An emergency contraceptive medicine works better when combined with an anti-inflammatory medication, according to the first study of its kind, reported today.
A randomised controlled trial in Hong Kong of 860 women requesting emergency contraception found 95% of pregnancies were prevented when they took levonorgestrel and the anti-inflammatory medication piroxicam, compared to 63% of pregnancies being prevented when levonorgestrel was taken alone.
Writing in The Lancet today, the authors say if these results can be reproduced in future studies, co-treatment with piroxicam and levonorgestrel should be adopted when levonorgestrel is the emergency contraception of choice.
The effectiveness of levonorgestrel is based on the results of a 1998 trial, which found levonorgestrel prevented 95% of expected pregnancies when it was taken within 24 hours of unprotected sex, 85% if taken within 25-48 hours, and 58% if taken within 49-72 hours.
However, more recent research suggests its efficacy might be lower.
Study co-investigator Dr Sue Lo from the Family Planning Association of Hong Kong, said: “The levonorgestrel emergency contraceptive pill is one of the most popular choices of emergency contraception in many parts of the world, so finding out that there is a widely available medication which increases levonorgestrel’s efficacy when they are taken together is really exciting.”
The study took place at a major community sexual and reproductive health service in Hong Kong between August 2018 and August 2022.
Women who needed levonorgestrel emergency contraception within 72 hours of unprotected sex were randomised to receive a single supervised dose of levonorgestrel 1.5 mg plus either piroxicam 40 mg or a placebo pill.
A follow up appointment was scheduled one to two weeks after the next expected period and if they had not had a normal period by that time, they had a pregnancy test.
Out of the 836 women followed up, there was one pregnancy among the 418 women who took piroxicam and levonorgestrel and seven pregnancies among the 418 women who had the placebo and levonorgestrel.
The percentage of expected pregnancies without contraception was estimated at 4.5% (19/418) in both groups, which means the percentage of pregnancies prevented following piroxicam- levonorgestrel co-treatment was 95% (18/19), compared with 63% (12/19) in those who took levonorgestrel and placebo.
Co-investigator Professor Kristina Gemzell-Danielsson from the Karolinska Institute, Sweden, said while levonorgestrel prevents pregnancy by blocking or postponing the luteinising hormone surge, piroxicam might work by targeting prostaglandins.
“Prostaglandins facilitate several reproductive processes including ovulation, fertilisation, and embryo implantation,” she said. “Therefore, we speculate that piroxicam may provide a contraceptive effect both pre-ovulation and post-ovulation, however our trial did not investigate piroxicam’s mechanism of action and further studies are required to confirm this.”
The authors acknowledge some limitations of the study, but they say they hope it leads to further research.
First author Dr Raymond Li, from The University of Hong Kong, said: “Our study is the first to suggest that a readily available and safe medication taken at the same time as the levonorgestrel pill can prevent more pregnancies than levonorgestrel alone. We hope these results will lead to further research and ultimately changes in clinical guidelines to enable women around the world to access more effective emergency contraception.”
Li, R, Lo S, Gemzell-Danielsson K et al. Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial. Lancet 17 August 2023
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