Induction of menstruation by antiprogesterone ZK 98.299 in cycling bonnet monkeys.

The antiprogestin ZK 98.299 (11 beta-(4-dimethylaminophenyl)-17 alpha-hydroxy-17 beta-(3-hydroxypropyl)-13 alpha-methyl-4,9-gonadien-3-one) was administered s.c. (30mg/day) to two groups of cycling bonnet monkeys. In Group I (n = 6), it was injected from day 16 to 18 and in Group II (n = 9) from day 21 to 23 of the cycle. Each animal served as its own control and in the pretreatment cycle the vehicle (benzyl benzoate: castor oil, 1:4) was administered. During the treatment cycle of these animals the peak in estradiol levels was observed between days 8 to 11 of the menstrual cycle. In Group I animals, administration of ZK 98.299 induced vaginal bleeding in three of the six animals within two days of its first injection. In the remaining three animals the menstrual cycle length was prolonged. However, in all the six animals a premature drop in serum progesterone levels was observed. On the other hand, in Group II in seven animals with ovulatory treatment cycles, administration of ZK 98.299 induced vaginal bleeding within four days of the first dose and significantly shortened the cycle length. A significant decline in progesterone levels was observed in these animals also. However, in two animals in each group, ZK 98.299 induced vaginal bleeding while the serum progesterone levels were still high. Post-treatment cycles were ovulatory but the cycle length was marginally increased in some animals. In two animals of Group II, in which the treatment cycle turned out to be anovulatory, ZK 98.299 did not induce bleeding and had no effect on serum progesterone levels. This study shows that when administered during the luteal phase ZK 98.299 induces vaginal bleeding and premature luteal regression in bonnet monkeys. However, induction of vaginal bleeding may not be associated with drop in progesterone levels. ZK 98.299, therefore, appears to have potential for fertility control which warrants clinical evaluation.