Single subcutaneous doses of a luteinizing hormone-releasing hormone antagonist suppress serum gonadotropin and testosterone levels in normal men.
The ability of single doses of a LHRH antagonist [Ac-delta 3Pro1, 4F-D-Phe2, D-Trp3,6]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 micrograms/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 mean serum 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 all 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.
D000328:Adult; D001681:Biological Assay; D005640:Follicle Stimulating Hormone / Q000097:blood*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D011863:Radioimmunoassay; D013739:Testosterone / Q000097:blood*; D013997:Time Factors
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C036959:LHRH, Ac-dehydro-Pro(1)-4-F-Phe(2)-Trp(3,6)-; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone