Age moderates the short-term effects of transdermal 17beta-estradiol on endothelium-dependent vascular function in postmenopausal women.
OBJECTIVE
We evaluated age and coronary heart disease (CHD) as potential moderators of the effects of 17beta-estradiol on vascular endothelial function in postmenopausal women.


RESULTS
In a double-blind crossover design, 100 postmenopausal women aged 50 to 80 years were randomized to each of 3 transdermal patches, releasing 17beta-estradiol (0.05 mg/d), 17beta-estradiol (0.05 mg/d) + norethindrone acetate (NETA, 0.14 mg/d), and placebo. Flow-mediated dilation (FMD) and response to 400 microg 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.
Sherwood
Andrew
A
Duke University Medical Center, Durham, NC 27710, USA. sherw002@mc.duke.edu
Bower
Julie K
JK
McFetridge-Durdle
Judith
J
Blumenthal
James A
JA
Newby
L Kristin
LK
Hinderliter
Alan L
AL
D000279:Administration, Cutaneous; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D016009:Chi-Square Distribution; D003327:Coronary Disease / Q000503:physiopathology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D005996:Nitroglycerin / Q000008:administration & dosage*; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D017698:Postmenopause / Q000187:drug effects; D011336:Probability; D012016:Reference Values; D012307:Risk Factors; D016896:Treatment Outcome; D014654:Vascular Patency / Q000187:drug effects
D004958:Estradiol; D000077563:Norethindrone Acetate; D005996:Nitroglycerin; D009640:Norethindrone