Estradiol Does Not Influence Lipid Measures and Inflammatory Markers in Testosterone-Clamped Healthy Men

CONTEXT: Experimentally controlled studies of estrogenic regulation of lipid measures and inflammatory cytokines in men are rare. OBJECTIVE: To delineate the effect of estradiol (E(2)) on lipids and inflammatory markers. DESIGN: This was a placebo-controlled, single-masked, prospectively randomized study comprising experimentally degarelix-downregulated healthy men [n = 74; age 65 years (range, 57 to 77)] assigned to four treatment groups: (1) IM saline and oral placebo; (2) IM testosterone and oral placebo; (3) IM testosterone and oral anastrozole (aromatase inhibitor); and (4) IM testosterone, oral anastrozole, and transdermal E(2) for 22 (±1) days. RESULTS: Mean mass spectrometry–quantified serum E(2) concentrations ranged from 1.2 to 82 pg/mL in the four treatment groups. E(2) extremes did not alter total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol (HDL-C) , non–HDL-C, apolipoprotein B, lipoprotein (a), IL-6, or high-sensitivity C-reactive protein (hsCRP) concentrations. Higher E(2) concentrations elevated both sex hormone-binding globulin and prolactin as positive controls. LDL cholesterol, adiponectin, and leptin were higher in hypogonadal subjects without testosterone or E(2) addback (P = 0.018, 0.039, and 0.023, respectively). Abdominal visceral fat area by CT (independent variable) correlated negatively with HDL-C (P = 0.017), and positively with triglycerides (P = 0.004), hsCRP (P = 0.005), and leptin (P < 0.0001). CONCLUSION: In this placebo-controlled prospectively randomized study, wide variations in circulating E(2) did not influence lipid measures and inflammatory markers when testosterone concentrations were controlled experimentally. However, medically induced central hypogonadism in older men was accompanied by increased LDL cholesterol and metabolic cytokines, adiponectin and leptin. Abdominal visceral fat correlated strongly and positively with triglycerides, hsCRP, and leptin, but negatively with HDL.