People with type 2 diabetes face an increased risk of heart attack, stroke, and other cardiovascular problems, according to the National Institutes of Health. However, the level of risk differs between men and women, and the underlying biological reasons for this disparity have remained unclear – until now. A new study led by Johns Hopkins Medicine suggests that sex hormones, specifically testosterone and estradiol, may play a significant role in these differing risks.
The research, published in Diabetes Care on February 4, 2026, builds upon data from the Look Ahead study, a long-term project initially focused on the impact of weight loss on heart health in individuals with type 2 diabetes. Researchers continued to follow participants even after the original trial concluded, allowing for a more comprehensive analysis of long-term health outcomes.
Hormonal Differences and Heart Disease Risk
“We are very interested in understanding why women who have diabetes have a greater risk for heart disease compared to men,” explains Dr. Wendy Bennett, M.D., M.P.H., an associate professor of medicine at Johns Hopkins University School of Medicine and lead researcher of the study. “Sex hormones matter and could explain some of the differences in heart disease outcomes in women and men.”
The team analyzed blood samples collected from Look Ahead participants at the beginning of the study and again one year later, measuring levels of sex hormones. Their analysis revealed distinct patterns in men and women. Among male participants, higher testosterone levels at the start of the study were associated with a lower risk of heart disease. Conversely, increases in estradiol levels over the one-year period were linked to a higher risk.
Interestingly, these hormonal correlations were not observed in women. Researchers did not find meaningful links between estradiol or testosterone levels and cardiovascular outcomes in female participants. This suggests that the influence of sex hormones on heart disease risk may differ significantly between sexes, or that other factors may be more prominent in women with diabetes.
Tracking Hormones for Personalized Prevention
The study’s findings highlight the potential for a more personalized approach to heart disease prevention in individuals with type 2 diabetes. Currently, prevention strategies often rely on traditional risk factors such as smoking, cholesterol levels, and blood pressure. This new research suggests that incorporating sex hormone levels into risk assessments could provide a more nuanced understanding of an individual’s cardiovascular health.
“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,” Dr. Bennett says. “The results could help clinicians personalize heart disease prevention strategies in the future.”
Looking Ahead: Further Research on Hormones and Diabetes
The Johns Hopkins Medicine team plans to continue investigating the relationship between sex hormones and various health outcomes in people with diabetes. Future research will explore the impact of weight loss and hormone changes on bone health, specifically looking at fracture risk. They are also preparing new studies focused on hormonal changes during perimenopause – the transition to menopause – and how these changes may affect cardiovascular risk, particularly in individuals with chronic conditions like diabetes.
The study received funding support from the National Institutes of Health through grants R01DK127222 and U01DK57149.
Study Team and Disclosures
The study team included Teresa Gisinger, M.D., Ph.D., Jiahuan Helen He, M.H.S., Chigolum Oyeka, MBBS, M.P.H., Jianqiao Ma, ScM, Nityasree Srialluri, M.D., M.S., M.H.S., Mark Woodward, Ph.D., Erin D. Michos, M.D., M.H.S., Rita R. Kalyani, M.D., M.H.S., Jeanne M. Clark, M.D., M.P.H., Alexandra Kautzky-Willer, M.D., and Dhananjay Vaidya, MBBS, Ph.D., M.P.H.
Certain team members have disclosed relevant affiliations. Dr. Clark has served as a scientific advisor to Boehringer Ingelheim and received writing support from Novo Nordisk. Dr. Michos has served as a consultant for a number of pharmaceutical companies, including Amgen, AstraZeneca, Bayer, and others. These affiliations are unrelated to the current research.
