Endogenous sex hormones, blood pressure change, and risk of hypertension in postmenopausal women: The Multi-Ethnic Study of Atherosclerosis

Objective: Sex steroid hormones have been postulated to involve in blood pressure (BP) regulation. We examine the association of endogenous sex hormone levels with longitudinal change of BP and risk of developing hypertension in initially normotensive postmenopausal women. Methods: We conducted prospective analysis among 619 postmenopausal women free of hypertension at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Change of BP and development of incident hypertension were assessed during a mean of 4.8 years follow-up. Results: After adjusting for age, race/ethnicity, and lifestyle factors, baseline serum estradiol (E₂), total and bioavailable testosterone (T), dehydroepiandrosterone (DHEA) were each positively associated and sex-hormone binding globulin (SHBG) was inversely associated with risk of hypertension. Additional adjustment for body mass index eliminated the associations for E₂ and T but only attenuated the associations for DHEA and SHBG. The corresponding multivariable hazard ratios (95% CIs) in the highest quartile were 1.28 (0.83-1.97) for E₂, 1.38 (0.89-2.14) for total T, 1.42 (0.90-2.23) for bioavailable T, 1.54 (1.02-2.31) for DHEA, and 0.48 (0.30-0.76) for SHBG. Adjustment for fasting glucose, insulin, and C-reactive protein further attenuated the association for DHEA but not for SHBG. Associations of sex hormones with longitudinal BP change were similar. Conclusion: In postmenopausal women, higher endogenous E₂, T, and DHEA and lower SHBG were associated with higher incidence of hypertension and greater longitudinal rise in BP. The associations for E₂, T, and DHEA were mostly explained by adiposity, while the association for SHBG was independent of measures of adiposity, insulin resistance, and systemic inflammation.