The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: A randomized, controlled trial

C-Reactive protein and homocysteine are independent risk factors for the de velopment of cardiovascular disease. This study compared the effects of hor mone replacement therapy (HRT) and raloxifene on serum C-reactive protein a nd homocysteine levels as markers of cardiovascular risk in healthy postmen opausal women. Healthy postmenopausal women (n = 390) were enrolled in a do uble blind, randomized, placebo-controlled, B-month trial at eight out-pati ent sites in the United States. Women were randomly assigned to receive con tinuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/da y medroxyprogesterone acetate), raloxifene (60 or 120 mg/day), or placebo f or 6 months. C-Reactive protein and homocysteine were measured in baseline and B-month serum samples. HRT increased C-reactive protein levels by 84% ( P < 0.001), whereas raloxifene (60 and 120 mg/day) had no significant effec t (-6% and -4%, respectively; P > 0.2). Raloxifene (60 and 120 mg/day) sign ificantly lowered serum levels of homocysteine by 8% (P = 0.014) and 6% (P = 0.024), respectively, similar to the 7% (P = 0.014) reduction obtained wi th HRT. We conclude that HRT and raloxifene lower serum homocysteine levels to a co mparable extent in postmenopausal women. Whereas cardiovascular risk predic ted by C-reactive protein in healthy postmenopausal women is not influenced by raloxifene, the relationship between elevated C-reactive protein levels with HRT and cardiovascular disease events requires further study.