In this study, we present novel insights into mechanisms that account for the ERα-dependent myocardial protection against myocardial injury, with more beneficial effects in female hearts. Using a transgenic mouse model with a cardiomyocyte-specific ERα-overexpression (ERα-OE), we first demonstrated that this was associated with an increase of LVM at the basal level in both female and male mice. After MI, the cardiomyocyte-specific ERα-OE inhibited changes in LV-volumes and wall thickness only in female mice. These beneficial effects in female ERα-OE hearts were associated with increased...