Testosterone Cypionate Sexual Function Impact: What the Clinical Evidence Shows

What does the label say about libido and erections?

The Depo-Testosterone label lists "increased or decreased libido" under nervous system reactions. Under endocrine and urogenital reactions it lists gynecomastia and excessive frequency and duration of penile erections, and says oligospermia may occur at high dosages [1]. The label introduces this list as reactions that have occurred "with some androgens", so the list does not predict a particular sexual benefit or harm for an individual man [1].

What does TRAVERSE tell us?

TRAVERSE tested daily 1.62% testosterone gel, not cypionate injections [2]. It enrolled 5,246 men aged 45 to 80 with hypogonadism and preexisting or high risk of cardiovascular disease, and its primary endpoint was major cardiovascular events [2]. It is a cardiovascular safety trial and does not tell us how cypionate injections affect sexual function.

What other effects does the label list?

Gynecomastia may develop and occasionally persists in men treated for hypogonadism [1]. Aromatase converts androgens to estrogens [3]. Estrogens stimulate male breast tissue growth and androgens inhibit it; most gynecomastia results from deficient androgen action or excessive estrogen action [4]. The label also lists oligospermia at high doses [1]. Exogenous testosterone inhibits pituitary LH, and at large doses FSH, which suppresses sperm production [1]. The Endocrine Society recommends against starting testosterone therapy in men planning fertility in the near term [5].

What about fertility recovery?

In an integrated analysis of 30 studies and 1,549 healthy eugonadal men using androgen or androgen-progestin contraception, the median time for sperm concentration to recover to 20 million per mL was 3.4 months. About 67% recovered within 6 months and 90% within 12 months, and recovery was faster with shorter-acting testosterone and shorter treatment [6]. Those men did not have hypogonadism, and the analysis is not specific to cypionate. In a retrospective study of 66 men with infertility after testosterone use, who stopped testosterone and received hCG plus a selective estrogen receptor modulator, 70% reached a total motile count above 5 million within 12 months. Older age and longer testosterone use predicted slower recovery [11].

What about blood pressure and hematocrit?

FDA says ambulatory blood pressure studies confirmed a blood pressure increase with all testosterone products, class-wide [7]. The Depo-Testosterone label says to monitor blood pressure periodically, especially in men with hypertension, and that testosterone products are not recommended in uncontrolled hypertension [1]. Erythrocytosis risk is well established with testosterone therapy, and short-acting injectable formulations have the highest incidence [8]. In a network meta-analysis of 29 placebo-controlled trials and 3,393 men, intramuscular enanthate or cypionate raised mean hematocrit by 4.0% versus placebo (95% CI 2.9 to 5.1) [9]. The label says to check hemoglobin and hematocrit periodically during long-term use [1].

How is testosterone cypionate used?

Before starting, the label says hypogonadism should be confirmed with morning serum testosterone measured on at least two separate days, both below the normal range [1]. For hypogonadal men, the label describes 50 to 400 mg every 2 to 4 weeks, given by deep gluteal intramuscular injection, and states it should not be given intravenously [1]. The half-life after intramuscular injection is about 8 days [1]. Testosterone is a Schedule III controlled substance [1]. The label says the drug has not been shown safe and effective for enhancing athletic performance and should not be used for that purpose [1]. The label still says safety and efficacy in age-related hypogonadism have not been established [1]; FDA has asked for removal of that limitation [10]. FDA says none of the approved testosterone products are approved for men with low testosterone who lack an associated medical condition [10].

The label contraindicates use in men with known or suspected prostate cancer, men with breast cancer, pregnant women, and patients with serious cardiac, hepatic or renal disease [1].