Hormone Replacement Therapy and Endothelial Function

The endothelium plays a central role in the regulation of vascular homeostasis by releasing paracrine factors that influence vascular tone, thrombosis, and inflammation in the arterial wall.1 A principal endothelial product responsible for homeostasis is nitric oxide (NO), which is synthesized by the endothelial isoform of NO synthase2 in response to a number of stimuli, including increased shear stress that accompanies increased arterial flow.3 Atherosclerosis and its risk factors are characterized by an impairment of endothelial NO-dependent vasodilation,1 and the magnitude of this defect in the coronary circulation predicts cardiovascular disease events, raising the possibility of a pathogenic relationship.4,5See page 1955 This notion of a causal relation between endothelial dysfunction and cardiovascular events is also supported by intervention data. For example, lipid-lowering therapy, angiotensin-converting enzyme inhibition, smoking cessation, and exercise all reverse endothelial dysfunction and have proven benefitial against cardiovascular disease events.1 This concordance between improved endothelial function and reduced cardiovascular events has prompted speculation that changes in endothelial function are partially responsible for the benefits.6–8 Thus, endothelial dysfunction could potentially be used as a surrogate marker for cardiovascular disease risk in study of risk reduction therapies.3Hormone replacement therapy has received considerable attention as a means for primary and secondary prevention of cardiovascular disease. This interest was initially based on population-based studies linking a reduced incidence of cardiovascular disease to hormone replacement therapy.9–11 Estrogen has many potential benefits, including favorable influence on serum lipids and thrombotic factors, and there is substantial evidence that …