title: Effect of lower dosage of oral conjugated equine estrogen on inflammatory markers and endothelial function in healthy postmenopausal women.
abstract: OBJECTIVE
  Although oral estrogen replacement therapy (ERT) in postmenopausal women improves endothelial function, it also increases plasma C-reactive protein (CRP) and interleukin-6 (IL-6) concentration. The proinflammatory effect of oral ERT may explain the increased risk of coronary heart disease (CHD) associated with this treatment. Recent observational studies have demonstrated that a lower dose of oral estrogen reduces the risk for CHD. The purpose of the present study was to investigate the effects of low-dose oral estrogen on vascular inflammatory markers and endothelium-dependent vasodilation in postmenopausal women.
  
  
  RESULTS
  Postmenopausal women were randomized into 3 groups to receive no treatment (n=14) or oral conjugated equine estrogen (CEE) at a dosage of 0.625 mg (n=15) or 0.3125 mg (n=15) daily for 3 months. CEE at a dosage of 0.625 mg resulted in significant increases in plasma concentrations of CRP from 690.9+/-749.5 to 1541.9+/-1608.0 ng/mL, serum amyloid A from 6.12+/-4.15 to 8.25+/-4.40 microg/mL, and IL-6 from 1.45+/-0.73 to 2.35+/-1.16 pg/mL. In contrast, CEE at a dosage of 0.3125 mg had no effect on these inflammatory markers. Both dosages of estrogen significantly decreased E-selectin concentration, whereas the concentrations of intercellular and vascular cell adhesion molecules remained unchanged. In both CEE groups, flow-mediated vasodilation in the brachial artery was increased significantly, whereas nitroglycerine-induced vasodilation was unaltered.
  
  
  CONCLUSIONS
  Oral CEE at a low dose of 0.3125 mg in postmenopausal women eliminated the adverse effects of high-dosage oral CEE on vascular inflammatory markers in addition to preserving the favorable effects of estrogen on cell adhesion molecules and endothelial function.
authors.affiliation: Department of Obstetrics and Gynecology, Kochi Medical School, Oko-cho, Nankoku, Kochi, Japan. wakatuki@kochi-ms.ac.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Wakatsuki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ikenoue
authors.forename: Koichi
authors.initials: K
authors.lastname: Shinohara
authors.forename: Kazushi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Takao
authors.initials: T
authors.lastname: Fukaya
mesh_terms: D000284:Administration, Oral; D015415:Biomarkers; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000097:blood; D003327:Coronary Disease / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D007564:Japan / Q000453:epidemiology; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D015588:Observer Variation; D017698:Postmenopause / Q000097:blood / Q000187:drug effects* / Q000502:physiology; D012016:Reference Values; D012306:Risk; D000685:Serum Amyloid A Protein / Q000032:analysis*; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D004966:Estrogens, Conjugated (USP); D006728:Hormones; D015850:Interleukin-6; D008055:Lipids; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D005996:Nitroglycerin