Gonadal and pituitary responses to progesterone antagonist ZK 98.299 during the follicular phase of the menstrual cycle in bonnet monkeys.

ZK 98.299 is a potent progesterone antagonist. Its effects on folliculogenesis, bioactive LH, ovulation and menstrual cycle (m.c.) length were studied in adult bonnet monkeys. ZK 98.299 (20 mg/day) was administered s.c., once daily on days 5 to 15 of m.c., to ten animals. The pretreatment m.c. was of 26.5 days (25 to 28 days, mean with 95% confidence limits) and on treatment it was significantly (p less than 0.001) prolonged to 46.9 days (39 to 54 days). The anticipated midcycle rise in estradiol and bioactive LH levels was completely blocked in six and attenuated in three animals during the treatment period. However, the levels did not drop below the early follicular phase levels. In one animal (#90), though the cycle length was prolonged by 5 days the midcycle rise in estradiol and bioactive LH levels was observed during the treatment period and this animal had normal luteal function. Seven animals had delayed ovulation whereas, two had anovulatory treatment cycles. The rise in estradiol and bioactive LH levels, prior to ovulation in the treatment cycles, was compatible with the midcycle rise observed in the pretreatment cycles. Serum progesterone levels during the luteal phase of the treatment cycles were normal in six animals whereas, in two they were indicative of luteal insufficiency. In two animals, the treatment cycles were anovulatory. ZK 98.299 had no effect on the duration of menses. The post-treatment cycles were of normal duration. This study suggests that the administration of ZK 98.299 during the follicular phase blocks estradiol and bioactive LH release and terminates the follicular phase in most of the animals. The follicular phase is reinitiated after the treatment is stopped.