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.


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.
Eilertsen
A L
AL
Department of Haematology, Ullevål University Hospital Trust, Oslo, and Faculty Division Ullevål University Hospital, Oslo, Norway. a.l.eilertsen@medisin.uio.no
Sandvik
L
L
Steinsvik
B
B
Sandset
P M
PM
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*
D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D009652:Norpregnenes; D020849:Raloxifene Hydrochloride; D002097:C-Reactive Protein; C027385:tibolone