Low-to-moderate doses of the anti-progestin mifepristone are significantly more effective at preventing pregnancy and trigger fewer side effects than standard levonorgestrel, according to a review published in Cochrane Collaboration.
Led by Dr Shaalini Ramanadhan and researchers from Oregon Health & Science University (OHSU), the review synthesised evidence from 87 randomised controlled trials involving roughly 36,000 reproductive-age women seeking emergency contraception within five days of unprotected sex.
The investigation compared mifepristone directly against other established postcoital interventions, including levonorgestrel (Plan B), the combined hormonal Yuzpe method, and copper intrauterine devices (Cu-IUDs).
However, the authors highlighted a distinct clinical trade-off: menstrual cycle disruption. Women receiving mifepristone had a higher likelihood of a delayed next menstrual period compared with alternative oral agents - a side effect that scaled with higher doses.
Dr Ramanadhan, lead author of the review, explained: "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.
"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."
The authors noted important geographic and clinical caveats: the vast majority of included trials were conducted in China, and none of the trials evaluated mifepristone against ulipristal acetate-another selective progesterone receptor modulator that serves as a first-line option in the UK and Europe.
In addition, while mifepristone is licensed at 200 mg in combination with misoprostol for early medical abortion, low-dose formulations are not currently licensed for emergency contraception across the UK or US.
