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 face a higher risk of pulmonary embolism and heart disease than those using transdermal patches, according to a study presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Vienna.

Researchers from the University of Liverpool analysed electronic health records for more than 36,000 women prescribed HRT and followed them for five years. The team found that women with type 2 diabetes taking oral oestrogen had about double the risk of pulmonary embolism — a blood clot that blocks an artery in the lung — compared with women using skin patches. The analysis also showed a 21 percent increased risk of heart disease among oral HRT users relative to the transdermal group.

Lead author Dr. Matthew Anson said the findings should influence prescribing decisions for postmenopausal 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 told delegates.

The investigators noted a plausible biological explanation for the difference. When oestrogen is taken orally it passes through the liver before entering the general circulation, a process known as first-pass metabolism, which can alter the balance of clotting and anti-clotting proteins. Transdermal preparations deliver lower doses of hormone directly through the skin and into the bloodstream, largely avoiding liver first-pass effects.

The study did not find significant differences between oral and transdermal HRT for deep vein thrombosis, stroke, or for breast, ovarian or endometrial cancer outcomes during the follow-up period. The authors caution that the research is observational and cannot prove causation, though the pattern of results and biological plausibility support concern over oral formulations in this population.

HRT is commonly prescribed to relieve menopausal symptoms such as hot flashes and night sweats. Preparations include tablets containing oestrogen alone or in combination with progesterone, as well as patches, gels and creams. Between 2023 and 2024, roughly 2.6 million women in the United Kingdom were estimated to be taking some form of HRT.

Clinicians and patients said the choice of HRT formulation should weigh symptom relief against potential risks. Dr. Anson and his co-authors said their findings should be considered by women with type 2 diabetes and their physicians when deciding which HRT method to use, and they urged personalised decision-making that accounts for individual risk factors.

Experts not involved in the study noted that while observational analyses of electronic health records can reveal associations across large populations, they are subject to confounding and cannot replace randomized clinical trials. The authors called for further research to confirm the findings and to explore whether specific doses or combined hormone regimens modify the observed risks.

The EASD presentation underscores growing attention to tailoring menopausal care for women with chronic conditions such as type 2 diabetes. Health professionals advising patients are likely to consider the study alongside existing guidance on HRT use, cardiovascular risk management, and thrombosis prevention when reviewing treatment options.