Different effect of hormone replacement therapy, DHEAS and tibolone on endothelial function in postmenopausal women with increased cardiovascular risk.
Menopause is associated with an increased cardiovascular risk and with a decrease in endothelial function. Hormone replacement therapy (HRT) improves endothelial function in post-menopausal women (PMW) without established atherosclerosis. New alternative treatments, among which tibolone (T) and DHEAS have been suggested to reduce postmenopausal cardiovascular risk. Although, in vitro animal studies have suggested that T and DHEAS improve endothelial function, their effect in humans has never been tested. The aim of the present study was to compare the effects of HRT (continuous combined 0.625 mg conjugated equine estrogen plus 2.5 mg/d medoxyprogesterone) DHEAS and T on endothelium-dependent flow-mediated vasodilatation (FMD), plasma nitrite, nitrate and endothelin-1 levels in 16 PMW with increased cardiovascular risk in a double-blinded, double-crossover study. Women were randomized and treated for 4 weeks with HRT, T or DHEAS. Brachial artery diameter, FMD, endothelin-1 and plasma nitrite and nitrate levels were measured at baseline and after each treatment phase. Brachial artery diameters remained unchanged after each treatment phase. HRT significantly improved FMD compared to both baseline and to T and DHEAS therapies while no effect of T or DHEAS on FMD was noted. In conclusion, HRT, but neither T nor DHEAS, improves endothelial function and reduces plasma levels of endothelin-1 in PMW at risk of CAD.
Silvestri
Antonello
A
Department of Medical Sciences, Cardiovascular Research Unit, San Raffaele--Roma, TOSINVEST Sanita', via della Pisana 235, 00163 Roma, Italy.
Gambacciani
Marco
M
Vitale
Cristiana
C
Monteleone
Patrizia
P
Ciaponi
Massimo
M
Fini
Massimo
M
Genazzani
Andrea R
AR
Mercuro
Giuseppe
G
Rosano
Giuseppe M C
GM
D001916:Brachial Artery / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology*; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008525:Medroxyprogesterone / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D005996:Nitroglycerin; D009652:Norpregnenes / Q000494:pharmacology* / Q000627:therapeutic use; D017698:Postmenopause; D011673:Pulsatile Flow; D012039:Regional Blood Flow; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D004966:Estrogens, Conjugated (USP); D009566:Nitrates; D009573:Nitrites; D009652:Norpregnenes; D003687:Dehydroepiandrosterone; C027385:tibolone; D005996:Nitroglycerin; D008525:Medroxyprogesterone