Impaired Procoagulant-anticoagulant Balance during Hormone Replacement Therapy?

Summary 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). As compared to placebo, plasma levels of AT III were reduced only in the E2 group (∼28%), plasma levels of protein C decreased only in the E2+P group (∼4%) and plasma levels of protein S decreased in both the E2 and E2+P group (∼21%). In both the E2 and E2+P groups, the plasma levels of factor VII (antigen and activity) showed a borderline significant increase (∼10%), whereas no significant change was observed in active factor VII. Plasma levels of tissue-type plasminogen activator (∼22%), urokinase plasminogen activator (∼25%) and plasminogen activator inhibitor type-1 (∼43%) decreased in the E2 and E2+P groups, whereas those of plasminogen increased (∼12%). Treatment was associated with an increase in levels of prothrombin fragment 1+2 (∼31%), but levels of thrombin-antithrombin III complexes, and of plasmin-α2-antiplasmin complexes and total fibrin(ogen) degradation products did not change significantly. 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.