Abstract
The potential of a gonadotropin-releasing hormone (GnRH) antagonist to inhibit reproductive functions in a male nonhuman primate (Macaca fascicularis) was evaluated. Continuous infusion of 2 mg/day of [N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Ala10]-GnRH (RS-68439) via osmotic minipumps for 9 weeks caused immediate and sustained reduction of serum luteinizing hormone and testosterone concentrations and led to azoospermia in three animals and to sperm counts less than 5 X 10(6) in a fourth. Testicular histology showed severe atrophy of Leydig cells and tubules. The endocrine parameters returned to normal within 2 weeks of termination of treatment. Seminiferous tubule function was restored 14 to 18 weeks after treatment, as indicated by normal ejaculate parameters. It is concluded that chronic GnRH antagonist treatment reversibly inhibits pituitary and testicular function in a nonhuman primate. GnRH antagonists may thus have a potential for clinical use in fertility control and in treatment of androgen-dependent tumors.
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