Objective: Monocyte chemoattractant protein-1 (MCP-1) is considered a propagator of atherosclerosis and a key modulator of monocyte activity. Hormone replacement therapy (HRT) is currently being investigated as a means towards prevention of atherosclerosis. We aimed to assess (1) the range of circulating MCP-1 levels in postmenopausal women, (2) the correlation between MCP-1 and atherosclerotic burden, and (3) the effects of commencement and discontinuation of HRT on MCP-1 serum levels.
Methods: This clinical prospective trial investigated 51 postmenopausal women at increased risk for cardiovascular events who were randomized to receive either no HRT or 1 mg 17 beta-estradiol continuously plus sequential progestagen over 1 year. Intima-media thickness (IMT) of carotid and femoral arteries was measured by ultrasound. Serum levels of MCP-1 and cellular adhesion molecules were measured by ELISA.
Results: At baseline, MCP-1 levels and overall mean maximum IMT correlated (r=0.589; P<0.0001, Pearson's coefficient). MCP-1 levels in serum gradually decreased after 3, 6, and 12 months of HRT by 16.8 +/- 15.7% at 12 months (P<0.0001, MANOVA). Similarly, all cellular adhesion molecules decreased significantly by 6-12%. After 12 months, women decided whether to continue or discontinue treatment. At 18 months, in women discontinuing HRT (n=17), MCP-1 levels rose by 21 +/- 20% (P=0.003), but remained lowered in women continuing HRT.
Conclusion: Our observations indicate that 17 beta-estradiol may have an antiatherosclerotic effect by reducing MCP-1 serum levels and cell adhesion molecules.