Oral Menopausal Hormone Therapy Linked to Thrombotic Events

Current use of oral menopausal hormone therapy was associated with higher rates of venous thromboembolism, ischemic stroke, and myocardial infarction than no current use in a nationwide Danish study published in BMJ. Overall, transdermal therapy was not associated with higher rates of these outcomes.

The nested case-control study included women aged 50 to 69 years in Danish registries from 2003 to 2021. Investigators identified 9,807 first venous thromboembolisms, 18,460 first ischemic strokes, and 11,974 first myocardial infarctions, matching each case by birth year to five controls. Current use was defined by prescriptions redeemed within 90 days before the index date. Estradiol accounted for more than 96% of hormone therapy use.

Compared with no current use, oral therapy was associated with venous thromboembolism (adjusted hazard ratio [HR], 1.6; 95% CI, 1.5-1.8), ischemic stroke (HR, 1.3; 95% CI, 1.2-1.4), and myocardial infarction (HR, 1.2; 95% CI, 1.1-1.3). The estimated annual absolute risk increases were 0.09%, 0.06%, and 0.03%, respectively.

The venous thromboembolism association persisted across oral doses and treatment durations. Among new users of high-dose oral estradiol (>1mg/day), higher ischemic stroke rates appeared after more than one year of use and higher myocardial infarction rates after more than five years. Low-dose oral therapy was not associated with either outcome. Transdermal therapy showed no overall association, although a small subgroup receiving combined cyclic transdermal therapy had a higher myocardial infarction estimate (HR, 2.1; 95% CI, 1.1-4.1).

The authors noted potential residual confounding. The registries lacked body mass index, smoking status, and age at menopause; the predominantly Danish population and studied formulations may limit generalizability. The observational findings cannot establish causality.

Source: Berggreen J, Pourhadi N, Wood-Kurland H, Løkkegaard E, Torp-Pedersen C, Meaidi A. Contemporary menopausal hormone therapy and thrombotic disease: nationwide nested case-control study. BMJ. 2026;394:e100688. doi:10.1136/bmj-2026-100688