Toward developing a once-a-month pill: a double-blind, randomized, controlled trial of the effect of three single doses of mifepristone given at midcycle on the pattern of menstrual bleeding.

OBJECTIVE

To test the feasibility of timing the administration of mifepristone as a once-a-month contraceptive pill on the 12th day before the next menses, as calculated from the length of the previous menstrual cycles.

DESIGN

Double-blind, randomized, controlled trial.

SETTING

Five family planning centers across the world.

PATIENT(S): Three hundred ninety-nine women attending family planning clinics.

INTERVENTION(S): Randomized to receive 10, 25, or 200 mg of mifepristone or a placebo.

MAIN OUTCOME MEASURE(S): Lengthening or shortening of the normal menstrual cycle length following administration of the drug by at least 5 days.

RESULT(S): The menstrual period came within 5 days of the predicted date in 88% of women receiving the placebo, 84% of women receiving 10 mg, 72% of women receiving 25 mg of mifepristone, and only 48% of women treated with 200 mg of mifepristone. Increasing the dose of mifepristone was associated with an increased chance of having a delayed period (P<.001). Only 45% of women were in the peri-ovulatory phase of the cycle according to LH and P measurements on the day of drug administration. Women treated before ovulation were more likely to have delayed menses with all three doses of mifepristone.

CONCLUSION(S): Because of the disruption in cycle length, it appears unlikely that mifepristone administered once a month, at a calendar-based time, would provide a reliable method of contraception.