NSAIDs, hormonal contraception, and venous thromboembolism

Venous thromboembolism is a multifactorial disease, involving interactions between inherited and acquired risk factors such as immobilisation, active cancer, trauma or fracture, recent surgery, and—in young women—pregnancy and hormonal contraception.1 The magnitude of the risk from combined hormonal contraception depends on the dose of oestrogen and type of progestin.2 Although oestrogen causes hypercoagulability by promoting gene transcription of multiple coagulation factors, the role of progestin is less clear.3

In a linked paper, Meaidi and colleagues (doi:10.1136/bmj-2022-074450) studied whether use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, diclofenac, and naproxen influences the risk of venous thromboembolism in otherwise healthy women using hormonal contraception.4 NSAID use has previously been linked to venous thromboembolism,5 although causality is debated. As most evidence comes from non-randomised studies,6 unmeasured confounding, particularly confounding by indication, is a concern. Another concern is the potential use of NSAIDs for prodromal symptoms from incipient deep vein thrombosis, but this cannot explain the increased risk in long term …