Single Subcutaneous Doses of a Luteinizing Hormone-Releasing Hormone Antagonist Suppress Serum Gonadotropin and Testosterone Levels in Normal Men*

Abstract

The ability of single doses of a LHRH antagonist [Ac-Δ³Pro¹, 4F-D-Phe², D-trp^3,6]LHRH (4F-antagonist) to suppress serum gonadotropin and testosterone levels was studied in six normal men. The 4F-antagonist was given sc at four doses: 40, 80, 160, and 320 µg/kg body weight. Serum immunoreactive LH, FSH, and testosterone and bioactive LH were measured at intervals for the subsequent 18 h. Serum LH decreased rapidly by (mean ± SE) 39.7 ± 2.7%, 41.6 ± 5.4%, 45.5 ± 4.7%, and 45.3 ± 5.4% after each of the four doses. The mean number of LH pulses and their amplitude decreased after each dose and remained suppressed for at least 6 h. After each of the four doses, mean serum FSH levels decreased by 20.0 ± 4.1%, 33.8 ± 6.8%, 25.8 ± 3.6%, and 33.3 ± 5.7%, and meanserum testosterone levels decreased by 47.7 ± 7.3%, 55.6 ± 10.5%, 58.2 ± 10.8%, and 76.0 ± 6.0%. Serum testosterone remained low for at least 18 h after the two higher doses. LH bioactivity and the ratio of bioactive LH to immunoreactive LH decreased in ali subjects, especially after higher doses of the 4F-antagonist. No side effects or adverse reactions occurred after 4F-antagonist administration, and toxicology studies were negative. These results demonstrate that a single sc injection of this potent LHRH antagonist inhibits the pituitary-gonadal axis in normal men.