite journal | vauthors = Toma M, McAlister FA, Coglianese EE, Vidi V, Vasaiwala S, Bakal JA, Armstrong PW, Ezekowitz JA | title = Testosterone Supplementation in Heart Failure: A Meta-Analysis | journal = Circulation: Heart Failure | volume = 5 | issue = 3 | pages = 315–21 | date = May 2012 | pmid = 22511747 | doi = 10.1161/CIRCHEARTFAILURE.111.965632 | doi-access = free }} However, both reviews advocate larger, longer term, randomized controlled trials.

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.{{cite journal | vauthors = Wang C, Festin MP, Swerdloff RS | title = Male Hormonal Contraception: Where Are We Now? | journal = Current Obstetrics and Gynecology Reports | volume = 5 | pages = 38–47 | date = 2016 | pmid = 26949570 | pmc = 4762912 | doi = 10.1007/s13669-016-0140-8 }}{{cite journal | vauthors = Chao JH, Page ST | title = The current state of male hormonal contraception | journal = Pharmacology & Therapeutics | volume = 163 | pages = 109–17 | date = July 2016 | pmid = 27016468 | doi = 10.1016/j.pharmthera.2016.03.012 }}

{{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.{{cite web |url=http://adisinsight.springer.com/drugs/800029680 |title=Testosterone intranasal (low-dose) |access-date=September 5, 2017 |url-status=live |archive-url=https://web.archive.org/web/20170906035736/http://adisinsight.springer.com/drugs/800029680 |archive-date=September 6, 2017}}

Testosterone therapy may improve the management of type 2 diabetes.{{cite journal | vauthors = Traish AM, Saad F, Guay A | title = The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance | journal = Journal of Andrology | volume = 30 | issue = 1 | pages = 23–32 | year = 2009 | pmid = 18772488 | doi = 10.2164/jandrol.108.005751 }} Low testosterone has been associated with the development of Alzheimer's disease.{{cite journal | vauthors = Pike CJ, Rosario ER, Nguyen TV | s2cid = 13852805 | title = Androgens, aging, and Alzheimer's disease | journal = Endocrine | volume = 29 | issue = 2 | pages = 233–41 | date = Apr 2006 | pmid = 16785599 | doi = 10.1385/ENDO:29:2:233 }}{{cite journal | vauthors = Rosario ER, Chang L, Stanczyk FZ, Pike CJ | title = Age-related testosterone depletion and the development of Alzheimer disease | journal = JAMA | volume = 292 | issue = 12 | pages = 1431–32 | date = Sep 2004 | pmid = 15383512 | doi = 10.1001/jama.292.12.1431-b }}

Topical androgens like testosterone have been used and studied in the treatment of cellulite in women.{{cite journal | vauthors = Gruber CJ, Wieser F, Gruber IM, Ferlitsch K, Gruber DM, Huber JC | s2cid = 37424524 | title = Current concepts in aesthetic endocrinology | journal = Gynecol. Endocrinol. | volume = 16 | issue = 6 | pages = 431–41 | date = December 2002 | pmid = 12626029 | doi = 10.1080/gye.16.6.431.441 }}

{{Reflist}}

{{refbegin}}

• {{cite book|vauthors=Nieschlag E, Behre JM, Nieschlag S|title=Andrology: Male Reproductive Health and Dysfunction|url=https://books.google.com/books?id=mEgckDNkonUC|date=January 13, 2010|publisher=Springer Science & Business Media|isbn=978-3-540-78355-8|access-date=November 13, 2016|archive-date=June 23, 2016|archive-url=https://web.archive.org/web/20160623203518/https://books.google.com/books?id=mEgckDNkonUC|url-status=live}}
• {{cite book|vauthors=Nieschlag E, Behre HM, Nieschlag S|title=Testosterone: Action, Deficiency, Substitution|url=https://books.google.com/books?id=MkrAPaQ4wJkC|date=July 26, 2012|publisher=Cambridge University Press|isbn=978-1-107-01290-5|access-date=July 31, 2018|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215108/https://books.google.com/books?id=MkrAPaQ4wJkC|url-status=live}}
• {{cite book|vauthors=Hohl A|title=Testosterone: From Basic to Clinical Aspects|url=https://books.google.com/books?id=Et6TDgAAQBAJ|date=March 30, 2017|publisher=Springer|isbn=978-3-319-46086-4|access-date=July 31, 2018|archive-date=April 14, 2019|archive-url=https://web.archive.org/web/20190414215052/https://books.google.com/books?id=Et6TDgAAQBAJ|url-status=live}}
• {{cite journal | vauthors = Nieschlag E, Nieschlag S | title = Testosterone deficiency: a historical perspective | journal = Asian J. Androl. | volume = 16 | issue = 2 | pages = 161–8 | date = 2014 | pmid = 24435052 | pmc = 3955324 | doi = 10.4103/1008-682X.122358 | doi-access = free }}
• {{cite book|vauthors=Llewellyn W|title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC|year=2011|publisher=Molecular Nutrition Llc|isbn=978-0-9828280-1-4|access-date=November 18, 2016|archive-date=April 14, 2021|archive-url=https://web.archive.org/web/20210414083125/https://books.google.com/books?id=afKLA-6wW0oC|url-status=live}}
• {{cite journal | vauthors = Shoskes JJ, Wilson MK, Spinner ML | title = Pharmacology of testosterone replacement therapy preparations | journal = Translational Andrology and Urology | volume = 5 | issue = 6 | pages = 834–843 | date = December 2016 | pmid = 28078214 | pmc = 5182226 | doi = 10.21037/tau.2016.07.10 | doi-access = free }}
• {{cite journal | vauthors = Celec P, Ostatníková D, Hodosy J | title = On the effects of testosterone on brain behavioral functions | journal = Frontiers in Neuroscience | volume = 9 | pages = 12 | date = February 2015 | pmid = 25741229 | pmc = 4330791 | doi = 10.3389/fnins.2015.00012 | doi-access = free }}

{{refend}}

• {{cite web | title=Testosterone Transdermal Patch | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a601118.html }}
• {{cite web | title=Testosterone Buccal | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a603034.html }}
• {{cite web | title=Testosterone Topical | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a605020.html }}
• {{cite web | title=Testosterone Injection | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a614041.html }}
• {{cite web | title=Testosterone Nasal Gel | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a615025.html }}

{{Testosterone}}

{{Androgens and antiandrogens}}

{{Navboxes

| title = Pharmacodynamics

| titlestyle = background:#ccccff

| list1 =

{{Androgen receptor modulators}}

{{Estrogen receptor modulators}}

{{GABAA receptor positive allosteric modulators}}

{{Growth factor receptor modulators}}

}}

{{Portal bar|Medicine}}

Category:1935 in biology

Category:1935 in Germany

Category:Alkene derivatives

Category:Anabolic–androgenic steroids

Category:Androstanes

Category:Cyclopentanols

Category:Drugs acting on the gastrointestinal system and metabolism

Category:Drugs developed by Eli Lilly and Company

Category:Drugs developed by AbbVie

Category:Enones

Category:Erectile dysfunction drugs

Category:Estrogens

Category:GABAA receptor positive allosteric modulators

Category:Hormonal antineoplastic drugs

Category:Testosterone

Category:Masculinizing hormone therapy

Category:World Health Organization essential medicines

Category:Wikipedia medicine articles ready to translate