Large Israeli Study Finds Contemporary Hormone Therapy Not Linked to Heart Risk in Women 45 to 59

A study of 52,330 women in Israel, followed for an average of 12 years, has found no sign that modern hormone replacement therapy raises the risk of heart attack, stroke, blood clots or early death in women who start it between the ages of 45 and 59. The work is preliminary and independent, and it will be presented at the American Heart Association's Scientific Sessions 2026, held Nov. 6-9 in Chicago.

The lead researcher, Ronen Arbel, Ph.D., works in the community medical services division of Clalit Health Services in Tel Aviv and with Sapir College's Maximizing Health Outcomes Research Lab in Sderot. He says worry about the heart is among the most common reasons women decline hormone therapy for menopause symptoms, and a reason some health professionals hesitate to offer it.

That worry has a history. Earlier randomized trials linked HRT to cardiovascular harm, though their results were mixed. Much of that evidence came from older formulations no longer in common use, given at higher doses, and to women who began treatment long after menopause. Current guidance from the American College of Obstetricians and Gynecologists is to start within 10 years of menopause onset and before age 60. In November 2025, the FDA removed the boxed warnings from HRT products after a review of current data that found no increased risk of cardiovascular disease, breast cancer or dementia.

The researchers used Clalit Health Services records for women aged 45 to 59 with no history of heart disease, blood clots or cancer. Half had started HRT, mostly oral or transdermal patch. The other half had recently seen a gynecologist but did not begin HRT, and stayed off it throughout the study. The two groups were matched on age, BMI, blood pressure, cholesterol, diabetes diagnosis, smoking status and socioeconomic status. Records were tracked for up to 23 years.

The outcomes were close. Heart attack, stroke or related heart disease occurred in 2,311 women on HRT (4.4%) and 2,383 women not on it (4.6%). Death before age 80 occurred in 659 women on HRT (1.3%) and 653 women not on it (1.2%). Blood clots affected 0.33% of each group: 174 women in the HRT group and 175 in the comparison group. Results were similar across formulations and across oral, patch and gel 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.

Stacey E. Rosen, M.D., a past volunteer president of the American Heart Association (2025-2026) who was not involved in the research, said the study adds to growing evidence that today's options may not raise the risk of heart disease, stroke or blood clots for healthy women who begin treatment around menopause. Rosen, who is 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, said the findings can support better-informed conversations between women and their care teams.

The limits are plain. This is an observational study, so it cannot prove a direct link, or lack of one, between HRT and heart health. The records may not capture differences between the groups in exercise, diet, other health conditions or the severity of menopause symptoms. Women were also grouped by the first type of hormone therapy they used, so later changes in type or formulation were not counted. The Chicago presentation is the next step, and the findings remain preliminary until then.