Rethinking Blood Clot Risks: Route Alone May Not Define Menopausal Hormone Therapy Safety

New research is reshaping our understanding of blood clot risks associated with menopausal hormone therapy (MHT), suggesting that simply choosing a transdermal (skin patch, gel, or spray) over an oral route might not guarantee safety for all women. While a major Danish study recently published in The BMJ confirmed higher venous thromboembolism (VTE) risk with oral MHT, particularly high doses over a year, it also flagged that specific transdermal regimens could still pose risks, such as a doubled risk of myocardial infarction with transdermal combined cyclic therapy. This nuanced view challenges the long-held belief that transdermal options are uniformly safer, pushing for a more personalized approach to treatment. The traditional wisdom favoring transdermal MHT stemmed from its ability to bypass liver metabolism, which oral forms undergo, affecting clotting factors. However, recent evidence, including a 2024 Swedish nationwide study, linked transdermal combined MHT to increased VTE compared to non-use, highlighting the complexity beyond just the administration route. Experts now emphasize that the full MHT regimen, including the type and dose of progestogen and the specific combination with oestrogen, plays a critical role in determining a woman's overall thrombotic risk. This evolving understanding also builds on the foundational, albeit often misinterpreted, findings of the 2002 Women's Health Initiative (WHI) trial, which demonstrated cardiovascular and thromboembolic harms with a specific oral regimen, but didn't directly compare oral with transdermal oestradiol. Looking ahead, the medical community is calling for more detailed, head-to-head comparative studies between oral and transdermal MHT, carefully stratified by oestrogen dose, progestogen type and route, and whether the regimen is cyclic or continuous. Until then, clinical guidance for menopausal women must integrate a holistic assessment, considering the route, dose, progestogen used, alongside a patient's individual baseline risks for VTE and cardiovascular disease, and their personal treatment priorities. This shift means clinicians will need to delve deeper than ever before into the specifics of each MHT prescription.