Emergency contraception with mifepristone and levonorgestrel: mechanism of action.

OBJECTIVE To study the effect of mifepristone and levonorgestrel on ovarian function and endometrial development in doses effective as emergency contraception. METHODS Twelve fertile women were treated with either 10 mg of mifepristone as a single dose (n = 6) or two doses of 0.75 mg of levonorgestrel, 12 hours apart (n = 6) before and after ovulation. An endometrial biopsy performed during the implantation period was analyzed for endometrial maturation and expression of markers of endometrial receptivity. The markers tested for were integrin alpha4 and beta3, cyclooxygenase-1 and -2, progesterone receptors, Dolichos biflorus agglutinin lectin binding, and pinopodes. Urinary excretion of luteinizing hormone, estrone, and pregnanediol were also determined. RESULTS Treatment with mifepristone and levonorgestrel before ovulation inhibited the luteinizing hormone surge showing no significant differences between the means of luteinizing hormone measurements. When mifepristone was administered in the early luteal phase, downregulation of progesterone receptors was inhibited in five of six women. No significant alteration was found in any of the remaining markers of endometrial receptivity. CONCLUSION The mode of action of emergency contraception with mifepristone or levonorgestrel is primarily due to inhibition of ovulation rather than inhibition of implantation.