A new study led by researchers at Penn State College of Medicine suggests that long-term use of estrogen-based hormone therapy during menopause may help improve heart health, especially by reducing levels of a genetic risk factor linked to heart attacks and strokes.
The findings, published in Obstetrics & Gynecology, bring fresh insight into the ongoing debate about the risks and benefits of hormone therapy during the menopause transition.
Hormone therapy (HT), which replaces the body’s declining levels of estrogen and sometimes progesterone, is often prescribed to relieve common menopause symptoms such as hot flashes and night sweats.
However, concerns about its long-term safety—especially related to cardiovascular disease (CVD)—have led to confusion among patients and healthcare providers.
Led by Dr. Matthew Nudy, assistant professor of medicine at Penn State, the study analyzed data from the Women’s Health Initiative (WHI)—a large, long-term national study focused on menopausal women.
Researchers looked at blood samples from 2,696 postmenopausal women, aged 50 to 79, who participated in a WHI hormone therapy trial. These women were tracked over six years and assigned to either an estrogen-only group or an estrogen-plus-progesterone group.
Key cardiovascular biomarkers were measured at baseline and at years one, three, and six. Here’s what they found:
- LDL cholesterol (“bad” cholesterol) decreased by 11%
- Total cholesterol and insulin resistance also decreased
- HDL cholesterol (“good” cholesterol) increased by 13% in the estrogen-only group and 7% in the combined group
- However, triglycerides and coagulation factors (proteins involved in blood clotting) increased
One of the most important—and surprising—findings was that hormone therapy significantly reduced lipoprotein(a) (or Lp(a)), a type of cholesterol particle mostly determined by genetics. High Lp(a) levels are strongly linked to early heart attack, stroke, and aortic stenosis (narrowing of a heart valve).
- Lp(a) levels dropped by 15% in the estrogen-only group
- Lp(a) levels dropped by 20% in the estrogen-plus-progesterone group
Dr. Nudy called this the study’s “most interesting” result because no FDA-approved medications currently exist to lower Lp(a). Hormone therapy may offer an unexpected benefit for women with high levels of this cholesterol particle.
Even more notably, women who self-identified as American Indian/Alaska Native or Asian/Pacific Islanderexperienced even greater Lp(a) reductions—41% and 38%, respectively. The reasons for this are still unclear and will be explored in future research.
The women in the study took oral estrogen therapy, specifically conjugated equine estrogens, which are processed by the liver. This processing—known as first-pass metabolism—can raise inflammatory markers, triglycerides, and blood clotting proteins, which may partially explain the negative side effects observed in the study.
Today, transdermal estrogen (absorbed through the skin via patches or gels) is a popular alternative. It may avoid increases in triglycerides or inflammation, according to more recent studies, and might offer safer cardiovascular outcomes.
Despite these encouraging findings, Dr. Nudy emphasized that hormone therapy is not currently FDA-approved to prevent heart disease or stroke. Still, this new evidence may help refine how hormone therapy is considered and personalized, especially for women who are generally healthy, younger than 60, and within 10 years of starting menopause.
Before starting hormone therapy, Nudy recommends that women undergo a cardiovascular risk assessment—even if they have no history of heart problems. This extra step can help doctors tailor treatment choices, whether to manage menopause symptoms or support long-term health goals.
Bottom Line
- Hormone therapy can improve several cardiovascular health markers, including reducing a hard-to-treat genetic risk factor: lipoprotein(a)
- Benefits were observed in both estrogen-only and estrogen-plus-progesterone treatments over a six-year period
- Some side effects such as increased triglycerides and blood clotting proteins were also noted
- Transdermal estrogen may offer similar benefits with fewer risks
This study adds to growing evidence that for some women, hormone therapy during menopause—especially when started early—may offer more benefits than risks, particularly for heart health. As always, decisions about hormone therapy should be individualized and made in close consultation with a trusted healthcare provider.
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The research findings can be found in Obstetrics & Gynecology.
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