Oral HRT linked to higher clot and heart disease risk in women with type 2 diabetes, study finds

Women with type 2 diabetes who take oral hormone replacement therapy (HRT) tablets have a higher risk of pulmonary embolism and heart disease than those using transdermal patches, researchers reported Monday.

An analysis of more than 36,000 women on HRT followed for five years found that oral oestrogen was associated with roughly double the risk of pulmonary embolism — a blood clot that blocks an artery in the lung — and a 21% increased risk of heart disease compared with skin patches. The findings were presented at the annual meeting of the European Association for the Study of Diabetes in Vienna.

The study team, led by researchers at the University of Liverpool, examined electronic health records to compare outcomes for women with type 2 diabetes prescribed different HRT formulations. In addition to the elevated risks for pulmonary embolism and coronary heart disease with oral preparations, the investigators found no significant difference between oral and transdermal HRT for deep vein thrombosis, stroke, or for breast, ovarian or endometrial cancer.

Lead author Dr. Matthew Anson said the results support reconsidering oral oestrogen prescriptions for women with type 2 diabetes. "Given increased risks with oral HRT, we propose that women with type 2 diabetes should not be prescribed oral oestrogen therapy," he said in remarks reported by the study authors.

The authors noted a plausible biological mechanism for the observed differences: oral oestrogen is subject to first-pass metabolism in the liver, which can alter the balance of clotting and anti-clotting proteins. Transdermal delivery delivers lower systemic doses and bypasses the liver, potentially reducing effects on coagulation.

HRT is commonly used to relieve menopausal symptoms such as hot flashes, night sweats and vaginal dryness and is available as oestrogen-only or combined oestrogen-progestogen regimens delivered by tablets, patches, gels or creams. The researchers cited national prescribing data indicating that about 2.6 million women in the United Kingdom were taking some form of HRT between 2023 and 2024.

The analysis drew on routine clinical records and is observational, meaning it can identify associations but cannot definitively establish cause and effect. The investigators adjusted for measured confounders in their models, but residual confounding cannot be ruled out. The study's presentation at a scientific meeting precedes peer-reviewed publication, and the authors urged clinicians and patients to consider the findings alongside individual circumstances when choosing HRT formulations.

Clinicians who manage menopausal care said treatment decisions should balance symptom relief and individual cardiovascular risk profiles. The lead author acknowledged that HRT decisions are complex. "The decision to use HRT, even for a short period of time, is very difficult for many women," he said, adding that the data should help postmenopausal women with type 2 diabetes and their physicians weigh risks and benefits.

Menopause typically occurs between ages 45 and 55 and can cause a range of symptoms that HRT aims to alleviate. The researchers said further work, including peer-reviewed analyses and studies examining formulation, dose and duration, would help refine guidance for women with diabetes considering HRT.