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

Objective: Oestradiol (E2) and its metabolites 2-hydroxyoestrone (2-OHE1) and 16α-hydroxyoestrone (16α-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 16α-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 ρ_Y|X = 0.44 and ρ_Y|X = 0.43 in pre- and postmenopausal women, respectively). Similarly, 16α-OHE1 concentrations were positively and highly correlated with F_2a-isoprostane concentrations (ρ_Y|X = 0.52 and ρ_Y|X = 0.59 in pre- and postmenopausal women, respectively). E2 was significantly correlated with F_2a-isoprostanes only in postmenopausal women (ρ_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.