Sex and age are the major determinants of serum levels of dehydroepiandrosterone sulfate (DHEA-S): they are about twice in men than in women and show a progressive reduction from the end of the puberty to aging in both sexes. It has been reported that DHEA-S levels are also negatively influenced by insulin. Moreover, DHEA-S levels reduction has been associated to increased risk for cardiovascular disease, which connotes hyperinsulinemic states, such as obesity. We have evaluated serum levels of DHEA-S and insulin as function of age and body mass index (BMI) in 376 adult women (age 18.1-89.6 yrs, median 42.2; BMI 15.7-57.8 kg/m2, median 32.7) by multiple regression and piecewise regression analysis. Insulin levels positively associated to BMI (p=0.000002) and DHEA-S levels negatively associated with age (p=0.000001). Considering the whole population, DHEA-S levels were related positively with BMI (p=0.0013) independently of age. DHEA-S were also directly related to insulin levels independently of age (p=0.042), but this association disappeared after correction for BMI. Piecewise regression analysis did not reveal a threshold level for the increase of BMI (p=0.0004). Interestingly, DHEA-S levels and BMI were positively associated before but not after menopause. Taking into account only obese population, (no.=143, age 18.7-67.3 yrs, mean 39.0, median 39.4) DHEA-S levels were again related negatively with age and positively with BMI, while were unrelated with waist to hip ratio (p=0.391). Our data show that increasing body mass and insulin secretion is not associated to DHEA-S reduction in women. This evidence suggests that DHEA-S is unlikely implicated in the pathogenesis of cardiovascular disease in obese women.