Effect of long-term treatment with low-dose mifepristone on the endometrium.
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.
Baird
D T
DT
Contraceptive Development Network, Centre for Reproductive Biology, University of Edinburgh, Academic Centre, 49 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SB,UK. dtbaird@ed.ac.uk
Brown
A
A
Critchley
H O D
HO
Williams
A R
AR
Lin
S
S
Cheng
L
L
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D008598:Menstruation / Q000187:drug effects; D015735:Mifepristone / Q000008:administration & dosage*; D008940:Mitotic Index; D010053:Ovary / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014463:Ultrasonography
D003280:Contraceptives, Oral, Synthetic; D015735:Mifepristone