There are many differences between the sexes in the susceptibility and the development of chronic metabolic and cardiovascular diseases, which may be partly explained by the disparate alterations of androgen balance particularly in the presence of obesity. Notably, available studies support the concept that the prevalence of insulin resistance, the metabolic syndrome, type 2 diabetes, and cardiovascular pathologies is different between the sexes. With respect to women, it is particularly evident from a recent meta-analysis that those with the abdominal phenotype of excess weight or obesity, who are characterized by a condition of relative hyperandrogenic state, are at high risk for a specific morbidity for these diseases. The paradigm of PCOS is a good example for investigating the relationship between hyperandrogenemia and insulin resistance and metabolic and cardiovascular disorders, since most affected women are overweight or obese, approximately two-thirds have insulin resistance and show a very high susceptibility to develop the metabolic syndrome and type 2 diabetes, even earlier than expected, based on trends reported in the general population. Therefore, reducing androgen levels in abdominally obese women with or without PCOS may represent a clinical challenge for treatment and, possibly, for preventive intervention strategies.