title: Differential impact of conventional-dose and low-dose postmenopausal hormone therapy, tibolone and raloxifene on C-reactive protein and other inflammatory markers.
abstract: BACKGROUND
  Postmenopausal hormone therapy (HT) is associated with an increased risk for arterial and venous thrombosis.
  
  
  OBJECTIVE
  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 17beta-estradiol and 0.5 mg of norethisterone acetate (NETA) (n = 50), conventional-dose HT containing 2 mg of 17beta-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.
authors.affiliation: Department of Haematology, Ullevål University Hospital Trust, Oslo, and Faculty Division Ullevål University Hospital, Oslo, Norway. a.l.eilertsen@medisin.uio.no
authors.forename: A L
authors.initials: AL
authors.lastname: Eilertsen
authors.forename: L
authors.initials: L
authors.lastname: Sandvik
authors.forename: B
authors.initials: B
authors.lastname: Steinsvik
authors.forename: P M
authors.initials: PM
authors.lastname: Sandset
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000096:biosynthesis*; D002448:Cell Adhesion; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007249:Inflammation; D008875:Middle Aged; D009652:Norpregnenes / Q000494:pharmacology*; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D009652:Norpregnenes; D020849:Raloxifene Hydrochloride; D002097:C-Reactive Protein; C027385:tibolone