Testosterone Cypionate

Testosterone cypionate is the 17-beta cyclopentylpropionate ester of testosterone and a Schedule III controlled substance. The FDA-approved reference product is Depo-Testosterone (Pfizer), an intramuscular injection in cottonseed oil with benzyl benzoate and benzyl alcohol as preservative; generic equivalents are also approved. Compounded testosterone cypionate injections are oil solutions prepared under USP <797>.

FDA-labeled indication: replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone, either primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired). The labeled intramuscular dose range for males is 50 to 400 mg every 2 to 4 weeks, individualized by the prescriber.

The label notes that safety and efficacy have not been established for age-related hypogonadism. There is no FDA-labeled indication or dose in women; prescribers use compounded testosterone cypionate in women at low doses with the cautions under Warnings & Precautions.

After hydrolysis of the ester, testosterone binds the androgen receptor directly and after conversion by 5-alpha-reductase to dihydrotestosterone, and is aromatized to estradiol. These actions support male sexual development and secondary sex characteristics, spermatogenesis, muscle and bone mass, and erythropoiesis.

Testosterone cypionate is absorbed slowly from the intramuscular oil depot; the ester has a half-life of about 8 days, with peak testosterone concentrations a few days after injection and decline over the following 1 to 2 weeks. 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; about 90% of a dose is excreted in urine as glucuronide and sulfate conjugates and about 6% in feces.

• Men with breast cancer or known or suspected prostate cancer.
• Pregnancy.
• Serious cardiac, hepatic or renal disease.
• Known hypersensitivity to testosterone cypionate or any vehicle component, such as the oil or preservative used in the specific product.

• 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; the class update also removed boxed-warning language on adverse cardiovascular outcomes, and Depo-Testosterone carries no boxed warning. 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.
• Hepatic: prolonged use of high-dose androgens has been associated with peliosis hepatis, hepatic neoplasms and cholestatic jaundice.
• Benzyl alcohol, the preservative in the reference product, has been associated with fatal gasping syndrome in neonates.
• For intramuscular use only; do not give intravenously.

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, injection-site pain or inflammation, increased hematocrit, gynecomastia, fluid retention, increased or decreased libido, mood changes and headache. Less common: hypertension, venous thromboembolism, priapism, prostate enlargement, hepatic enzyme changes and male-pattern hair loss. In women, androgen excess causes virilizing effects and menstrual changes.

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.

• Depo-Testosterone (testosterone cypionate injection) Prescribing Information, Pfizer.
• USP General Chapter <797> Pharmaceutical Compounding: Sterile Preparations.
• 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).