Oestrogen metabolites in relation to isoprostanes as a measure of oxidative stress

OBJECTIVE: Oestradiol (E2) and its metabolites 2-hydroxyoestrone (2-OHE1) and 16alpha-hydroxyoestrone (16alpha-OHE1) are thought to curtail the greater oxidative stress found in the development and progression of disease conditions including atherosclerosis. We related oestrogen levels to F(2a)-isoprostane levels, a biomarker of oxidative stress. DESIGN AND PARTICIPANTS: Data were obtained from 1647 women, aged 47-57 years, participating in the fifth annual follow-up of the Study of Women\u27s Health Across the Nation (SWAN), a study of the menopausal transition. MEASUREMENTS: Serum E2 and urinary 2-OHE1 and 16alpha-OHE1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and urinary F(2a)-isoprostanes were measured by enzyme immunoassay (EIA). RESULTS: F(2a)-isoprostane concentrations were elevated in women who smoked, a behaviour associated with increased oxidative stress, but not in stages of the natural menopause. Mean F(2a)-isoprostane concentrations among pre- and postmenopausal women who smoked were 1082 and 1064 pg/ml, respectively, values double those in pre- (343 pg/ml) and postmenopausal (379 pg/ml) nonsmoking women. 2-OHE1 and F(2a)-isoprostane concentrations were positively and highly correlated (partial correlations rho(Y|X) = 0.44 and rho(Y|X) = 0.43 in pre- and postmenopausal women, respectively). Similarly, 16alpha-OHE1 concentrations were positively and highly correlated with F(2a)-isoprostane concentrations (rho(Y|X) = 0.52 and rho(Y|X) = 0.59 in pre- and postmenopausal women, respectively). E2 was significantly correlated with F(2a)-isoprostanes only in postmenopausal women (rho(Y|X) = 0.20). Associations were adjusted for age, body mass index (BMI), race/ethnicity, lipids, physical activity level and alcohol consumption. CONCLUSIONS: This study does not support the commonly held hypothesis that levels of endogenous E2 or its oestrone metabolites favourably modify oxidative stress by decreasing F2(a)-isoprostane levels