Effect of lower dosage of oral conjugated equine estrogen on inflammatory markers and endothelial function in healthy postmenopausal women.
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.
Wakatsuki
Akihiko
A
Department of Obstetrics and Gynecology, Kochi Medical School, Oko-cho, Nankoku, Kochi, Japan. wakatuki@kochi-ms.ac.jp
Ikenoue
Nobuo
N
Shinohara
Koichi
K
Watanabe
Kazushi
K
Fukaya
Takao
T
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
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