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From the Department of Cardiology, Skejby University Hospital (K.E.S.,
I.D.), and the Department of Endocrinology and Metabolism, Aarhus County
Hospital (A.P.H., L.M.), Aarhus, Denmark.
Background—Improvement in
endothelial function may be an important mechanism by
which estrogen replacement therapy protects postmenopausal women
against coronary artery disease. However, combined hormone
replacement therapy is more frequently used owing to the risk of
uterine cancer with estrogen-only therapy. Concurrent progesterone
treatment may attenuate the beneficial effects of estrogens not only on
the lipid profile but also on the endothelium.
Methods and Results—We studied endothelial
vasomotor function in 100 healthy postmenopausal women aged 53.3±2.9
years randomized to either combined hormone replacement therapy (n=46)
or no substitution (n=54) 2.9±0.5 years earlier. In addition, 30
healthy premenopausal women aged 30.3±4.2 years were studied. With
external ultrasound, brachial artery diameter was measured at rest,
during reactive hyperemia (with increased flow causing
endothelium-dependent dilation), and after sublingual
nitroglycerin (causing
endothelium-independent dilation). Compared with
premenopausal women, flow-mediated dilation was significantly reduced
in both postmenopausal groups. In the postmenopausal women, total
cholesterol was lower in the treated women (5.66±0.83
versus 6.13±0.92 mmol/L; P=.025), whereas HDL
cholesterol was similar (1.91±0.53 versus 1.85±0.46
mmol/L; P=NS). Dilation to flow and to
nitroglycerin was similar in the two postmenopausal
groups (flow: 2.5±2.9% versus 2.2±2.2%, P=NS;
nitrate: 18.7±5.9% versus 17.2±6.2%, P=NS).
Conclusions—Long-term combined oral hormone replacement therapy
is without beneficial effects on endothelial vasomotor
function in healthy postmenopausal women. This supports the view that
progesterone may attenuate the beneficial effects of unopposed estrogen
replacement.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Combined Hormone Replacement Therapy Does Not Protect Women Against the Age-Related Decline in Endothelium-Dependent Vasomotor Function
Key Words: women • hormones • endothelium • ultrasonics • cholesterol
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|
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