Estrogen use in general has been associated with increased risk of venous thromboemboli and has been shown to activate dose-dependently coagulation pathways. We have recently shown that estrogen therapy of conventional dosage potentiates fibrinolysis in postmenopausal women, a process that could be a consequence of primary estrogen-induced coagulation activation. To assess the mechanism of estrogen-induced fibrinolysis, we measured parameters of coagulation activation [prothrombin Framents1+2 (F1+2), thrombin-antithrombin (TAT) complexes] and parameters of fibrinolysis potentiation [tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) activities] at baseline and following one month of conjugated equine estrogen .625 mg administered to 9 postmenopausal women. We found that conjugated equine estrogen marginally increased F1+2 by 18+/-31% (p=.14) and nonsignificantly increased TAT by 6+/-50% (p=1.00). Conjugated estrogen reduced PAI-1 activity by 38+/-30% (p=.03) and increased t-PA activity of 68+/-85% (p=.09). There was no association between % delta TAT and % delta t-PA (r=.05), and the associations between % delta TAT and % delta PAI-1 (R=.393), % delta F1+2 and % delta t-PA (r=-.60) or % delta F1+2 and % delta PAI-1 (r=.527) were directionally opposite anticipated correlations if potentiation of fibrinolysis was the result of coagulation activation. We conclude that potentiation of fibrinolysis is a primary effect of conjugated equine estrogen at the dosage used in our study and likely accounts for low risk of venous thromboemboli in postmenopausal women taking the conventional dosage of this preparation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL005002-01
Application #
6162753
Study Section
Cell Biology Integrated Review Group (CB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1997
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Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
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Country
United States
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