A novel estrogen-free oral contraceptive pill for women: multicentre, double-blind, randomized controlled trial of mifepristone and progestogen-only pill (levonorgestrel).
BACKGROUND
The acceptability and continuation rate of oral contraceptive steroids are limited by unpredictable bleeding and the fear of long-term risks such as breast cancer. By inhibiting ovulation and by altering the receptivity of the endometrium, antagonists of progesterone, such as mifepristone, could be developed as estrogen-free novel contraceptives.


METHODS
Multicentre, double-blind, randomized controlled trial comparing frequency of amenorrhoea (primary outcome), bleeding patterns, side effects and efficacy in women taking daily 5 mg mifepristone (n = 73) or 0.03 mg levonorgestrel (progestogen-only pill; POP, n = 23) for 24 weeks.


RESULTS
More women were amenorrhoeic while taking mifepristone than POP (49 versus 0% P < 0.001), and fewer women bled or spotted for >5 days per month (4 versus 39% P < 0.001). Forty-eight percent of women who took mifepristone for 6 months had cystic glandular dilatation of the endometrium but none showed hyperplasia or atypia. There were no pregnancies in 356 months of exposure in women who used only mifepristone for contraception. Two pregnancies occurred in women taking mifepristone who were also using condoms for dual protection.


CONCLUSIONS
Daily mifepristone (5 mg) is an effective oral contraceptive pill which has a better pattern of menstrual bleeding than an existing POP (levonorgestrel).
Lakha
F
F
Centre for Reproductive Biology, Simpson Centre for Reproductive Health, University of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK.
Ho
P C
PC
Van der Spuy
Z M
ZM
Dada
K
K
Elton
R
R
Glasier
A F
AF
Critchley
H O D
HO
Williams
A R W
AR
Baird
D T
DT
D000293:Adolescent; D000328:Adult; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects*; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects*; D008595:Menorrhagia / Q000139:chemically induced*; D015735:Mifepristone / Q000008:administration & dosage / Q000009:adverse effects*; D010053:Ovary / Q000187:drug effects* / Q000503:physiopathology; D014463:Ultrasonography; D014599:Uterus / Q000000981:diagnostic imaging
D003271:Contraceptive Agents, Female; D003280:Contraceptives, Oral, Synthetic; D015735:Mifepristone; D016912:Levonorgestrel