title: Postmenopausal oral estrogen therapy affects hemostatic factors, but does not account for reduction in the progression of subclinical atherosclerosis.
abstract: BACKGROUND
  Hemostatic factors influenced by postmenopausal hormone therapy may contribute to atherosclerosis. The Estrogen in the Prevention of Atherosclerosis Trial (EPAT), a 2-year, randomized, double-blind, placebo-controlled trial, demonstrated reduced subclinical atherosclerosis progression measured by change in common carotid artery intima-media thickness (CIMT) with unopposed oral 17beta-estradiol.
  
  
  OBJECTIVE
  To assess the effect of postmenopausal hormone therapy on the levels of several hemostatic factors, and the relationship between these factors and the progression of subclinical atherosclerosis.
  
  
  METHODS
  We measured tissue plasminogen activator (t-PA) antigen, factor (F) VII, D-dimer and albumin longitudinally, and plasminogen activator inhibitor type 1 (PAI-1) and fibrinogen at trial-end, in 186 postmenopausal women.
  
  
  RESULTS
  Estradiol vs. placebo was associated with greater FVII and lower t-PA, albumin, PAI-1 and fibrinogen (all P < or = 0.001), with no estradiol effect on D-dimer (P = 0.42). Only mean on-trial t-PA was positively associated with the absolute level of CIMT on-trial (r = 0.29, P < 0.0001), but this was attenuated with age and body mass index adjustment. No longitudinally measured hemostatic factor was associated with CIMT progression. However, higher CIMT during the trial was significantly related to increases in t-PA.
  
  
  CONCLUSIONS
  These results confirm previous findings regarding estrogen's effect on hemostatic factors and show that albumin is negatively associated with estrogen therapy. These hemostatic factors did not account for the reduction of CIMT progression with 17beta-estradiol seen in EPAT. Atherosclerosis itself may affect levels of hemostatic factors (reverse causality), with subsequent involvement in atherosclerosis-associated thrombosis.
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: C
authors: C
authors: Vigen
authors: H N
authors: HN
authors: Hodis
authors: W L
authors: WL
authors: Chandler
authors: R A
authors: RA
authors: Lobo
authors: W J
authors: WJ
authors: Mack
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D017536:Carotid Artery, Common / Q000473:pathology; D004311:Double-Blind Method; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005167:Factor VII / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D012709:Serum Albumin; D004958:Estradiol; D005167:Factor VII; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator