Oral menopausal hormone therapy linked to higher blood clot risk; transdermal treatment shows no overall increase
· Medical Xpressedited by Sadie Harley, reviewed by Robert Egan
Sadie Harley
Scientific Editor
Meet our editorial team
Behind our editorial process
Robert Egan
Senior Editor
Meet our editorial team
Behind our editorial process Editors' notes
This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:
fact-checked
peer-reviewed publication
trusted source
proofread
The GIST Add as preferred source
Current use of oral menopausal hormone therapy (commonly known as hormone replacement therapy or HRT) is associated with an increased risk of blood clots in the legs or lungs regardless of dose or treatment duration, finds a large Danish study published by The BMJ.
Conversely, stroke and heart attack risks were limited to prolonged use of high-dose oral hormone therapy, while transdermal hormone therapy (delivered via the skin as patches, gels or sprays) showed no general increased blood clot risk.
Hormone therapy relieves menopausal symptoms such as hot flashes and night sweats. Some studies have linked oral hormone therapy to rare but serious blood clots known as venous thromboembolism and stroke, but evidence for heart attack remains inconsistent.
Danish records track treatment and clots
To explore this further, researchers searched Danish health registry data for women ages 50–69 living in Denmark between 2003 and 2021 who were diagnosed with a first venous thromboembolism, ischemic stroke or heart attack (myocardial infarction).
They identified 9,807 women with venous thromboembolism, 18,460 women with ischemic stroke and 11,974 women with heart attack. These women were matched by birth year to a total of 49,035, 92,300 and 59,870 women without thrombotic disease, respectively.
Prescription records were then used to assess links between hormone therapy use and thrombotic disease according to several variables, including route of administration, dose, duration of use and age at treatment initiation.
None of the women had a history of blood clots, cancer, liver disease, endometriosis, polycystic ovary syndrome, fertility treatment or surgery to remove ovaries (oophorectomy). Other potentially influential factors, such as income, education, medication use and pre-existing conditions, were also taken into account.
Oral therapy raises clot risk
Among women unexposed to hormone therapy, rates of venous thromboembolism, ischemic stroke and heart attack were 15.8, 20.3 and 13.0 per 10,000 person-years, respectively.
Oral estrogen therapy (alone or with progestin) was associated with absolute increases of 0.09% for venous thromboembolism, 0.06% for ischemic stroke and 0.03% for heart attack per year. This corresponds to one extra venous thromboembolism case per 1,055 women taking oral hormone therapy for one year, one extra stroke per 1,642 and one extra heart attack per 3,846.
Oral therapy was consistently associated with increased venous thromboembolism risk, whereas increased stroke and heart attack risks were confined to those taking high-dose oral estradiol (above 1 mg/day) for more than a year, rising with longer use.
Transdermal therapy shows a different pattern
Conversely, transdermal therapy showed no general increased thrombotic risk regardless of regimen, dose or duration, which the authors say highlights the importance of delivery route in minimizing risk.
One exception was an increased heart attack rate among women using combined transdermal cyclic therapy (continuous estrogen through the skin with progestogen added for part of the cycle to induce a monthly bleed), although the authors note this estimate is based on sparse data.
This is an observational study, so it cannot establish cause and effect. The authors acknowledge a lack of data on age at menopause, body mass index and smoking, and note that the results may not apply to other, more ethnically diverse populations. However, they say the large population-based design, use of detailed prescription data, extensive health and sociodemographic information on the study population and long follow-up suggest the results are robust.
They conclude, "Current use of any oral menopausal hormone therapy was associated with an increased venous thromboembolism risk, whereas ischemic stroke and myocardial infarction risk was only increased with oral high-dose therapy used for more than one year."
They add, "Transdermal therapy was not associated with increased thrombotic rates regardless of regimen, active ingredients, dose and duration of use."
Publication details
Contemporary menopausal hormone therapy and thrombotic disease: nationwide nested case-control study, The BMJ (2026). DOI: 10.1136/bmj-2026-100688
Journal information: British Medical Journal (BMJ)
Key medical concepts
Venous ThromboembolismIschemic StrokeMyocardial infarction
Clinical categories
Obstetrics & gynecologyWomen's healthCardiology Provided by British Medical Journal Who's behind this story?
Sadie Harley
BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →
Robert Egan
Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →
Citation: Oral menopausal hormone therapy linked to higher blood clot risk; transdermal treatment shows no overall increase (2026, September 23) retrieved 23 September 2026 from https://medicalxpress.com/news/2026-09-oral-menopausal-hormone-therapy-linked.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.