Effect of hormone replacement therapy on inflammatory biomarkers.

Cardiovascular disease is the leading cause of death among women. Inflammation plays a central role in the pathogenesis of many forms of vascular disease, including atherosclerosis. Women present with cardiovascular disease a decade after men and this has been attributed to the protective effect of female ovarian sex hormones. Hormone replacement therapy (HRT), including a variety of estrogen preparations with or without a progestin, has negative effects on most of these soluble inflammatory markers, including E-selectin, cell adhesion molecules, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha, inconsistent effects on interleukin-6, and stimulatory effects on vasoprotective cytokine, such as the transforming growth factor-alpha. C-reactive protein, a circulating proinflammatory cytokine produced in both liver and atherosclerotic arteries, increases in response to oral conjugated estrogens but not to transdermal estrogen. Animal and observational studies have shown beneficial effects of hormone therapy in the perimenopausal period or before the development of significant atherosclerosis, whereas randomized trials in older women have not shown any benefit in either primary prevention or secondary prevention of cardiovascular events. Many important questions about the effects of ovarian hormones on vascular inflammation and the pathogenesis of vascular disease cannot be answered in human subjects. This review outlines the effects of HRT on inflammatory biomarkers, summarizes results from observational and randomized trials, and highlights unanswered questions of hormone therapy and cardiovascular risk.