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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:571.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Akihiko Wakatsuki; Nobuo Ikenoue; Koichi Shinohara; Kazushi Watanabe; Takao Fukaya

From the Department of Obstetrics and Gynecology, Kochi Medical School, Kochi, Japan.

Correspondence to Dr Akihiko Wakatsuki, Department of Obstetrics and Gynecology, Kochi Medical School, Oko-cho, Nankoku, Kochi, Japan, 783-8505. E-mail wakatuki{at}kochi-ms.ac.jp

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.

Key Words: estrogen • postmenopausal women • C-reactive protein • endothelium • cell adhesion molecules

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