Effect of postmenopausal hormones on inflammation-sensitive proteins - ThePostmenopausal Estrogen/Progestin Interventions (PEPI) Study

Background-Observational studies in healthy women suggest postmenopausal ho rmone therapy reduces risk of coronary events. In contrast, in a recent cli nical trial of women with coronary disease, a subgroup analysis demonstrate d increased risk during the early months of therapy. Because higher levels of inflammation factors predict vascular disease outcomes, the effect of ho rmones on these factors is of interest. Methods and Results-Four inflammation-sensitive factors, C-reactive protein , soluble E-selectin, von Willebrand factor antigen, and coagulation factor VIIIc were measured at baseline, 12, and 36 months in 365 participants of the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomi zed, placebo-controlled trial of the effects of 4 hormone preparations on c ardiovascular disease risk factors. Compared with placebo, all 4 active pre parations resulted in a large sustained increase in the concentration of C- reactive protein and a decrease in soluble E-selectin (P=0.0001), There wer e no effects of treatment on concentrations of von Willebrand factor or fac tor VIIIc. There were no differences in effects among treatment arms. Relat ive to placebo, when combining active treatment arms, final concentrations of C-reactive protein were 85% higher whereas E-selectin was 18% lower comp ared with baseline. Conclusions-Postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein. Such an effect may be related t o adverse early effects of estrogen therapy. In contrast, hormones reduced the concentration of soluble E-selectin, and this might be considered an an ti-inflammatory effect. Because PEPI was not designed to assess clinical en dpoints, studies of the impact of hormone-mediated changes in inflammation on risk of subsequent coronary events are needed.