Hormone therapies and vascular outcomes: who is at risk?

Postmenopausal hormone replacement therapy (HRT), such as estrogen with a progestin (E+P), is associated with an increased risk of myocardial infarction (MI), stroke, and venous thrombosis. Subgroups of susceptible women for these clinical outcomes have not been clearly identified, although women with a prior history of venous thrombosis and women with factor V Leiden are at higher risk of venous thrombosis on HRT than others. Effects of HRT on atherosclerosis, coagulation, and inflammation have been investigated, and might improve our understanding of the pathogenesis of this drug effect. In 2 trials E+P did not alter the progression of coronary atherosclerosis, while in a third trial unopposed estradiol retarded atherosclerosis progression in the carotid arteries. HRT is associated with an increase in high-sensitivity C-reactive protein (CRP), an inflammation marker associated with arterial disease risk, and an increase in activated protein C resistance, the biochemical defect associated with factor V Leiden. Given recent data, the only current indication for E+P is the short-term treatment of symptoms of estrogen deficiency, such as hot flashes. Testing for coagulation disorders or inflammatory factors, such as factor V Leiden or CRP, for use in decision-making about HRT use would be premature in unselected patients. Further research is needed to identify pathophysiological mechanisms of vascular harm from these hormones.