BACKGROUND: Dehydroepiandrosterone (DHEA) is an androgen precursor, and is known to be decreased by the aging process. DHEA has been known to have a protective effect on insulin resistance and cardiovascular disease in men, but remains controversial in women. The aim of this study was to elucidate the role of DHEA on insulin resistance, and the risk for cardiovascular disease, in women. METHODS: We analyzed the relationship between DHEA sulfate (DHEAS), known to have a longer half-life and less diurnal variation than DHEA, and insulin resistance syndrome (IRS) in 471 non-diabetic women from an urban community diabetes prevalence study. Serum DHEAS concentrations were measured using a commercially available radioimmunoassay kit. RESULTS: 1. The frequencies of obesity, impaired glucose tolerance, hypertension and dyslipidemia were 25.3, 8.5, 21.9 and 6.2%, respectively, and the frequency of IRS was 16.5%. 2. DHEAS was significantly inversely correlated with age (r=-0.47, p<0.001), systolic blood pressure (r=-0.18, p<0.001), diastolic blood pressure (r=-0.10, p<0.05), fasting serum glucose (r=-0.10, p<0.05), postchallenge 2 hour glucose (r=-0.12, p<0.01) and triglycerides (r=-0.16, p<0.01). 3. As serum DHEAS concentrations, by quartiles, were decreased, the age-adjusted frequency of hypertension was significantly increased (p<0.05). 4. A Multiple linear regression analysis revealed that DHEAS was significantly associated with age (p<0.0001) and BMI (p<0.05). 5. A Logistic regression analysis showed that DHEAS was not associated with IRS after adjustment for age. CONCLUSION: DHEAS is inversely associated with age. DHEAS has no harmful effect, and may even have a protective role, on insulin resistance syndrome. Prospective examinations of DHEAS and insulin resistance syndrome in women are needed to confirm the mechanism for the association between DHEAS and the development of cardiovascular disease.