Oral Menopausal Hormone Therapy Linked to Higher Blood Clot Risk

Study Analyzes Nationwide Records on Menopausal Hormone Therapy

Current use of oral menopausal hormone therapy, commonly called hormone replacement therapy (HRT), is associated with a higher risk of blood clots in the legs or lungs regardless of dose or duration.

Researchers analyzed Danish health registry data collected between 2003 and 2021 for women aged 50 to 69 who experienced a first venous thromboembolism, ischemic stroke, or heart attack.

The observational analysis evaluated 9,807 women with venous thromboembolism, 18,460 with ischemic stroke, and 11,974 with heart attack against matched control participants without thrombotic disease.

Oral Menopausal Hormone Therapy Linked to Higher Blood Clot Risk

Oral estrogen treatment produced measurable annual increases in venous thromboembolism, ischemic stroke, and heart attack across the evaluated cohort.

Among women unexposed to hormone therapy, baseline rates were 15.8 for venous thromboembolism, 20.3 for ischemic stroke, and 13.0 for heart attack per 10,000 person-years.

Oral treatment resulted in absolute yearly increases of 0.09 percent for venous thromboembolism, 0.06 percent for stroke, and 0.03 percent for heart attack, which reflects one extra blood clot case per 1,055 women treated for one year.

Transdermal Hormone Treatments Avoid General Clot Increases

Transdermal hormone therapy administered through patches, gels, or sprays showed no general increased blood clot risk regardless of regimen, dose, or duration.

Risks for ischemic stroke and heart attack on oral regimens were confined to individuals taking high-dose oral estradiol above 1 milligram per day for more than one year.

The investigators recorded an elevated heart attack rate for combined transdermal cyclic regimens where progestogen is added cyclically, though the authors note this specific finding rests on sparse data.

Study Design Caveats and Unmeasured Risk Factors

The observational design of the Danish registry study cannot establish direct cause and effect.

Registry files lacked information on participant body mass index (BMI), smoking status, and exact age at menopause.

The authors also note that these findings from a Danish population sample may not apply directly to more ethnically diverse populations.