Wasn’t hormone replacement therapy (HRT) considered dangerous for the heart? Newer research shows the risks are more nuanced and depend on factors like age, timing of therapy, and overall health. But when it comes to heart rhythm disorders such as atrial fibrillation, the connection is still less clear and actively being studied.
If you’ve been following women’s health news lately, you’ve probably heard that the FDA has removed some of the earlier warnings from hormone therapy products.
For years, concerns about hormone therapy and cardiovascular health were based on findings from large studies published in the late 1990s and early 2000s. They reported increased rates of heart attacks, stroke, and blood clots among some women using hormone therapy, leading to widespread caution and prominent safety warnings.
Researchers have taken a closer look at those findings over the past two decades. Additional analyses and newer studies reveal nuances that were not fully appreciated at the time of the original studies, and suggest a more complex relationship between hormone therapy and cardiovascular risk.
The Black Box Warnings and What Changed
In the early 2000s, hormone replacement therapy (HRT) came with strong safety warnings, commonly referred to as “black box warnings.” They were based mainly on two large studies, HERS and the Women’s Health Initiative (WHI), and raised concern because they suggested higher rates of heart attack, stroke, and blood clots in some women using hormone therapy. The impact it had was huge, and it made both patients and doctors more cautious about using HRT.
Since then, major medical organizations in North America have updated their guidance, and in 2025, the FDA lifted many of the warnings.
The earlier studies weren’t “wrong,” but they also didn’t tell the whole story. The risks of hormone therapy are not the same for every woman. Even with updated guidance, there is still a lot of confusion.
One important detail that became clearer over time is that the WHI study included many women who were older than the typical age when hormone therapy is started, and when researchers later separated results by age, a more detailed pattern appeared. Women who started hormone therapy closer to menopause (roughly in their 50s) tended to have different outcomes than women who started it later in life. Timing has since become an important factor in how clinicians think about hormone therapy, helping doctors better evaluate when HRT is appropriate and when it carries higher cardiovascular risk.
How Hormones Affect the Heart
Hormones interact with many parts of the body, including the heart and blood vessels. Studies show that estrogen may be associated with cardioprotective qualities.1 Prior to menopause, estrogen keeps blood vessels more flexible and responsive, which enables healthy blood flow. Some research also suggests it may reduce inflammation in the blood vessels.2
Estrogen also affects cholesterol levels. In many studies, it is associated with higher HDL (“good” cholesterol) and lower LDL (“bad” cholesterol). It’s involved with metabolic processes like blood sugar control and how the body stores fat, too.2
However, that doesn’t translate into HRT preventing heart disease or cardiovascular-related problems. The only approved reason for starting HRT is to treat menopause symptoms such as hot flashes, sleep disruption, and night sweats. Any effects on the heart are considered secondary and can vary from person to person.
HRT and Heart Rhythm Disorders
Most of the research has focused on outcomes like heart attacks, stroke, blood clots, and heart failure. Far fewer studies have specifically looked at heart rhythm disorders such as atrial fibrillation or other types of arrhythmias.
Within normal physiology, and outside of HRT, hormones interact with the heart’s electrical system. Estrogen and testosterone can affect how heart cells respond to electrical signals, how quickly the heart resets between beats, and how stable the rhythm is overall.3 The interaction is complex and not always predictable from person to person or at different stages of life.
Observational studies examining hormone therapy and atrial fibrillation have produced mixed and sometimes inconsistent results, with some suggesting increased risk, others showing no clear association.3 There are also other biological influences on the heart’s electrical system that potentially affect rhythm stability. Because of the variability and uncertainty, hormone therapy decisions are made with multiple risk factors in mind.
Women in the low-risk category are typically younger, closer to the start of menopause, and have fewer cardiovascular risk factors. Women with conditions like high blood pressure, diabetes, or high cholesterol are considered moderate-risk. High-risk patients are those with a history of heart attack, stroke, blood clots, or cardiovascular disease, and are further away from the start of menopause.
Extra caution is warranted for women with atrial fibrillation. Some forms of hormone therapy can increase the tendency for blood to clot, and atrial fibrillation itself can also increase the risk of stroke because it allows blood to pool in the heart.
When in doubt, a cardiology consultation in conjunction with the prescribing clinician can be helpful before starting or continuing hormone therapy. Hormone therapy also isn’t a “set it and forget it” treatment – it should be revisited over time as symptoms, health status, and cardiovascular risk change.
Dr. Tordini is a part of Florida Medical Clinic Orlando Health
REFERENCES:
- Venkatakrishnan, A., Srinivasan, D., Malik, A., Hazareh, M., Nizami, M. A., Chen, J. Y., & Ng, F. S. (2026). Effect of estrogen and testosterone on cardiac electrophysiology and atrial fibrillation. Heart Rhythm O2, 7(2), 393–403. https://doi.org/10.1016/j.hroo.2025.11.007.
- Cho, L., Kaunitz, A. M., Faubion, S. S., Hayes, S. N., Lau, E. S., Pristera, N., Scott, N. S., Shifren, J. L., Shufelt, C., Stuenkel, C. A., & Lindley, K. J. (2023). Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long? Circulation, 147(7). https://doi.org/10.1161/circulationaha.122.061559.
- Venkatakrishnan, A., Srinivasan, D., Malik, A., Hazareh, M., Nizami, M. A., Chen, J. Y., & Ng, F. S. (2026). Effect of estrogen and testosterone on cardiac electrophysiology and atrial fibrillation. Heart Rhythm O2, 7(2), 393–403. https://doi.org/10.1016/j.hroo.2025.11.007.
