Scientists uncover the link between estrogen and heart health in women

A new preclinical study from Monash University has uncovered the role of the female sex hormone estrogen in protecting the hearts of women with high blood pressure—a link that, until now, has not been fully understood by scientists.

The study, led by the Monash Institute of Pharmaceutical Sciences (MIPS) and published in Communications Biology, identified that estrogen increases the levels of a natural protein called “annexin-A1” (ANXA1) in female mice. The MIPS team had previously shown that ANXA1 plays a critical role in regulating blood pressure.

In the current study, the researchers discovered that when ANXA1 is missing, high blood pressure leads to more severe damage in the heart and main blood vessels, especially in females.

The findings suggest that the estrogen-ANXA1 association plays an important role in protecting women’s hearts from damage caused by high blood pressure. This discovery could pave the way for new treatments, such as medicines that mimic ANXA1—explicitly designed to improve heart health in women.

First author and Monash University Honorary Fellow Dr. Jaideep Singh said this research helps explain why women may experience heart disease differently from men, especially when they have high blood pressure.

“Our study reveals a biological link between the female hormone estrogen and the protein ANXA1 that protects the heart—something scientists didn’t fully understand before. Essentially, we found that estrogen helps increase ANXA1 protein, and when ANXA1 is missing, the heart is more vulnerable to damage due to poor mitochondrial function, the body’s energy system,” Dr. Singh said.

This discovery is an important step toward developing heart disease treatments tailored specifically for women, addressing a gap that has been overlooked in medical research for a long time.

“We’re really excited about what this discovery could mean for future new treatments that enhance ANXA1, providing better protection for women with high blood pressure,” Dr. Singh said. “These therapies might help prevent serious problems like heart failure by focusing on the unique ways women’s hearts and blood vessels work. It also highlights the importance of doctors considering sex differences when deciding how to treat heart disease.”

Dr. Chengxue Helena Qin, co-lead author from MIPS said, “There has been a major gap in understanding how high blood pressure and its treatments affect men and women differently. Clinical trials have historically overlooked sex-specific responses, leaving women underrepresented and underserved.”

“There’s an urgent need to uncover the distinct mechanisms driving hypertension and its cardiovascular complications in females—an underexplored population. Closing this knowledge gap is essential for developing more effective, sex-specific treatments,” Dr. Qin said.

“Our goal is to move toward studying how estrogen controls ANXA1 in humans to see if it works the same way as in animals. This process will involve testing new medicines that boost ANXA1 in animal studies to check if these can protect the heart from damage caused by high blood pressure.

“Additionally, our team will investigate whether this protective system plays a role in other heart conditions that impact men and women differently.”

Professor David Greening, joint senior author and Head of Molecular Proteomics at the Baker Heart and Diabetes Institute, said, “This study reveals the power of proteomics—the large-scale study of proteins—in advancing our understanding of the causes of heart and blood vessel diseases. It also provides detailed molecular insights into why men and women experience these conditions differently, helping us move toward more precise and targeted therapies for high blood pressure and related heart problems.”

Ultimately, the team aims to advance these findings toward clinical testing, particularly to benefit women with high blood pressure.

A new preclinical study from Monash University has uncovered the role of the female sex hormone estrogen in protecting the hearts of women with high blood pressure—a link that, until now, has not been fully understood by scientists.

The study, led by the Monash Institute of Pharmaceutical Sciences (MIPS) and published in Communications Biology, identified that estrogen increases the levels of a natural protein called “annexin-A1” (ANXA1) in female mice. The MIPS team had previously shown that ANXA1 plays a critical role in regulating blood pressure.

In the current study, the researchers discovered that when ANXA1 is missing, high blood pressure leads to more severe damage in the heart and main blood vessels, especially in females.

The findings suggest that the estrogen-ANXA1 association plays an important role in protecting women’s hearts from damage caused by high blood pressure. This discovery could pave the way for new treatments, such as medicines that mimic ANXA1—explicitly designed to improve heart health in women.

First author and Monash University Honorary Fellow Dr. Jaideep Singh said this research helps explain why women may experience heart disease differently from men, especially when they have high blood pressure.

“Our study reveals a biological link between the female hormone estrogen and the protein ANXA1 that protects the heart—something scientists didn’t fully understand before. Essentially, we found that estrogen helps increase ANXA1 protein, and when ANXA1 is missing, the heart is more vulnerable to damage due to poor mitochondrial function, the body’s energy system,” Dr. Singh said.

This discovery is an important step toward developing heart disease treatments tailored specifically for women, addressing a gap that has been overlooked in medical research for a long time.

“We’re really excited about what this discovery could mean for future new treatments that enhance ANXA1, providing better protection for women with high blood pressure,” Dr. Singh said. “These therapies might help prevent serious problems like heart failure by focusing on the unique ways women’s hearts and blood vessels work. It also highlights the importance of doctors considering sex differences when deciding how to treat heart disease.”

Dr. Chengxue Helena Qin, co-lead author from MIPS said, “There has been a major gap in understanding how high blood pressure and its treatments affect men and women differently. Clinical trials have historically overlooked sex-specific responses, leaving women underrepresented and underserved.”

“There’s an urgent need to uncover the distinct mechanisms driving hypertension and its cardiovascular complications in females—an underexplored population. Closing this knowledge gap is essential for developing more effective, sex-specific treatments,” Dr. Qin said.

“Our goal is to move toward studying how estrogen controls ANXA1 in humans to see if it works the same way as in animals. This process will involve testing new medicines that boost ANXA1 in animal studies to check if these can protect the heart from damage caused by high blood pressure.

“Additionally, our team will investigate whether this protective system plays a role in other heart conditions that impact men and women differently.”

Professor David Greening, joint senior author and Head of Molecular Proteomics at the Baker Heart and Diabetes Institute, said, “This study reveals the power of proteomics—the large-scale study of proteins—in advancing our understanding of the causes of heart and blood vessel diseases. It also provides detailed molecular insights into why men and women experience these conditions differently, helping us move toward more precise and targeted therapies for high blood pressure and related heart problems.”

Ultimately, the team aims to advance these findings toward clinical testing, particularly to benefit women with high blood pressure.