Estrogen metabolites and systolic blood pressure in a population-based sample of postmenopausal women

Context: Lower systolic blood pressure (SBP) and lower rates of coronary heart disease among premenopausal women compared with similarly aged men and postmenopausal women suggest that female sex hormones may confer cardiovascular protection. 2-Hydroxyestradiol, a product of 17β-estradiol oxidative metabolism, inhibits the proliferation of vascular smooth muscle cells in vitro. The other major product of 17β-estradiol oxidative metabolism, 16α-hydroxyestradiol, does not demonstrate similar inhibitory effects. Concentrations of 2-hydroxyestrone (2-OHE) and 16α-hydroxyestrone (16-OHE) in urine reflect the relative activity of the 2- and 16α-hydroxylation pathways of 17β-estradiol. Objective: The objective of this study was to determine the relationship between SBP and the ratio of 2-OHE to 16-OHE in urine. Design and Participants: This was a cross-sectional study of 80 postmenopausal women living in Cook County, Illinois. Setting: This study was performed in an academic clinical laboratory. Main Outcome Measure: The main outcome measure was SBP. Results: Women taking hormone replacement therapy had higher levels of urinary 2-OHE and 16-OHE, but their mean 2:16-OHE ratio and SBP did not differ from that of women not taking hormone replacement therapy. In a multivariate regression model that controlled for age, body mass index, race/ethnicity, and antihypertensive medication use, a SD increase in the 2:16-OHE ratio was associated with a 6.7-mm Hg decrease (P < 0.05) in SBP. Conclusions: The ratio of urinary 2-OHE to 16-OHE is a significant predictor of SBP among postmenopausal women and may reflect the effects of 2-hydroxyestradiol, a potent inhibitor of vascular smooth muscle cell proliferation.