NSAID-linked clot risk in contraceptive users may stem from underlying illness
A study of more than 3 million women using hormonal contraceptives in Denmark, Norway, Spain, and the U.K. examined whether NSAIDs raise venous thromboembolism risk. The findings suggest the higher clot risk around NSAID use is largely explained by the condition that prompted the painkiller, although a direct drug effect could not be excluded. Risk was already elevated in the two weeks before NSAID treatment, peaked on the first day, and decreased after use ended.
Researchers analyzed records for women aged 15–49 on hormonal contraceptives across Denmark, Norway, Spain, and the UK from 2014 to 2024. The self-controlled design compared each participant's clot risk while using contraceptives alone with periods before, during, and after prescribed NSAID use. Prescribed acetaminophen served as a negative control because it is not associated with higher venous thromboembolism risk.
Venous thromboembolism risk was already higher in the fortnight preceding NSAID treatment, peaked on initiation day, remained elevated during use, and declined afterward. Similar patterns appeared for ibuprofen, diclofenac, naproxen, and across contraceptive products with differing baseline clot risk. Because few women had a VTE, some estimates were imprecise, and a direct NSAID contribution could not be ruled out.
This finding may reassure some women using hormonal contraceptives who need short-term NSAIDs, though it does not establish safety. Clinicians could focus more on existing clot risk factors, including the condition prompting pain relief. Patients and prescribers may benefit from clearer counseling about warning signs. Researchers and regulators might await further studies that separate drug effects from underlying illness.