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A Comparison of the Suppressive Effects of Testosterone and a Potent New Gonadotropin-Releasing Hormone Antagonist on Gonadotropin and Inhibin Levels in Normal Men^*

Medical Service, Veterans Administration Medical Center, Department of Medicine and Population Center for Research in Reproduction, University of Washington School of Medicine Seattle, Washington 98108
Department of Anatomy, Monash University and Medical Research Centre, Prince Henry's Hospital Melbourne, Victoria, Australia
Salk Institute La Jolla, California 92138

Address all correspondence and requests for reprints to: Carrie J. Bagatell, M.D., Seattle Veterans Administration Medical Center, Medical Service (111), 1660 South Columbian Way, Seattle, Washington 98108.

GnRH antagonists have been developed in large part because of their potential use as contraceptive agents, particularly in men. Specifically, it was hoped that GnRH antagonists combined with testosterone (T) would be a more effective contraceptive regimen than T alone. We compared the suppressive effects of a potent GnRH antagonist, Nal-Glu [AcD2NaL¹, D4ClPhe², D3Pal³, Arg⁵, DGlu⁶(AA), DAla¹⁰-GnRH], and of T together and separately on serum and urinary gonadotropin and serum inhibin levels in normal men. Ten-day courses of Nal-Glu (75 µg/kg; Nal-Glu alone), 200 mg testosterone enanthate, im, on days 0 and 7 (T alone), and the combination (Nal-Glu + T) were given to nine men. Serum gonadotropin and inhibin concentrations decreased after 1–2 days of Nal-Glu administration, while gonadotropin suppression occurred more slowly after T alone. Serum T fell to 30% of baseline values during Nal-Glu administration. The combination of Nal-Glu + T was more effective in suppressing serum LH, FSH, and inhibin than was either Nal-Glu alone or T alone. All hormone levels returned to baseline levels within 2.5 weeks after the end of the three regimens. We conclude that the Nal-Glu GnRH antagonist effectively inhibits gonadotropin, inhibin, and sex steroid secretion when given daily for 10 days and that the administration of Nal-Glu + T results in more complete gonadotropin and gonadal suppression than that produced by either agent given alone. These results encourage further investigation of the combination of a GnRH antagonist and T as a male contraceptive regimen and of the antagonist alone as a treatment for hormone-dependent neoplasia.

^* This work was supported in part by NIH Grant P-50-HD-12629, the V.A., and the Clinical Research Center at the University of Washington, supported by NIH Grant RR-37.

Received October 4, 1988.

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