COMMENTARY

Sex- and Gender-Informed Medicine: Why It Matters

JoAnn E. Manson, MD, DrPH

Disclosures

September 14, 2020

This transcript has been edited for clarity.

Hello. This is Dr JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women's Hospital.

I'd like to talk with you about and bring to your attention to two recent papers that address the critically important role of sex and gender in health and disease, including the impact on disease incidence, clinical manifestations, and response to treatment. One of the papers was published very recently in The Lancet, and the other paper was published earlier this year in JAMA Internal Medicine from our research group in the Connors Center at Brigham and Women's Hospital.

Both papers review the growing evidence that biological sex and sociocultural factors encompassed by gender, including lifestyle factors, social determinants of health, and interactions with healthcare systems, are critically important in influencing health and are also important to precision medicine. After all, precision medicine begins with understanding the role of sex and gender in health.

These two papers discuss several domains, including genetic and chromosomal differences, epigenetic programming, gene expression, sex steroid hormones (including exposure to hormones in utero and throughout the life course), and immune function differences.

It's well known that there are several differences between men and women in terms of prevalence risk for various diseases. Women are much more susceptible to autoimmune disorders, such as lupus and rheumatoid arthritis, whereas men are more likely to have autism and attention deficit disorders. But even within certain diseases, there are major differences that are due to sex and gender.

I'm going to focus on heart disease and COVID-19. In terms of heart disease, we know that women are diagnosed at older ages and are more likely to experience a delay in diagnosis. There are differences in symptom presentation. Although chest pain is very common in both sexes, women are more likely to have pain in the neck or jaw, nausea, and shortness of breath.

Women are less likely to receive evidence-based interventions in prevention, such as statins. They are less likely to receive reperfusion after a myocardial infarction (MI), and they are more likely to die after MI. Women are more susceptible to heart failure with preserved ejection fraction, and men are more susceptible to heart failure with reduced ejection fraction.

Women are more likely to have microvascular dysfunction and reduced coronary reserve, whereas men are more likely to have obstructive coronary artery disease. In the context of atrial fibrillation, women are more likely to have stroke and to die of stroke.

With COVID, it's been recognized that men are more likely to have severe illness and to die of COVID. They are more likely to develop acute respiratory distress and to require mechanical ventilation.

It's been proposed that some of these differences may relate to sex steroid hormones. Estrogen and progesterone may have some anti-inflammatory effect in tamping down inflammation. This knowledge is being harnessed in some randomized clinical trials going on now to look at whether estrogen and progesterone administration can reduce the severity of COVID illness.

There is also some evidence that women have a more robust response to immunizations. It will be important to look at response to vaccines related to COVID in the future, and whether there is any way to harness information about these sex differences to improve vaccination response in both sexes.

Overall, these papers highlight the critically important role of sex and gender in improving patient care and the practice of precision medicine, and also the role of sex and gender knowledge and research in improving population health.

Thank you so much for your attention. This is JoAnn Manson.

Dr JoAnn Manson is a professor of medicine at Harvard Medical School and chief of the Division of Preventive Medicine at Brigham and Women's Hospital in Boston, Massachusetts.

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