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Estrogen is the primary female sex hormone. It plays critical roles in sexual and reproductive health. Evidence suggests that estrogen is protective against cardiovascular disease. Findings from a recent review suggest that estrogen protects women from severe outcomes associated with COVID-19.

COVID-19, the disease caused by the SARS-CoV-2, is characterized by fever, cough, shortness of breath, and indications of widespread respiratory system involvement. Evidence indicates that SARS-CoV2 can attack other organ systems, as well, including the cardiovascular system. Men are at greater risk for severe outcomes with COVID-19 illness.

SARS-CoV2 exploits the angiotensin-converting enzyme 2, or ACE2, receptor to gain entry into cells. The ACE2 receptor is widely distributed among the body’s tissues but is particularly abundant in lung alveolar epithelial cells and small intestine enterocytes.

The authors of the review summarized data describing sex-specific differences in ACE2 expression and activity, which may be due to differences in estrogen exposure or differences in the mixture of sex hormones present in women versus men. The authors pointed out that the ACE2 gene is located on the X-chromosome, so differences in ACE2 expression levels between women and men might be related to the number of X chromosomes present, with two in women and two in men.

The findings presented in the review raise many questions about the role of estrogen in protection against COVID-19, some of which may be addressed in ongoing trials involving short-term treatment of male COVID-19 patients with estrogen or progesterone.

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