Sex hormones affect heart disease risk differently in diabetic men and women

A new study from Johns Hopkins Medicine reveals that sex hormones like testosterone and estradiol influence heart disease risk in type 2 diabetes differently for men and women. In men, higher testosterone levels were linked to lower risk, while rising estradiol was associated with higher risk; no such patterns emerged in women. The findings suggest potential for more personalized prevention strategies.

People with type 2 diabetes face elevated risks of heart attacks, strokes, and other cardiovascular issues, according to the National Institutes of Health. However, these risks vary between men and women, with biological explanations remaining unclear until now.

Led by Wendy Bennett, M.D., M.P.H., an associate professor at Johns Hopkins University School of Medicine, researchers explored the role of sex hormones. "We are very interested in understanding why women who have diabetes have a greater risk for heart disease compared to men," Bennett said. "Sex hormones matter and could explain some of the differences in heart disease outcomes in women and men."

The study drew on data from the Look AHEAD trial, a long-term investigation into how weight loss impacts heart health in type 2 diabetes patients. Even after the trial concluded, follow-up continued, providing ongoing health data. Researchers measured testosterone and estradiol levels in blood samples taken at enrollment and one year later.

Among men, those with higher testosterone at the start showed lower heart disease risk. Increases in estradiol over the year correlated with higher risk. "We were able to see whether the changes in hormones affected their heart disease risk," Bennett explained. "We saw that there were differences in the male participants. If they had higher testosterone when they joined the study, they had a lower risk. If they had increases in estradiol levels after one year in the study, they also had a higher risk of heart disease."

In women, no significant links between hormone levels and cardiovascular outcomes were observed, indicating other factors may dominate for them.

The research, published in Diabetes Care in 2026, was funded by National Institutes of Health grants. Bennett noted the implications: "Results from this study contribute to our understanding of how tracking sex hormones in people with diabetes could complement what we already know about traditional heart disease risk factors [like smoking and cholesterol levels]. The results could help clinicians personalize heart disease prevention strategies in the future."

Future work will examine hormone changes during perimenopause and their effects on cardiovascular risk in diabetes, as well as links to bone health and fractures.

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Realistic illustration depicting men's cardiovascular disease risk diverging higher than women's from age 35, based on CARDIA study data.
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