Mifepristone offers effective emergency contraception with fewer side effects

Emergency contraception containing mifepristone prevents more pregnancies with fewer side effects than some other common emergency contraceptive pills such as levonorgestrel, according to a new Cochrane review involving 87 trials.

Emergency contraception is used to prevent pregnancy after unprotected sex. It can be used when no contraception was used or if a contraceptive method fails, as with a broken condom, or in the event of sexual assault.

Common methods of emergency contraception include copper intrauterine devices and pills. The most widely used pill is levonorgestrel, a progestin-only medication sold in many countries as "Plan B," "Next Choice," or similar brand names. An alternative is the Yuzpe regimen, an older method that combines estrogen and progestin.

More effective, fewer side effects

The review, led by researchers from Oregon Health & Science University, USA, pooled data from 87 randomized controlled trials involving approximately 36,000 women of reproductive age. The majority of studies (79 trials) were conducted in China, with additional trials from the UK, Cuba, and multi-country settings. The authors compared mifepristone against levonorgestrel, the Yuzpe regimen, and copper intrauterine devices.

Compared with levonorgestrel, both low-dose (under 25 mg) and mid-dose mifepristone (25-50 mg) prevented more pregnancies and were associated with fewer overall side effects. Low-dose mifepristone showed a 27% relative reduction in pregnancies compared with levonorgestrel. This was rated as high-certainty evidence, meaning that further research is very unlikely to change the result.

When compared with the Yuzpe regimen, mifepristone showed an even larger advantage, cutting pregnancy risk substantially while also sharply reducing rates of nausea and vomiting. Evidence comparing mifepristone with copper intrauterine devices remained too limited to draw firm conclusions, based on only two included trials.

Mifepristone in low-to-mid doses is a highly effective emergency contraceptive option that clinicians should know about. As an anti-progestin, it works differently than the other steroid hormone-based methods like levonorgestrel and combined estrogen and progestin pills to delay or block ovulation. This different mechanism is part of why it has a different side-effect profile compared to the other two methods."

Dr. Shaalini Ramanadhan, lead author of the review

The main trade-off identified across nearly all comparisons was a lower risk of nausea and vomiting with mifepristone, but a higher likelihood of delayed menstruation compared with other types of emergency contraception. Given that a delay in menstruation could be interpreted as a sign of treatment failure or pregnancy, the authors explain that this side effect could be a potential source of stress and anxiety for individuals seeking emergency contraception.

Where reported, however, treatment satisfaction was equal to or higher among those who received mifepristone versus alternative methods. 

Political and legal barriers limit access

Despite the strong evidence behind the drug's effectiveness as emergency contraception, the authors note there are still many barriers to access.

In some countries, drug authorities have approved mifepristone at higher doses (typically 200 mg) in combination with misoprostol specifically for medical termination of early pregnancy, not as emergency contraception. Scientific evidence is growing around the potential use of mifepristone and other anti-progestins as a routine method of contraception, for treating fibroids, for preventing and treating breast cancer, and for treating abnormal bleeding. However, because mifepristone is widely associated with abortion, it also faces intense political scrutiny, legal restrictions, and targeted bans and barriers in various countries.

"Expanding options for emergency contraception is important," says Dr Ramanadhan. "The evidence shows that mifepristone has benefits beyond abortion care, including as an effective form of emergency contraception. In some countries, recognition of this additional use may help expand access, increase familiarity with the medication, and create new opportunities for people to benefit from it."