Reversible Induction of Azoospermia in Rhesus Monkeys by Constant Infusion of a Gonadotropin-Releasing Hormone Agonist Using Osmotic Minipumps

Abstract

This study documents the long term, reversible, antireproductive effects of GnRH agonist treatment in adult male rhesus monkeys. Constant sc infusion of the GnRH agonist buserelin by osmotic minipumps over 20 weeks resulted in an initial rise in serum LH, followed by a decline to undetectable levels, indicating pituitary desensitization. This rise and fall of plasma LH was paralleled by serum testosterone concentrations. The RHLH response to an iv bolus injection of GnRH was completely abolished, and the corresponding Leydig cell response was also lost. Testicular volumes decreased markedly, and spermatogenesis was inhibited to azoospermic levels. Spontaneous and electrostimulated ejaculatory activities were lost under prolonged buserelin infusion. The animals were then supplemented with exogenous testosterone to reestablish ejaculatory behavior which had been curtailed under low circulating androgen levels, and azoospermia persisted. Such pronounced effects could not be demonstrated in our previous studies using daily or twice daily injections with higher agonist doses. When treatment was stopped after 20 weeks, the inhibitory effects of the GnRH agonist were reversible, and full pituitary and gonadal functions were recovered. It is concluded that constant infusion of GnRH agonist is far more effective in male rhesus monkeys than daily injections and that the suppressive effects of GnRH agonist application are fully reversible. Thus, a suitable primate model for further research on a GnRH agonist-based male contraceptive has been established. (J Clin Endocrinol Metab56: 534, 1983)