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The higher risk of blood clots (venous thromboembolism, VTE) seen in women who use nonsteroidal anti-inflammatory drugs (NSAIDs) with hormonal contraceptives (HCs) is likely due to the health problem for which the painkillers are taken, rather than the painkillers themselves, according to a large observational study of more than 3 million women using HCs in four European countries, published in the journal The Lancet Obstetrics, Gynaecology, & Women's Health.

The authors caution that the study cannot rule out a direct effect of NSAIDs on VTE risk.

HCs and NSAIDs can each increase the risk of VTE, a serious, potentially life-threatening condition in which a blood clot forms in a deep vein, but the risk when they are used together is unclear. Researchers used national registries from Denmark and Norway and electronic health records from Spain and the U.K. to study women ages 15 to 49 who used HCs between 2014 and 2024.

Using a self-controlled case-series design, they focused on women who were prescribed NSAIDs and had a VTE while using HCs (over-the-counter NSAID use was not captured). Each woman's VTE risk during HC use alone (the baseline period) was compared with her risk before, during and after taking NSAIDs with HCs. The analysis was then repeated for prescribed acetaminophen, which is not linked to increased VTE risk, as a "negative control."

In all four countries, compared with the baseline period, VTE risk rose in the two weeks before women began taking an NSAID, peaked on the day they started it, stayed elevated while they were taking it and fell after they stopped.

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