Fig. 3.

The roles of sex hormones in COVID-19. The differences in COVID-19 severity between genders have directed studies toward the roles of sex hormones in this context. Based on sex hormones, the susceptibility to SARS-CoV-2 has a range from “higher androgen” to “higher estrogen”; with this regard, men are more susceptible to experience the severe types of COVID-19 and women seem to show much milder disease. This difference is interestingly observed in ADT-treated men and menopausal women who have different levels of androgen and estrogen compared with non-treated men and non-menopausal women. Higher androgen results in neutrophil infiltration and higher expression of TMPRSS2 which are related to the severity of the disease. Higher estrogen, on the other hand, induces upregulation of TLR-7, TLR-8, CD40L, CXCR3, and IFNs that consequently promotes immune responses. Estrogen can also hamper inflammation via downregulation of IL-6, IL-8, IL-2R, and TNF-a.