A large, long-term study of more than 52,000 women in Israel found that initiation of contemporary hormone replacement therapy (HRT) among women ages 45 to 59 did not increase the risk of heart attack, stroke, blood clots or death, according to preliminary research to be presented at the American Heart Association’s Scientific Sessions 2026. The meeting, scheduled for Nov. 6-9 in Chicago, is a premier global exchange of the latest scientific advancements in cardiovascular science.
The findings address one of the most persistent concerns surrounding menopause treatment. “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,” said lead study researcher Ronen Arbel, Ph.D., a researcher in the community medical services division of Clalit Health Services in Tel Aviv, Israel, and a researcher with Sapir College’s Maximizing Health Outcomes Research Lab in Sderot, Israel.
Previous randomized trials found associations between HRT and cardiovascular harm, but results were mixed, and much of that evidence came from studies using older HRT formulations that are no longer commonly used, with higher doses and in women who started HRT long after menopause. Current clinical guidelines from the American College of Obstetricians and Gynecologists recommend starting HRT within 10 years of menopause onset and before age 60. In November 2025, the FDA removed the “black box” warnings from HRT products after a comprehensive review of current scientific data indicating that HRT is not associated with increased risk of cardiovascular disease, breast cancer or dementia.
“For many women, menopause symptoms can significantly affect their quality of life, yet questions about the cardiovascular safety of hormone therapy have remained,” said Stacey E. Rosen, M.D., FAHA, an expert in women’s heart health and past volunteer president of the American Heart Association (2025-2026). “This large, long-term 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. These findings can help women and their healthcare teams have more informed conversations about the benefits and risks of treatment based on their individual health needs.” Rosen, who was not involved in this study, is also executive director of the Katz Institute for Women’s Health and senior vice president of women’s health at Northwell Health in New York City.
The study evaluated data for over 52,000 women, ages 45 to 59, to assess whether the use of contemporary HRT is associated with an increased risk of atherosclerotic cardiovascular disease, venous thromboembolism (blood clots) or premature death (before age 80) in women who had not been previously diagnosed with cardiovascular disease. After an average of 12 years of follow-up, the health outcomes were similar between the two groups: 2,311 women in the HRT group (4.4%) experienced a heart attack, stroke or related heart disease versus 2,383 (4.6%) in the no-HRT group. Death before age 80 occurred in 659 (1.3%) of the women taking HRT versus 653 (1.2%) of those not on HRT. Blood clots occurred in 0.33% of women in both groups (174 in the HRT group vs. 175 in the no-HRT group). The results were similar across all HRT formulations and administration routes (oral, patch or gel).
“Our results indicate that, for women in their mid-forties to late fifties with no history of heart disease or blood clots, the currently available hormone therapies prescribed to manage menopause symptoms do not appear to raise the risk of heart attack, stroke, clots or early death, even after long-term use,” Arbel said.
The study used records from Clalit Health Services in Israel, evaluating 52,330 women aged 45-59 with no history of heart disease, blood clots or cancer. Half had started HRT, primarily via oral and/or transdermal methods, while the other half had recently visited a gynecologist but did not begin HRT. Researchers matched the groups by age, BMI, cardiometabolic risk factors, smoking status and socioeconomic status, and followed health records for up to 23 years.
The research has limitations: it is observational and cannot prove a direct connection between HRT and heart health. Other differences among the women, such as exercise, diet, other health conditions and severity of menopause symptoms, may not have been captured in health records. Additionally, the study grouped women by the first type of hormone therapy they used and did not account for changes in HRT type or formulation during follow-up.
The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal. The abstract and the American Heart Association’s Online Program Planner are available. Additional resources include a Spanish news release and the American Heart Association’s health information on Menopause and Cardiovascular Risk.
