Daily low-dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: a double-blind randomized control trial of 2 and 5 mg per day for 120 days.

Daily administration of progesterone (P) antagonists to women inhibits ovulation and disrupts endometrial function. In this double-blind randomized trial, we have explored the contraceptive potential of two doses of the P antagonist mifepristone in healthy volunteers in Edinburgh and Shanghai. Ninety-eight women (58 in Edinburgh and 40 in Shanghai) were randomized to receive either 2 or 5 mg mifepristone daily for 120 d. Ovarian activity was monitored by the weekly measurement of steroid metabolites in urine and of E2 and P in plasma every month. Endometrial function was assessed by menstrual records, and ultrasound measurement of endometrial thickness was assessed every month. Endometrial biopsy was collected on d 12 of the control cycle and after 60 and 120 d of treatment. Ninety women (50 in Edinburgh and 40 in Shanghai) completed the study. Follicular activity continued during treatment with both doses in Edinburgh women, although ovulation was suppressed in the majority of cycles (90 and 95% of cycles in 2- and 5-mg groups, respectively). The women in Shanghai showed evidence of ovulation in only 3 of 160 months of treatment (2 in 2-mg group and 1 in 5-mg group). The majority of women in both centers were amenorrheic (65% in 2-mg group and 88% in 5-mg group in Edinburgh, and 90% in both dose groups in Shanghai). The endometrial thickness increased significantly in women in Edinburgh and decreased in Shanghai; histology showed either atrophic or cystic changes without evidence of hyperplasia. There was no pregnancy reported in the 200 months of exposure in 50 sexually active women who had used no other method of contraception during the study. We conclude that mifepristone in low daily doses inhibits ovulation and induces amenorrhea in the majority of women and has the potential to be developed as a novel estrogen- free oral contraceptive pill.