Global Sex Disparity of COVID-19: A Descriptive Review of Sex Hormones and Consideration for the Potential Therapeutic Use of Hormone Replacement Therapy in Older Adults

The 2019-2020 SARS-related coronavirus-2 (SARS-CoV-2) pandemic has brought unprecedented challenges to healthcare sectors around the world. As of November 2020, there have been over 64 million confirmed cases and approaching 2 million deaths globally. Despite the large number of positive cases, there are very limited established standards of care and therapeutic options available. To date, there is still no Food and Drug Administration (FDA) approved vaccine for COVID-19, although there are several options in various clinical trial stages. Herein, we have performed a global review evaluating the roles of age and sex on COVID-19 hospitalizations, ICU admissions, deaths in hospitals, and deaths in nursing homes. We have identified a trend in which elderly and male patients are significantly affected by adverse outcomes. There is evidence suggesting that sex hormone levels can influence immune system function against SARS-CoV-2 infection, thus reducing the adverse effects of COVID-19. Since older adults have lower levels of these sex hormones, we therefore speculate, within rational scientific context, that sex steroids, such as estrogen and progesterone, needs further consideration for use as alternative therapeutic option for treating COVID-19 elderly patients. To our knowledge, this is the first comprehensive article evaluating the significance of sex hormones in COVID-19 outcomes in older adults.