For many years, doctors and scientists have known that women tend to have lower rates of heart disease than men before menopause.
However, after menopause, the risk of heart disease in women rises sharply. This increase often happens even when there are no major lifestyle changes such as poor diet, smoking, or lack of exercise.
Researchers have long suspected that estrogen, one of the main female hormones, plays an important protective role.
But exactly how estrogen protects the body—and what happens when estrogen levels fall—has remained a mystery.
Now, a new study from the University of Texas at Arlington has uncovered important clues. The research suggests that the liver and the immune system may play a major role in explaining why heart disease risk increases after menopause.
The study was led by Subhrangsu S. Mandal, professor of chemistry and biochemistry, and Linda Perrotti, professor of psychology. Their findings were published in the scientific journal Scientific Reports.
The researchers discovered that estrogen helps regulate several important systems inside the body. These include liver health, inflammation control, cholesterol balance, and the way the body processes energy. When estrogen levels drop, many of these systems begin to work less effectively.
The liver is especially important because it helps control cholesterol, remove toxins, process nutrients, and manage fats in the bloodstream. According to the researchers, low estrogen levels appear to trigger harmful changes in the liver that may increase the risk of cardiovascular disease.
Professor Mandal explained that estrogen and cholesterol have been a long-standing focus of his laboratory’s work. Scientists already knew that estrogen helps control cholesterol levels in the blood. When estrogen decreases, cholesterol often rises, increasing the risk of clogged arteries and heart disease.
The new research aimed to better understand the chain reaction that happens after estrogen levels fall.
The researchers found that estrogen deficiency led to more inflammation in the liver and unhealthy changes in cholesterol metabolism. Inflammation is the body’s natural defense response, but when inflammation becomes chronic, it can damage tissues and organs over time.
One of the most important discoveries involved an enzyme called indoleamine 2,3-dioxygenase-1, or IDO1. This enzyme is already known in cancer research because it affects how the immune system works.
The study found that low estrogen levels increased IDO1 activity in the liver. This appears to interfere with how immune cells manage nutrients and cholesterol.
Professor Mandal explained that when IDO1 becomes activated, immune cells lose some of their ability to remove cholesterol properly. This may contribute to dangerous cholesterol buildup and increased heart disease risk.
The researchers also found evidence that the effects were not limited to the liver alone. Blood tests showed signs of inflammation throughout the body, suggesting that estrogen loss may trigger a widespread inflammatory response affecting multiple organs and systems.
According to the researchers, this means menopause-related hormone changes may affect the entire body’s metabolism, not just reproductive health.
The findings may also help explain why hormonal imbalance is linked to many other medical conditions besides heart disease. Low estrogen and hormonal disruption have previously been connected to conditions such as osteoporosis, weight gain, infertility, polycystic ovary syndrome, endometriosis, autoimmune disorders, and nonalcoholic fatty liver disease.
The study also showed that restoring estrogen reversed many of the harmful changes seen in the body. This suggests that estrogen-related pathways may be important targets for future treatments designed to protect women’s heart health after menopause.
However, the researchers cautioned that hormone replacement therapy is not a perfect solution.
Although hormone therapy can improve liver and cardiovascular function, it may also increase the risk of certain cancers, including breast and ovarian cancer. Because of these risks, many scientists are searching for safer alternatives that provide the benefits of estrogen without the dangers linked to hormone treatment.
Professor Mandal said the new findings open the door to possible new treatments that target inflammation and metabolism directly instead of replacing hormones themselves.
For example, future medicines might focus on blocking harmful pathways involving enzymes like IDO1. Researchers hope this could eventually lead to simple pill-based treatments that reduce inflammation, improve cholesterol control, and protect heart health in women after menopause.
The study is important because cardiovascular disease remains one of the leading causes of death among women worldwide. While awareness has improved in recent years, heart disease in women is still sometimes underdiagnosed or overlooked.
The findings also highlight how menopause affects much more than reproductive health. Hormonal changes can influence the immune system, metabolism, liver function, cholesterol balance, and overall inflammation throughout the body.
The research appears promising because it connects several biological systems together and helps explain long-standing questions about women’s heart health. However, more studies will still be needed before new treatments become available.
Scientists must now determine whether targeting pathways such as IDO1 can safely reduce heart disease risk without causing unwanted side effects.
Even so, the study provides a valuable new understanding of how estrogen protects the body and why losing it can create widespread health changes after menopause.
If you care about heart health, please read studies about top 10 foods for a healthy heart, and how to eat right for heart rhythm disorders.
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