The relevance of estrogen signaling in counteracting NAFLD has been outlined by several pre-clinical studies recapitulating the increased prevalence of NAFLD in estrogen deficient conditions (Figure 5), such as occurs in post-menopausal women and in men with mutations in the aromatase gene [79,146,348,349]. This evidence concerns the gene CYP19A1 and metabolic dysfunction-associated steatotic liver disease.