Oral menopause hormone therapy increases thrombosis risk. Transdermal treatments, however, show no such association.
The Danish Findings on Oral and Transdermal Risks
Published in the British Medical Journal on September 23, a Danish study confirmed that oral hormone replacement therapy (HRT) for menopause is linked to a heightened risk of venous thrombosis. This includes blood clots in the legs or lungs. Crucially, this danger persists regardless of dose or treatment duration.
Transdermal HRT tells a different story. Administered via patches, gels, or sprays, it did not show an increased thrombotic risk, even with varying dosages or treatment lengths. These findings were reviewed by the French High Authority of Health (HAS), which subsequently revised its opinion on October 14, 2025.
Weighing Cardiovascular Hazards and Coagulation
The stakes are high. Prolonged oral HRT use exceeding one year with high-dose estradiol over 1 mg/day correlates directly with elevated risks of heart attack and stroke.
Yet, the primary focus remains thrombosis. Here, oral administration consistently showed a heightened risk compared to transdermal methods. This aligns with broader concerns about estrogen’s role in blood clot formation, as outlined in a National Center for Biotechnology Information (NCBI) review on estrogen’s physiological mechanisms.
Biological Mechanisms of 17β-estradiol
Research published in the NCBI details how estrogen, particularly 17β-estradiol (E2), interacts with estrogen receptors (ERα and ERβ) to influence physiological processes.
These receptors are present in tissues like the cardiovascular system and liver, where they actively modulate clotting factors.
Clinical Guidance and French Treatment Patterns
The HAS highlighted in its 2025 review that while HRT remains effective for managing menopausal symptoms like hot flashes and osteoporosis, its use must balance benefits against risks.
Systemic risks—such as venous thrombosis, cardiovascular events, and breast or endometrial cancer—vary based on treatment type, dosage, and duration.
Unresolved Questions and Patient Safety
Uncertainties remain.
The HAS advises that HRT is not universally recommended due to its complex risk profile, which includes effects on the venous, cardiovascular, breast, ovarian, and endometrial systems. For those opting for oral HRT, careful monitoring of thrombotic risks is essential, while transdermal options may offer a safer alternative for many.