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(Circulation. 2000;102:2687.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Differential Effects of Oral and Transdermal Estrogen Replacement Therapy on Endothelial Function in Postmenopausal Women

Satu Vehkavaara, MD; Tiina Hakala-Ala-Pietilä, MD; Antti Virkamäki, MD; Robert Bergholm, MD; Christian Ehnholm, MD; Outi Hovatta, MD; Marja-Riitta Taskinen, MD; Hannele Yki-Järvinen, MD

From the Department of Medicine, University of Helsinki (S.V., R.B., H.Y.-J., M.-R.T.); the Minerva Foundation Institute for Medical Research (A.V.); the Family Federation of Finland (T.H.-A.-P.); and the Department of Biochemistry, National Public Health Institute (C.E.), Helsinki, Finland; and the Karolinska Institute, Department of Obstetrics and Gynecology, Huddinge University Hospital, Huddinge, Sweden (O.H.).

Correspondence to Hannele Yki-Järvinen, MD, University of Helsinki, Department of Medicine, PO Box 340, 00029 HUCH, Helsinki, Finland. E-mail ykijarvi{at}helsinki.fi

Background—We determined whether the vascular effects of estradiol depend on the route of administration by comparing the effects of oral estradiol and transdermal placebo, transdermal estradiol and oral placebo, and transdermal placebo and oral placebo on in vivo endothelial function in 27 postmenopausal women.

Methods and Results—Endothelial function was assessed from blood flow responses to intrabrachial artery infusions of endothelium-dependent (7.5 and 15 µg/min acetylcholine) and endothelium-independent (3 and 10 µg/min of sodium nitroprusside) vasodilators at 0, 2, and 12 weeks. In the oral estradiol group, the increase in flow above basal during infusion of the low dose of acetylcholine at 0, 2, and 12 weeks averaged 6.0±0.8, 6.9±0.8, and 11.3±1.2 (P<0.01 versus 0 and 2 weeks) mL · dL^-1 · min^-1 at 0, 2, and 12 weeks. The percentage increases versus 0 weeks averaged 21±14% at 2 and 120±34% at 12 weeks. During the high-dose acetylcholine infusion, the increase in flow above basal averaged 8.6±1.3, 10.2±1.5, and 15.1±1.8 (P<0.05 versus 0 weeks) mL · dL^-1 · min^-1, respectively. The percentage increases versus 0 weeks averaged 22±10% at 2 weeks and 119±46% at 12 weeks. In the oral estradiol group, endothelium-independent vasodilatation also improved significantly, but less markedly than endothelium-dependent responses. In the transdermal and placebo groups, all vascular responses remained unchanged. Oral but not transdermal estradiol also induced significant decreases in LDL cholesterol and Lp(a) concentrations and an increase in HDL cholesterol within 2 weeks.

Conclusions—We conclude that oral but not transdermal estradiol induces potentially antiatherogenic changes in in vivo endothelium-dependent vasodilatation and lipid concentrations.

Key Words: atherosclerosis • blood flow • endothelium

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