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Differential effects of estradiol on carotid artery inflammation when administered early versus late after surgical menopause.
MedLine Citation:
PMID:  23321944     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: The aim of this study was to determine the effects of estrogen therapy (ET) on carotid artery inflammation when initiated early and late relative to surgical menopause. METHODS: Female cynomolgus macaques consuming atherogenic diets were ovariectomized and randomized to control or oral estradiol (E2; human equivalent dose of 1 mg/d micronized E2) initiated at 1 month (early menopause, n = 24) or 54 months (late menopause, n = 40) after ovariectomy. The treatment period was 8 months. Carotid artery expression of the markers of monocyte/macrophages (CD68 and CD163), dendritic cells (CD83), natural killer cells (neural cell adhesion molecule-1), and interferon-γ was significantly lower in E2-treated animals in the early menopause group but not in the late menopause group (P < 0.05). In contrast, carotid artery transcripts for T-cell markers (CD3, CD4, CD8, and CD25), interleukin-10, type I collagen, monocyte chemoattractant protein-1, matrix metalloproteinase-9, and tumor necrosis factor-α were lower in E2-treated monkeys regardless of menopausal stage (P < 0.05). CONCLUSIONS: ET initiated soon after menopause inhibits macrophage accumulation in the carotid artery, an effect that is not observed when E2 is administered after several years of estrogen deficiency. No evidence for pro-inflammatory effects of late ET is observed. The results provide support for the timing hypothesis of postmenopausal ET with implications for the interpretation of outcomes in the Women's Health Initiative.
Authors:
Areepan Sophonsritsuk; Susan E Appt; Thomas B Clarkson; Carol A Shively; Mark A Espeland; Thomas C Register
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-14
Journal Detail:
Title:  Menopause (New York, N.Y.)     Volume:  -     ISSN:  1530-0374     ISO Abbreviation:  Menopause     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9433353     Medline TA:  Menopause     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
From the 1Section on Comparative Medicine, Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC; 2Reproductive Endocrinology and Infertility Unit, Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; and 3Division of Public Health Sciences, Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
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