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| Pronunciation | /tɛˈstɒstəroʊn/teh-STOS-tə-rohn[1] |
| Trade names | AndroGel, Testim, TestoGel,others |
| Other names | Androst-4-en-17β-ol-3-one |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a619028 |
| License data | |
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| Dependence liability | Moderate[3] |
| Addiction liability | Moderate[3] |
| Routes of administration | Buccal,intranasal,subcutaneous implant,transdermal (gel,cream,patch). |
| Drug class | Androgen,anabolic steroid |
| ATC code | |
| Legal status | |
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| Pharmacokinetic data | |
| Bioavailability | Oral: very low (due to extensivefirst pass metabolism) |
| Protein binding | 97–99.5% (toSHBGTooltip sex hormone-binding globulin andalbumin)[7] |
| Metabolism | Liver (mainlyreduction andconjugation) |
| Eliminationhalf-life | 2–4 hours[citation needed] |
| Excretion | Urine (90%),feces (6%) |
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| IUPHAR/BPS | |
| DrugBank |
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| UNII | |
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| ChEBI | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C19H28O2 |
| Molar mass | 288.431 g·mol−1 |
| 3D model (JSmol) | |
| Specific rotation | +110.2° |
| Melting point | 155 °C (311 °F) |
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| (verify) | |
Testosterone is amedication and naturally occurringsteroid hormone.[8] It is used to treatmale hypogonadism,gender dysphoria, and certain types ofbreast cancer.[8][9] It may also be used to increaseathletic ability in the form ofdoping.[8] It is unclear if the use of testosterone forlow levels due to aging is beneficial or harmful.[10] Testosterone can be administered through several different routes, includingtopicalgels orpatches,nasal sprays, subdermal implants, ortablets dissolved inside the mouth.[8] Testosterone therapy has been associated with improvements indepressive symptoms (especially inhypogonadal men), increased exercise capacity and muscle strength in men withchronic heart failure, andmale contraception effectiveness.
Commonside effects of testosterone includeacne,swelling, andbreast enlargement in men.[8] Serious side effects may includeliver toxicity,heart disease, and behavioral changes.[8] Women and children who are exposed may developmasculinization.[8] It is recommended that individuals withprostate cancer should not use the medication.[8] It can cause harm to the baby if used duringpregnancy orbreastfeeding.[8] Testosterone is in theandrogen family of medications.[8]
Testosterone was first isolated in 1935, and approved for medical use in 1939.[11][12] Rates of use have increased three times in the United States between 2001 and 2011.[13] It is on theWorld Health Organization's List of Essential Medicines.[14] It is available as ageneric medication.[8] In 2023, it was the 119th most commonly prescribed medication in the United States, with more than 5 million prescriptions.[15][16]
The primary use of testosterone is the treatment of males with too little or no natural testosterone production, also termedmale hypogonadism orhypoandrogenism (androgen deficiency).[17] This treatment is referred to ashormone replacement therapy (HRT), or alternatively, and more specifically, as testosterone replacement therapy (TRT) orandrogen 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.[18]
A 2020 guideline from theAmerican College of Physicians supports the discussion of testosterone in adult men with age-relatedlow levels of testosterone who havesexual 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.[19][20]
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 becongenital or acquired.[21]
| Route | Medication | Major brand names | Form | Dosage |
|---|---|---|---|---|
| Oral | Testosteronea | – | Tablet | 400–800 mg/day (in divided doses) |
| Testosterone undecanoate | Andriol, Jatenzo | Capsule | 40–80 mg/2–4× day (with meals) | |
| Methyltestosteroneb | Android, Metandren, Testred | Tablet | 10–50 mg/day | |
| Fluoxymesteroneb | Halotestin, Ora-Testryl, Ultandren | Tablet | 5–20 mg/day | |
| Metandienoneb | Dianabol | Tablet | 5–15 mg/day | |
| Mesteroloneb | Proviron | Tablet | 25–150 mg/day | |
| Sublingual | Testosteroneb | Testoral | Tablet | 5–10 mg 1–4×/day |
| Methyltestosteroneb | Metandren, Oreton Methyl | Tablet | 10–30 mg/day | |
| Buccal | Testosterone | Striant | Tablet | 30 mg 2×/day |
| Methyltestosteroneb | Metandren, Oreton Methyl | Tablet | 5–25 mg/day | |
| Transdermal | Testosterone | AndroGel, Testim, TestoGel | Gel | 25–125 mg/day |
| Androderm, AndroPatch, TestoPatch | Non-scrotal patch | 2.5–15 mg/day | ||
| Testoderm | Scrotal patch | 4–6 mg/day | ||
| Axiron | Axillary solution | 30–120 mg/day | ||
| Androstanolone (DHT) | Andractim | Gel | 100–250 mg/day | |
| Rectal | Testosterone | Rektandron, Testosteronb | Suppository | 40 mg 2–3×/day |
| Injection (IMTooltip intramuscular injection orSCTooltip subcutaneous injection) | Testosterone | Andronaq, Sterotate, Virosterone | Aqueous suspension | 10–50 mg 2–3×/week |
| Testosterone propionateb | Testoviron | Oil solution | 10–50 mg 2–3×/week | |
| Testosterone enanthate | Delatestryl | Oil solution | 50–250 mg 1x/1–4 weeks | |
| Xyosted | Auto-injector | 50–100 mg 1×/week | ||
| Testosterone cypionate | Depo-Testosterone | Oil solution | 50–250 mg 1x/1–4 weeks | |
| Testosterone isobutyrate | Agovirin Depot | Aqueous suspension | 50–100 mg 1x/1–2 weeks | |
| Testosterone phenylacetateb | Perandren, Androject | Oil solution | 50–200 mg 1×/3–5 weeks | |
| Mixed testosterone esters | Sustanon 100, Sustanon 250 | Oil solution | 50–250 mg 1×/2–4 weeks | |
| Testosterone undecanoate | Aveed, Nebido | Oil solution | 750–1,000 mg 1×/10–14 weeks | |
| Testosterone buciclatea | – | Aqueous suspension | 600–1,000 mg 1×/12–20 weeks | |
| Implant | Testosterone | Testopel | Pellet | 150–1,200 mg/3–6 months |
| Notes: Men produce about 3 to 11 mg of testosterone per day (mean 7 mg/day in young men).Footnotes:a = Never marketed.b = No longer used and/or no longer marketed.Sources: See template. | ||||
Testosterone levels may decline gradually with age.[22][23] The United StatesFood 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.[10] The FDA has required that labels on testosterone include warnings about increased risk of heart attacks and stroke.[10]
To take advantage of itsvirilizing effects, testosterone, often shortened toT, is administered totransgender men and othertransmasculine individuals as part ofmasculinizing hormone therapy,[24] titrated to clinical effect with a "target level" of the average male's testosterone level.[25]
| Medication | Brand name | Type | Route | Dosage[a] |
|---|---|---|---|---|
| Testosterone undecanoate | Andriol, Jatenzo | Androgen | Oral | 40–80 mg up to three times/day |
| Testosterone | Striant | Androgen | Buccal | 30mg twice daily |
| Natesto | Androgen | Nasal spray | 11mg three times daily | |
| AndroGel[b] | Androgen | TD gel | 25–100mg/day | |
| Androderm[b] | Androgen | TD patch | 2.5–10mg/day | |
| Axiron | Androgen | TD liquid | 30–120mg/day | |
| Testopel | Androgen | SC | 150–600mg every3–6 months | |
| Testosterone enanthate | Delatestryl[b] | Androgen | IM, SC | 50–100mg once/week or 100–250mg every2–4 wks |
| Testosterone cypionate | Depo-Test[b] | Androgen | IM, SC | 50–100mg once/week or 100–250mg every2–4 wks |
| Testosterone isobutyrate | Agovirin Depot | Androgen | IM, SC | 50–100mg once/week |
| Mixed testosterone esters | Sustanon 250[b] | Androgen | IM, SC | 250mg every2–3 wks or 500mg every3–6 wks |
| Testosterone undecanoate | Aveed[b] | Androgen | IM, SC | 750–1,000mg every10–14 wks |
| Nandrolone decanoate | Deca-Durabolin | Androgen | IM, SC | ?[35] |
| GnRH analogues | Various | GnRH modulator | Various | Variable |
| Elagolix | Orilissa | GnRH antagonist | Oral | 150mg/day or 200mg twice/day |
| Medroxyprogesterone acetate[c] | Provera[b] | Progestin | Oral | 5–10mg/day |
| Depo-Provera[b] | Progestin | IM | 150mg every 3 months | |
| Depo-SubQ Provera 104 | Progestin | SC | 104mg every 3 months | |
| Lynestrenol[c] | Orgametril[b] | Progestin | Oral | 5–10mg/day |
| Finasteride[d] | Propecia[b] | 5αR inhibitor | Oral | 1mg/day |
| Dutasteride[d] | Avodart | 5αR inhibitor | Oral | 0.5mg/day |
Testosterone therapy is effective in the short-term for the treatment ofhypoactive sexual desire disorder (HSDD) in women.[36] However, its long-termsafety is unclear.[36] Because of a lack data to support its efficacy and safety, theEndocrine Society recommends against the routine use of testosterone in women to treatlow androgen levels due tohypopituitarism,adrenal insufficiency,surgical removal of the ovaries, high-dosecorticosteroid therapy, or other causes.[36] 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 generalwell-being, to treatinfertility,sexual dysfunction due to causes other than HSDD, or to improvecognitive,cardiovascular,metabolic, and/orbone health.[36]
A 2014 systematic review and meta-analysis of 35 studies consisting of over 5,000postmenopausal women with normaladrenal gland function found that testosterone therapy was associated with significant improvement in a variety of domains of sexual function.[37] These domains included frequency ofsexual activity,orgasm,arousal, and sexual satisfaction, among others.[37] Women who were menopausal due toovariectomy showed significantly greater improvement in sexual function with testosterone relative to those who had normal menopause.[37] In addition to beneficial effects on sexual function, testosterone was associated with unfavorable changes inblood lipids.[37] These included decreased levels of totalcholesterol,triglycerides, andhigh-density lipoprotein (HDL) cholesterol, and increased levels oflow-density lipoprotein (LDL) cholesterol.[37] However, the changes were small in magnitude, and the long-term significance in relation tocardiovascular outcomes is uncertain.[37] The changes were more pronounced with oraltestosterone undecanoate than withparenteral routes, such astransdermal testosterone.[37] Testosterone showed no significant effect ondepressedmoodanxiety,bone mineral density (BMD), oranthropomorphic measures likebody weight orbody mass index.[37] Conversely, it was associated with a significant incidence of androgenic side effects, includingacne andhirsutism (excessive facial/body hair growth).[37] Other androgenic side effects, such asweight gain,pattern hair loss, andvoice deepening, were also reported in some trials, but were excluded from analyses due to insufficient data.[37] 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.[37]
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.[38] 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.[38]
Although testosterone has been found to be effective at improving sexual function in postmenopausal women, the doses employed have been supraphysiological.[39][40] 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.[39][40] 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.[39] 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.[40][39] 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.[39][40] In accordance, men experiencesexual 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.[40] The high doses of testosterone required to increase sexual desire in women may have a significant risk of masculinization with long-term therapy.[40][39] For this reason, and due to the unknown health effects and safety of testosterone therapy, its use may be inappropriate.[40][39] In 2003, the FDA rejected Intrinsa, a 300 μg/daytestosterone patch for the treatment of sexual dysfunction in postmenopausal women.[39][40] 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 inappropriateoff-label use.[39][40] 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 ofestradiol to increase sexual desire in women is limited.[39][41][42]
There are no testosterone products approved for use in women in the United States and many other countries.[43] 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,[44] and some European countries.[43] Testosterone pellet implants are approved for use in postmenopausal women in the United Kingdom.[45][46] Testosterone products for men can be usedoff-label in women in the United States.[43] Alternatively, testosterone products for women are available fromcompounding pharmacies in the United States, although such products are unregulated and manufacturing quality is not ensured.[47]
| Route | Medication | Major brand names | Form | Dosage |
|---|---|---|---|---|
| Oral | Testosterone undecanoate | Andriol, Jatenzo | Capsule | 40–80 mg 1x/1–2 days |
| Methyltestosterone | Metandren, Estratest | Tablet | 0.5–10 mg/day | |
| Fluoxymesterone | Halotestin | Tablet | 1–2.5 mg 1x/1–2 days | |
| Normethandronea | Ginecoside | Tablet | 5 mg/day | |
| Tibolone | Livial | Tablet | 1.25–2.5 mg/day | |
| Prasterone (DHEA)b | – | Tablet | 10–100 mg/day | |
| Sublingual | Methyltestosterone | Metandren | Tablet | 0.25 mg/day |
| Transdermal | Testosterone | Intrinsa | Patch | 150–300 μg/day |
| AndroGel | Gel, cream | 1–10 mg/day | ||
| Vaginal | Prasterone (DHEA) | Intrarosa | Insert | 6.5 mg/day |
| Injection | Testosterone propionatea | Testoviron | Oil solution | 25 mg 1x/1–2 weeks |
| Testosterone enanthate | Delatestryl, Primodian Depot | Oil solution | 25–100 mg 1x/4–6 weeks | |
| Testosterone cypionate | Depo-Testosterone, Depo-Testadiol | Oil solution | 25–100 mg 1x/4–6 weeks | |
| Testosterone isobutyratea | Femandren M, Folivirin | Aqueous suspension | 25–50 mg 1x/4–6 weeks | |
| Mixed testosterone esters | Climacterona | Oil solution | 150 mg 1x/4–8 weeks | |
| Omnadren, Sustanon | Oil solution | 50–100 mg 1x/4–6 weeks | ||
| Nandrolone decanoate | Deca-Durabolin | Oil solution | 25–50 mg 1x/6–12 weeks | |
| Prasterone enanthatea | Gynodian Depot | Oil solution | 200 mg 1x/4–6 weeks | |
| Implant | Testosterone | Testopel | Pellet | 50–100 mg 1x/3–6 months |
| Notes:Premenopausal women produce about 230 ± 70 μgtestosterone per day (6.4 ± 2.0 mg testosterone per 4 weeks), with a range of 130 to 330 μg per day (3.6–9.2 mg per 4 weeks).Footnotes:a = Mostly discontinued or unavailable.b =Over-the-counter.Sources: See template. | ||||
| Route | Medication | Form | Dosage | |
|---|---|---|---|---|
| Oral | Methyltestosterone | Tablet | 30–200 mg/day | |
| Fluoxymesterone | Tablet | 10–40 mg 3x/day | ||
| Calusterone | Tablet | 40–80 mg 4x/day | ||
| Normethandrone | Tablet | 40 mg/day | ||
| Buccal | Methyltestosterone | Tablet | 25–100 mg/day | |
| Injection (IMTooltip intramuscular injection orSCTooltip subcutaneous injection) | Testosterone propionate | Oil solution | 50–100 mg 3x/week | |
| Testosterone enanthate | Oil solution | 200–400 mg 1x/2–4 weeks | ||
| Testosterone cypionate | Oil solution | 200–400 mg 1x/2–4 weeks | ||
| Mixed testosterone esters | Oil solution | 250 mg 1x/week | ||
| Methandriol | Aqueous suspension | 100 mg 3x/week | ||
| Androstanolone (DHT) | Aqueous suspension | 300 mg 3x/week | ||
| Drostanolone propionate | Oil solution | 100 mg 1–3x/week | ||
| Metenolone enanthate | Oil solution | 400 mg 3x/week | ||
| Nandrolone decanoate | Oil solution | 50–100 mg 1x/1–3 weeks | ||
| Nandrolone phenylpropionate | Oil solution | 50–100 mg/week | ||
| Note: Dosages are not necessarily equivalent.Sources: See template. | ||||
Testosterone has been marketed for use byoral,sublingual,buccal,intranasal,transdermal (patches),topical (gels),intramuscular (injection), andsubcutaneous (implant)administration.[48][49][50][51] It is provided unmodified and as atestosterone ester such astestosterone cypionate,testosterone enanthate,testosterone propionate, ortestosterone undecanoate, which act asprodrugs of testosterone.[48][49][50] The most commonroute of administration for testosterone is by intramuscular injection.[48] 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.[49]
| Route | Ingredient | Form | Dose[b] | Brand names[c] | |
|---|---|---|---|---|---|
| Oral | Test. undecanoate | Capsule | 40 mg | Andriol, Jatenzo | |
| Sublingual | Testosterone | Tablet | 10 mg | Testoral | |
| Buccal | Testosterone | Tablet | 30 mg | Striant | |
| Intranasal | Testosterone | Nasal gel | 5.5 mg/spray, 120 sprays | Natesto | |
| Transdermal | Testosterone | Non-scrotal patch | 2.5, 4, 5, 6 mg/day | Androderm | |
| Non-scrotal patch | 150, 300 μg/day | Intrinsa | |||
| Scrotal patch[d] | 4, 6 mg/day | Testoderm | |||
| Topical gel | 25, 50, 75, 100, 125 mg/pump | AndroGel, Testim | |||
| Axillary solution | 30 mg/pump | Axiron | |||
| Rectal | Testosterone | Suppository | 40 mg | Rektandron | |
| Injection[e] | Test. enanthate | Oil solution | 50, 100, 180, 200, 250 mg/mL | Delatestryl | |
| Test. cypionate | Oil solution | 50, 100, 200, 250 mg/mL | Depo-Testosterone | ||
| Mixed test. esters[f] | Oil solution | 100, 250 mg/mL | Sustanon | ||
| Test. undecanoate | Oil solution | 750, 1000 mg | Aveed, Nebido | ||
| Implant | Testosterone | Pellet | 50, 75, 100, 200 mg | Testopel | |
Footnotes and sources:
| |||||
Testosterone is used as a form ofdoping amongathletes in order to improve performance.[64] Testosterone is classified as ananabolic agent and is on theWorld Anti-Doping Agency (WADA) List of Prohibited Substances and Methods.[64] 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]
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]
After a series of scandals and publicity in the 1980s (such asBen Johnson's improved performance at the1988 Summer Olympics),prohibitions of AAS use were renewed or strengthened by many sports organizations. Testosterone and other AAS were designated a "controlled substance" by theUnited States Congress in 1990, with theAnabolic Steroid Control Act.[65] 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 Canadianprofessional wrestlerChris Benoit's double murder-suicide in 2007; however, there is no evidence implicating steroid use as a factor in the incident.[citation needed]
Some female athletes may have naturally higher levels of testosterone than others, and may be asked to consent tosex verification and either surgery or drugs to decrease testosterone levels.[66] This has proven contentious, with theCourt of Arbitration for Sport suspending the IAAF policy due to insufficient evidence of a link between high androgen levels and improved athletic performance.[67][68]
A number of methods for detecting testosterone use by athletes have been employed, most based on aurine test. These include the testosterone/epitestosterone ratio (normally less than 6), the testosterone/luteinizing hormone ratio and thecarbon-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.[69][70][71][72]
Absolutecontraindications of testosterone includeprostate cancer,elevated hematocrit (>54%), uncontrolledcongestive heart failure, various othercardiovascular diseases, and uncontrolledobstructive sleep apnea.[73]Breast cancer is said by some sources to be an absolute contraindication of testosterone therapy,[73] but androgens including testosterone have also actually been used to treat breast cancer.[74] Relative contraindications of testosterone include elevatedprostate-specific antigen (PSA) in men with a high risk of prostate cancer due toethnicity or family history, severelower urinary tract symptoms, and elevated hematocrit (>50%).[73]
In February 2025, the USFood and Drug Administration (FDA) specified label changes for products containing testosterone.[75] The changes include removing language from theboxed warning related to an increased risk of adverse cardiovascular outcomes and adding a new warning about increased blood pressure.[75]
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 with5α-reductase inhibitors. In women, testosterone can producehirsutism (excessive facial/body hair growth),deepening of the voice, and other signs ofvirilization. Exogenous testosterone may cause suppression ofspermatogenesis in men, leading to, in some cases, reversibleinfertility.[76]Gynecomastia andbreast tenderness may occur with high dosages of testosterone due to peripheral conversion of testosterone byaromatase into excessive amounts of theestrogenestradiol.[77] Testosterone treatment, particularly in high dosages, can also be associated withmood changes, increasedaggression, increasedsex drive,spontaneous erections, andnocturnal emissions.[78][79][80][81]
Other side effects include increasedhematocrit, which can requirevenipuncture in order to treat, and exacerbation ofsleep apnea.[82]
The FDA stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging.[10] The FDA has required that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke.[10] They have also required the label include concerns about abuse and dependence.[83]
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.[84][85] 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.[86]
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.[75][87]
Adverse effects of testosterone supplementation may include increased cardiovascular events (includingstrokes andheart attacks) anddeaths based on three peer-reviewed studies involving men taking testosterone replacement.[88] In addition, an increase of 30% in deaths and heart attacks in older men has been reported.[89] Due to an increased incidence of adverse cardiovascular events compared to aplacebo group, a Testosterone in Older Men with Mobility Limitations (TOM) trial (aNational Institute of Aging randomized trial) was halted early by theData Safety and Monitoring Committee.[90] On January 31, 2014, reports ofstrokes,heart attacks, anddeaths in men taking FDA-approved testosterone-replacement led the FDA to announce that it would be investigating the issue.[91] 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).[92][93][94] The FDA now requires warnings in the drug labeling of all approved testosterone products regardingdeep vein thrombosis andpulmonary embolism.[95]
Up to the year 2010, studies had not shown any effect on the risk of death,prostate cancer orcardiovascular disease;[96][97] more recent[when?] studies, however, do raise concerns.[98] 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."[89]
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.[99][100]
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 withbenign prostatic hyperplasia, a condition that involves the noncancerous enlargement of the prostate gland, which can lead to urinary symptoms.[101]
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.[102] Nevertheless, physicians are cautioned about the cancer risk associated with testosterone supplementation.[103]
Testosterone may accelerate pre-existingprostate cancer growth in individuals who have undergone androgen deprivation.[82] It is recommended that physicians screen for prostate cancer with a digital rectal exam andprostate-specific antigen (PSA) level before starting therapy, and monitor PSA and hematocrit levels closely during therapy.[22]
Ethnic groups have different rates of prostate cancer.[104] Differences in sex hormones, including testosterone, have been suggested as an explanation for these differences.[104] 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.[105]
Testosterone iscontraindicated inpregnancy and not recommended duringbreastfeeding.[106] Androgens like testosterone areteratogens and are known to causefetal harm, such as producingvirilization andambiguous genitalia.
5α-Reductase inhibitors likefinasteride anddutasteride can slightly increase circulating levels of testosterone by inhibiting itsmetabolism.[107] However, these drugs do this via prevention of the conversion of testosterone into its more potentmetabolitedihydrotestosterone (DHT), and this results in dramatically reduced circulating levels of DHT (which circulates at much lower relative concentrations).[107][108] In addition, local levels of DHT in so-called androgenic (5α-reductase-expressing) tissues are also markedly reduced,[107][108] and this can have a strong impact on certain effects of testosterone.[50][109] For instance, growth of body and facial hair andpenile 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.[109][110] On the other hand, 5α-reductase inhibitors may prevent or reduce adverse androgenic side effects of testosterone likescalp hair loss,oily skin,acne, andseborrhea.[50] In addition to the prevention of testosterone conversion into DHT, 5α-reductase inhibitors also prevent the formation ofneurosteroids like3α-androstanediol from testosterone, and this may have neuropsychiatric consequences in some men.[111]
Aromatase inhibitors likeanastrozole prevent the conversion of testosterone intoestradiol byaromatase.[50] As only a very small fraction of testosterone is converted into estradiol, this does not affect testosterone levels, but it can preventestrogenic side effects like gynecomastia that can occur when testosterone is administered at relatively high dosages.[50] However, estradiol exertsnegative feedback on thehypothalamic–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.[112] Testosterone therapy is sometimes combined with an aromatase inhibitor for men with secondary hypogonadism who wish to conceive children with their partners.[113]
Inhibitors andinducers ofcytochrome P450enzymes likeCYP3A4 have been associated with little or no effect on circulating testosterone levels.[citation needed]
Antiandrogens likecyproterone acetate,spironolactone, andbicalutamide can block the androgenic and anabolic effects of testosterone.[114][58]Estrogens can reduce the effects of testosterone by increasing the hepatic production and in turn circulating levels ofsex hormone-binding globulin (SHBG), acarrier protein that binds to and occupies androgens like testosterone and DHT, and thereby reducing free concentrations of these androgens.[58][115]
| Medication | Ratioa |
|---|---|
| Testosterone | ~1:1 |
| Androstanolone (DHT) | ~1:1 |
| Methyltestosterone | ~1:1 |
| Methandriol | ~1:1 |
| Fluoxymesterone | 1:1–1:15 |
| Metandienone | 1:1–1:8 |
| Drostanolone | 1:3–1:4 |
| Metenolone | 1:2–1:3 |
| Oxymetholone | 1:2–1:9 |
| Oxandrolone | 1:13–1:3 |
| Stanozolol | 1:1–1:3 |
| Nandrolone | 1:3–1:16 |
| Ethylestrenol | 1:2–1:19 |
| Norethandrolone | 1:1–1:2 |
| Notes: In rodents.Footnotes:a = Ratio of androgenic to anabolic activity.Sources: See template. | |
Testosterone is a highaffinityligand for andagonist of thenuclearandrogen receptor (AR). In addition, testosterone binds to and activatesmembrane androgen receptors (mARs) such asGPRC6A andZIP9. Testosterone is also potentiated viatransformation by5α-reductase into the morepotent androgen DHT in so-called androgenictissues such as theprostate gland,seminal vesicles,skin, andhair follicles. In contrast to the case of testosterone, such potentiation occurs to a reduced extent or not at all with mostsynthetic AAS (as well as with DHT), and this is primarily responsible for the dissociation ofanabolic and androgenic effects with these agents.[116] In addition to DHT, testosterone is converted at a rate of approximately 0.3% into theestrogenestradiol viaaromatase.[117] This occurs in many tissues, especiallyadipose tissue, theliver, and thebrain, but primarily in adipose tissue.[117] Testosterone, after conversion into DHT, is also metabolized into 3α-androstanediol, aneurosteroid and potentpositive allosteric modulator of theGABAA receptor, and3β-androstanediol, a potent and preferential agonist of theERβ.[118] These metabolites, along with estradiol, may be involved in a number of the effects of testosterone in the brain, including itsantidepressant,anxiolytic,stress-relieving,rewarding, andpro-sexual effects.[118] 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,[119] the relative potency of these effects exerted by testosterone can depend on various factors and is a topic of ongoing research.[120][121]
The ARs are expressed widely throughout the body, including in thepenis,testicles,epididymides,prostate gland,seminal vesicles,fat,skin,bone,bone marrow,muscle,larynx,heart,liver,kidneys,pituitary gland,hypothalamus, and elsewhere throughout thebrain.[122][123] Through activation of the ARs (as well as the mARs), testosterone has many effects, including the following:[122][48][additional citation(s) needed]
Testosterone can be taken by a variety of differentroutes of administration.[124] These includeoral,buccal,sublingual,intranasal,transdermal (gels,creams,patches),rectalsuppositories), byintramuscular orsubcutaneousinjection (inoil oraqueous), and as asubcutaneous implant.[124] Thepharmacokinetics of testosterone, including itsbioavailability, circulating testosterone levels,metabolism,biological half-life, and other parameters, differ by route of administration.[124]
Testosterone is anaturally occurringandrostanesteroid and is also known by the chemical name androst-4-en-17β-ol-3-one.[125] It has adouble bond between the C4 and C5 positions (making it anandrostene), aketonegroup at the C3 position, and ahydroxyl (alcohol) group at the C17β position.[125]
Testosterone esters aresubstituted at the C17β position with alipophilicfatty acidestermoiety of varyingchain length.[126] Major testosterone esters includetestosterone cypionate,testosterone enanthate,testosterone propionate, andtestosterone undecanoate.[58][125][127] A C17βetherprodrug of testosterone,cloxotestosterone acetate, has also been marketed, although it is little known and is used very rarely or no longer.[125] Another C17β ether prodrug of testosterone,silandrone, also exists but was never marketed, and is notable in that it is orally active.[125] In addition to ester and ether prodrugs,androgen prohormones orprecursors of testosterone, such asdehydroepiandrosterone (DHEA),androstenediol, andandrostenedione, exist as well, and convert into testosterone to variable extents upon oral ingestion.[128] Unlike testosterone ester and ether prodrugs however, these prohormones are only weakly androgenic/anabolic.[128]
All synthetic AAS arederivatives of testosterone.[128] Prominent examples includenandrolone (19-nortestosterone),metandienone (17α-methyl-δ1-testosterone), andstanozolol (a 17α-alkylated derivative of DHT). Unlike testosterone, AAS that are17α-alkylated, like metandienone and stanozolol, are orally active. This is due tosteric 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, asnandrolone decanoate ornandrolone phenylpropionate.
| Androgen | Structure | Ester | Relative mol. weight | Relative T contentb | logPc | ||||
|---|---|---|---|---|---|---|---|---|---|
| Position(s) | Moiet(ies) | Type | Lengtha | ||||||
| Testosterone | | – | – | – | – | 1.00 | 1.00 | 3.0–3.4 | |
| Testosterone propionate |  | C17β | Propanoic acid | Straight-chain fatty acid | 3 | 1.19 | 0.84 | 3.7–4.9 | |
| Testosterone isobutyrate |  | C17β | Isobutyric acid | Branched-chain fatty acid | – (~3) | 1.24 | 0.80 | 4.9–5.3 | |
| Testosterone isocaproate |  | C17β | Isohexanoic acid | Branched-chain fatty acid | – (~5) | 1.34 | 0.75 | 4.4–6.3 | |
| Testosterone caproate |  | C17β | Hexanoic acid | Straight-chain fatty acid | 6 | 1.35 | 0.75 | 5.8–6.5 | |
| Testosterone phenylpropionate |  | C17β | Phenylpropanoic acid | Aromatic fatty acid | – (~6) | 1.46 | 0.69 | 5.8–6.5 | |
| Testosterone cypionate |  | C17β | Cyclopentylpropanoic acid | Cyclic carboxylic acid | – (~6) | 1.43 | 0.70 | 5.1–7.0 | |
| Testosterone enanthate |  | C17β | Heptanoic acid | Straight-chain fatty acid | 7 | 1.39 | 0.72 | 3.6–7.0 | |
| Testosterone decanoate |  | C17β | Decanoic acid | Straight-chain fatty acid | 10 | 1.53 | 0.65 | 6.3–8.6 | |
| Testosterone undecanoate |  | C17β | Undecanoic acid | Straight-chain fatty acid | 11 | 1.58 | 0.63 | 6.7–9.2 | |
| Testosterone buciclated |  | C17β | Bucyclic acide | Cyclic carboxylic acid | – (~9) | 1.58 | 0.63 | 7.9–8.5 | |
| Footnotes:a = Length ofester incarbonatoms forstraight-chain fatty acids or approximate length of ester in carbon atoms foraromatic orcyclic fatty acids.b = Relative testosterone content by weight (i.e., relativeandrogenic/anabolicpotency).c = Experimental or predictedoctanol/water partition coefficient (i.e.,lipophilicity/hydrophobicity). Retrieved fromPubChem,ChemSpider, andDrugBank.d = Never marketed.e =Bucyclic acid =trans-4-Butylcyclohexane-1-carboxylic acid.Sources: See individual articles. | |||||||||
Testosterone was first isolated andsynthesized in 1935.[129] Shortly thereafter, in 1937, testosterone first became commercially available as apharmaceutical drug in the form ofpellets and then in ester form for intramuscular injection as the relatively short-acting testosterone propionate.[50][48][130]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.[130] In the mid-1950s, the longer-acting testosterone esterstestosterone enanthate andtestosterone cypionate were introduced.[130] They largely superseded testosterone propionate and became the major testosterone esters used medically for over half a century.[130] In the 1970s,testosterone undecanoate was introduced for oral use in Europe,[130] although intramuscular testosterone undecanoate had already been in use in China for several years.[131] Intramuscular testosterone undecanoate was not introduced in Europe and the United States until much later (in the early to mid 2000s and 2014, respectively).[7][132]
The history of testosterone as a medication has been reviewed.[133][134][135][136]
In the US in the 2000s, companies and figures in the popular media have heavily marketed notions of "andropause" as something parallel tomenopause; these notions have been rejected by the medical community.[137][138] Additionally, advertising from drug companies selling testosterone and human growth hormone, as well asdietary supplement companies selling all kinds of "boosters" for aging men, have emphasized the "need" of middle-aged or ageing men for testosterone.[139] There is a medical condition calledlate-onset hypogonadism; according to Thomas Perls and David J. Handelsman, writing in a 2015 editorial in theJournal of the American Geriatrics Society, it appears that this condition isoverdiagnosed andovertreated.[139] 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."[139]
Testosterone is thegeneric name of testosterone in English and Italian and theINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name,USPTooltip United States Pharmacopeia,BANTooltip BAN, andDCITTooltip Denominazione Comune Italiana of the drug, whiletestostérone is its French name and theDCFTooltip Dénomination Commune Française.[125][140][141] It is also referred to inLatin astestosteronum, in Spanish and Portuguese astestosterona, and in German,Dutch, and Russian and otherSlavic languages astestosteron.[140][141] TheCyrillic script of testosterone isтестостерон.[142]
Testosterone is marketed under a large number of brand names throughout the world.[140] 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.[58][116][140]
As of November 2016[update], unmodified (non-esterified) testosterone is available in the United States in the following formulations:[56]
And the following ester prodrugs of testosterone are available in the United States in oil solutions for intramuscular injection:[56]
Unmodified testosterone was also formerly available for intramuscular injection but was discontinued.[56]
Testosterone cypionate and testosterone enanthate were formerly available in combination withestradiol cypionate andestradiol valerate, respectively, under the brand names Depo-Testadiol and Ditate-DS, respectively, as oil solutions for intramuscular injection, but these formulations have been discontinued.[56]
Unlike in Europe, Canada, and much of the rest of the world, oral testosterone undecanoate is not available in the United States.[56]
As of November 2016[update], testosterone is available in Canada in the form of topical gels (AndroGel, Testim), topical solutions (Axiron), transdermal patches (Androderm), and intranasal gels (Natesto).[145] 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.[145] Testosterone buccal tablets and pellet implants do not appear to be available in Canada.[145]
Testosterone and/or its esters are widely available in countries throughout the world in a variety of formulations.[140]
Testosterone and its esters, along with other AAS, areprescription-onlycontrolled substances in many countries throughout the world. In the United States, they areSchedule III drugs under theControlled Substances Act, in Canada, they areSchedule IV drugs under theControlled Drugs and Substances Act, and in the United Kingdom, they areClass C drugs under theMisuse of Drugs Act.[146][147]
As of 2014[update], 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.[148][needs update]
There are many known cases ofdoping in sports with testosterone and its esters byprofessionalathletes.
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.[149] A 2014 meta-analysis found that testosterone improves mood, especially in middle-agedhypogonadal men with subthresholddepression, but shows limited effect in older or eugonadal men.[150] A 2009 review found that testosterone had an antidepressant effect in men with depression, especially those with hypogonadism,HIV/AIDS, and in the elderly.[151]
Testosterone replacement can significantly improveexercise capacity,muscle strength and reduceQT intervals in men withchronic 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.[152] A similar 2012 review also found increased exercise capacity and reasoned the benefits generlizable to women.[153] However, both reviews advocate larger, longer term,randomized controlled trials.[152][153]
Testosterone, as esters such as testosterone undecanoate or testosterone buciclate, has been studied and promoted as amale contraceptive analogous toestrogen-based contraceptives in women. Otherwise considered an adverse effect of testosterone, reduced spermatogenesis can be further suppressed with the addition of aprogestin such asnorethisterone enanthate orlevonorgestrel butanoate, improving the contraceptive effect.[154][155]
Testosterone is under development in a low-dose intranasal formulation for the treatment ofanorgasmia in women.[156]
Testosterone therapy may improve the management oftype 2 diabetes.[157] Low testosterone has been associated with the development ofAlzheimer's disease.[158][159]
Topical androgens like testosterone have been used and studied in the treatment ofcellulite in women.[160]
Rektandron FERRING supp. 40 mg • individ. dos. • 10 st.
This article incorporates text from this source, which is in thepublic domain.
