Scientists find a way to make the morning-after pill more effective

A cheap anti-inflammatory drug could make a common morning-after pill more effective, scientists have found.

Piroxicam, a drug often used to manage the pain of arthritis, was paired with levonorgestrel, a widely-used emergency contraceptive.

Levonorgestrel only works if taken before ovulation – when an egg is released by an ovary – with one study showing it is only 58% effective at preventing pregnancies if taken 49 to 72 hours after unprotected sex.

Anti-inflammatory drugs often work by inhibiting prostaglandins, compounds made of fats that have hormone-like effects and play a role in ovulation.

The study showed that, by pairing the two, levonorgestrel  was significantly more effective.

In the trial, which took place in Hong Kong, 95% of pregnancies were prevented after combined treatment with the drugs, compared to 63% of pregnancies being prevented when levonorgestrel was taken alone.

The study followed women who required levonorgestrel emergency contraception within 72 hours of unprotected sex. Participants were randomly assigned to receive a single supervised dose of levonorgestrel 1.5mg plus either piroxicam 40mg or a placebo pill. Neither the participant nor the healthcare professionals knew who received the placebo or the treatment.

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 team, based in both Hong Kong and Sweden, hopes that if their findings can be reproduced in further studies, clinical guidelines should change to offer both piroxicam and levonorgestrel when levonorgestrel is the emergency contraception of choice.

‘The levonorgestrel emergency contraceptive pill is one of the most popular choices of emergency contraception in many parts of the world,’ said co-author Dr Sue Lo, from the Family Planning Association of Hong Kong. ‘Finding out that there is a widely available medication which increases levonorgestrel’s efficacy when they are taken together is really exciting.’

First author of the study Dr Raymond Li, from the University of Hong Kong, added: ‘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.’

Two types of emergency contraceptive pills – containing either levonorgestrel or ulipristal acetate – are the most widely used emergency contraception method in most countries.

Both work by preventing or delaying ovulation and neither are effective post-ovulation.

However, the study was unable to pinpoint exactly how piroxicam, a non-steroidal anti-inflammatory that costs around 30p per tablet, made levonorgestrel more effective.

Speaking to New Scientist, co-author Professor Kristina Gemzell-Danielsson, from the Karolinska Institute in Sweden, said: ‘We know that prostaglandin is important for [reproductive] processes, but we need to do more mechanistic studies to know for sure what’s happening.’

While there was no difference in side-effects between the two groups, Dr Janet Nooney, expert scientific assessor in the UK Medicines and Healthcare products Regulatory Agency benefit risk management unit, noted piroxicam is not suitable for all.

‘This study raises an interesting possible improvement in emergency contraceptive effect when levonorgestrel is used in combination with piroxicam tablets,’ she said.

‘Importantly, in the UK oral piroxicam tablets are no longer recommended for acute pain relief or inflammatory conditions as it is associated with serious gastro-intestinal side effects and rare but possibly fatal skin reactions.

‘These side effects may limit its suitability for wider use in combination with emergency contraception.’

In 2020/21, three in every 1,000 women were provided emergency contraception by sexual and reproductive health services, including pharmacists and GPs.

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