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To determine the effects of intermittent administration of the antiprogestin RU486 on ovarian function.Three different regimens of RU486 were tested.Nine healthy regularly menstruating volunteers protected by an intrauterine device or surgical sterilization.Two groups of three women each received 10 mg or 50 mg RU486 at weekly intervals for 5 weeks. Another three women received 50 mg RU486 for 3 consecutive days at 10-day intervals for 80 days.Serum E2, P and RU486 levels. Ovarian ultrasound (US) and serum LH and FSH in select subjects.The predominant effect was partial inhibition of E2 secretion and suppressed P levels. During a total aggregate of 16 treatment months, there were seven episodes of elevated P levels; however, US did not always indicate the occurrence of normal ovulation.Intermittent RU486 administration can interfere with normal follicular development and function, but its clinical application may require a more effective dose and/or timing of administration.The effect of 3 intermittent dose and schedules of RU486 in cycling women was studied to examine the effect of the anti-progestin on follicular development. 25 mg RU486 given weekly to monkeys blocks ovulation. Here 9 Chilean women aged 26-36 who were protected by IUD or sterilization took either 10 or 50 mg RU486 weekly for 5 weeks (3 women each) or 50 mg for 3 consecutive days every 10 days for 80 days (3 women). All treatments were begun on cycle days 1-3. Serum estradiol, progesterone, RU486, ovarian ultrasound, LH, FSH and endometrial biopsies were followed. In group 1 follicular development was delayed, as estradiol and progesterone levels were suppressed until the day of the last dose of RU486. In group 2 there were variable responses: complete suppression of follicular development, defective luteinization, and normal luteal development. In group 3 estradiol and progesterone were suppressed and follicular development proceeded in waves of development and collapse of dominant follicles. No distinct LH surge appeared, however. Thus intermittent RU486 failed to consistently inhibit follicular development in this small preliminary study. |
