From the Department of Medicine (M.G., A.T., E.A.H., S.J.C., E.W.S.,
P.G., M.A.C.) and the Department of Obstetrics and Gynecology (B.W.W.),
Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
Background—Epidemiological studies
indicate that estrogen replacement therapy decreases the risk of
cardiovascular events in postmenopausal women. Estrogen
may confer cardiovascular protection by improving
endothelial function because it increases
endothelium-dependent vasodilation. It is not known
whether progesterone attenuates the beneficial effects of estrogen on
endothelial function.
Methods and Results—Seventeen postmenopausal women with mild
hypercholesterolemia were enrolled in a
placebo-controlled, crossover trial to evaluate the effect of
transdermal estradiol, with and without vaginal micronized
progesterone, on endothelium-dependent vasodilation in
a peripheral conduit artery. Brachial artery diameter was
measured with high-resolution B-mode ultrasonography. To assess
endothelium-dependent vasodilation, brachial artery
diameter was determined at baseline and after a flow stimulus induced
by reactive hyperemia. To assess
endothelium-independent vasodilation, brachial artery
diameter was measured after administration of sublingual
nitroglycerin. During estradiol therapy, reactive
hyperemia caused an 11.1±1.0% change in brachial artery
diameter compared with 4.7±0.6% during placebo therapy
(P<0.001). Progesterone did not significantly attenuate
this improvement. During combined estrogen and progesterone therapy,
flow-mediated vasodilation of the brachial artery was 9.6±0.8%
(P=NS versus estradiol alone).
Endothelium-independent vasodilation was not altered by
estradiol therapy, either with or without progesterone, compared with
placebo. There was a modest decrease in total and LDL
cholesterol during treatment both with estradiol alone and
when estradiol was combined with progesterone (all
P<0.001 versus placebo). In a
multivariate analysis that included serum
estradiol, progesterone, total and LDL cholesterol
concentrations, blood pressure, and heart rate, only the estradiol
level was a significant predictor of
endothelium-dependent vasodilation.
Conclusions—The addition of micronized progesterone does not
attenuate the favorable effect of estradiol on
endothelium-dependent vasodilation. The vasoprotective
effect of hormone replacement therapy may extend beyond its beneficial
actions on lipids.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Estradiol Therapy Combined With Progesterone and Endothelium-Dependent Vasodilation in Postmenopausal Women
Key Words: endothelium • hormones • vasodilation • women
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