Sequential regimen of the antiprogesterone RU486 and synthetic progestin for contraception.

ABSTRACT

PIP: To assess the effectiveness of an estrogen-free oral contraceptive (OC) involving the sequential administration of an antiprogesterone and synthetic progestin, 11 healthy Finnish women 20-34 years of age were enrolled in a prospective investigation for 1-3 cycles. 25 mg of RU-486 was administered for the first 21 days of the cycle, followed by 5 mg of norethisterone or medroxyprogesterone acetate for the next 10 days. It was hypothesized that prolonged RU-486 administration would prevent the follicle from surviving for ovulation. During the RU-486 phase, P increases above 3 ng/ml (suggestive of ovulation) were recorded in only four of the 24 treatment cycles analyzed. Mean serum estradiol concentrations were 147 pg/ml in ovulatory women and 72 pg/ml in anovulatory women, indicating that follicle development was subnormal and delayed, but not completely inhibited. Baseline secretion of luteinizing hormone (LH) increased during RU-486 administration, while an LH surge greater than 100% over baseline was recorded in the majority of cycles during progestin administration. No significant changes occurred in follicle-stimulating hormone levels. Menstrual bleeding began 1-5 days after progestin discontinuation; women who took norethisterone experienced no breakthrough bleeding or spotting during treatment. It is concluded that the main antiovulatory effect of RU-486 is attributable to its antiprogestational effect on the preovulatory P rise.