In fact, men with E2 deficiency or E2 resistance, due to specific mutations in the cytochrome P450 aromatase gene (Cyp19a1) or in the ERα gene (ESR1), respectively, show an increased risk of CDV in association with total cholesterol level rise, insulin resistance (IR) and type 2 diabetes (T2D) development, defects in glucose tolerance and vasodilation [27,28,29,30,31]. This evidence concerns the gene ESR1 and type 2 diabetes mellitus.