Reversible inhibition of testicular steroidogenesis and spermatogenesis by a potent gonadotropin-releasing hormone agonist in normal men: an approach toward the development of a male contraceptive.

We studied the antifertility effects of a potent gonadotropin-releasing hormone agonist, D-Trp6-Pro9-N-ethylamide-LHRH (LHRHA) in eight normal men, who received daily subcutaneous injections for six to 10 weeks. Plasma testosterone levels fell substantially in all eight. Plasma 17-hydroxyprogesterone and serum estradiol-17 beta levels decreased concordantly with plasma testosterone. Impotence developed in five men between the sixth and seventh weeks of treatment, with resolution in each case within two weeks of stopping treatment. Serum gonadotropin levels also fell during treatment, briefly rebounding above basal levels when therapy ended. Sperm density and motility fell t a nadir during the seventh to 18th week after therapy. In six subjects sperm levels fell to 6 X 10(6) sperm per milliliter or less, and in the other two they decreased 70 and 86 per cent below basal mean values. Sperm density returned to pretreatment levels in all men during the 10-to-14-week recovery period. These results are consistent with LHRHA-induced pituitary "desensitization" but do not exclude a direct inhibitory effect of LHRHA on testicular steroidogenesis and spermatogenesis.