Document Detail

Differential effects of estradiol on carotid artery inflammation when administered early versus late after surgical menopause.
MedLine Citation:
PMID:  23615645     Owner:  NLM     Status:  MEDLINE    
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.
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; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Menopause (New York, N.Y.)     Volume:  20     ISSN:  1530-0374     ISO Abbreviation:  Menopause     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-25     Completed Date:  2014-01-06     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  9433353     Medline TA:  Menopause     Country:  United States    
Other Details:
Languages:  eng     Pagination:  540-7     Citation Subset:  IM    
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MeSH Terms
Antigens, CD / genetics,  metabolism*
Atherosclerosis / complications
Carotid Artery Diseases / drug therapy*,  etiology,  metabolism*
Cholesterol, HDL / blood
Collagen Type I / genetics,  metabolism
Cytokines / genetics,  metabolism*
Diet, Atherogenic
Estradiol / administration & dosage*,  blood,  therapeutic use
Estrogens / administration & dosage*,  blood,  therapeutic use
Gene Expression
Inflammation / drug therapy,  etiology,  metabolism
Macrophages / metabolism
Matrix Metalloproteinase 9 / genetics,  metabolism
RNA / metabolism
T-Lymphocytes / metabolism
Time Factors
Grant Support
Reg. No./Substance:
0/Antigens, CD; 0/Cholesterol, HDL; 0/Collagen Type I; 0/Cytokines; 0/Estrogens; 4TI98Z838E/Estradiol; 63231-63-0/RNA; EC Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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