In conclusion, in this study the hepatic ERα stands as a valuable target for preventive therapies aimed at maintaining the hepatic functions necessary for women metabolic health: our findings suggest that, together with pharmacological therapies aimed at specifically activating the hepatic ERα, appropriate dietary interventions might prove very successful to limit the metabolic derangements consequent to ovarian failure and their countless consequences for women health in the course of ageing. Here, ESR1 is linked to ovarian dysfunction.