title: Association of Serum Sex Hormones with Hemostatic Factors in Women On and Off Hormone Therapy: The Multiethnic Study of Atherosclerosis.
abstract: BACKGROUND
  Hormone therapy (HT) is associated with increased risk of both venous and arterial thrombosis, which are multifactorial in origin.
  
  
  OBJECTIVE
  Our objectives were twofold: first, we sought to examine associations between endogenous serum sex hormone levels and biomarkers of thrombosis and/or coagulation in postmenopausal hormone nonusers. Second, we separately studied the associations between serum sex hormone levels and biomarkers of thrombosis and/or coagulation in postmenopausal hormone users considering the fact that pattern of circulating hormones is different in women taking exogenous hormones.
  
  
  METHODS
  We performed a cross-sectional analysis of postmenopausal women enrolled in a large multiethnic community-based cohort study, The Multiethnic Study of Atherosclerosis. We hypothesized that higher levels of estrogen-related sex hormones would be associated with biomarkers of thrombosis, suggesting mechanisms for differences in thrombotic risk from HT. Women (n = 2878) were included if they were postmenopausal and had thrombotic biomarkers (homocysteine, fibrinogen, C-reactive protein [CRP], factor VIII, and d-dimer) and sex hormone levels (total testosterone [T], bioavailable testosterone, sex hormone binding globulin [SHBG], estradiol [E2], and dehydroepiandrosterone [DHEA]) measured. A smaller random sample of 491 women also had von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1), and tissue factor pathway inhibitor (TFPI) levels measured.
  
  
  CONCLUSIONS
  We found that elevated levels of estradiol and SHBG in HT users were associated with elevated levels of CRP and lower levels of TFPI, both of which may be related to a prothrombotic milieu in HT users. HT nonusers had far more prothrombotic associations between elevated serum sex hormone levels and thrombotic biomarkers when compared with HT users.
authors.affiliation: 1 Department of Medicine, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Marlene S
authors.initials: MS
authors.lastname: Williams
authors.affiliation: 2 Department of Medicine, The University of Vermont , Colchester, Vermont.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: 1 Department of Medicine, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ouyang
authors.affiliation: 3 Department of Epidemiology, University of Washington , Seattle, Washington.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: 1 Department of Medicine, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Rita Rastogi
authors.initials: RR
authors.lastname: Kalyani
authors.affiliation: 1 Department of Medicine, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Dhanajay
authors.initials: D
authors.lastname: Vaidya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003430:Cross-Sectional Studies; D003687:Dehydroepiandrosterone / Q000097:blood*; D004958:Estradiol / Q000097:blood*; D015914:Estrogen Replacement Therapy; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006490:Hemostatics; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008137:Longitudinal Studies; D008875:Middle Aged; D017698:Postmenopause; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D012739:Gonadal Steroid Hormones; D006490:Hemostatics; D008074:Lipoproteins; D012738:Sex Hormone-Binding Globulin; C036309:fibrin fragment D; C051928:lipoprotein-associated coagulation inhibitor; D003687:Dehydroepiandrosterone; D004958:Estradiol; D002097:C-Reactive Protein