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Background Testosterone (T) gel, administered transdermally in combination with injections of medroxyprogesterone acetate (DMPA) every 3 months, results in effective suppression of spermatogenesis in 90% of men. There are few data available regarding the acceptability of male hormonal contraceptive regimens, and none to date have examined the use of daily gel for contraception in normal men. Therefore, we questioned subjects enrolled in a combination T-gel plus DMPA male contraceptive trial regarding the acceptability of T-gel for male contraception and the impact of the T-gel/DMPA regimen on sexual function and satisfaction during treatment. Study Design Thirty-eight healthy men, ages 18 to 55, were treated with T-gel (100 mg daily) + DMPA (300 mg/3 months) for 24 weeks. Sexual function was assessed using a validated questionnaire at baseline, after 12 and 24 weeks of treatment, and 12 weeks into recovery. The overall acceptability of the method and attitudes regarding the daily self-administration of T-gel were assessed by a questionnaire 12 weeks into recovery. Results Fifty percent of subjects were either satisfied or very satisfied with the T-gel-based contraceptive regimen, and 45% indicated that they would use the regimen if it were commercially available. The T-gel was found to be easy to use by 76% of men, but a third of subjects felt that T-gel administration interfered with their daily routine. Sexual function was largely preserved during treatment; however, slight decreases in sexual function were observed during recovery. Conclusions The experimental male hormonal contraceptive regimen of T-gel + DMPA is acceptable to approximately half of study volunteers, most of whom would use the method if it were commercially available. Given its appeal to a significant proportion of men, additional studies using T-gel and DMPA for male contraception are warranted.

Gonadotropin-releasing hormone (GnRH) is the hypothalamic decapeptide that stimulates LH and FSH secretion from the pituitary and thereby controls reproduction. GnRH antagonists potently suppress gonadotropin production at the pituitary within hours of administration and have the potential to improve the degree and/or rapidity of sperm suppression in male hormonal contraceptive regimens. The long-acting GnRH antagonist Acyline suppresses gonadotropin levels for 2 weeks after a single dose. We are currently conducting a trial to determine the suppressive effects of 12 weeks of acyline on spermatogenesis and pituitary gonadotropin secretion when administered in combination with testosterone (T) in a transdermal gel form and the progestin depot-medroxyprogesterone acetate (DMPA). Forty-four men, ages 18-55, in good health and with normal spermatogenesis and hormonal status have been randomized to T gel (100 mg daily) + DMPA (300 mg IM q 3 months) or T gel + DMPA + acyline (300 μg/kg SQ q 2 weeks × 12 weeks). Six men did not complete the drug exposure period. To date, 37 men have completed the 24-week treatment protocol with the following sperm concentrations: The T/DMPA/Acyline combination exhibited a trend towards more rapid suppression of sperm concentrations to less than 1 million sperm/mL (the primary end point) after 12 weeks of administration compared with T gel + DMPA alone. There were no significant differences in sperm concentrations between groups after 24 weeks of treatment. There were no serious adverse effects of treatment. Acyline induced transient itching in most subjects that lasted for less than 24 hours. The addition of 12 weeks of the potent GnRH antagonist Acyline may accelerate and enhance the suppression of spermatogenesis by testosterone-progestogen male hormonal contraceptive regimens in men.

Purpose Testosterone (T) therapy in older men with low serum T levels increases lean body mass (LBM) and decreases fat mass (FM). These changes might improve physical performance and strength; however, it has not been established whether T therapy improves functional outcome in older men. Moreover, concerns exist about the impact of T therapy on the prostate in older men. The administration of finasteride, which blocks the conversion of T to the more potent androgen, dihydrotestosterone (DHT), attenuates the impact of T replacement on prostate size and PSA. We hypothesized that T replacement in older hypogonadal men would improve physical performance and that the addition of finasteride to T would not impact these T-induced improvements. Methods and Results Seventy men with low serum T (≤350ng/dl), age 65 and older, were randomly assigned to receive one of three regimens for 36 months: T enanthate 200 mg intramuscularly every two weeks with placebo pills daily (T-only), T enanthate 200 mg every two weeks with 5 mg finasteride daily (T+F), or placebo injections and pills (placebo). We obtained serial measurements of timed physical performance, grip strength, lower extremity strength, body composition (by DEXA), fasting cholesterol profiles and hormones. After 36 months, T therapy significantly improved performance in a timed functional test when compared to baseline and placebo (4.3±1.6% [mean± SEM, T-only] and 3.8±1.0% [T+F] vs. -5.6±1.9% for placebo, [P≤0.002 for both T and T+F versus placebo; and increased handgrip strength compared to baseline and placebo [P≤0.05]. T therapy increased LBM, and decreased FM, total cholesterol, low-density lipoprotein (LDL-C), and leptin, without affecting high-density lipoprotein (HDL), adiponectin or fasting insulin levels. Summary T therapy in older men with low serum T improves physical performance, strength, LBM, FM, and serum cholesterol over 36 months both when administered alone or when combined with finasteride. Conclusion These data suggest that T therapy may improve functional outcome in older men with low serum T and that DHT is likely not essential for these beneficial effects of T.