Updates in Contraception From The XVI World Congress of the International Federation of Gynecology and Obstetrics

David A. Grimes, MD

Disclosures

September 20, 2000

In This Article

Mifepristone (RU486): An Antiprogestin Oral Contraceptive?

The antiprogestin mifepristone (RU486) is an effective abortifacient in early pregnancy when combined with a prostaglandin. Since its first licensing in 1988 in France, several hundred thousand women in Europe and several million women in China have had safe medical abortions in early pregnancy (up to 7 or 9 weeks from last menstrual period).[4] In addition, research conducted by the World Health Organization (WHO) has shown that a single oral dose of mifepristone as low as 10 mg taken within 5 days of unprotected coitus is an effective emergency contraceptive. This low dose was as effective as a much higher dose (600 mg) and caused less delay in the onset of the next menses.[5]

An exciting presentation from Edinburgh, Scotland, and Shanghai, China, suggested that the potential use of mifepristone may expand from emergency contraception to ongoing contraception as well. Audrey Brown[6] of the University of Edinburgh, Scotland, described preliminary experience with daily administration of low doses of this antiprogestin. In a 6-month trial, she and her colleagues randomized 98 women in the 2 cities to receive either 2 mg or 5 mg of mifepristone daily for 120 days; 90 women completed the study.

With both dosage regimens, most women were amenorrheic. In addition, most women did not ovulate with either regimen: only 1% to 10% of cycles were ovulatory, depending on the regimen and site. Among women in Edinburgh, biochemical evidence of ovulation was seen in 15 of the 200 months of treatment. In Shanghai, the number was 3 of 160 months. Substantial differences emerged between women in the 2 cities with regard to their responses to the regimens, not all of which can be readily explained by differences in average body mass index. For example, urinary estrone was suppressed more in women in Shanghai than in Edinburgh. In Edinburgh, the endometrial thickness increased with time, whereas in Shanghai it decreased over 20 days. Of importance, both regimens maintained normal follicular phase ovarian activity. Stated alternatively, the ovaries were not suppressed with these regimens.

Although clinical efficacy in preventing pregnancy was not the aim of the trial, a number of women in both cities relied on no alternative contraception. A total of 200 cycles with coitus occurred in the absence of alternative contraception, and no pregnancies were found. This preliminary study suggests that a daily low dose of mifepristone may suppress both ovulation and menstruation. This approach might provide women with an estrogen-free oral contraceptive if subsequent testing shows the feasibility and efficacy of this novel approach.

This pilot study opens yet another new chapter in the history of antiprogestins. Because abortion is such a divisive issue in many cultures, mifepristone has become symbolic of the struggle concerning abortion. Indeed, mifepristone has become a political football in some countries. Hence, the discovery that mifepristone could prevent pregnancy (and thus decrease the need for abortion) when used as an emergency contraceptive may have defused somewhat the controversy surrounding this drug. Thus, mifepristone is an abortifacient that can be used as an emergency contraceptive to prevent abortion.[7] Now Brown and her associates have suggested that it may be possible to use mifepristone as a daily oral contraceptive. Were mifepristone to be developed as an oral contraceptive, women might enjoy some of the current health benefits of combination oral contraceptives without running the estrogen-related, small risk of venous thromboembolism.

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