Our findings regarding, particularly, the early mortality in correlation with the demographic differences described above (Figure 1), have led us and also other investigators to the proposed hypothesis that hormonal pathways, including abnormalities of the estrogen receptor, ovarian dysfunction, premature menopause and proinflammatory properties of hormone replacement therapy, may be a potentially important cause for increased mortality rates in female patients after cardiac operations [8,9]. Here, ESR1 is linked to ovarian dysfunction.