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), D Glu(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: Pl acebo controlled clinical study. Setting: A university community. Subj ects: Thirty normal male volunteers. Interventions: We administered Na l-Glu at doses of 0, 100, and 200 mu g/kg body weight per day in combi nation 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 immunologi cally active and biologically active gonadotropins were suppressed sim ilarly in both groups of men who received Nal-Glu; this suppression wa s significantly greater than in the men who received placebo + T. Loca l side effects were more severe in the Nal-Glu 200 mu g/kg per day gro up. Conclusions: Administration of Nal-Glu in combination with T suppr esses 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 s ide effects with the higher dosage. These findings suggest that dosage s of Nal-Glu of >100 mu g/kg per day may have no advantage over the 10 0-mu g/kg dose in a male contraceptive regimen.