Testosterone (medication)
Testosterone (T) is a medication and naturally occurring steroid hormone.[8] It is used to treat male hypogonadism, gender dysphoria, and certain types of breast cancer.[8][9] It may also be used to increase athletic ability in the form of doping.[8] It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful.[10] Testosterone can be used as a gel or patch that is applied to the skin, injection into a muscle, tablet that is placed in the cheek, or tablet that is taken by mouth.[8]
This article is about testosterone as a medication. For the natural hormone, see Testosterone.Clinical data
AndroGel, Testim, TestoGel, others
Androst-4-en-17β-ol-3-one
- US DailyMed: Testosterone
- AU: D[2]
- Contraindicated due to teratogenic effects
Oral: very low (due to extensive first pass metabolism)
Liver (mainly reduction and conjugation)
2–4 hours
C19H28O2
288.431 g·mol−1
+110.2°
155 °C (311 °F)
Common side effects of testosterone include acne, swelling, and breast enlargement in men.[8] Serious side effects may include liver toxicity, heart disease, and behavioral changes.[8] Women and children who are exposed may develop masculinization.[8] It is recommended that individuals with prostate cancer should not use the medication.[8] It can cause harm to the baby if used during pregnancy or breastfeeding.[8] Testosterone is in the androgen 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 the World Health Organization's List of Essential Medicines.[14] It is available as a generic medication.[8] In 2021, it was the 143rd most commonly prescribed medication in the United States, with more than 4 million prescriptions.[15][16]
Contraindications[edit]
Absolute contraindications of testosterone include prostate cancer, elevated hematocrit (>54%), uncontrolled congestive heart failure, various other cardiovascular diseases, and uncontrolled obstructive 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 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%).[73]
Interactions[edit]
5α-Reductase inhibitors[edit]
5α-Reductase inhibitors like finasteride and dutasteride can slightly increase circulating levels of testosterone by inhibiting its metabolism.[105] 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).[105][106] In addition, local levels of DHT in so-called androgenic (5α-reductase-expressing) tissues are also markedly reduced,[105][106] and this can have a strong impact on certain effects of testosterone.[50][107] 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.[107][108] 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.[50] 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.[109]
Aromatase inhibitors[edit]
Aromatase inhibitors like anastrozole prevent the conversion of testosterone into estradiol by aromatase.[50] 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.[50] 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.[110] Testosterone therapy is sometimes combined with an aromatase inhibitor for men with secondary hypogonadism who wish to conceive children with their partners.[111]
Cytochrome P450 inhibitors[edit]
Inhibitors and inducers of cytochrome P450 enzymes like CYP3A4 have been associated with little or no effect on circulating testosterone levels.
Antiandrogens and estrogens[edit]
Antiandrogens like cyproterone acetate, spironolactone, and bicalutamide can block the androgenic and anabolic effects of testosterone.[112][58] 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.[58][113]
Research[edit]
Depression[edit]
Testosterone has been used to treat depression in men who are of middle age with low testosterone. However, a 2014 review showed no benefit on the mood of the men with normal levels of testosterone or on the mood of the older men with low testosterone.[147] Conversely, a 2009 review found that testosterone had an antidepressant effect in men with depression, especially those with hypogonadism, HIV/AIDS, and in the elderly.[148]
Heart failure[edit]
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.[149] A similar 2012 review also found increased exercise capacity and reasoned the benefits generlizable to women.[150] However, both reviews advocate larger, longer term, randomized controlled trials.[149][150]
Male contraception[edit]
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.[151][152]