Effects of continuous treatment with low dose mifepristone throughout one menstrual cycle

The effects of continuous low dose mifepristone (RU 486) 10, 5 or 1 mg/day on the menstrual cycle were assessed in groups of five volunteers, who were treated for 30 days from the beginning of the cycle. Hormonal determinations in blood and urine samples, ovarian ultrasonography and an endometrial biopsy taken on day 22-29 of treatment were used to monitor the cycle. Pre- and post-treatment cycles presented a normal profile. During treatment, concentrations of RU 486 in plasma ranged from 65 nmol/l with 1 mg/day to 1000 nmol/l with 10 mg/day. With 10 or 5 mg/day, all treated cycles were prolonged as a result of arrested or slower follicular growth during treatment. Gonadotrophins, sex steroids and their urinary metabolites remained at early follicular phase levels throughout treatment, whereas androstenedione, prolactin and cortisol were unaffected. Follicular maturation resumed after discontinuation of treatment and several days later a luteinizing hormone surge followed by a luteal phase was observed in all cases. Ovulation was suppressed during treatment only in one of the five cycles treated with 1 mg/day. Endometrial maturation was disturbed by all doses. These data demonstrate a differential threshold of the follicle and the endometrium to mifepristone. This finding has potential application in the contraceptive field.