Effect of hormone replacement therapy on nitric oxide bioactivity and monocyte chemoattractant protein-1 levels

Background: Vascular inflammation plays an important role in the pathogenesis of atherosclerosis. We investigated the effect of hormone replacement therapy (HRT) on vasomotor function and monocyte chemoattractant protein (MCP)-1 levels, an important serological marker of inflammation. Methods: We administered micronized progesterone (MP) 200 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and remaining 5 days off cyclically during 2 months to 20 healthy postmenopausal women (PMW). We measured NO bioactivity and plasma levels of MCP-1 before and after HRT in 20 PMW And we measured plasma levels of MCP-1 in each 20 subjects of premenopausal women, men < 50, and men > 50 years, respectively. Results: MP combined with CEE significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements (P <0.001). PMW receiving HRT had lower levels of MCP-1 than those not receiving HRT (121 +/- 38 versus 146 +/- 44 pg/ml, P <0.001). In an comparisons, subjects with high estrogen status had significantly lower MCP-1 levels than subjects-with low estrogen status (P <0.001 by ANOVA). Premenopausal women had lower levels of MCP-1 than men of a similar age (106 +/- 14 versus 164 +/- 40 pg/ml, P <0.001). PMW not receiving HRT had similar levels of MCP-1 compared with men of a similar age (146 +/- 44 versus 143 +/- 29 pg/ml, P=0.816). Premenopausal women had markedly lower levels of MCP-1 than PMW not receiving HRT (106 +/- 14 versus 146 +/- 44 pg/ml, P=0.001). PMW receiving HRT had similar levels of MCP-I compared with premenopausal women (121 +/- 38 versus 106 +/- 14 pg/ml, P=0.323). Conclusion: These findings might provide at least a partial explanation for the protection against cardiovascular disease experienced by premenopausal women, and the loss of that protection following menopause. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.