Cyclic progestin administration brings about luteinization during continuous antiprogestin treatment

The antiprogestin RU 486 has been proposed for use as a contraceptive because it disturbs folliculogenesis and inhibits ovulation when given continuously. In order to achieve regular and predictable withdrawal bleeding and to counteract the continuous influence of estrogen on the endometrium, a sequential, cyclic progestin regimen has been added. The drawback has been the frequent rise in the concentration of serum P, suggesting ovulation. The present pilot study with three subjects was carried out to test whether simultaneous administration of RU 486 and progestin during the second half of the cycle would eliminate the rise in serum P concentrations. Based on elevated serum P values, five of the seven cycles were apparently ovulatory. RU 486 alone, when given throughout the cycle at a dose of 8 mg per day without added progestin, resulted in anovulatory cycles, but the lengths of these cycles were prolonged. We conclude that both simultaneous and sequential cyclic co-administration of progestin with RU 486 abolishes the antiovulatory action of RU 486. This decreases the possibility of using antiprogestins in non-estrogenic contraceptive regimens (unless contraceptive effects of RU 486 exist at the endometrial level).