title: Circulating chemoattractants RANTES, negatively related to endogenous androgens, and MCP-1 are differentially suppressed by hormone therapy and raloxifene.
abstract: BACKGROUND
  The cardinal role of chronic inflammation in the development of atherosclerosis is increasingly being recognized. Estrogens may prevent the evolution of atherosclerosis by suppressing immune response. Furthermore, the conflicting reports on the cardiovascular effects of hormone therapy between observational and clinical trials have triggered interest on the effect of alternative therapies on the cardiovascular system.
  
  
  OBJECTIVE
  The aim of this study was to assess the effect of estrogen, estrogen-progestin, tibolone and raloxifene therapy on circulating markers of chemotaxis in healthy postmenopausal women.
  
  
  METHODS
  Eighty-eight postmenopausal women aged 44-62 years were randomly allocated to daily: (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured at baseline and at 3 months.
  
  
  RESULTS
  Endogenous testosterone and free androgen index (FAI) correlated negatively, while SHBG correlated positively with serum RANTES (testosterone: r=-0.27, p=0.033; FAI: r=-0.43, p=0.004: SHBG: r=0.34, p=0.026). Serum MCP-1 decreased significantly in the CEE group (baseline 125.3+/-51 pg/ml, 3 months 84.5+/-36.1 pg/ml, p=0.043), while no difference was detected between baseline and post-treatment levels in the other groups. Furthermore, a significant decrease in serum RANTES was observed at the end of 3 months only in the E2/NETA and the raloxifene group (E2/NETA baseline 8690.6+/-3880.0 pg/ml, 3 months 6894.0+/-1720.0 pg/ml, p=0.007; raloxifene baseline 9042.4+/-3765.6 pg/ml, 3 months 6718.1+/-2366.2 pg/ml, p=0.011).
  
  
  CONCLUSIONS
  Endogenous androgens may suppress chemotactic response. Postmenopausal hormone therapy and raloxifene may inhibit the expression of chemoattractant molecules and thus attenuate inflammation. The relevance of these findings in terms of clinically established caridoprotection remains to be clarified.
authors.affiliation: 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital, Athens, Greece.
authors.forename: George E
authors.initials: GE
authors.lastname: Christodoulakos
authors.forename: Irene V
authors.initials: IV
authors.lastname: Lambrinoudaki
authors.forename: Emmanuel V
authors.initials: EV
authors.lastname: Economou
authors.forename: Constantinos
authors.initials: C
authors.lastname: Papadias
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vitoratos
authors.forename: Constantinos P
authors.initials: CP
authors.lastname: Panoulis
authors.forename: Evangelia E
authors.initials: EE
authors.lastname: Kouskouni
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Vlachou
authors.forename: George C
authors.initials: GC
authors.lastname: Creatsas
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood*; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D002319:Cardiovascular System / Q000187:drug effects; D018932:Chemokine CCL2 / Q000097:blood*; D018946:Chemokine CCL5 / Q000097:blood*; D002633:Chemotaxis / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives / Q000494:pharmacology; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000494:pharmacology; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*
chemical_list: D000728:Androgens; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone