Effect of estradiol valerate alone or in association with cyproterone acetate upon vascular function of postmenopausal women at increased risk for cardiovascular disease.
OBJECTIVE
a large body of evidence has been accumulated suggesting that impairment of vascular endothelial function is an initial step in the development of atherosclerosis. Recent studies have shown that estrogen replacement therapy in postmenopausal women (PMW) improves endothelium-dependent, flow-mediated dilatation (FMD) while the cyclical adjunct of a progestin may reverse this effect.


METHODS
the purpose of this study was to evaluate endothelium-dependent, FMD in the brachial artery and the plasma levels of Endothelin-1 in menopausal females treated with estradiol valerate with and without cyclical cyproterone acetate in 20 PMW (mean age 64+/-6 years) with more than one risk factor for coronary artery disease. After a baseline evaluation, PMW entered a double-blinded, placebo controlled single cross-over study and were randomized to receive either estradiol valerate (2 mg) for 21 days or estradiol valerate (2 mg) for 11 days and estradiol valerate (2 mg) and cyproterone acetate (1 mg) for 10 days. Patients were crossed-over the complementary treatment 7 days after completing the first treatment phase. The study of forearm blood flow was repeated at the end of each treatment period.


RESULTS
estradiol valerate significantly increased FMD as compared with baseline (12+/-3 vs. 7+/-4%, P<0.01) the adjunct of cyproterone acetate did not affect the effect of estradiol valerate upon FMD (12+/-3 vs. 11+/-4%, P=NS). Similarly reactive hyperemic flow increased after estradiol valerate alone (24%) or in association with cyproterone acetate (24%) compared with baseline. Plasma levels of Endothelin-1 were significantly reduced by estradiol valerate alone or in association with cyproterone acetate.


CONCLUSIONS
in conclusion hormone replacement therapy with estradiol valerate and cyproterone acetate improves endothelial function and reduces plasma levels of Endothelin-1 in PMW at risk of coronary artery disease. These effects may be relevant for cardioprotection.
Vitale
C
C
Department of Internal Medicine, Cardiovascular Research Unit, Via della Pisana 235, San Raffaele-Roma, TOSINVEST SANITA', 00163 Rome, Italy.
Fini
M
M
Leonardo
F
F
Rossini
P
P
Cerquetani
E
E
Onorati
D
D
Rosano
G M
GM
D001916:Brachial Artery / Q000502:physiology; D003324:Coronary Artery Disease / Q000517:prevention & control*; D018592:Cross-Over Studies; D017373:Cyproterone Acetate / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D005542:Forearm / Q000098:blood supply; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D045167:Progesterone Congeners / Q000008:administration & dosage*; D012039:Regional Blood Flow; D016896:Treatment Outcome
D019332:Endothelin-1; D004966:Estrogens, Conjugated (USP); D045167:Progesterone Congeners; D017373:Cyproterone Acetate; D004958:Estradiol