The impact a patient’s sex can have on disease has come into sharp focus during the COVID-19 pandemic. While the number of confirmed cases is about the same for males and females, men have been dying at significantly higher rates than women since the beginning of the global health crisis.

This gender gap prompted a pilot study at Cedars-Sinai published earlier this year. In a study led by Sara Ghandehari, MD, COVID-19 patients receiving the female hormone progesterone had fewer days in the hospital and less need for supplemental oxygen or mechanical ventilation.

Sex matters. And the impact sex and gender can have on healthcare—from basic research to drug development and patient outcomes—was explored at Cedars-Sinai’s third annual symposium of the Center for Research in Women’s Health and Sex Differences (CREWHS). This year’s virtual science meeting was held on Oct. 15 and focused on precision medicine.

"The goal of improving women’s health is fueled by a critical knowledge deficit in understanding the role sex and gender plays in medicine, from the lab bench to the patient’s bedside," said Sarah Kilpatrick, MD, PhD, professor and Helping Hand of Los Angeles Chair in Obstetrics and Gynecology at Cedars-Sinai.

Kilpatrick, one of the co-founders of CREWHS, opened the symposium by emphasizing the need to address the impact of critical choices in basic research where often only male cells or lab animals are used, to the underrepresentation of women in clinical trials.

"Precision medicine is a vital tool for improving women’s health and health outcomes by filling the knowledge gap about the impact of sex and gender on medical science and care that persists today," said Kilpatrick.

The symposium’s keynote speaker was Londa Schiebinger, PhD, director of the Gendered Innovations in Science, Health & Medicine, Engineering and Environment Project at Stanford University. Schiebinger is a leading international authority on gender and science and her work has been devoted to teasing apart analytically distinct but interlocking pieces of the gender and science puzzle.

"Integral to biomedical research and the development pipeline for drugs, devices, and biologics are preclinical studies that start with nonhuman animals and cell cultures, however most biomedical research has been conducted with inadequate consideration of sex—the most evolutionarily well-conserved of differences in biology," said Schiebinger.

In 2016, the National Institutes of Health (NIH) moved to address the problem by requiring sex as a biological variable be factored into all funded research.

Schiebinger discussed one of the most costly and harmful fallouts of the invisibility of the female sex in research—drug recalls.

"Ten drugs have been withdrawn from the U.S. market because of life threatening health effects; eight of those posed greater threats to women. Not only did these drugs cost billions of dollars to develop, but when they fail, they cause human death and suffering. Doing research right can save lives and money; doing it wrong comes at a high cost," said Schiebinger.

The impact of sex and gender in the study of pain and the AI development of "wearables" used increasingly to collect health information and assess risk were also explored by Schiebinger.

"In a study investigating if data collected from smartphones could produce digital biomarkers for Parkinson’s disease, researchers found that only 18% of the data gathered came from women. An algorithm trained on a data set that overrepresents male patients, it may only lead to better detection of symptoms manifested in men."

CREWHS provides $30,000 grants to investigators researching women’s health or sex differences.

In addition to the keynote speaker, the 2020 Award Winners presented an update on their research, which is funded entirely by philanthropic donors including the William H. Donner Foundation and Louis B. Mayer Foundation.

Alexandra Moser, PhD, is investigating interactions between sex and APOE gene in Alzheimer’s Disease.  Moser is a postdoctoral scientist in the Regenerative Medicine Institute. Clinical psychologist Eynav E. Accortt, PhD, discussed her work to identify protein signatures that may produce biomarkers for estimating risk for perinatal mood and anxiety disorders (PMAD).

Caroline Jefferies, PhD, associate professor in the department of Medicine, Rheumatology and Biomedical Sciences, and the scientific director for CREWHS, announced three new research grants for 2021.

• Ritchie Ho, PhD, assistant professor of Biomedical Sciences, is investigating sex differences in Amyotrophic Lateral Sclerosis (ALS).
• Nethika Ariyasinghe, PhD, MD, Smidt Heart Institute, is researching the role of female hormones in pregnancy related aortic damage and rupture.
• Pooja A. Nawathe, MD, associate director of Congenital Cardiac Intensive Care, is studying whether the sex of mannequins used in CPR training affect resuscitation rates of women, following sudden cardiac arrest.

A lively panel discussion about a precision medicine approach to women’s health research followed the awards announcement and was led by Sarah Parker, PhD, associate director, Proteomics and Metabolic in the Advanced Biosystems Research Institute. The participants featured Jennifer Van Eyk, PhD, director of the Advanced Clinical Biosystems Research Institute in the Smidt Heart Institute, Clive Svendsen, PhD, executive director of the Regenerative Medicine Institute and professor of Biomedical Sciences and Medicine and Ananth Karumanchi, MD, director of Nephrology.

"Over the past few years, thanks to leadership from CREWHS, we've identified this sex and gender bias in research and healthcare and it's a problem many investigators are aware of now. We have a lot of medical science expertise at Cedars-Sinai, and I think we can become a national leader in this space," said Karumanchi.

Svendsen agreed, calling for the work to be an institutional priority.

"I think we should double down on what we are already accomplishing by incorporating the significance of sex and gender in research design, outcomes and patient care," he said. "I think we need more of just these kinds of collaborations soon."

Added Van Eyk: "Across all disease investigation there has to be the component of addressing sex and gender as a variable. It has to become a major part of the innovation center and the new department of Computational Biomedicine.  We have to push collectively."