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Emergency Contraception With Mifepristone and Levonorgestrel: Mechanism of Action

Marions, Lena MD, PhD; Hultenby, Kjell PhD; Lindell, Ingrid; Sun, Xiaoxi MD; Ståbi, Berit; Danielsson, Kristina Gemzell MD, PhD

Original Research

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 α4 and β3, 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.

Emergency contraception with mifepristone and levonorgestrel acts mainly by inhibition of ovulation rather than inhibition of implantation.

From the Department of Women and Child Health, Karolinska Hospital, Stockholm, Sweden; and Unit of Electronmicroscopy, Huddinge Hospital, Stockholm, Sweden.

Address reprint requests to: Lena Marions, MD, PhD, Karolinska Hospital, Department of Obstetrics and Gynecology, Stockholm, 171 76, Sweden; E‐mail:

The authors are very grateful to Professor Sune Bergström, Karolinska Institute, and Professor Marc Bygdeman, Karolinska Hospital, Stockholm, Sweden, for financial support and valuable help in study planning and data analysis. The authors are also grateful to Professor Elisabeth Johannisson, Geneva, Switzerland, for performing the morphometric examinations.

Received May 15, 2001. Received in revised form January 15, 2002. Accepted January 31, 2002.

© 2002 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.