Effect of a gonadotropin-releasing hormone agonist on luteinizing hormone and testosterone secretion and testicular histology in male rhesus monkeys.

Three adult male rhesus monkeys were treated for 20 weeks with a gonadotropin-releasing hormone (GnRH) agonist (Ag; Wy-40972; Wyeth Laboratories, Philadelphia, PA) using osmotic minipumps. Ag administration resulted in a transient increase and then a precipitous decrease in the concentration of luteinizing hormone (LH) and testosterone (T). After 5 weeks, serum levels of LH were undetectable (less than 0.2 microgram/ml), while serum T was always detectable, but continued to fall throughout the period of Ag administration. The serum LH and T response to 50 micrograms of GnRH was abolished by 4 weeks of Ag treatment, and this effect persisted through the treatment period. Testicular histology at 20 weeks of Ag treatment exhibited diffuse atrophy of seminiferous tubules, suppressed germinal cell division, and the absence of spermatids or spermatozoa. There was no evidence of testicular necrosis or calcification of the seminiferous tubules. Following the termination of Ag infusion, serum LH and T concentrations rebounded to levels that exceeded pretreatment values for a 5-week period before falling back to baseline levels. A complete restoration of spermatogenesis and testicular volume occurred by 12 weeks after treatment. These data suggest that continuous Ag administration is an effective method of reversibly disrupting spermatogenesis in the male rhesus monkey.