Taking the anti-inflammatory agent piroxicam at the same time as the emergency contraceptive levonorgestrel after unprotected sex may prevent “significantly more” pregnancies compared to levonorgestrel alone, according to a study in The Lancet. 

A randomised controlled trial of 860 women requesting emergency contraception found 95 per cent of pregnancies were prevented following combined usage of levonorgestrel and piroxicam, compared to 63 per cent of pregnancies prevented with levonorgestrel alone.

This is believed to be the first trial where piroxicam has been studied for its contraceptive action.

If the results can be reproduced in future studies, co-treatment with piroxicam and levonorgestrel should be adopted clinically when levonorgestrel is the emergency contraception of choice, the researchers say.

The study took place at a community sexual and reproductive health clinic in Hong Kong between between August 2018 and August 2022. Women who required levonorgestrel within 72 hours of unprotected sex were randomised to receive a single dose of levonorgestrel 1.5mg plus either piroxicam 40mg or placebo.

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. 

Levonorgestrel prevents pregnancy by blocking or postponing the luteinising hormone surge, which disrupts the ovulatory process. Piroxicam might work by targeting prostaglandins, which facilitate several reproductive processes including ovulation, fertilisation and embryo implantation. 

Piroxicam may provide a contraceptive effect both pre-ovulation (by blocking the ovulatory process) and post-ovulation (by preventing the implantation of the embryo), the authors suggest.

The trial did not investigate piroxicam’s mechanism of action and further studies are required to confirm this, they add.

The authors acknowledge some limitations of the study, including the application of the findings to other settings. As the study excluded women with current or recent use of hormonal contraception, as well as those with more than one episode of unprotected sex before taking emergency contraception, it is not certain whether piroxicam-levonorgestrel co-treatment would be equally effective when applied to women in those circumstances. 

Similarly, the study was limited to participants mostly of Asian ethnicity and weighing less than 70kg. Levonorgestrel is less effective in people with obesity, so the efficacy shown in this study might not apply to patients with higher BMIs.