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

Background: Vascular inflammation plays an important role in the pathogenes is of atherosclerosis. We investigated the effect of hormone replacement th erapy (HRT) on vasomotor function and monocyte chemoattractant protein (MCP )-1 levels, an important serological marker of inflammation. Methods: We ad ministered micronized progesterone (MP) 200 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and remaining 5 days off cyclica lly during 2 months to 20 healthy postmenopausal women (PMW). We measured N O 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 wo men, men < 50, and men > 50 years, respectively. Results: MP combined with CEE significantly improved the percent flow-mediated dilator response to hy peremia 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 sta tus had significantly lower MCP-1 levels than subjects-with low estrogen st atus (P <0.001 by ANOVA). Premenopausal women had lower levels of MCP-1 tha n 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 simila r age (146 +/- 44 versus 143 +/- 29 pg/ml, P=0.816). Premenopausal women ha d markedly lower levels of MCP-1 than PMW not receiving HRT (106 +/- 14 ver sus 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 explan ation for the protection against cardiovascular disease experienced by prem enopausal women, and the loss of that protection following menopause. (C) 2 001 Elsevier Science Ireland Ltd. All rights reserved.