A comprehensive Swedish population-based cohort study of over 900,000 women aged 50-58 years, including 77,000 hormone therapy users, has revealed important safety distinctions between different forms of estrogen delivery. The study, published in the British Medical Journal, found that transdermal estradiol demonstrated superior cardiovascular safety compared to oral formulations. While oral estrogen alone increased thrombotic risk by 50% and combination therapy with synthetic progestins doubled the risk, transdermal estradiol showed no increased risk of venous thromboembolism and suggested a potential reduction in myocardial infarction and ischemic heart disease. These
findings align with the earlier French ESTHER study and suggest that transdermal estrogen may be appropriate even for women with genetic pro-coagulation disorders, though such women should avoid oral formulations. The researchers attribute the improved safety profile of transdermal delivery to the avoidance of first-pass hepatic metabolism, which
produces prothrombotic metabolites with oral administration.
Zhuo K, Guldbrand C, Reutfors J, et al. Contemporary menopausal hormone therapy and risk of cardiovascular disease: Swedish nationwide register based emulated target trial. BMJ. 2024;387:e078784. doi:10.1136/bmj-2023-078784
