Oral HRT linked to increased heart risks in T2D patients

Oral HRT linked to increased heart risks in T2D patients | Image Credit: © Krakenimages.com - © Krakenimages.com - stock.adobe.com.

Data presented at the Annual Meeting of The European Association for the Study of Diabetes between September 15 and September 19, 2025, has indicated increased cardiovascular risk in patients taking oral hormone replacement therapy (HRT).¹

Prior data has indicated no significant impact of HRT on blood clot or stroke risk in women with type 2 diabetes (T2D). However, this research has unveiled a 2-fold increase in pulmonary embolism (PE) risk among T2D patients taking oral HRT vs transdermal HRT, alongside a 21% increased risk of heart disease.

“Our study suggests that up to 5 years of regulator-approved doses of transdermal HRT appears safe in a large cohort of women in midlife with T2D and that the use of HRT skin patches is not associated with an excess increased risk of cardiovascular complications,” said Matthew Anson, BSc, researcher at the University of Liverpool.

“However, given increased risks with oral HRT, we propose that women with T2D should not be prescribed oral oestrogen therapy,” added Anson.

Assessing cardiovascular outcomes

The data was gathered from 3 analyses evaluating the impact of oral and transdermal HRT and cardiovascular, gynecological, and oestrogen-related cancer risks in women with T2D. The TriNetX global database, including 140 health care organizations from the United States and Europe, was evaluated for electronic health records.

Of participants, 75% were White, 17% Black, and 2% Asian. The study population was aged a mean 59 years, and the mean follow-up duration was 5 years. Participants were classified as either initiating HRT and statin, or controls initiating statin alone.

Relevant outcomes included PE, deep vein thrombosis (DVT), ischemic stroke, ischemic heart disease, and ovarian, breast, and endometrial cancer. In the first analysis, these outcomes were compared between women taking transdermal oestrogen HRT with T2D vs without T2D, matched 1:1 based on age and ethnicity.

T2D and transdermal HRT assessments

A 90% increase in DVT risk, 77% increase in heart disease risk, and 89%increase in stroke risk were observed in women with T2D vs those without T2D. No increases in PE or breast cancer risks were observed.

According to authors, these increased risks are largely because of the impacts of T2D on cardiovascular health. This leads women with T2D to experience increased risks vs those without T2D before considering additional factors.

In the second analysis, transdermal HRT use was compared to no HRT use in women with T1D matched 1:1 based on age, ethnicity, body mass index, blood glucose, and hypertension history. The risk of heart disease was reduced 25% in those taking HRT, but no other risks were significantly impacted.

Impact of oral HRT

Finally, investigators compared risks based on oral vs transdermal HRT use. Patients were matched 1:1 using the same characteristics as the second analysis. While no significant impacts on stroke, DVT, heart disease, or cancer risks were reported, the results highlighted the 2-fold increase in PE risk and 21% increase in heart disease risk from oral vs transdermal HRT.

Menopausal women often experience symptoms such as hot flashes and night sweats. Additionally, data has indicated HRT may reduce the need for antidepressants in these patients.² Therefore, HRT may be prescribed as a form of symptom relief.¹

“The decision to use HRT, even for a short period of time, is very difficult for many women," said Anson. "We hope our data will provide the increasing number of postmenopausal women living with T2D and their physicians with more evidence to consider when weighing the risks versus benefits of the most appropriate HRT formulation."

References

1. Researchers sound warning about women with type 2 diabetes taking oral HRT. European Association for the Study of Diabetes. September 14, 2025. Accessed September 16, 2025. https://www.eurekalert.org/news-releases/1098060.
2. Krewson C. HRT may reduce antidepressant need in menopausal women. Contemporary OB/GYN. March 1, 2025. Accessed September 16, 2025. https://www.contemporaryobgyn.net/view/hrt-may-reduce-antidepressant-need-in-menopausal-women.