Scientists have long known that women usually have lower rates of heart disease than men before menopause.
However, after menopause, women’s risk of heart disease rises sharply.
This increase has puzzled researchers for decades because it often happens even when lifestyle habits such as diet and exercise stay the same.
A new study from the University of Texas at Arlington now offers important clues about why this happens.
The research suggests that estrogen, the liver, and the immune system work closely together to protect women’s cardiovascular health. When estrogen levels fall after menopause, this protective system may begin to break down.
The study was led by researchers Subhrangsu S. Mandal, professor of chemistry and biochemistry, and Linda Perrotti, professor of psychology. Their findings were published in the scientific journal Scientific Reports.
Estrogen is one of the body’s most important female hormones. It affects many organs and systems, not only reproduction. Scientists have known for years that estrogen helps control cholesterol levels and supports heart health, but the exact biological mechanisms remained unclear.
The new research focused on how estrogen affects inflammation, metabolism, and liver function. The liver plays a major role in managing fats and cholesterol in the body. It also helps process nutrients, remove toxins, and regulate energy use.
The researchers found that when estrogen levels drop, important systems inside the liver become disrupted. This can lead to inflammation, unhealthy cholesterol changes, and other metabolic problems linked to heart disease.
According to Professor Mandal, the research team wanted to better understand the chain reaction that begins when estrogen disappears after menopause.
The study identified one particularly important enzyme called indoleamine 2,3-dioxygenase-1, or IDO1. This enzyme is already well known in cancer research because it influences how immune cells behave.
The researchers discovered that low estrogen levels increased IDO1 activity in the liver. This change appears to interfere with how immune cells process cholesterol and nutrients.
When IDO1 becomes too active, immune cells may lose their ability to clear cholesterol efficiently. Over time, this could contribute to the buildup of harmful cholesterol inside blood vessels, increasing the risk of cardiovascular disease.
The study also found evidence that estrogen loss affects the entire body, not just the liver. Blood tests showed signs of widespread inflammation, suggesting that menopause may trigger a systemwide inflammatory response.
Inflammation is a natural defense mechanism used by the body to fight infections and repair damage. However, long-term inflammation can gradually damage tissues and organs. Chronic inflammation has already been linked to many conditions including heart disease, diabetes, arthritis, and Alzheimer’s disease.
The findings help explain why menopause may affect so many areas of health at once. Hormonal changes after menopause are linked to osteoporosis, weight gain, fatty liver disease, infertility, polycystic ovary syndrome, endometriosis, autoimmune disorders, and cardiovascular disease.
The researchers also found that restoring estrogen reversed many of the harmful biological changes. This suggests that estrogen-related pathways may be important targets for future treatments.
However, the researchers stressed that hormone replacement therapy is not a perfect solution. While estrogen therapy may improve heart and liver function, it may also increase the risk of breast cancer and ovarian cancer in some women.
Because of these risks, scientists are searching for safer alternatives that could provide similar health benefits without directly replacing hormones.
Professor Mandal said future treatments may focus on targeting inflammatory and metabolic pathways such as IDO1 instead of giving patients estrogen itself.
Researchers hope this approach could eventually lead to simple medications that reduce inflammation, improve cholesterol control, and lower heart disease risk after menopause.
The findings are important because cardiovascular disease remains one of the leading causes of death among women worldwide. Heart disease in women has sometimes received less attention than in men, even though it causes millions of deaths each year.
The study also highlights how menopause affects much more than reproductive health. Hormonal changes appear to influence metabolism, immunity, liver function, and inflammation throughout the body.
The research seems especially valuable because it connects several biological systems together and provides a clearer explanation for the rise in heart disease risk after menopause. Still, more studies will be needed before new therapies become available.
Scientists must now determine whether targeting enzymes like IDO1 can safely reduce inflammation and improve heart health without causing serious side effects.
Even so, the findings provide a promising new direction for women’s health research and may eventually lead to safer treatments that protect women’s hearts after menopause.
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