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 ovulati on. To assess the feasibility of using this property to inhibit ovulat ion without losing cycle control, an intermittent administration of RU 486 alternated with medroxyprogesterone acetate (MPA) was tested in a phase I study. RU486 at a dose of 50 mg/day was given on menstrual cyc le days 9-11 and 27-29, and 10 mg/day of MPA was given on cycle days 1 7-26 for three consecutive cycles to six Finnish and five Chilean wome n. Blood samples were collected two to three times a week for serum pr ogesterone and oestradiol assays in three treatment cycles. One contro l cycle and one post-treatment recovery cycle were also monitored by s erum samplings. Ultrasonography was carried out to measure follicular diameters in the treatment cycles. In 29 of 32 cycles, bleeding commen ced 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 progester one greater than or equal to 9 nmol/l), a clear rupture of a pre-ovula tory follicle >15 mm, verified by ultrasonography, was seen in only on e treatment cycle. During the treatment cycles with luteal activity (s erum progesterone levels greater than or equal to 9 nmol/l), serum oes tradiol concentrations were significantly higher on cycle days 9-18 an d significantly lower at the end of the cycle compared with the cycles without luteal activity. The regimen used in this study disturbed fol liculogenesis and ovulation (apparently), and was able to provide good cycle central in the majority of the cycles.