Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: Implications for male contraceptive development

Weekly intramuscular administration of testosterone esters such as testoste rone enanthate (TE) suppresses gonadotropins and spermatogenesis and has be en studied as a male contraceptive. For unknown reasons, however, some men fail to achieve azoospermia with such regimens. We hypothesized that either 1) daily circulating serum fluoroimmunoreactive gonadotropins were higher or testosterone levels were lower during the weekly injection interval, or 2) monthly circulating bioactive gonadotropin levels were higher in nonazoo spermic men. We therefore analyzed daily testosterone and fluoroimmunoreact ive gonadotropin levels as well as pooled monthly bioactive and fluoroimmun oreactive gonadotropin levels in normal men receiving chronic TE injections and correlated these levels with sperm production. After a 3-month control period, 51 normal men were randomly assigned to receive intramuscular TE a t 25 mg (n = 10), 50 mg (n = 9), 100 mg (n = 10), 300 mg (n = 10), or place bo (n = 12) weekly for 6 months. After 5 months of testosterone administrat ion, morning testosterone and fluoroimmunoreactive follicle-stimulating hor mone (FSH) and luteinizing hormone (LH) levels were measured daily for a 1- week period between TE injections. In addition, fluoroimmunoreactive and bi oactive FSH and LH levels were measured in pooled monthly blood samples dra wn just before the next TE injection. In the 100-mg and 300-mg TE groups, m ean monthly fluoroimmunoreactive FSH and LH levels were suppressed by 86%-9 7%, bioactive FSH and LH levels by 62%-80%, and roughly half the subjects b ecame azoospermic. In the 1-week period of month 6, daily testosterone leve ls between TE injections were within the normal range in men receiving plac ebo, or 25 or 50 mg of weekly TE, but were significantly elevated in men re ceiving 100 or 300 mg of weekly TE. At no point during treatment, however, were there significant differences in daily testosterone or fluoroimmunorea ctive gonadotropin levels, or monthly bioactive gonadotropin levels between men achieving azoospermia and those with persistent spermatogenesis. This study, therefore, demonstrates that neither monthly nor daily differences i n serum testosterone, or fluoroimmunoreactive or bioactive gonadotropins ex plain why some men fail to completely suppress their sperm counts to zero w ith weekly TE administration. Innate differences in the testicle's ability to maintain spermatogenesis in a low-gonadotropin environment may explain p ersistent spermatogenesis in some men treated with androgen-based contracep tive regimens.