Published online before print October 30, 2003, doi: 10.1161/01.RES.0000103633.57225.BC
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© 2003 American Heart Association, Inc.
Clinical Research |
Endogenous Estrogens Influence Endothelial Function in Young Men
From the Baker Medical Research Institute and Alfred Hospital, Prahran, Victoria, Australia, and Department of Medicine (K.S.), Stanford University, Stanford, Calif.
Correspondence to Krishnankutty Sudhir, MD, PhD, Stanford University, H3554, 300 Pasteur Dr, Stanford, CA 94305. E-mail ksudhir{at}cvmed.stanford.edu
Males produce endogenous estrogen from testosterone via the enzyme aromatase. Previous studies have suggested a role for endogenous estrogens in cardiovascular function in men. We examined the effects of endogenous estrogen suppression via aromatase inhibition on endothelial function, systemic arterial compliance, and lipoprotein levels in healthy young men. Using a placebo-controlled double-blind randomized design, 20 healthy men, aged 18 to 32 years, were randomized to receive either the aromatase inhibitor anastrozole (1 mg) or matching placebo. Hormone, lipid levels, C-reactive protein (CRP), and homocysteine were measured. Endothelial function, determined by flow-mediated dilation of the brachial artery, and systemic arterial compliance were assessed at baseline and after 6 weeks of treatment. There was a significant decrease in 17ß-estradiol concentrations with aromatase inhibition, from 85.4±4.2 to 64.3±8.1 pmol/L (mean±SD, P=0.042). Compared with baseline, a significant decrease in flow-mediated dilation was observed in subjects taking anastrozole [median, 6.1% (range, 5.2 to 13.4) to 3.5% (2.0 to 5.7), P=0.034] but not in the placebo group. No changes were observed in nitroglycerin-induced endothelium-independent dilation in either group. There was no change in systemic arterial compliance with either aromatase therapy or placebo. There were no significant changes in lipoproteins, testosterone, DHEA, CRP, or homocysteine levels in either the anastrozole or placebo group. We conclude that suppression of endogenous estrogens with an aromatase inhibitor resulted in impairment of flow-mediated dilation without significant changes in lipoproteins, homocysteine, or CRP. Our results suggest that endogenous estrogens play a direct regulatory role in endothelial function in young healthy men.
Key Words: estrogens • males • aromatase • endothelium • arterial compliance
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