The emergency contraceptive levonorgestrel prevents “significantly more” pregnancies when taken with anti-inflammatories, according a study published in the Lancet yesterday (August 16).
A combined treatment of levonorgestrel and piroxicam, an anti-inflammatory medication often used to treat arthritis, prevented 95% of pregnancies, according to the results of a randomised controlled trial of 860 women that took place between August 2018 and August 2022.
This compared to 63% of pregnancies when only levonorgestrel was taken, the study showed. Of the 860 women who started the trial, 836 followed up with the researchers.
Women who had requested emergency contraception at a community sexual and reproductive health service in Hong Kong after having unprotected sex in the preceding 72 hours were randomly recruited into two groups, one of which received levonorgestrel 1.5 mg and a placebo, and the other levonorgestrel 1.5 mg and piroxicam 40mg.
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Levonorgestrel is a popular method of emergency contraception. However, it is not effective as an emergency contraception when taken after ovulation has begun; only before, the study said.
The paper explains that this is because levonorgestrel disrupts the ovulatory process before the onset of the “luteinising hormone surge” but does not do so when taken after the surge has begun.
The study indicated that other “most widely used” emergency contraceptive, ulipristal acetate (UPA), is also less effective when taken after ovulation has begun. The search for an oral emergency contraceptive method “with effective post-ovulatory action continues”, the paper said.
It suggested that levonorgestrel and piroxicam might be one such method. Just one of the 418 women in the test group fell pregnant after taking the combination, compared to seven in the placebo group.
The researchers hypothesised that cyclo-oxygenase (COX) enzyme inhibitors, such as piroxicam, might act “synergistically” with levonorgestrel to “improve their efficacy in regulating both ovulatory and post-ovulatory processes''. COX enzymes are key to prostaglandin production, which is known to facilitate a number of reproductive processes, according to the paper.
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According to the paper, if the results of the study can be reproduced in the future, the levonorgestrel and piroxicam regimen could be adopted in settings where levonorgestrel is administered as emergency contraception. This could potentially change “practice and clinical guidelines”, it said.
Lead author Dr Raymond Li of The University of Hong Kong said that the study was “the first to suggest'' that combining levonorgestrel with “a readily available and safe medication” could be more effective at preventing pregnancies than taking only levonorgestrel.
Dr Li hoped that their findings would lead to “changes in clinical guidelines” to help more women across the world from having unwanted pregnancies.
“Finding out that there is a widely available medication that increases levonorgestrel’s efficacy when they are taken together is really exciting,” said Dr Sue Lo of the Family Planning Association of Hong Kong, who was one of the researchers involved in the study.
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The study’s authors excluded women who were using or had recently used hormonal contraception, and women who had unprotected sex more than once before taking emergency contraception. They noted that the combination regimen may not work as effectively in these cases.
Dr Erica Cahill from Stanford University School of Medicine, who was not involved in the study, noted that the findings may face a further limitation, since most women involved were of Asian ethnicity and weighed less than 70kg.
Dr Cahill said that levonorgestrel emergency contraception is “less effective in people with obesity”, which means that results of the study “might not be generalisable to patients with higher body mass indexes (BMIs)”.
