Testosterone

Testosterone is the principal endogenous androgen and a Schedule III controlled substance. FDA-approved testosterone products include topical gels and solutions (for example AndroGel, Testim, Fortesta), a nasal gel (Natesto), subcutaneous pellets (Testopel), injectable esters (cypionate, enanthate including the Xyosted autoinjector, and undecanoate) and oral testosterone undecanoate capsules. A buccal system (Striant) was previously approved. Compounded testosterone is prepared as creams, gels, rapid-dissolve tablets, troches and other forms.

FDA-labeled indication across products: testosterone replacement therapy in males with conditions associated with a deficiency or absence of endogenous testosterone, either primary hypogonadism or hypogonadotropic hypogonadism (congenital or acquired). Testosterone enanthate injection is also labeled for delayed puberty in males and, secondarily, for women with advancing inoperable metastatic breast cancer who are 1 to 5 years postmenopausal.

Labels note safety and efficacy are not established for age-related hypogonadism. Prescribers also use compounded low-dose testosterone in women; no labeled dose exists for women's androgen replacement.

Testosterone binds the intracellular androgen receptor, which regulates gene transcription. 5-alpha-reductase converts it to the more potent dihydrotestosterone in prostate, skin and hair follicles, and aromatase converts it to estradiol, which mediates effects on bone, brain and lipids. Androgens maintain male secondary sex characteristics, spermatogenesis, muscle, bone and erythropoiesis, and suppress LH and FSH.

Swallowed unesterified testosterone undergoes extensive hepatic first-pass metabolism, so it is given by transdermal, mucosal (buccal, sublingual, nasal), subcutaneous or intramuscular routes, or as oral undecanoate absorbed through the lymphatics. About 98% of circulating testosterone is bound to sex hormone-binding globulin and albumin. Testosterone is metabolized in the liver to estradiol, dihydrotestosterone and 17-ketosteroids and excreted mainly in urine as conjugates. Its plasma half-life is short (minutes); duration depends on the delivery form.

• Men with breast cancer or known or suspected prostate cancer.
• Pregnancy.
• Known hypersensitivity to testosterone or a product component.
• Some injectable labels also list serious cardiac, hepatic or renal disease.

• Blood pressure: testosterone can raise blood pressure; FDA class labeling (2025) adds this warning to all testosterone products and adds results of the TRAVERSE cardiovascular safety trial. Testosterone can increase blood pressure, which can increase the risk of major adverse cardiovascular events. Monitor blood pressure.
• Polycythemia: hematocrit can rise; interrupt therapy if it exceeds label thresholds.
• Venous thromboembolism: DVT and pulmonary embolism have been reported, including in patients without polycythemia.
• Prostate: worsening of benign prostatic hyperplasia and possible increased risk of prostate cancer; evaluate before and during therapy.
• Abuse and dependence: supraphysiologic misuse is linked to serious cardiovascular and psychiatric events; withdrawal can occur.
• Reduced spermatogenesis and testicular atrophy at higher doses; may impair fertility.
• Edema, with or without heart failure, in patients with cardiac, renal or hepatic disease; gynecomastia; sleep apnea, especially with risk factors; lipid changes; hypercalcemia in patients with cancer and bone metastases; decreased thyroxine-binding globulin.
• Pediatric use: androgens can accelerate bone maturation without matching linear growth.

Women: no testosterone product is FDA-labeled for androgen replacement or sexual desire concerns in women. Prescribers use compounded testosterone in women at doses far below male doses, targeting the premenopausal female range. Cautions include virilization (acne, hirsutism, scalp hair loss, voice deepening and clitoral enlargement, which may be permanent), lipid changes, and excluding pregnancy.

• Insulin and oral antidiabetic drugs: androgens can lower blood glucose; dose reduction of the antidiabetic drug may be needed.
• Warfarin and other oral anticoagulants: androgens can increase anticoagulant effect; monitor INR more often when starting or stopping testosterone.
• Corticosteroids and ACTH: additive fluid retention; use caution in cardiac, renal or hepatic disease.
• Laboratory tests: androgens lower thyroxine-binding globulin, so total T4 falls while free thyroid hormone is unchanged.

Common: acne, increased hematocrit, increased PSA, gynecomastia, fluid retention, mood changes and headache. Form-specific: application-site irritation (topical), nasal symptoms (nasal gel), gum or mouth irritation and taste change (buccal or sublingual), injection-site pain (injections). In women, androgen excess causes virilization.

Testosterone is contraindicated in pregnancy. Exposure can virilize a female fetus. Pregnancy should be excluded before women start testosterone, and women of reproductive potential should use reliable contraception per prescriber guidance.

Lactation: testosterone use is not recommended while breastfeeding because of potential adverse effects in the infant. Male fertility: high doses suppress spermatogenesis, which may be prolonged.

• Serum testosterone at the timing the product label specifies, after starting and after dose changes.
• Hematocrit at baseline, during the first months of therapy and periodically.
• Blood pressure at baseline and periodically.
• PSA and prostate assessment in men, per guideline and patient age; lipids; symptoms of sleep apnea, edema and venous thromboembolism.
• In women: serum testosterone, signs of virilization, lipids, and pregnancy status.
• Topical forms: counsel and check for secondary exposure of children and partners.

• AndroGel (testosterone gel) Prescribing Information, AbbVie.
• Depo-Testosterone (testosterone cypionate injection) Prescribing Information, Pfizer.
• Testosterone Enanthate Injection USP Prescribing Information.
• Xyosted (testosterone enanthate) injection Prescribing Information.
• Endocrine Society Clinical Practice Guideline: Testosterone Therapy in Men with Hypogonadism (2018).
• Global Consensus Position Statement on the Use of Testosterone Therapy for Women (2019).