Physiology: Effects of intermittent antiprogestin RU486 combined with cyclic medroxyprogesterone acetate on folliculogenesis and ovulation

The results of several studies have suggested an inhibitory effect of the antiprogestin RU486 on late stages of folliculogenesis and ovulation. To assess the feasibility of using this property to inhibit ovulation without losing cycle control, an intermittent administration of RU486 alternated with medroxyprogesterone acetate (MPA) was tested in a phase I study. RU486 at a dose of 50 mg/day was given on menstrual cycle days 9-11 and 27-29, and 10 mg/day of MPA was given on cycle days 17-26 for three consecutive cycles to six Finnish and five Chilean women. Blood samples were collected two to three times a week for serum progesterone and oestradiol assays in three treatment cycles. One control cycle and one post-treatment recovery cycle were also monitored by serum samplings. Ultrasonography was carried out to measure follicular diameters in the treatment cycles. In 29 of 32 cycles, bleeding commenced within 3 days after the last MPA pill intake. Out of 32 treatment cycles, 20 were without luteal activity (serum progesterone <9 nmol/l). Although 12 treatment cycles showed luteal activity (serum progesterone ≥9 nmol/l), a clear rupture of a pre-ovulatory follicle >15 mm, verified by ultrasonography, was seen in only one treatment cycle. During the treatment cycles with luteal activity (serum progesterone levels ≥9 nmol/1), serum oestradiol concentrations were significantly higher on cycle days 9-18 and significantly lower at the end of the cycle compared with the cycles without luteal activity. The regimen used in this study disturbed folliculogenesis and ovulation (apparently), and was able to provide good cycle control in the majority of the cycles.