Modern HRT gets a heart safety check

Clinical takeaway: Use these findings to inform individualized discussions about hormone replacement therapy (HRT) for menopausal symptoms in women aged 45-59 years without prior cardiovascular disease, venous thromboembolism, or cancer. The results provide reassurance regarding long-term cardiovascular safety but do not establish that HRT is risk-free.

Concern about heart risks can discourage women from seeking HRT and clinicians from prescribing it. Much of the earlier evidence involved older formulations, higher doses, and treatment started long after menopause.

Researchers used Israeli health records to emulate a randomized trial, matching 26,165 HRT initiators with 26,165 non-initiators on age, BMI, cardiometabolic risk, smoking, and other factors. Follow-up averaged 12 years and extended to 23 years. Treatment primarily involved contemporary oral and transdermal formulations.

Event rates were virtually identical between HRT initiators and non-initiators. ASCVD occurred at rates of 7.82 versus 7.99 events per 1,000 person-years, venous thromboembolism at 0.56 versus 0.56, and deaths before age 80 at 2.13 versus 2.10 per 1,000 person-years.

Adjusted analyses found no significant increase in cardiovascular disease, blood clots, or premature death. Findings were consistent across treatment formulations and administration routes.

The observational design leaves potential for unmeasured differences in diet, exercise, and symptom severity to influence results. The analysis also did not account for subsequent changes in treatment formulation.

The findings were presented at the American Heart Association’s Scientific Sessions 2026 and have not yet been peer reviewed.

“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,” said lead researcher Ronen Arbel, Ph.D.

Source: Arbel R, et al. (2026 Nov 2) American Heart Association Scientific Sessions 2026, Abstract MDP0654. Contemporary Hormone Replacement Therapy and Long-Term Cardiovascular Safety: Target-Trial Emulation in 52,330 Women