Cardiovascular pharmacology
Effect of Transdermal Hormone Replacement Therapy on the Monocyte Chemoattractant Protein-1 Concentrations and Other Vascular Inflammatory Markers and on Endothelial Function in Postmenopausal Women

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Monocyte chemoattractant protein-1 (MCP-1) is related to the progression of atherosclerosis. However, little is known about the effects of transdermal hormone replacement therapy (HRT) on circulating MCP-1, vascular inflammatory marker concentrations, and endothelial function in postmenopausal women. The effects of transdermal HRT on circulating MCP-1, vascular inflammatory marker concentrations, and endothelium-dependent vasodilation were investigated in postmenopausal women. Thirty-three women received transdermal HRT (continuous 17-β estradiol patch 36 μg/day plus cyclic oral medroxyprogesterone acetate 2.5 mg/day for 12 days/month) for 12 months, and 27 control patients did not. Brachial artery flow-mediated vasodilation (FMD), assessed by ultrasound, and circulating MCP-1 and vascular inflammatory marker (C-reactive protein, intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin) concentrations were measured before and after 12 months of treatment. In the HRT group, MCP-1 concentrations decreased significantly (p <0.001), and ICAM-1, VCAM-1, and E-selectin concentrations decreased significantly (p <0.01 for all), but C-reactive protein concentrations did not change. MCP-1 and other marker concentrations did not change in the control group. FMD increased significantly in the HRT group (p <0.001) but did not change in the control group. Nitroglycerin-induced vasodilation did not change in either group. In conclusion, transdermal HRT decreased MCP-1 and cell adhesion molecule concentrations and improved endothelial function in postmenopausal women. Transdermal HRT may exert an antiatherosclerotic effect by improving MCP-1 and cell adhesion molecule expression and endothelial function.

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Subjects

Sixty-six postmenopausal Japanese women participated in this study. Each subject had experienced natural menopause for ≥1 year at the time of entry into the study. Menopausal status was confirmed by a serum estradiol concentration <20 pg/ml and a serum follicle-stimulating hormone concentration >40 mIU/ml. None of the subjects smoked or had a history of thyroid disease, liver disease, hypertension, diabetes mellitus, cardiovascular disease, hormone-dependent malignancy, or breast cancer. None

Results

There were no significant differences between the groups with respect to age and the baseline values (Table 1, Table 2, Table 3). HRT increased estradiol concentrations and decreased follicle-stimulating hormone concentrations. Lipid profiles in the 2 groups remained unchanged throughout the study (Table 1).

MCP-1 concentrations at baseline were similar in the 2 groups. MCP-1 concentrations decreased significantly in the HRT group (p <0.001) but did not change in the control group (Figure 1).

Discussion

Estradiol has decreased MCP-1 messenger ribonucleic acid and circulating MCP-1 concentrations in animal13 and human studies.10, 14, 15 In rabbits fed a cholesterol-enriched diet, physiologic doses of estradiol dose-dependently reduced MCP-1 messenger ribonucleic acid and protein expression in the thoracic aorta tissue to values observed in ovary-intact rabbits,13 and estradiol has been found to dose-dependently downregulate MCP-1 messenger ribonucleic acid expression in human coronary artery

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