The effects of RU486 on the luteal phase of the rhesus monkey

RU486 is a steroid which possesses great affinity for the progesterone (P) receptor, but which has no P activity. It has been shown to be, as a result, a potent P antagonist. In the present study, we investigated the effect of this compound on the luteal phase of the rhesus monkey. The day of ovulation was diagnosed with a +/- 12 h accuracy, using serial laparoscopies and serum estradiol (E2) determinations, in regularly cycling rhesus monkeys. RU486 was administered by gavage (10 mg daily) in different regimens during the luteal phase: Group 1, days 1-5; Group 2, days 5-9; Group 3, days 9-13; and Groups 4, days 9-13, plus hCG (30, 60, 90, 180 and 360 IU i.m. on days 6-10). RU486 induced vaginal bleeding within 24-72 h after the initial administration in Groups 1-3. Animals of Group 4 presented luteal lengths ranging from 9-12 days. Progesterone concentrations at the onset of vaginal bleeding were 2.1 +/- 0.3, 4.9 +/- 0.6, 2.6 +/- 0.4 and 11.2 +/- 1.5 ng/ml (x +/- SEM) for animals of Groups 1-4, respectively. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), E2 and P levels were not altered during treatment. The availability of a compound such as RU486, that consistently induces vaginal bleeding due to its action at the target level (endometrium) without affecting the hormonal events of the menstrual cycle, opens a new approach to post-coital and interceptive contraception.