Objectives: To investigate the effects of conjugated equine estrogen (CEE), CEE plus medroxyprogesterone acetate (MPA), CEE plus Nomegestrol acetate (NA), and raloxifene on serum high sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) levels in healthy postmenopausal women. Materials: One hundred seven healthy postmenopausal women were recruited in a prospective, randomized, and placebo-controlled 6 months study. Of these, 18 were hysterectomized and received daily oral 0.625 mg CEE. Eighty nine non-hysterectomized women were randomly allocated to one of four groups: a group (22 patients) treated with CEE, 0.625 mg/daily plus MPA 2.5 mg/daily; a group (22 patients) treated with CEE, 0.625 mg/daily plus NA 5 mg/daily; a group (23 patients) treated with raloxifene hydrocloride, 60 mg once daily; and a placebo group (22 patients). Hcy and hs-CRP were measured at baseline and at 3 and 6 months. Results: CEE (20%, P = 0.03) and CEE + MPA (59%, P = 0.006) increased serum hs-CRP levels significantly, whereas CEE + NA decreased serum hs-CRP by 25% (P = 0.01). Raloxifene had no significant effect on serum hs-CRP levels during and after the treatment. In all active treatment groups serum Hcy levels decreased significantly compared to baseline and placebo. Conclusions: Conjugated equine estrogen, hormone replacement therapies, and raloxifene lower serum Hcy levels to a comparable extent in postmenopausal women. Hs-CRP, as a cardiovascular risk factor, is not influenced by raloxifene, whereas CEE and CEE plus MPA significantly increase hs-CRP levels. Treatment with CEE plus NA reduces serum hs-CRP levels. (c) 2005 Elsevier Ireland Ltd. All rights reserved.