Hormonal Emergency Contraception

Melissa Sanders Wanner, Pharm.D., Rachel L. Couchenour, Pharm.D.

Disclosures

Pharmacotherapy. 2002;22(1) 

In This Article

Mifepristone

Mifepristone (RU-486) is a progesterone and glucocorticoid antagonist derived from norethindrone. Since its discovery in the early 1980s, it has been studied for a variety of clinical applications, including cervical ripening, labor induction, contraception, medical abortion, endometriosis, and emergency contraception.[33,34,35,36] Mifepristone has several pharmacologic actions that play a role in its effectiveness as an emergency contraceptive. It competes with endogenous progesterone and binds with very high affinity to progesterone receptors. This leads to a conformational change in the mifepristone-progesterone receptor complex.[33] Since progesterone receptors are located predominantly in the reproductive organs, the effects of mifepristone are primarily in the uterus.[36] The conformational change in the receptors block the effects of endogenous progesterone on endometrial development and prevents the promotion of transcription of cellular DNA.[35] When administered during the follicular phase, mifepristone inhibits folliculogenesis and the normal surge of luteinizing hormone that triggers ovulation. These disruptions prevent further follicular development and ovulation.[33,35] When mifepristone is administered to women during the early and midluteal phases of the menstrual cycle, endometrial changes occur that are consistent with the withdrawal of progesterone and that disrupt or prevent implantation of a fertilized ovum.[35,37] In addition, these antiprogestogenic actions prevent further development of an implanted embryo.[36] Unlike the Yuzpe, progestin-only, and high-dose ethinyl estradiol regimens, mifepristone is an effective emergency contraceptive when given before or after implantation has occurred and may be effective up to 12-17 days after a single episode of unprotected intercourse.[33,36]

During the past decade, many studies have shown that a single dose of mifepristone 600 mg is highly effective for emergency contraception. One study compared the effectiveness of mifepristone 600 mg with the Yuzpe regimen in a randomized trial of 386 women aged 16-45 years.[8] Women were eligible for the study if they had only a single act of unprotected intercourse during their present cycle and had regular menstrual cycles. The single dose of mifepristone and the first dose of the Yuzpe regimen were begun within 72 hours of unprotected intercourse. Raw pregnancy rates were 0% (95% CI 0-1.87%) in the mifepristone group and 2.6% (95% CI 0.86-6.0%) in the Yuzpe group (p=0.061). Mifepristone prevented 100% of the 12 expected pregnancies (p<0.001), whereas the Yuzpe regimen prevented 6 (55%) of 11 expected pregnancies (p=0.061). A similarly designed randomized study compared the effectiveness of mifepristone 600 mg and the Yuzpe regimen in 800 women.[24] Women were included if they had regular menstrual cycles for the previous 3 months and were aged 16-45 years. The initial dose of both regimens was given within 72 hours of intercourse. Four pregnancies (raw pregnancy rate 1%) occurred among the women who received the Yuzpe regimen compared with zero pregnancies in the mifepristone group. The difference in pregnancy rates was not statistically significant (p=0.12). All pregnancies occurred in the women who had unprotected intercourse 3 days before or after the expected date of ovulation.[24] The authors did not report the number of expected pregnancies that were prevented by either regimen. Overall, mifepristone is a highly effective emergency contraceptive when administered within 72 hours and may be effective up to 12-17 days after a single episode of unprotected intercourse.

Mifepristone is better tolerated than the Yuzpe regimen.[8,24] The authors of one study reported a lower frequency of nausea (37% vs 70%) and vomiting (3% vs 22%) with mifepristone compared with the Yuzpe regimen.[8] Breast tenderness occurred in a similar percentage of women in both groups (18%). In another study,[24] a similar pattern of adverse effects were identified. The occurrence rates of nausea (40% vs 60%), vomiting (3% vs 17%), headache (49% vs 70%), and breast tenderness (27% vs 46%) were all significantly lower with mifepristone than with the Yuzpe regimen. The most troubling adverse effect reported with mifepristone is a disruption in the timing of the next menstrual period.[8,24] This can be disturbing to patients who are awaiting their next period as an indication that they are not pregnant. Mifepristone causes bleeding more than 3 days early in 19% of women, and more than three days late in 39%. Among women who are more than 3 days late, almost 25% will have their period more than a week later than expected.[8]

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