Testosterone-induced inhibition of spermatogenesis is more closely relatedto suppression of FSH than to testicular androgen levels in the cynomolgusmonkey model (Macaca fascicularis)

We have investigated the antigonadotropic and antispermatogenic effects of exposure to a long-acting testosterone eater in the cynomolgus monkey model . Groups of five adult animals were exposed either to vehicle or to 10 mg/k g or 20 mg/kg testosterone buciclate (TB) over a 26-week period with inject ions given in weeks 0, 11 and 18. In week 26, testicular biopsy tissue was collected. Serum testosterone levels were in the upper normal range with 10 mg/kg TB and were approximately twofold higher with 20 mg/kg TB. The estra diol pattern followed that of testosterone and body weights increased in a testosterone-dependent manner. TB completely abolished serum LH bioactivity . Serum concentrations of FSH and inhibin-a were suppressed in a TB dose-de pendent manner. During weeks 4-8 after the first injection, a rebound of FS H and inhibin but not bioactive LH secretion occurred. This rebound was fol lowed immediately by a restimulation of testis size and sperm numbers. Afte r the next TB injections these parameters were once again suppressed. Nadir testis size was 30-40% of baseline and animals were severely oligozoosperm ic or transiently azoospermic. Consistent azoospermia was not achieved. Qua ntitation of serum inhibin B, proliferating cell-nuclear antigen staining a nd flow cytometric analysis of germ cell populations revealed pronounced su ppression of spermatogenesis in both TB-treated groups whereas androgen rec eptor expression remained unchanged. Testicular androgens levels, determine d in week 26, did not differ among all three groups and did not correlate w ith sperm numbers, histological and immunocytochemical findings. All suppre ssive effects were fully reversed during the recovery period. We have concl uded that pronounced suppression of primate spermatogenesis seemingly requi res inhibition of FSH rather than testicular androgen levels, at least in t his preclinical non-human primate model. For the purpose of male contracept ion, FSH inhibition appears mandatory.