Cardiovascular Disease Risk and Hormone Replacement Therapy (HRT): A Review Based on Randomised, Controlled Studies in Postmenopausal Women

W.   Marchien van   Baal; Teake   initial   Kooistra; Coen   D.A.   Stehouwer

Abstract

Epidemiological data suggest that the use of oestrogen replacement therapy (ERT) and combined oestrogen / progestagen replacement therapy (HRT) in healthy postmenopausal women is associated with a decreased risk of cardiovascular events. In sharp contrast, the HERS study, a secondary prevention trial in postmenopausal women with established coronary heart disease, did not show a favourable effect, with a trend towards an increased risk of cardiovascular disease in the first year of treatment. This paper provides an overview of randomised, controlled trials (RCTs) in postmenopausal women published in the literature and discusses possible explanations for the contrast between data from the epidemiological studies and the results of the HERS study. ERT and HRT are associated with 1) an improved lipid profile and 2) a decrease in homocysteine and endothelin levels. Data on factor VII and fibrinogen were not consistent. There were insufficient data on the effects on blood pressure, glucose metabolism, vasomotor regulation, arterial stiffness, thrombomodulin, adhesion molecules, and clotting and fibrinolysis, as well as on the effects of route of administration and the role of progestagens. Finally, endothelium-dependent vasodilatation appears to increase with ERT, but the effects of HRT are less clear This paucity of controlled data indicates that, although ERT and HRT improve surrogate measures of risk of atherothrombosis, adverse effects of ERT and HRT on biological mechanisms related to risk of atherothrombosis can by no means be excluded.

Keywords: cardivascular disease Risk, hormone replacement therapy HRT, Postmenopausal women, oestrogen replacement therapy ERT, randomised, controlled trials RCTs, atherothrombosis, CVD, cholesterol, HDL chol, LDT chol, hypercholesterolaemia, blood pressure, ERT, HRT, fibrinogen, plasminogen activator inhibitor 1 PAI1, tissue type plasminogen activator tPA, homocysteine, vasomotor regulation, flow mediated vasodilatation, endothelin, thrombomodulin, soluble adhesion molecules, clotting, fibrinolysis, coagulation system, in vivo fibrinolytic activity