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Estrogen Improves Endothelium-Dependent, Flow-Mediated Vasodilation in Postmenopausal Women

Eric H. Lieberman, MD; Marie D. Gerhard, MD; Akimi Uehata, MD; Brian W. Walsh, MD; Andrew P. Selwyn, MD; Peter Ganz, MD; Alan C. Yeung, MD; and Mark A. Creager, MD
[+] Article, Author, and Disclosure Information

From Brigham and Women's Hospital, Boston, Massachusetts; Mt. Sinai Hospital, Miami, Florida; National Defence Medical College, Tokorozawa, Saitama, Japan; and Stanford University Medical Center, Stanford, California. Requests for Reprints: Mark A. Creager, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. Grant Support: By the National Heart, Lung, and Blood Institute (grants HL02663, HL38780, and HL02566).

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1994;121(12):936-941. doi:10.7326/0003-4819-121-12-199412150-00005
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Objective: To assess the effect of estrogen replacement therapy on endothelium-dependent vasodilation in postmenopausal women.

Design: Double-blind, placebo-controlled, cross-over trial.

Setting: University medical center.

Patients: 13 postmenopausal women aged 44 to 69 years (average age, 55 ±7 years).

Intervention: Patients were randomly assigned to receive placebo, oral estradiol at a dose of 1 mg/d, and oral estradiol at a dose of 2 mg/d. Each treatment phase lasted 9 weeks.

Measurements: High-resolution ultrasonography was used to measure vascular reactivity in a peripheral conduit vessel, the brachial artery. Endothelium-dependent vasodilation was determined by measuring the change in brachial artery diameter during increases in flow induced by reactive hyperemia. Endothelium-independent vasodilation was measured after sublingual nitroglycerin was administered.

Results: Flow-mediated, endothelium-dependent vasodilation of the brachial artery was greater when patients received estradiol (13.5% and 11.6% for 1-mg and 2-mg doses, respectively) than when patients received placebo (6.8%; P < 0.05 for each dose compared with placebo). In contrast, estrogen administration had no effect on endothelium-independent vasodilation as assessed by sublingual nitroglycerin.

Conclusion: Short-term estrogen replacement therapy improves flow-mediated endothelium-dependent vasodilation in postmenopausal women. This improvement may be mediated by a direct effect of estrogen on vascular function or may be induced through modification of lipoprotein metabolism.


Grahic Jump Location
Figure 1.
Effect of estradiol on flow-mediated, endothelium-dependent vasodilation in 12 postmenopausal women.P

Oral estradiol at 1 mg/d and at 2 mg/d significantly increased the brachial artery diameter during a flow stimulus induced by reactive hyperemia ( < 0.05 for each dose compared with placebo).

Grahic Jump Location




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