Can Hormone Therapy Improve Heart Health in Women Going Through Menopause?

The decision on whether to start hormone therapy during menopause, the phase of life that follows puberty and during which a woman’s menstrual cycle comes to an end, is a hotly debated topic. While hormone therapy, which involves replacing hormones previously produced by the body with synthetic drugs, is recommended to alleviate unpleasant symptoms such as hot flashes and night sweats, according to Matthew Nudy, assistant professor of medicine at Penn State College of Medicine, there is uncertainty about the long-term effects of hormone therapy, particularly on cardiovascular health.

However, a new study led by Nudy has found that long-term use of estrogen-based hormone therapies may have positive effects on heart health. A multidisciplinary team analyzed data from clinical trials on hormone therapy that were part of the Women’s Health Initiative (WHI) — a long-term national study focusing on women in menopause — and found that estrogen-based hormone therapy improved biomarkers for cardiovascular health over time. In particular, the study suggests that hormone therapy may lower levels of lipoprotein(a), a genetic risk factor associated with a higher risk of heart attacks and strokes.

Oral Hormone Therapy May Improve Cardiovascular Health Biomarkers in Postmenopausal Women Over Time

According to Nudy, the study contributes to the understanding of the complex interactions between hormone therapy and heart health and provides additional guidance for patients and physicians. “Opinion on whether hormone therapy is safe for menopausal women, particularly with regard to cardiovascular disease, has long been divided,” said Nudy. “More recently, however, we are recognizing that hormone therapy is safe for younger menopausal women who have been in menopause for less than ten years, are generally healthy, and have no known cardiovascular disease.”

Hot flashes and night sweats are symptoms commonly associated with menopause, but the hormonal changes that accompany this stage of life bring with them another major change—an increased risk of cardiovascular disease. The decline in the hormone estrogen can lead to changes in cholesterol levels, blood pressure, and plaque formation in the blood vessels, which increases the risk of heart attacks and strokes. The research team wanted to investigate the long-term effects of hormone therapy on cardiovascular biomarkers, which had not yet been evaluated over a longer period of time. Previous research in this area has mainly focused on short-term effects.

Here, the team analyzed biomarkers related to cardiovascular health in a subgroup of women who had participated in a clinical trial of oral hormone therapy as part of the WHI over a period of six years. The participants were randomly assigned to one of two groups—one group received estrogen alone and the other received estrogen plus progesterone. They were between the ages of 50 and 79 at the time of assignment and were postmenopausal. They provided blood samples at the start of the study and after one, three, and six years. A total of 2,696 women were analyzed, representing about 10% of the total study participants.

The research team found that hormone therapy had a positive effect over time on most biomarkers in both the estrogen-alone group and the estrogen-plus-progesterone group. Levels of LDL cholesterol, the so-called “bad” cholesterol, fell by about 11%, while total cholesterol and insulin resistance decreased in both groups. HDL cholesterol, the so-called “good” cholesterol, increased by 13% in the estrogen-only group and by 7% in the estrogen and progesterone group. However, triglycerides and coagulation factors, proteins in the blood that contribute to blood clot formation, increased. Even more surprising to the research team was that lipoprotein (a) levels, a type of cholesterol molecule, decreased by 15% in the estrogen-only group and by 20% in the estrogen plus progesterone group. Unlike other types of cholesterol, which can be influenced by lifestyle and health factors such as diet and smoking, the concentration of lipoprotein(a) is primarily determined by genetics, according to Nudy. Patients with high lipoprotein(a) concentrations have an increased risk of heart attacks and strokes, especially at a younger age. There is also an increased risk of aortic stenosis, in which calcium deposits build up on a heart valve.

Test to Assess Risk of Cardiovascular Disease

“As a cardiologist, this finding is the most interesting aspect of this study,” said Nudy. According to the researcher, there are currently no drugs approved by the Food and Drug Administration (FDA) for lowering lipoprotein(a). Here, the experts essentially found that oral hormone therapy significantly reduces lipoprotein(a) concentrations in the long term. When the research team examined the results by self-reported ethnic groups, they found that the decline in lipoprotein(a) concentrations was more pronounced in participants of Native American or Alaska Native descent and Asian or Pacific Islander descent, at 41% and 38%, respectively. Nudy said it was unclear why the declines were greater in these groups, but the team hoped to investigate this further in future research studies. He pointed out that the women in the clinical trial received estrogen therapy with conjugated equine estrogens, a commonly prescribed form of oral estrogen therapy. Before oral hormone preparations are absorbed by the body, they are processed in the liver in a process called first-pass metabolism. This process could increase inflammation markers, which could explain the increase in triglycerides and clotting factors.

According to the researcher, there are now common forms of estrogen hormone therapy, such as transdermal estrogen, which is administered through the skin. Recent studies have found that transdermal estrogen does not increase triglyceride levels, coagulation factors, or inflammatory markers. For women considering hormone therapy during menopause, Nudy recommends an assessment of their risk for cardiovascular disease, even if they have not had a heart attack or stroke and have not been diagnosed with cardiovascular disease. This gives healthcare providers more information to find the best option for treating menopausal symptoms. “Currently, hormone therapy is not approved by the FDA to reduce the risk of coronary heart disease or stroke,” said Nudy.