DOSE EFFECTS OF THE GONADOTROPIN-RELEASING-HORMONE ANTAGONIST, NAL-GLU, COMBINED WITH TESTOSTERONE ENANTHATE ON GONADOTROPIN-LEVELS IN NORMAL MEN

Objective: To test the hypothesis that over a 4-week treatment period, Nal-Glu GnRH antagonist ([AcD2Nal(1), D4ClPhe(2), D3Pal(3), Arg(5), DGlu(6) [AA], DAla(10)] GnRH) at a dose of 200 mu g/kg per day SC would suppress levels of immunologically active and biologically active LH and FSH more completely than a dose of 100 mu g/kg per day. Design: Placebo controlled clinical study. Setting: A university community. Subjects: Thirty normal male volunteers. Interventions: We administered Nal-Glu at doses of 0, 100, and 200 mu g/kg body weight per day in combination with T enanthate, 50 mg IM weekly, to separate groups of men (9 or 10 men per group) for 4 weeks. Results: Serum levels of immunologically active and biologically active gonadotropins were suppressed similarly in both groups of men who received Nal-Glu; this suppression was significantly greater than in the men who received placebo + T. Local side effects were more severe in the Nal-Glu 200 mu g/kg per day group. Conclusions: Administration of Nal-Glu in combination with T suppresses gonadotropins more completely than does T alone, but at doses > 100 mu g/kg, gonadotropins are not suppressed additionally with larger doses of Nal-Glu. Subjects experienced greater local discomfort and side effects with the higher dosage. These findings suggest that dosages of Nal-Glu of >100 mu g/kg per day may have no advantage over the 100-mu g/kg dose in a male contraceptive regimen.