COMPARISON OF A GONADOTROPIN-RELEASING-HORMONE ANTAGONIST PLUS TESTOSTERONE (T) VERSUS-T ALONE AS POTENTIAL MALE CONTRACEPTIVE REGIMENS

Efforts to develop a hormonal contraceptive regimen for men have focus ed on administration of testosterone (T), alone or together with other agents. Previous regimens have successfully induced azoospermia in on ly 50-70% of subjects, however. GnRH antagonists, alone or in combinat ion with T, have been shown to induce azoospermia in a very high perce ntage of nonhuman primates. We tested the hypothesis that the addition of a GnRH antagonist to a high-dose T regimen would lead to a higher percentage of men developing azoospermia than would T alone. We admini stered the GnRH antagonist, Nal-Glu (100 mug/kg. day sc), plus T enant hate, 200 mg im weekly or placebo sc injections daily plus T enanthate , 200 mg im weekly, to separate groups of healthy men for 16-20 weeks. Seven of 10 men who received Nal-Glu plus T and 6 of 9 men who receiv ed T alone became azoospermic; gonadotropin levels were suppressed and T levels were increased similarly in both groups. There was a trend t oward higher pretreatment gonadotropin levels and lower sperm counts i n men who became azoospermic. Weight gain, development of acne, and in creases in hematocrit and hemoglobin were similar in the two groups. I n the majority of the men, sperm counts returned to the baseline level s within 4-5 months after treatment ended. We conclude that with the d osages of Nal-Glu and T we used in this study, the addition of GnRH an tagonist to a high-dose T regimen does not increase the ability of T t o suppress spermatogenesis in healthy men. Use of a higher dose of Nal -Glu, a lower dose of T, delaying the start of T replacement until sev eral weeks after Nal-Glu injections are initiated, or prolonged hormon al administration might lead to a combination regimen that will suppre ss spermatogenesis more fully than does T alone.