title: Impaired procoagulant-anticoagulant balance during hormone replacement therapy? A randomised, placebo-controlled 12-week study.
abstract: In this randomised, placebo-controlled 12-week study, sixty healthy postmenopausal women received either placebo (N = 16) or daily 2 mg micronised oestradiol, either unopposed (N = 16, E2 group) or combined with a progestagen for 14 days of each cycle (N = 28, E2+P group).
  
  
  RESULTS
  As compared to placebo, plasma levels of AT III were reduced only in the E2 group (approximately 28%), plasma levels of protein C decreased only in the E2+P group (approximately 4%) and plasma levels of protein S decreased in both the E2 and E2+P group (approximately 21%). In both the E2 and E2+P groups, the plasma levels of factor VII (antigen and activity) showed a borderline significant increase (approximately 10%), whereas no significant change was observed in active factor VII. Plasma levels of tissue-type plasminogen activator (approximately 22%), urokinase plasminogen activator (approximately 25%) and plasminogen activator inhibitor type-1 (approximately 43%) decreased in the E2 and E2+P groups, whereas those of plasminogen increased (approximately 12%). Treatment was associated with an increase in levels of prothrombin fragment 1+2 (approximately 31%), but levels of thrombin-antithrombin III complexes, and of plasmin-alpha2-antiplasmin complexes and total fibrin(ogen) degradation products did not change significantly.
  
  
  CONCLUSIONS
  Short-term E2 and E2+P treatment is associated with a shift in the procoagulant-anticoagulant balance towards a procoagulant state. A substantial proportion of women do not have a net increase in fibrinolytic activity. These data may be relevant in explaining the increased risk of venous thromboembolism associated with ERT and HRT, and possibly also in explaining the negative results of the Heart and Estrogen/progestin Replacement Study.
authors.affiliation: Department of Obstetrics & Gynaecology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: W M
authors.initials: WM
authors.lastname: van Baal
authors.forename: J J
authors.initials: JJ
authors.lastname: Emeis
authors.forename: M J
authors.initials: MJ
authors.lastname: van der Mooren
authors.forename: H
authors.initials: H
authors.lastname: Kessel
authors.forename: P
authors.initials: P
authors.lastname: Kenemans
authors.forename: C D
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011372:Progestins; D004958:Estradiol