Human Reproduction, Vol. 18, No. 1, 61-68,
January 2003
© 2003 European Society of Human Reproduction and Embryology
Effect of long-term treatment with low-dose mifepristone on the endometrium
1 Contraceptive Development Network, Centre for Reproductive Biology, University of Edinburgh, Academic Centre, 49 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SB, 2 Medical School, Teviot Place, Edinburgh EH8 9AG, UK and 3 Shanghai Institute of Family Planning Technical Instruction, Shanghai, People’s Republic of China 4 To whom correspondence should be addressed. e-mail: dtbaird{at}ed.ac.uk
BACKGROUND: Mifepristone in low daily doses has contraceptive potential by inhibiting ovulation and menstruation. Because follicular development is maintained, the endometrium is exposed to estrogen for prolonged periods unopposed by progesterone. METHODS: Endometrial biopsies were collected from 90 women in Edinburgh and Shanghai before (late proliferative) and 60 and 120 days after taking 2 or 5 mg mifepristone per day for 120 days. RESULTS: Ovulation and menstruation were inhibited in >90% of cycles and estrogen production was similar to that observed during the follicular phase of the control cycle. By 120 days, endometrial thickness increased significantly in women in Edinburgh but decreased in Shanghai. Endometrial histology showed inactive proliferative or cystic changes with dense stroma. There was a significant decrease in markers of proliferation, i.e. mitotic index and Ki67 staining. There were no pregnancies in a total of 200 women-months in 50 sexually active women who used no other method of contraception. CONCLUSIONS: We confirm that ovulation and menstruation were suppressed in the majority of cycles and there was asynchrony between ovarian activity and endometrial histology, which showed no signs of hyperplasia or atypia. These preliminary data suggest that daily low-dose mifepristone is potentially a safe estrogen-free contraceptive pill which has the added health benefit of amenorrhoea.
Key words: antigestogen/antiproliferation/contraception/mifepristone
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