Suppression of ovarian estradiol secretion by a single injection of antide in cynomolgus monkeys during the early follicular phase: immediate, sustained, and reversible actions

Abstract

We examined the effects of the GnRH antagonist antide on ovarian estrogen secretion after a single administration in intact cycling cynomolgus monkeys (n = 5/group) during the early follicular phase. Antide treatment on menstrual cycle day 2 resulted in a dose-dependent increase in menstrual cycle lengths (mean +/- SEM) to 38 +/- 3, 49 +/- 8, and 96 +/- 15 days for 3.0, 10.0, and 30.0 mg/kg antide, respectively, in association with inhibition of folliculogenesis and suppression of estradiol concentrations to therapeutic levels. Subsequent resumption of apparently normal ovulatory menstrual cycles occurred in all 15 individuals. In addition, all four monkeys from the group treated with 30 mg/kg antide that were available for subsequent matings became pregnant and had normal babies. Thus, no irreversible consequences or adverse effects of antide on reproductive function in these primates was observed. No allergic or other adverse reactions were found locally or systemically in these primates, even at the highest dose of antide. To the extent that this primate model is a paradigm for clinical therapeutics, a single treatment of antide (30 mg/kg) provides sustained inhibition of ovarian estradiol secretion for about 2 months, thus demonstrating the feasibility of using antide for clinical management of steroid-dependent conditions.