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 E2 < or = 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 normal 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 menstrual cycles.

INTERVENTIONS

Ganirelix was administered subcutaneously daily for 8 days. Blood samples were obtained during dosing as well as before and after cessation of dosing.

MAIN OUTCOME MEASURES

Changes in serum E2, LH, FSH, P, and ganirelix.

RESULTS

Ganirelix treatment rapidly decreased serum levels of gonadotropins and E2 after both 1 and 2 mg administration. Twenty-four hours after the first dose of ganirelix, E2 decreased from a mean +/- SEM of 50 +/- 8 and 67 +/- 11 pg/mL at baseline to 25 +/- 4 and 20 +/- 3 in the 1 mg and 2 mg groups, respectively. Estradiol remained suppressed (mean levels < 26 pg/mL) on all subsequent 7 days of ganirelix dosing in both groups. After the final dose of ganirelix, there was a rapid return of ovarian function in all volunteers. All women had P levels indicative of ovulation in the subsequent cycle, and the mean number of days from the final ganirelix dose to the next menses was 25.8 +/- 2.1 and 27.3 +/- 1.6 in the 1 and 2 mg groups, respectively.

CONCLUSIONS

Daily ganirelix administration is effective in suppressing the pituitary-gonadal axis and has a side effect profile that should be well tolerated.