Impaired procoagulant-anticoagulant balance during hormone replacement therapy? A randomised, placebo-controlled 12-week study

In this randomised, placebo-controlled 12-week study, sixty healthy postmen opausal women received either placebo (N = 16) or daily 2 mg micronised oes tradiol, either unopposed (N = 16, E-2 group) or combined with a progestage n for 14 days of each cycle (N = 28, E-2+P group). Results: As compared to placebo, plasma levels of AT III were reduced only in the E-2 group (similar to 28%), plasma levels of protein C decreased onl y in the E-2+P group (similar to 4%) and plasma levels of protein S decreas ed in both the E-2 and E-2+P group (similar to 21%). In both the E-2 and E- 2+P groups, the plasma levels of factor VII (antigen and activity) showed a borderline significant increase (similar to 10%)? whereas no significant c hange was observed in active factor VII. Plasma levels of tissue-type plasm inogen activator (similar to 22%), urokinase plasminogen activator (similar to 25%) and plasminogen activator inhibitor type-1 (similar to 43%) decrea sed in the E-2 and E-2+P groups, whereas those of plasminogen increased (si milar to 12%). Treatment was associated with an increase in levels of proth rombin fragment 1+2 (similar to 31%), but levels of thrombin-antithrombin I II complexes, and of plasmin-alpha(2)-antiplasmin complexes and total fibri n(ogen) degradation products did not change significantly. Conclusion: Short-term E-2 and E-2+P treatment is associated with a shift i n the procoagulant-anticoagulant balance towards a procoagulant state. A su bstantial proportion of women do not have a net increase in fibrinolytic ac tivity. These data may be relevant in explaining the increased risk of veno us thromboembolism associated with ERT and HRT, and possibly also in explai ning the negative results of the Heart and Estrogen/progestin Replacement S tudy.