Circulation. 1998;97:1223-1226
(Circulation. 1998;97:1223-1226.)
© 1998 American Heart Association, Inc.
Estrogens, Progestins, and Heart Disease
Can Endothelial Function Divine the Benefit?
Robert A. Vogel, MD;
; Mary C. Corretti, MD
From the Division of Cardiology, Department of Medicine, University of
Maryland School of Medicine, Baltimore, Md.
Correspondence to Robert A. Vogel, MD, University of Maryland Hospital, Room S3B06, 22 S Greene St, Baltimore, MD 21201. E-mail RVOGEL@heart.ab.umd.edu
Key Words: Editorials • endothelium • heart diseases • hormones
Coronary atherosclerosis
is a prevalent, preventable, but slow disease. Demonstrating the
clinical effect of an intervention requires at least 3 to 5 years, even
in high-risk populations. Despite considerable supportive observational
data, the value of hormone replacement therapy in the treatment of
coronary heart disease in postmenopausal women remains
uncertain.1 2 3 4 It is therefore very attractive to
look for intermediate biological outcomes that may more quickly predict
the results of event trials. One intermediate biological outcome, the
anatomic progression of coronary
atherosclerosis, has been shown to correlate with the
incidence of cardiovascular
events.5 Changes in angiographic disease
progression, however, even with clinically successful interventions
such as cholesterol lowering, do not occur in less than 1
to 2 years.6 The endothelium is
thought to play an important role in the genesis of
atherosclerosis, and changes in
endothelial function have been reported within an hour
of either estrogen administration or cholesterol
lowering.7 8 9 If changes in
endothelial function were found to predict the clinical
benefit of interventions, then drug and lifestyle changes could be
evaluated more rapidly. In this issue, Sorensen and
coworkers10 report that cyclical estradiol and
norethisterone hormone replacement therapy administered for 2.9±0.5
years did not improve endothelial function, measured as
brachial artery flow–mediated vasodilation. The authors conclude that
the addition of a progestin in a hormone replacement regimen may
counteract the beneficial effects of estrogen alone on
cardiovascular disease. If confirmed by other
investigations, this study suggests that clinical trials of combined
hormone replacement therapy will not find a beneficial effect . . . [Full Text of this Article]
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