Abstract P220: Low Levels Of Endogenous Estrogen Are Associated With Elevated Risk Of Cardiovascular Disease Mortality In Young And Middle-Aged Men In The United States

Abstract

Background: While endogenous estrogen deficiency in men due to inactivating mutations of the aromatase gene results in profound metabolic dysfunction, evidence for the association of estradiol with cardiovascular disease (CVD) in men overall is inconsistent, with most studies performed among older men or patients with CVD. We investigated the association of total estradiol (E2) or free estradiol (FE2) and CVD mortality in a nationally representative sample of US men. Hypothesis: Low levels of E2 or FE2 will be associated with elevated risk of CVD mortality. Methods: Data on 954 men without CVD, cancer, diabetes and not on androgen therapy or taking anabolic steroids who participated in Phase 1 (1988 to 1991) of the third National Health and Nutrition Examination Survey and for whom E2 was measured, and were followed for mortality through to December 31, 2015 were included. Fasting serum levels of E2 were measured using competitive electrochemiluminescence immunoassays. Free estradiol was estimated from estradiol, sex hormone binding globulin, and albumin. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: The average age of participants at baseline was 35.7 (Standard deviation (SD) ±11.6) years with 11% and 6% of them reporting Black and Hispanic race and ethnicity, respectively. During a median follow-up of 25.2 years, 40 CVD deaths were recorded, with the cumulative incidence greater among men with low E2 or FE2 (Figure). Controlling for baseline age, race/ethnicity, education, systolic blood pressure, body mass index, physical activity, smoking status, alcohol intake, HDL cholesterol, c-reactive protein and total testosterone levels, a 1 log SD decrease in E2 (HR: 2.38, 95%CI: 1.11-5.00) or FE2 (HR: 1.96, 95%CI: 1.03-3.70) was associated with elevated CVD mortality. Conclusions: In this nationally representative sample of U.S young and middle-aged men, low levels of total estradiol or free estradiol were associated with elevated risk for CVD mortality.