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's 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.