Postmenopausal hormone replacement therapy and atherosclerosis.

The role of postmenopausal hormone replacement therapy (HRT) in the prevention of cardiovascular disease (CVD) has evolved since estrogen was first proposed to be vasoprotective. The discovery of novel molecular signaling pathways involving the estrogen receptor in vascular cells and the elucidation of numerous biologic mechanisms have suggested that HRT may exert its potentially beneficial or adverse cardiovascular effects through multiple mechanisms. Estrogen has genomic, as well as rapid nongenomic, effects that alter vasodilation, coagulation, inflammation, and the vascular injury response, some of which may have potentially beneficial or adverse cardiovascular consequences. Current guidelines do not support the use of HRT in the secondary prevention of CVD, and recent results of primary prevention trials show evidence of increased early cardiovascular risk and no overall health benefit with combination estrogen-progestin treatment. The role of estrogen alone in the primary prevention of CVD awaits the results of ongoing trials. The key to the use of estrogen replacement therapy for the prevention of CVD may be to target therapy before atherosclerosis is evident, and to identify women with genetic susceptibility who may be at increased risk for an adverse outcome associated with therapy.