Dydrogesterone does not reverse the effects of estradiol on endothelium-dependant vasodilation in postmenopausal women: a randomised clinical trial.
OBJECTIVE
The purpose of this study was to evaluate endothelium-dependent flow-mediated dilation (FMD) in the brachial artery and the plasma levels of endothelin-1 in postmenopausal women at risk for coronary artery disease before and after treatment with both estradiol and estradiol plus dydrogesterone.


METHODS
Sixteen postmenopausal women (PMW) (mean age 58+/-9 years) with more than two risk factors for coronary artery disease, were randomized to receive either oral estradiol (2 mg) for 28 days or oral estradiol (2 mg) for 14 days and oral estradiol (2 mg) and dydrogesterone (10 mg) for 14 days, in a double-blind, placebo-controlled, single cross-over study. Patients were crossed-over the complementary treatment 7 days after completing the first treatment. The study of forearm blood flow and the measurement of plasma endothelin-1 levels was carried out before and after each treatment.


RESULTS
Estradiol significantly increased FMD as compared to baseline; the addition of dydrogesterone did not affect the effect of estradiol on FMD. Similarly reactive hyperemic flow increased after estradiol alone or in association with dydrogesterone compared to baseline. Plasma levels of endothelin-1 were significantly reduced by estradiol both when administered alone or in association with dydrogesterone.


CONCLUSIONS
Hormone replacement therapy with estradiol and dydrogesterone improves endothelial function and reduces plasma levels of endothelin-1 in PMW at risk for coronary artery disease.
Gambacciani
Marco
M
Department of Reproductive Medicine and Child development, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy.
Monteleone
Patrizia
P
Vitale
Cristiana
C
Silvestri
Antonello
A
Fini
Massimo
M
Genazzani
Andrea R
AR
Rosano
Giuseppe M C
GM
D018592:Cross-Over Studies; D004311:Double-Blind Method; D004394:Dydrogesterone / Q000494:pharmacology*; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017697:Premenopause; D045167:Progesterone Congeners / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D019332:Endothelin-1; D045167:Progesterone Congeners; D004958:Estradiol; D004394:Dydrogesterone