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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1782.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Age Moderates the Short-Term Effects of Transdermal 17ß-Estradiol on Endothelium-Dependent Vascular Function in Postmenopausal Women

Andrew Sherwood; Julie K. Bower; Judith McFetridge-Durdle; James A. Blumenthal; L. Kristin Newby; Alan L. Hinderliter

From the Duke University Medical Center (A.S., J.K.B., J.M., J.A.B., L.K.N.), Durham, and the University of North Carolina at Chapel Hill (A.L.H.).

Correspondence to Dr Andrew Sherwood, Box 3119, Duke University Medical Center, Durham, NC 27710. E-mail sherw002{at}mc.duke.edu

Objective— We evaluated age and coronary heart disease (CHD) as potential moderators of the effects of 17ß-estradiol on vascular endothelial function in postmenopausal women.

Methods and Results— In a double-blind crossover design, 100 postmenopausal women aged 50 to 80 years were randomized to each of 3 transdermal patches, releasing 17ß-estradiol (0.05 mg/d), 17ß-estradiol (0.05 mg/d)+ norethindrone acetate (NETA, 0.14 mg/d), and placebo. Flow-mediated dilation (FMD) and response to 400 µg sublingual glyceryl trinitrate (GTN-D) were assessed approximately 18 hours after patch placement. Age, but not CHD, moderated the FMD response to treatment (P=0.01). For women in their fifties, the estradiol patch was associated with improved FMD (7.69±4.79%) compared with placebo (4.81±5.97%, P<0.05), but the estradiol+norethindrone patch response (5.81±4.85%) was not significantly different from placebo. Women in their sixties and seventies showed no alterations in FMD response to either active patch. GTN-D response declined with advancing age (P<0.01), with women in their seventies exhibiting blunted GTN-D response compared with younger women.

Conclusions— The cardiovascular benefits of natural estrogen supplementation on vascular endothelial function may be dependent on postmenopausal age, with improved vascular function evident only in the early postmenopausal years. Short-term FMD response to estradiol might help stratify individual differences in risks versus benefits of HRT.

We sought to evaluate whether age and coronary heart disease moderate the effects of 17ß-estradiol on vascular endothelial function. For younger postmenopausal women, short-term estradiol transdermal patch exposure was associated with improved flow mediated dilation. Benefits of estrogen supplementation on vascular endothelial function may be dependent on postmenopausal age.

Key Words: aging • coronary disease • endothelium • hormones • women

Related Article:

Hormone Replacement Therapy and Atherosclerosis in Postmenopausal Women: Does Aging Limit Therapeutic Benefits?

Matthias Barton, Matthias R. Meyer, and Elvira Haas
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