Experimental results show that estrogen upregulates the expression of TMPRSS2 through the ERb2/Src-IGF-1R/NFκB pathway, which means that AIs may inhibit the production of estrogen and subsequent TMPRSS2 expression through this pathway rather than androgen/AR signaling, to promote the upregulation of TMPRSS2 and exert potent anti-COVID-19 activity (36, 78). The gene discussed is TMPRSS2; the disease is COVID-19.