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  • Title: Reversible inhibition of testicular function by a gonadotropin hormone-releasing hormone antagonist in monkeys (Macaca fascicularis).
    Author: Weinbauer GF, Surmann FJ, Akhtar FB, Shah GV, Vickery BH, Nieschlag E.
    Journal: Fertil Steril; 1984 Dec; 42(6):906-14. PubMed ID: 6389185.
    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. The potential of a gonadotropin-releasing hormone (GnRH) antagonist to inhibit reproductive functions in a male nonhuman primate was evaluated in the Macaca fascicularis monkey. The monkeys were chronically infused with a GnRH antagonist through subcutaneously implanted osmotic minipumps for 9 weeks; their pituitary and testicular functions were monitored throughout the study period. Single injections of 1.0, 2.5, and 5.0 mg of the antagonist in castrated monkeys caused an immediate and marked decrease in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Suppression was so effective that with 7-9 weeks of the onset of treatment, azoospermia occurred in 3 of the 4 monkeys studied and extremely low sperm counts were measured in the 4th animal. 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 14-18 weeks after treatment. It was concluded that chronic GnRH treatment reversibly inhibits pituitary and testicular function in a nonhuman primate and thus may have potential for use in fertility control and the treatment of androgen-dependent tumors.
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