Oral menopause hormone therapy linked to clot risk even at low doses

Clinical takeaway: When prescribing menopausal hormone therapy, consider a transdermal option for patients concerned about blood clot risk. Review the need for prolonged high-dose oral therapy, particularly in patients with cardiovascular risk factors.

Hormone therapy can relieve hot flashes and night sweats, but the way estrogen is delivered may affect thrombotic risk. In a large Danish study, current oral menopausal hormone therapy was associated with more blood clots in the legs or lungs across doses and treatment durations. Transdermal therapy showed no overall increase in the events studied.

Researchers compared women aged 50 to 69 who had a first venous thromboembolism (VTE), ischemic stroke, or heart attack with women of the same birth year who had not had one of those events, using national records from 2003 to 2021.

Oral estrogen use was associated with a 60% higher relative rate of VTE than no current hormone therapy use. The estimated absolute increase was about nine additional cases per 10,000 women treated for one year, or one extra case for every 1,055 users. Higher oral doses carried greater VTE risk than lower doses. Among new users, the relative risk was highest during the first year of high-dose treatment.

Increased stroke and heart attack risks were most evident with oral estradiol doses above 1 mg/day used for more than a year. Transdermal treatment was not associated with an overall increase in VTE, stroke, or heart attack. An apparent heart attack increase with one cyclic transdermal regimen was based on sparse data.

The study was observational and could not account for smoking or body mass index. Its findings primarily reflect estradiol formulations used in Denmark.

“Current use of any oral menopausal hormone therapy was associated with an increased venous thromboembolism risk,” the authors concluded.

Source: Berggreen J, et al. (2026 Sep 23) BMJ. Contemporary menopausal hormone therapy and thrombotic disease: nationwide nested case-control study