Modern HRT Not Linked to Heart Risk in Large Study

A large, long-term study of more than 52,000 women in Israel found that contemporary hormone replacement therapy (HRT) was not associated with an increased risk of heart attack, stroke, blood clots, or premature death among women ages 45 to 59. The preliminary research, led by Ronen Arbel, Ph.D., a researcher in the community medical services division of Clalit Health Services in Tel Aviv and with Sapir College’s Maximizing Health Outcomes Research Lab, will be presented at the American Heart Association’s Scientific Sessions 2026 in Chicago. The study evaluated data from 52,330 women with no history of heart disease, blood clots, or cancer, half of whom started HRT—primarily oral or transdermal (patch)—while the other half did not. After an average follow-up of 12 years, health outcomes were similar between the groups: 4.4% of women on HRT experienced a heart attack, stroke, or related heart disease versus 4.6% in the no-HRT group; death before age 80 occurred in 1.3% versus 1.2%; and blood clots occurred in 0.33% of both groups. Results were consistent across all HRT formulations and administration routes, including oral, patch, or gel.

“Concerns that hormone replacement therapy may affect the heart is one of the most common reasons women decline hormone therapy to manage menopause symptoms, and why some healthcare professionals may hesitate to offer it,” Arbel said. The findings challenge older randomized trials that suggested cardiovascular harm from HRT, which largely used older formulations, higher doses, and women who started therapy long after menopause. Current guidelines from the American College of Obstetricians and Gynecologists recommend starting HRT within 10 years of menopause onset and before age 60, and in November 2025 the FDA removed “black box” warnings from HRT products after a comprehensive review found no increased risk of cardiovascular disease, breast cancer, or dementia. Stacey E. Rosen, M.D., FAHA, past volunteer president of the American Heart Association and executive director of the Katz Institute for Women’s Health at Northwell Health, noted that the study “adds to growing evidence that today’s hormone therapy options may not increase the risk of heart disease, stroke or blood clots for healthy women who begin treatment around the time of menopause.”

The research specifically assessed atherosclerotic cardiovascular disease and venous thromboembolism (blood clots), as well as premature death before age 80. While the observational study cannot prove a direct connection and has limitations—including potential differences in lifestyle factors not captured in health records—the researchers matched women by age, BMI, cardiometabolic risk factors, smoking status, and socioeconomic status. The results suggest that for women in their mid-forties to late fifties without a history of heart disease or blood clots, currently available hormone therapies do not appear to raise cardiovascular risk, even with long-term use. The findings are considered preliminary until published in a peer-reviewed journal, but they offer reassurance to women and healthcare providers weighing the benefits and risks of menopause treatment.