Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy

Objective: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. Design: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. Results: In all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% ± 11%, intracellular adhesion molecule: -21% ± 4%, vascular cell adhesion molecule: -15% ± 6%, E-selectin: -18% ± 4%, s-thrombomodulin -10.5% ± 3.7%, IL-6 -14% ± 6%; percent changes, P <0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% ± 8%, intracellular adhesion molecule: -3% ± 2%, vascular cell adhesion molecule: -5% ± 2%, E-selectin: +6% ± 2%, s-thrombomodulin: +5% ± 2%, IL-6: +12% ± 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. Conclusions: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.