ACUTE HORMONAL RESPONSES TO THE GONADOTROPIN-RELEASING-HORMONE AGONIST LEUPROLIDE - DOSE-RESPONSE STUDIES AND COMPARISON TO NAFARELIN - A CLINICAL RESEARCH-CENTER STUDY

The hormonal responses to single subcutaneous injection of the GnRH ag onist nafarelin have been shown to have considerable potential as a di agnostic test in a number of settings. Since nafarelin injection is no longer produced, studies were conducted to determine the dosage of le uprolide that would yield equivalent responses. Nafarelin 100 mu g sti mulates LH and FSH for 24 h, releasing about 7-fold more gonadotropin than this dose of natural GnRH, which accounts for its ability to elic it gonadal steroid responses. Normal adult men and women were randomiz ed to receive leuprolide doses of 0.1, 1.0, or 10 mu g/kg; a study ext ension evaluated doses up to 20 mu g/kg in men. The responses of LH, F SH, testosterone, and estradiol were monitored for 24 h, and the data were compared to those previously obtained on nafarelin. Leuprolide do se of 10 mu g/kg yielded LH responses similar to 1-1.5 mu g/kg nafarel in. However, this leuprolide dose unexpectedly released less FSH than nafarelin. Nevertheless, the gonadotropin responses were sufficient to elicit equivalent or greater sex steroid responses to leuprolide. The se studies also further delineated sex-specific differences in pituita ry responsiveness to challenge with GnRH agonists: men had a significa ntly lower baseline FSH level, greater LH release within the first hou r, and lesser secretion of LH and FSH over the 24-h period. These stud ies indicate that leuprolide in a dosage of 10 mu g/kg would be expect ed to be efficacious in testing the pituitary-gonadal axis in men and women.