Blood-clot risk with painkillers and the pill may stem from the underlying illness, large European study suggests

The higher risk of blood clots in the veins (venous thromboembolism, VTE) seen in women who take non-steroidal anti-inflammatory drugs (NSAIDs) while using hormonal contraceptives may be driven largely by the health problem the painkillers are taken for, rather than by the drugs themselves, according to a study in The Lancet Obstetrics, Gynaecology, & Women’s Health.

The study

• Researchers used national registries from Denmark and Norway and electronic health records from Spain and the UK, covering more than 3 million women aged 15–49 who used hormonal contraceptives between 2014 and 2024.
• With a self-controlled case-series design, each woman who had a VTE was compared with herself: periods on contraceptives alone versus before, during and after a prescribed NSAID.
• In all four countries, clot risk began rising in the two weeks before NSAIDs were started, peaked on the first day, stayed raised during use and fell afterwards. Results were similar for ibuprofen, diclofenac and naproxen.
• A similar pattern appeared for prescribed paracetamol (acetaminophen), used as a “negative control” because it is not linked to higher VTE risk — pointing to the underlying condition as a contributor.

What the authors advise

Rather than discouraging short-term NSAID use in women on hormonal contraception, they suggest clinicians focus on identifying and managing existing clot risk factors, including the reason the NSAID was prescribed.

Limitations

This is an observational study and the authors say it cannot rule out a direct effect of NSAIDs on clot risk. Over-the-counter NSAID use was not captured, and some estimates were imprecise because few women had a VTE. More research is needed. Anyone with questions about contraception or painkillers should talk to their doctor or pharmacist.