A large, long-term study of more than 52,000 women in Israel found that initiating contemporary hormone replacement therapy (HRT) did not increase the risk of heart attack, stroke, blood clots or death among women ages 45 to 59, according to preliminary research presented at the American Heart Association’s Scientific Sessions 2026. The findings, which have not yet been peer-reviewed, may help ease decades of concern that have led many women and their doctors to avoid hormone therapy for menopause symptoms.
“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.
The study evaluated health records for 52,330 women ages 45 to 59 with no history of heart disease, blood clots or cancer. Half had started HRT, primarily via oral and/or transdermal (patch) methods, while the other half had recently visited a gynecologist but did not begin HRT. Researchers matched the groups by age, body mass index, cardiometabolic risk factors, smoking status and socioeconomic status, then followed them for up to 23 years, with an average follow-up of 12 years.
After an average of 12 years, health outcomes were similar between the two groups. In the HRT group, 2,311 women (4.4%) experienced a heart attack, stroke or related heart disease, compared with 2,383 (4.6%) in the no-HRT group. Death before age 80 occurred in 659 (1.3%) of women taking HRT versus 653 (1.2%) of those not on HRT. Blood clots occurred in 0.33% of women in both groups (174 versus 175). Results were consistent across all HRT formulations and administration routes, including 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 findings come amid evolving clinical guidance. 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 indicated that HRT is not associated with increased risk of cardiovascular disease, breast cancer or dementia. The new study adds to that shift by focusing on modern formulations and younger women near menopause.
“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,” said Stacey E. Rosen, M.D., FAHA, past volunteer president of the American Heart Association (2025-2026) and executive director of the Katz Institute for Women’s Health at Northwell Health in New York City. Rosen was not involved in the study.
The research has limitations. It is observational, so it cannot prove a direct connection between HRT and heart health. The researchers also noted that other differences among the women, such as exercise, diet, other health conditions and severity of menopause symptoms, were not available in the 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 study evaluated outcomes related to atherosclerotic cardiovascular disease and venous thromboembolism, and detailed results are available in the abstract. The full Online Program Planner for the meeting is also available. A Spanish news release accompanies the findings.
The American Heart Association provides resources on menopause and cardiovascular risk, including a scientific statement on the menopause transition and cardiovascular disease risk and health information on menopause and cardiovascular risk. The study will be presented during Scientific Sessions 2026, held Nov. 6-9 in Chicago. More information about the Association’s funding and financial policies is available here, and general heart health information can be found at heart.org and stroke.org.
