Intratesticular Androgens and Spermatogenesis During Severe Gonadotropin Suppression Induced by Male Hormonal Contraceptive Treatment

Male hormonal contraceptive regimens function by suppressing gonadotropin secretion, resulting in a dramatic decrease in testicular androgen biosynthesis and spermatogenesis. Animal studies suggest that persistent intratesticular (iT)‐androgen production has a stimulatory effect on spermatogenesis in the setting of gonadotropin suppression. We hypothesized that men with incompletely suppressed spermatogenesis (>1 000 000 sperm/mL) during male hormonal contraceptive treatment would have higher iT‐androgen concentrations than men who achieved severe oligospermia (≤1 000 000 sperm/mL). Twenty healthy men ages 18–55 years enrolled in a 6‐month male contraceptive study of transdermal testosterone (T) gel (100 mg/d) plus depomedroxyprogesterone acetate (300 mg intramuscularly every 12 weeks) with or without the gonadotropin releasing hormone (GnRH) antagonist acyline (300 μg/kg subcutaneously every 2 weeks for 12 weeks) were studied. During the 24th week of treatment, subjects underwent fine needle aspirations of the testes and iT‐T and iT‐dihydrotestosterone (iT‐DHT) were measured in testicular fluid by liquid chromatography—tandem mass spectrometry. All men dramatically suppressed spermatogenesis; 15 of 20 men were severely oligospermic, and 5 of 20 suppressed to 1.5 million −3.2 million sperm per milliliter. In all subjects, mean iT‐T and iT‐DHT concentrations were 35 ± 8 and 5.1 ± 0.8 nmol/L. IT‐androgen concentrations did not significantly differ in men who did and did not achieve severe oligospermia (P = .41 for iT‐T; P = .18 for iT‐DHT). Furthermore, there was no significant correlation between iT‐T or iT‐DHT and sperm concentration after 24 weeks of treatment. In this study of prolonged gonadotropin suppression induced by male hormonal contraceptive treatment, differences in iT‐androgens did not explain differences in spermatogenesis. Additional studies to identify factors involved in persistent spermatogenesis despite gonadotropin suppression are warranted.