Effects of transdermal and oral postmenopausal hormone therapy on vascular function: a randomized, placebo-controlled study in healthy postmenopausal women.
OBJECTIVE
To compare the effect of transdermal and oral estrogen therapy, the latter with or without the addition of gestodene, on plasma concentrations of markers of endothelial function and on ultrasonographic parameters of vascular function in healthy postmenopausal women.


METHODS
In a 15-month, randomized, double-blind, placebo-controlled study, 152 healthy hysterectomized postmenopausal women received daily doses of placebo (n = 49), 50 microg of transdermal 17ss-estradiol (tE2, n = 33), 1 mg of oral E2 (oE2, n = 37), or 1 mg of oral estradiol combined with 25 microg of gestodene (oE2+ G, n = 33) for 13 cycles of 28 days, followed by four washout cycles with placebo in each group. At baseline and in cycles 4, 13, and 17, we measured plasma levels of endothelial markers and ultrasonographic markers of vascular function (pulsatility index [PI] and, at baseline and cycle 13, arterial stiffness).


RESULTS
Compared with placebo, we found reductions in soluble vascular cell adhesion molecule (oE2, P < 0.01; oE2+ G, P < 0.001), sE-selectin (oE2 + G, P < 0.05), von Willebrand factor (tE2, P < 0.05), and divergent effects in PI and stiffness parameters in the carotid artery. We found no effect on PI in the retinal and femoral arteries, or on stiffness parameters in the femoral and brachial artery.


CONCLUSIONS
Oral hormone therapy reduced plasma levels of adhesion molecules, whereas transdermal estrogen therapy reduced von Willebrand factor. Effects on ultrasonographic parameters of vascular function in the carotid artery were inconclusive.
Hemelaar
Majoie
M
Project 'Aging Women' , Department of Obstetrics, VU University Medical Center Amsterdam, The Netherlands.
van der Mooren
Marius J
MJ
van Baal
W Marchien
WM
Schalkwijk
Casper G
CG
Kenemans
Peter
P
Stehouwer
Coen D A
CD
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009652:Norpregnenes / Q000008:administration & dosage*; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage*; D011673:Pulsatile Flow; D018615:Ultrasonography, Doppler, Color; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D019040:E-Selectin; D009652:Norpregnenes; D011372:Progestins; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; C033273:Gestodene; D004958:Estradiol