Mifepristone more effective than levonorgestrel for emergency contraception

Clinical takeaway: Low-dose mifepristone may be more effective and better tolerated than levonorgestrel, but it is more likely to delay the next menstrual period and its use for emergency contraception is off-label in the US.

Emergency contraception choices must balance effectiveness, tolerability, timing, and access. In the United States, mifepristone is not FDA-approved for emergency contraception, but a Cochrane review suggests that low- and mid-dose regimens may prevent more pregnancies than levonorgestrel.

The review included 87 randomized trials involving approximately 36,000 women who sought emergency contraception within five days of unprotected intercourse. Most trials were conducted in China between 1992 and 2015, and 41 compared mifepristone with levonorgestrel.

The review estimated pregnancy rates of 2.3% with mid-dose mifepristone (25–50 mg) and 3.5% with levonorgestrel, a reduction of about one-third. With low-dose mifepristone (<25 mg), estimated rates were 1.5% versus 2.0%, a reduction of about one-quarter. Although the absolute differences were modest, both mifepristone regimens were also associated with fewer overall side effects.

The advantage was larger compared with the Yuzpe method, an older emergency contraception approach that uses combined estrogen-progestin birth control pills. Estimated pregnancy rates were approximately 0.3% with mifepristone and 2.5% with the Yuzpe method. Mifepristone also caused less nausea and vomiting. Its main trade-off was delayed menstruation, which occurred more often at higher doses and could cause concern about treatment failure or pregnancy.

The review does not establish whether mifepristone is preferable to all current options. No included trials compared it with ulipristal acetate, and evidence comparing mifepristone with copper IUDs was too limited to draw conclusions.

For US practice, the findings identify a potentially useful future option rather than a routinely available alternative. “Expanding options for emergency contraception is important,” said lead author Shaalini Ramanadhan, MD, an assistant professor of obstetrics and gynecology at Oregon Health & Science University. “The evidence shows that mifepristone has benefits beyond abortion care, including as an effective form of emergency contraception.”

Source: Ramanadhan S, et al. (2026 Sep 21) Cochrane Database Syst Rev. Mifepristone versus other interventions for the prevention of pregnancy in reproductive-age women using emergency contraception