A widely used morning-after pill is far more effective when taken alongside an anti-inflammatory drug, a clinical trial has found.
Levonorgestrel is one of the cheapest and most widely used emergency contraceptives in the world. But the drug only works before an egg is released from one of the ovaries. One study found that the drug is only 58 per cent effective at preventing pregnancies when taken 49 to 72 hours after unprotected sex.
Anti-inflammatory drugs generally work by inhibiting prostaglandins, chemicals with hormone-like effects that also play a role in many processes in reproduction such as ovulation and fertilisation. Kristina Gemzell-Danielsson at the Karolinska Institute in Sweden suspected that these drugs could further reduce the likelihood of unwanted pregnancy.
To test this, Gemzell-Danielsson and her colleagues conducted a randomised trial involving 860 women who requested emergency contraception within 72 hours of unprotected sex at a family planning clinic in Hong Kong between August 2018 and 2022. The participants didn’t include any transgender or non-binary people.
Half the women were given levonorgestrel and piroxicam, an anti-inflammatory drug used to treat arthritis, while the other half received levonorgestrel and a placebo pill. Neither the participants nor the healthcare professionals knew which participants received which treatment.
Just one woman became pregnant in the anti-inflammatory drug group, whereas seven women became pregnant in the placebo group. There were no differences in side effects between the two groups.
Based on a model of expected pregnancy after unprotected sex, 95 per cent of expected pregnancies were prevented in the anti-inflammatory drug group compared with just 63 per cent in the placebo group.
The trial only included women who weren’t on any hormonal contraceptives as the researchers wanted to study the impact of the treatments on those who were most at risk of an unwanted pregnancy.
Gemzell-Danielsson says it is unclear exactly how the anti-inflammatory drug helps to stop unwanted pregnancies. “We know that prostaglandin is important for [reproductive] processes, but we need to do more mechanistic studies to know for sure what’s happening,” she says.
She hopes that the findings have a quick impact on how healthcare professionals worldwide prescribe emergency contraceptives. Piroxicam is cheap and widely available, she says, and would be straightforward to prescribe alongside levonorgestrel.
Combining piroxicam with the other widely used emergency contraceptive, ulipristal, is also likely to be effective as that contraceptive works in a similar way to levonorgestrel, says Gemzell-Danielsson, but this hasn’t yet been tested.
Judith Stephenson at University College London says the findings could lead to major changes in clinical practice, but she hopes other studies will confirm the result. “Though well designed, it is only one trial, so it would be reassuring to have the findings confirmed in another study,” she says.
She also says it would be useful to find out if the drug combination works in people who have missed one of their daily contraceptive pills.