Effects of hormone therapy on C-reactive protein and IL-6 in postmenopausal women: a review article

The results of the Women's Health Initiative, showing an increase in coronary heart disease events in postmenopausal women on estrogen and medroxyprogesterone acetate, have created considerable interest in finding an underlying mechanism that may confer cardiovascular risk in women on hormone therapy (HT). Inflammation is thought to play a key role in the progression of atherosclerosis. C-reactive protein (CRP) is an inflammatory marker that has been studied as a predictor of future coronary risk. Interleukin 6 (IL-6) is felt to be an important cytokine in the inflammatory cascade and instrumental in CRP expression. The purpose of this article is to summarize the observational and randomized studies that examine the difference in IL-6 and CRP concentrations with respect to oral versus transdermal hormone therapy. We also review studies looking at differences in CRP levels based on the progestin component of HT and trials examining the effect of estrogen agonists on IL-6 and CRP. In our review, we found CRP levels to be elevated in the majority of postmenopausal women on oral HT. There was no correlation between IL-6 and CRP levels. Studies examining the effect of progestins produced varying results. Transdermal estrogen, in contrast, showed no elevation in levels of IL-6 or CRP alone or with the addition of progestins. Selective estrogen receptor agonists (SERMs) did not demonstrate an effect on CRP levels, although tibolone did increase CRP in one reviewed trial. Questions remain about the role of progestins and transdermal HT therapy in the inflammatory process and the underlying mechanism of CRP activation. More research is needed to understand how HT may be involved in the inflammatory process.