Oral menopausal hormone therapy is linked to a higher risk of venous thromboembolism, but the size of that risk and whether it extends to stroke and heart attack depend on dose, route, and duration, according to a nationwide Danish registry study published in The BMJ.
Among women ages 50-69, current use of oral estrogen with or without progestin was associated with a hazard ratio of 1.6 for venous thromboembolism versus no current use, or an absolute risk of about 0.09% per year. Stroke and myocardial infarction risk were elevated only for high-dose oral estradiol (more than 1 mg/day) used for more than a year. Low-dose oral estradiol showed no increased risk for those outcomes.
Transdermal therapy appeared safer: no elevated venous thromboembolism or stroke risk was seen, and the only increased risk was for myocardial infarction with combined cyclic therapy (HR 2.1). The authors caution that these observational findings cannot prove causation, and data on body mass index, smoking, and age at menopause were unavailable.
An outside expert said the results confirm that oral estrogen stimulates clot formation while patches do not, but noted the stroke and heart attack findings should be interpreted cautiously. The researchers argue the message for patients should be nuanced: menopausal hormone therapy has no single risk profile.