High blood pressure, or hypertension, affects more than one billion people worldwide and is a leading cause of heart disease and stroke. For decades, researchers have observed that premenopausal women are less likely to develop high blood pressure than men or postmenopausal women. Researchers have known for years that estrogen is the deciding factor, but exactly how it offers this protection has remained unclear.  

New research from the University of Waterloo helps answer that question. 

Using a mathematical model of the cardiovascular and kidney systems, Waterloo researchers have identified which of estrogen’s many effects play the biggest role in protecting against hypertension. Their findings suggest that estrogen’s ability to relax and widen blood vessels, known as vasodilation, is the key factor.  

The research also points to more effective treatment options for women after menopause, when estrogen levels naturally decline.  

“Estrogen is often thought of only in terms of reproductive health, but it plays a much broader role in how the body functions,” said Anita Layton, Canada 150 Research Chair Laureate in Mathematical Biology and Medicine and professor of Applied Mathematics. “It affects how blood vessels respond, how the kidneys regulate fluids and how different systems communicate with one another. What we found is that its impact on blood vessels is especially important for regulating blood pressure.”  

Layton’s team has worked for years on their award-winning mathematical model of women’s kidneys and the cardiovascular system. This model allows far more flexibility and precision than scientists would have working in a lab or with human subjects. “We can turn on one effect, then another, and see exactly how each one affects the body,” Layton said. While no mathematical model is perfect, Layton’s model is based on existing laboratory data and its results are continually validated when compared to real-world observations, suggesting its accuracy and reliability.  

Between the two popular anti-hypertensive drugs, the model predicted that angiotensin receptor blockers will be more effective than angiotensin converting enzyme inhibitors in treating women with hypertension, even after their estrogen levels decline post-menopause.  

“For too long, women’s health, especially older women’s health, has been overlooked by medicine,” Layton said. “Understanding how age and sex affect the body and, therefore, treatment, is an equity issue.”  

The research reflects the University of Waterloo’s Health Futures focus, bringing together experts in mathematics, engineering and health sciences to develop more equitable, technology-enabled approaches to improving health outcomes. 

The research, “Modulation of blood pressure by estrogen: A modeling analysis,” appears in Math Biosci.  

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