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

Abstract

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.

Keywords: Fibrinolysis; Hormone therapy; Postmenopausal age; Thrombin generation.