Differential impact of conventional-dose and low-dose postmenopausal hormone therapy, tibolone and raloxifene on C-reactive protein and other inflammatory markers

Background: Postmenopausal hormone therapy (HT) is associated with an increased risk for arterial and venous thrombosis. Objectives: To compare the impact of HT, tibolone, and raloxifene on C-reactive protein (CRP) and other inflammatory markers, and to investigate possible underlying mechanisms for changes in CRP and D-dimer. Methods: Two hundred and two healthy women were randomly assigned to treatment for 12 weeks with either low-dose HT containing 1 mg of 17 beta-estradiol and 0.5 mg of norethisterone acetate (NETA) (n = 50), conventional-dose HT containing 2 mg of 17 beta-estradiol and 1 mg of NETA (n = 50), 2.5 mg of tibolone (n = 51), or 60 mg of raloxifene (n = 51). Results: CRP increased in the conventional-dose HT and low-dose HT groups. These changes were significantly more pronounced in the conventional-dose HT group (RMANOVA, P = 0.02). Also, tibolone was associated with an increase in CRP, in contrast to raloxifene, which reduced CRP. Reductions in levels of Lp(a), intercellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin, monocyte chemotactic protein 1 (MCP-1) and interleukin-6 (IL-6) were observed in all treatment groups. The changes were most pronounced for the conventional-dose HT group, and least pronounced for the raloxifene group, whereas the changes in those allocated to tibolone and low-dose HT were intermediary. Increased levels of tumor necrosis factor (TNF)-alpha and von Willebrand factor (VWF) were seen in the raloxifene group. We observed positive associations between changes in IL-6, VWF, MCP-1, and CRP. Conclusions: The regimens had markedly different impacts on markers of inflammation. The average increase in CRP was not accompanied by increases in the average levels of IL-6, TNF-alpha or other markers, but women with large reductions in IL-6 had reduced increases in CRP.