Oral menopausal hormone therapy linked to higher blood clot risk; transdermal treatment shows no overall increase

A recent Danish study published in The BMJ has found that current use of oral menopausal hormone therapy is linked to an increased risk of blood clots in the legs or lungs, regardless of the dose or treatment duration. The study, which analyzed data from over 150,000 women in Denmark between 2003 and 2021, revealed that oral estrogen therapy, whether alone or combined with progestin, led to a small increase in venous thromboembolism (0.09% for venous thromboembolism, 0.06% for ischemic stroke, and 0.03% for heart attack per year).

However, these risks were only significant for high-dose oral estrogen therapy (above 1 mg/day) used for more than a year, with the risk of venous thromboembolism increasing by one case per 1,055 women, stroke by one per 1,642, and heart attack by one per 3,846. In contrast, transdermal hormone therapy, administered through patches, gels, or sprays, did not show a general increased risk of blood clots, regardless of the regimen, dose, or duration of use.

The researchers emphasize that the route of administration plays a crucial role in minimizing thrombotic risk. One exception was found in women using combined transdermal cyclic therapy, in which continuous estrogen through the skin was combined with progestogen for part of the cycle to induce a monthly bleed, leading to an increased rate of heart attacks.

The study, while observational, cannot establish causation and cannot account for factors such as age at menopause, body mass index, and smoking. The researchers note that their findings may not apply to other, more ethnically diverse populations.