Atherosclerosis in humans is associated with inflammation. Therapies that increase nitric oxide (NO) bioactivity may reduce synthesis of proinflammatory proteins within the vessel wall by inhibiting transcriptional activation of target genes. As estrogen and vitamin E therapies improve endothelial NO bioactivity, we administered conjugated equine estrogen (CEE) .625 mg daily, vitamin E 800 IU daily, and the combination, each for 6 weeks to 28 postmenopausal women in a randomized, double-blind , 3-period crossover study. Brachial artery flow-mediated dilation (FMD) following forearm ischemia (a bioassay for endothelial NO), and serum levels of inflammatory cell adhesion molecules E-selectin, intercellular adhesion molecule (ICAM-1), and vascular cell adhesion molecule (VCAM-1) were measured before and after each therapy. All therapies improved FMD (all P<0.001) and to a similar degree (P=0.267 by ANOVA), but not the dilator response to nitroglycerin (all P<0.235). However, only therapies including CEE significantly reduced levels of cell adhesion molecules. Compared with respective baseline values, levels of E-selectin were lowered on CEE (-13+/-15%, p<0.001), CEE combined with vitamin E (-20+/-17%, p<0.001), but not vitamin E alone (+3+/-28%). Levels of ICAM-1 were lowered by CEE (-7+/-17%, p<.05), CEE combined with vitamin E (-7+/-19%, p<0.05), but not vitamin E alone. Levels of VCAM-1 were lowered by CEE (-6+/-21%, p<0.01), but not by CEE combined with vitamin E (-2+/-21%), or vitamin E alone (-3+/-14%). Differences among therapies were highly significant for E-selectin (P<0.001 by ANOVA). We conclude that therapies that improve endothelial NO may not have comparable effects on markers of vascular inflammation, suggesting a primary anti-inflammatory mechanism for estrogen in postmenopausal women.
