A large, long-term study of more than 52,000 women in Israel found that among women ages 45 to 59, initiation of contemporary hormone replacement therapy (HRT) did not increase the risk of heart attack, stroke, blood clots, or death. The independent, preliminary research, presented at the American Heart Association’s Scientific Sessions 2026, followed participants for an average of 12 years and included oral, transdermal (patch), and gel forms of HRT.
“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 older HRT formulations that are no longer commonly used, with higher doses and in women who started HRT 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. 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.”
The study evaluated data for over 52,000 women ages 45 to 59 to assess whether contemporary HRT use is associated with increased risk of atherosclerotic cardiovascular disease, venous thromboembolism (blood clots), or premature death before age 80 in women without prior cardiovascular disease. After an average of 12 years of follow-up, health outcomes were similar between the two groups: 2,311 women (4.4%) in the HRT group 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%) versus 653 (1.2%); and 0.33% in both groups experienced a blood clot (174 vs. 175). Results were consistent across all HRT formulations and administration routes.
“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 researchers used records from Clalit Health Services to evaluate 52,330 women with no history of heart disease, blood clots, or cancer. Half had started HRT, primarily oral and/or transdermal, while the other half had recently visited a gynecologist but did not begin HRT. The groups were matched by age, BMI, cardiometabolic risk factors, smoking status, and socioeconomic status, and followed for up to 23 years.
The research has limitations: it is observational and cannot prove a direct connection; other differences among women, such as exercise, diet, other health conditions, and severity of menopause symptoms, were not available; and the study grouped women by the first type of hormone therapy used without accounting 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 Scientific Sessions 2026 Online Program Planner are available. Additional resources include the release link with multimedia and a Spanish news release. For more information on women’s heart health, see : Menopause and Cardiovascular Risk and the American Heart Association Scientific Statement Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention. Overall financial information for the American Heart Association is available here.
