SUPPRESSION OF FOLLICULAR PHASE PITUITARY-GONADAL FUNCTION BY A POTENT NEW GONADOTROPIN-RELEASING-HORMONE ANTAGONIST WITH REDUCED HISTAMINE-RELEASING PROPERTIES (GANIRELIX)

Objective: To determine if daily subcutaneous doses of ganirelix will suppress and maintain E(2) less than or equal to 30 pg/mL (conversion factor to SI unit, 3.671), the serum profiles of LH and FSH during and after cessation of treatment, the time-course of the resumption of no rmal ovarian function after ganirelix cessation, and to identify side effects of daily treatment. Design: Open-label nonrandomized clinical study. Setting: Normal human volunteers in an academic research center . Patients: Women 21 to 45 years of age, with documented ovulatory men strual cycles. Interventions: Ganirelix was administered subcutaneousl y daily for 8 days. Blood samples were obtained during dosing as well as before and after cessation of dosing. Main Outcome Measures: Change s in serum E(2), LH, FSH, P, and ganirelix. Results: Ganirelix treatme nt rapidly decreased serum levels of gonadotropins and E(2) after both 1 and 2 mg administration. Twenty-four hours after the first dose of ganirelix, E(2) decreased from a mean +/- SEM of 50 +/- 8 and 67 +/- 1 1 pg/mL at baseline to 25 +/- 4 and 20 +/- 3 in the 1 mg and 2 mg grou ps, respectively. Estradiol remained suppressed (mean levels < 26 pg/m L) on all subsequent 7 days of ganirelix dosing in both groups. After the final dose of ganirelix, there was a rapid return of ovarian funct ion in all volunteers. All women had P levels indicative of ovulation in the subsequent cycle, and the mean number of days from the final ga nirelix dose to the next menses was 25.8 +/- 2.1 and 27.3 +/- 1.6 in t he 1 and 2 mg groups, respectively. Conclusions: Daily ganirelix admin istration is effective in suppressing the pituitary-gonadal axis and h as a side effect profile that should be well tolerated.