endothelin-1 and tibolone

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.

Topics: Brachial Artery; Cardiovascular Diseases; Cross-Over Studies; Dehydroepiandrosterone; Double-Blind Method; Endothelin-1; Endothelium, Vascular; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Forearm; Humans; Medroxyprogesterone; Middle Aged; Nitrates; Nitrites; Nitroglycerin; Norpregnenes; Postmenopause; Pulsatile Flow; Regional Blood Flow; Treatment Outcome; Vasodilation

To assess risk factors for cardiovascular disease in healthy postmenopausal women who had been uninterruptedly on menopausal hormone replacement therapy (HRT) for at least 5 years or who had not received any HRT.. Cross-sectional study.. The Royal Free Hospital and The Middlesex Hospital.. A total of 256 healthy postmenopausal women were analyzed: 73 were taking tibolone, 60 were taking transdermal E(2), 58 were taking conjugated equine estrogens (E), and 65 were not taking any menopausal therapy.. Cardiovascular disease risk factors measurement.. Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, lipoprotein(a), insulin, glycated hemoglobin, high sensitivity C-reactive protein, fibrinogen, total antioxidants, and endothelin-1.. The different types of HRT induced disparate changes in the various markers of cardiovascular disease. Significantly higher high sensitivity C-reactive protein concentrations were found in women receiving conjugated equine E and tibolone than in women who were not taking any therapy. Glycated hemoglobin was significantly lower in women receiving transdermal E(2) and tibolone compared to women not on HRT. Women on tibolone had significantly higher systolic blood pressure.. Because high sensitivity C-reactive protein has recently emerged as an important predictor of cardiovascular disease, the higher high sensitivity C-reactive protein levels observed in women on conjugated equine estrogens and on tibolone have potential important clinical implications.

Topics: Administration, Cutaneous; Aged; Antioxidants; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Endothelin-1; Estradiol; Estrogen Receptor Modulators; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Fibrinogen; Glycated Hemoglobin; Humans; Insulin; Lipids; Middle Aged; Norpregnenes; Postmenopause; Risk Factors