Hormone replacement therapy: prothrombotic vs. protective effects.

Hormone replacement therapy (HRT) is associated with reduced risk of coronary heart disease (CHD) and stroke in observational studies; however the possibility of confounding by other risk factors requires prospective assessment of its risks and benefits in randomised controlled trials. The HERS trial of oral HRT in secondary CHD prevention observed an early increased risk of myocardial infarction (MI) and venous thromboembolism (VTE) with HRT: the latter risk has been confirmed by other prospective and case-control studies, and a past history of VTE or MI is now a contraindication to oral HRT. Other prospective randomised trials of HRT, CHD and stroke are in progress. Potential prothrombotic effects of oral HRT (but probably not transdermal HRT) include increased plasma factors VII and IX, activated protein C resistance and C-reactive protein; and decreased antithrombin, protein C and S, and tissue factor pathway inhibitor. Potential protective effects of HRT include decreased blood pressure, lipids, glucose intolerance, fibrinogen, viscosity and plasminogen activator inhibitor; and increased endothelial function. The overall balance of prothrombotic and protective effects varies with HRT preparations and individual women: and may be clarified by ongoing large randomised trials and case-control studies (and substudies of trials).