Effect of Lower Dosage of Oral Conjugated Equine Estrogen on Inflammatory Markers and Endothelial Function in Healthy Postmenopausal Women

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 24; no. 3; pp. 571 - 576
• Main Authors: Wakatsuki, Akihiko, Ikenoue, Nobuo, Shinohara, Koichi, Watanabe, Kazushi, Fukaya, Takao
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-03-2004; Hagerstown, MD Lippincott
• Subjects: Administration, Oral; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biomarkers; Blood and lymphatic vessels; Brachial Artery - diagnostic imaging; Brachial Artery - drug effects; Brachial Artery - physiology; C-Reactive Protein - analysis; Cardiology. Vascular system; Cell Adhesion Molecules - blood; Coronary Disease - chemically induced; Coronary Disease - epidemiology; Coronary Disease - prevention & control; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Estrogen Replacement Therapy; Estrogens, Conjugated (USP) - administration & dosage; Female; Hemodynamics - drug effects; Hormones - blood; Humans; Inflammation - blood; Interleukin-6 - blood; Japan - epidemiology; Lipids - blood; Medical sciences; Middle Aged; Nitroglycerin - pharmacology; Observer Variation; Postmenopause - blood; Postmenopause - drug effects; Postmenopause - physiology; Reference Values; Risk; Serum Amyloid A Protein - analysis; Ultrasonography; Vasodilation - drug effects; Human; cell adhesion molecules; C-reactive protein; postmenopausal women; Estrogen; Cell adhesion molecule; Oral administration; Cardiovascular disease; Ovarian hormone; Endothelium; Vascular disease; Atherosclerosis; Sex steroid hormone; C reactive protein
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000115383.49802.0c

OBJECTIVE—Although oral estrogen replacement therapy (ERT) in postmenopausal women improves endothelial function, it also increases plasma C-reactive protein (CRP) and interleukin-6 (IL-6) concentration. The proinflammatory effect of oral ERT may explain the increased risk of coronary heart disease (CHD) associated with this treatment. Recent observational studies have demonstrated that a lower dose of oral estrogen reduces the risk for CHD. The purpose of the present study was to investigate the effects of low-dose oral estrogen on vascular inflammatory markers and endothelium-dependent vasodilation in postmenopausal women.
METHODS AND RESULTS—Postmenopausal women were randomized into 3 groups to receive no treatment (n=14) or oral conjugated equine estrogen (CEE) at a dosage of 0.625 mg (n=15) or 0.3125 mg (n=15) daily for 3 months. CEE at a dosage of 0.625 mg resulted in significant increases in plasma concentrations of CRP from 690.9±749.5 to 1541.9±1608.0 ng/mL, serum amyloid A from 6.12±4.15 to 8.25±4.40 μg/mL, and IL-6 from 1.45±0.73 to 2.35±1.16 pg/mL. In contrast, CEE at a dosage of 0.3125 mg had no effect on these inflammatory markers. Both dosages of estrogen significantly decreased E-selectin concentration, whereas the concentrations of intercellular and vascular cell adhesion molecules remained unchanged. In both CEE groups, flow-mediated vasodilation in the brachial artery was increased significantly, whereas nitroglycerine-induced vasodilation was unaltered.
CONCLUSIONS—Oral CEE at a low dose of 0.3125 mg in postmenopausal women eliminated the adverse effects of high-dosage oral CEE on vascular inflammatory markers in addition to preserving the favorable effects of estrogen on cell adhesion molecules and endothelial function.