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Gonadotropin-Releasing Hormone Antagonist plus Testosterone: A Potential Male Contraceptive^*

Medical Service, Veterans Affairs Medical Center Seattle, Washington 98108
The Department of Medicine Population Center for Research in Reproduction; Seattle, Washington 98108
The Departments Obstetrics and Gynecology Population Center for Research in Reproduction; Seattle, Washington 98108
The Departments Physiology and Biophysics Population Center for Research in Reproduction; Seattle, Washington 98108
The Regional Primate Research Center; University of Washington, Seattle, Washington 98108 Seattle, Washington 98108

Address requests for reprints to: Dr. William J. Bremner, Medical Service (111), Veterans Affairs Medical Center, 1660 South Columbian Way, Seattle, Washington 98108.

No effective hormonal contraceptive has yet been devised for men. Through their suppressive effect on gonadotropin secretion, GnRH antagonists inhibit both testosterone (T) production and spermatogenesis in animals. Long term administration of an antagonist alone would result in androgen deficiency; this would cause unacceptable physiological and behavioral sequellae in men. Therefore, androgen replacement must be included in any GnRH antagonist regimen used in human male contraception. We tested the hypothesis that the combination of a GnRH antagonist plus T would suppress spermatogenesis in the male primate to azoospermic levels while maintaining normal serum T levels. We examined the effects of the GnRH antagonist Deterelix [iV-Ac-DNal(2)¹-DpCl-Phe²-DTrp³-DhArg(Et2)⁶-DAla¹⁰-GnRH], alone and with simultaneous T replacement, on sperm production and serum T levels in adult male monkeys (n = 22). After 12 weeks of daily sc antagonist injection, all animals that received antagonist alone (n = 5) and those that 750 µg/kg-day antagonist plus T (n = 5) were azoospermic. After 16 weeks, four of five animals that received 250 µg/kg·day antagonist plus T became azoospermic. Control animals (n = 7) received daily injections of vehicle; sperm counts increased somewhat during the study period in that group. Castrate range T levels were achieved in animals receiving antagonist alone. T levels in the groups that received T supplementation and in the control group were in the normal male range throughout the treatment period. Sperm counts returned to the pretreatment range in all animals during the recovery period. We conclude that the combination of a GnRH antagonist plus T can induce azoospermia reversibly in this nonhuman primates species, and that a simlar combination may be an effective contraceptive regimen in men. The GnRH antagonist alone may be an effective treatment for androgen-dependent neoplasia.

^* This work was supported in part by the Contraceptive Development Branch, NIH; NIH Grants HD-12629, HD-12625, and RR-00166; and medical research funds from the Department of Veterans Affairs.

Received January 11, 1991.

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