Premium
Impact of Menopausal Hormone Treatments on Intravascular Cellular Activation and Development of White Matter Hyperintensities in Healthy Postmenopausal Women
Author(s) -
Jayachandran Muthuvel,
Lahr Brian D.,
Miller Virginia M.,
Kantarci Kejal
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.517.7
Subject(s) - thrombogenicity , medicine , estrogen , hyperintensity , placebo , hormone replacement therapy (female to male) , endocrinology , platelet activation , hormone , fibrinogen , estrone , platelet , pathology , magnetic resonance imaging , testosterone (patch) , alternative medicine , radiology
Objective Blood thrombogenicity and vascular inflammation may influence development of white matter hyperintensities (WMH) in the brain. This study aimed to determine if menopausal hormone treatments (MHT) modified that association in recently menopausal women who were enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic. Methods Women (n=95) underwent MRI prior to and at 18, 36 and 48 months after randomization to either transdermal 17β‐estradiol (tE2, n=30), conjugated equine estrogen (oCEE, n=29) both with progesterone for 12 days per month or placebo pills and patch (PBO, n=36). Fasting blood was analyzed for a set of 14 activation markers of platelets and endothelial cells, inflammation, and thrombogenicity. Principal components (PC) analysis was used to reduce dimensionality of these markers, and the first 5 PC identified were then assessed for association with treatment and changes in WMH. Results WMH increased in all groups over the 48 months of treatment with greater increases in the oCEE compared to tE2 and PBO (P=0.015). The 5 PC explained 62% of the variation in cellular activation markers. A global test of these 5 PC revealed a borderline association with treatment group (P=0.059), with the PC reflecting total platelet count, platelet microaggregates and ATP secretion showing higher scores in the oCEE compared to the other groups (P=0.006). The change in WMH over the 48 months of MHT showed an overall association with the 5 PC (P=0.026), the most prominent of which was the first PC reflecting vascular inflammation by number of blood microveicles (MV) from activated monocytes and endothelial cells and MV positive for intercellular adhesion molecule 1 (P=0.001). There was no evidence that this association differed by MHT. Conclusion Markers of blood thrombogenicity and inflammation may influence development of WMH in the brain but this relationship may be influenced by factors other than the type of MHT used in the KEEPS study. Support or Funding Information NIH P50 AG44170 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .