Effects of ultra-low-dose versus standard hormone therapy on fibrinolysis and thrombin generation in postmenopausal women.

OBJECTIVE

To assess the effects of different doses of oral hormone therapy (HT) on thrombin generation and fibrinolysis.

STUDY DESIGN

One hundred fifty postmenopausal women were assigned in a randomized controlled study in which the effect of standard dose (1mg 17β-estradiol/5mg dydrogesterone), ultra-low-dose HT (0.5mg 17β-estradiol/2.5mg dydrogesterone) on fibrinolysis and coagulation was compared to controls. Factors measured included plasma clot lysis time (CLT), fibrinolysis activators and inhibitors, thrombin generation (prothrombin fragments 1+2 [F1+2], endogenous thrombin potential [ETP]), normalized activated protein C sensitivity ratio (nAPCsr), and factor (F)VIII activity and were determined before and after 24 weeks of HT.

RESULTS

In ultra-low-dose group posttreatment CLT tended to be shorter when compared to standard HT (-7%) and control group (-4%) with reduced plasminogen activator inhibitor-1 (PAI-1) antigen (by -16% vs both groups). Higher mean changes from baseline between ultra-low-HT group and standard group in CLT (-7.4 vs 3.05) and PAI-1 antigen concentration (-5.1 vs 0.9) were observed. Standard HT, compared with the ultra-low-dose HT, led to higher F1+2 (+9%) and FVIII activity (+37%).

CONCLUSIONS

In contrast to the standard HT, ultra-low-dose HT may enhance fibrinolysis through reduced PAI-1 levels.