discoveries magazine

Women’s Health and Sex Differences: Research Update

A digital illustration of women from a variety of backgrounds and ethnicities.

In 2019, physician leaders at Cedars-Sinai assembled the Center for Research in Women’s Health and Sex Differences (CREWHS) to magnify efforts to undo medicine’s pervasive gender bias. 

Since then, the center has supported Cedars-Sinai investigators with 12 pilot grants that fund the study of female-focused conditions and concerns, such as postpartum depression and the impact of hormones on injury and disease. And just as significantly, the center fosters synergy and the sharing of ideas across the institution, says Caroline Jefferies, PhD, scientific director of CREWHS.

"The cumulative effect of this effort—the resulting collaboration and conversation—fosters a science-based team approach that has changed and inspired sex-based research at Cedars-Sinai," says Dr. Jefferies. "We’re creating a paradigm shift in the way we understand sex differences in healthcare."

The center’s impact is further exemplified by three recently awarded National Institutes of Health (NIH) grants to CREWHS-affiliated projects that explore sex-based mechanisms impacting health and disease.

Sex differences in lupus and heart disease

A 2021 NIH grant awarded to Dr. Jefferies funds work that aims to shed light on whether the underlying causes of cardiovascular disease, which is highly prevalent in lupus patients, are similar between men and women.

Dr. Jefferies says the study was inspired by previous work by rheumatologist Mariko Ishimori, MD, and C. Noel Bairey Merz, MD, the Irwin and Sheila Allen Chair in Women’s Heart Research, director of the Barbra Streisand Women’s Heart Center at the Smidt Heart Institute, and a founding CREWHS leader. In a 2011 paper published in JACC: Cardiovascular Imaging, Dr. Ishimori and Dr. Bairey Merz studied cardiac MRIs and found that cardiac ischemia was more common in lupus patients. With funding from the Department of Defense, the physicians analyzed cardiac MRIs and immune function to assess how immune cells drive ischemic heart disease.

Dr. Jefferies now hopes to understand how metabolism impacts the functionality of immune cells, how metabolism could drive the progression of lupus differently in women and men, and how disease mechanisms relate to the development of heart disease. The study will also address whether vitamin D levels contribute to immune cell reprogramming across genders.

Fetal development of immune disease across sex

In 2020, Margareta Pisarska, MD, director of the Division of Reproductive Endocrinology and Infertility, was awarded an NIH grant to study how and why biological sex impacts the development of immune function.

Immune system dysfunction develops at the maternal-fetal interface during the first trimester of pregnancy. In previous studies published in the journals Biology of Sex Differences and The Journal of Clinical Endocrinology and Metabolism, Dr. Pisarska and colleagues found that gene expression in first trimester placentas may be influenced by sex-specific hormones produced by the fetus. 

Now, she and her study co-authors hope to understand more about the complicated interplay between maternal and fetal cells and hormones. This relationship can have a lifelong impact, contributing to autoimmune diseases and asthma, and the team seeks to understand how that interplay differs by fetal sex.

Dr. Pisarska hopes to identify sex-unique regulators of immune dysfunction that can ultimately guide treatment of immunologic diseases. 

Female hormones and aortic rupture

Cardiovascular disease is a leading cause of death across genders, though conditions may manifest differently in men and women. Men are more prone to aortic aneurysm, but women who suffer severe aneurysms experience worse outcomes. 

Based partly on initial data achieved with a CREWHS pilot grant, Sarah Parker, PhD, a research scientist in the Smidt Heart Institute, was awarded a 2022 NIH grant to study how sex impacts arterial cells to influence such disparities.

In both animal models and human stem cell-derived muscle cells, Dr. Parker is examining cardiac development by gender in hopes that the findings will lead to better sex-specific interventions for women and men with heart disease.