News MedicalStudy Finds Oral Hormone Replacement Therapy Increases Venous Thromboembolism Risk

ℹ️ Observational Association Only Evidence

Investigators used nationwide Danish registry data from 2003 to 2021 to evaluate associations between menopausal hormone therapy and thrombotic outcomes among women aged 50 to 69 years. The analysis included 9,807 venous thromboembolism cases, 18,460 ischemic strokes, and 11,974 myocardial infarctions matched to controls. Current oral hormone therapy was associated with increased venous thromboembolism risk, while elevated stroke and myocardial infarction risks were primarily observed among women using high-dose oral estradiol for more than one year. Transdermal therapy generally showed no increased thrombotic risk.

Clinical Considerations

• Current oral estrogen therapy, alone or combined with progestin, was associated with increased venous thromboembolism risk regardless of dose or treatment duration.
• Oral hormone therapy was associated with an absolute annual increase of 0.09% for venous thromboembolism, equivalent to approximately 1 additional event per 1,055 women treated for one year.
• Increased ischemic stroke and myocardial infarction risk were largely confined to high-dose oral estradiol (>1 mg/day) used for more than one year.
• Transdermal hormone therapy was not associated with increased thrombotic rates overall, regardless of regimen, dose, or duration.
• One signal of increased myocardial infarction risk was observed with combined transdermal cyclic therapy, though estimates were based on sparse data.
• The study lacked information on smoking status, body mass index, and age at menopause, and retrospective findings did not establish causality.

Practice Applications

• Consider route of administration when discussing thrombotic risk during menopausal hormone therapy counseling.
• Discuss absolute as well as relative risks to support informed shared decision-making.
• Review cardiovascular and thrombotic risk factors before initiating oral hormone therapy.
• Interpret transdermal therapy findings within the context of individual patient risk profiles and existing guideline recommendations.
• Monitor emerging long-term comparative evidence evaluating oral and transdermal regimens.