Are sex hormones promising candidates to explain sex disparities in the COVID-19 pandemic?

Emerging evidence suggests that the novel Coronavirus disease-2019 (COVID-19) is deadlier for men than women both in China and in Europe. Male sex is a risk factor for COVID-19 mortality. The meccanisms underlying the reduced morbidity and lethality in women are currently unclear, even though hypotheses have been posed (Brandi and Giustina in Trends Endocrinol Metab. 31:918–27, 2020). This article aims to describe the role of sex hormones in sex- and gender-related fatality of COVID-19. We discuss the possibility that potential sex-specific mechanisms modulating the course of the disease include both the androgen- and the estrogen-response cascade. Sex hormones regulate the respiratory function, the innate and adaptive immune responses, the immunoaging, the cardiovascular system, and the entrance of the virus in the cells. Recommendations for the future government policies and for the management of COVID-19 patients should include a dimorphic approach for males and females. As the estrogen receptor signaling appears critical for protection in women, more studies are needed to translate the basic knowledge into clinical actions. Understanding the etiological bases of sexual dimorphism in COVID-19 could help develop more effective strategies in individual patients in both sexes, including designing a good vaccine.