title: Hormone replacement therapy in healthy postmenopausal women: a randomized, placebo-controlled study of effects on coagulation and fibrinolytic factors.
abstract: OBJECTIVE
  To evaluate effects of postmenopausal hormone replacement therapy (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen, antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and resistance to activated protein C.
  
  
  METHODS
  Part 1: double blind randomized trial for 3 months. Part 2: open study for 9 months.
  
  
  METHODS
  Department of Endocrinology, University Hospital, Malmö, Sweden.
  
  
  METHODS
  Fifty-one postmenopausal women with a history of amenorrhoea of at least 6 months and body mass index > or = 24 kg m-2 participated in part 1 and 46 participated in part 2.
  
  
  METHODS
  Randomization for placebo (n=24) or HRT (n=27). HRT was given as 2 mg oestradiol valerate for the first 3 months, with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter.
  
  
  METHODS
  At baseline and after 3 and 12 months.
  
  
  RESULTS
  During 0-3 months in the HRT group, FVII increased (P < 0.01), whereas fibrinogen, AT III and total protein S all decreased (P < 0.001 for all). Changes in variables were expressed as Delta-values. After 3 months Delta-values differed between groups for fibrinogen (P < 0.05), AT III (P < 0.001), total protein S (P < 0.001), and PAI-1 (P < 0.001). During 0-12 months, fibrinogen, total protein S, tPA (P < 0.01 for all) and AT III (P < 0.05) decreased. In the control group, all variables were unchanged during the study, except for increases (P < 0.05) in total protein S after 3 and 12 months, and a decrease (P < 0.01) in FVIII after 12 months. After 12 months Delta-values differed for fibrinogen (P < 0.05), AT III (P < 0.05) and total protein S (P < 0.001).
  
  
  CONCLUSIONS
  Unopposed oestrogen substitution was associated with both potentially beneficial effects, such as decreases in fibrinogen, and potentially thrombogenic effects such as decreasing AT III and protein S and increasing FVII. During prolonged follow-up and addition of progesterone, differences between groups concerning FVII were attenuated. These data suggest that effects of HRT upon coagulation are most pronounced early after institution of unopposed treatment.
authors: Department of Vascular Diseases, University of Lund, University Hospital, Malmö, Sweden. Anders.Gottsater@medforsk.mas.lu.se
authors: A
authors: A
authors: Gottsäter
authors: M
authors: M
authors: Rendell
authors: U L
authors: UL
authors: Hulthén
authors: E
authors: E
authors: Berntorp
authors: I
authors: I
authors: Mattiasson
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008593:Menopause / Q000502:physiology; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood
chemical_list: D004967:Estrogens; D017395:Plasminogen Activator Inhibitor 1