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 (1 mg 17 beta-estradiol/5 mg dydrogesterone), ultra-low-dose HT (0.5 mg 17 beta-estradiol/2.5 mg 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. (C) 2017 Elsevier B.V. All rights reserved.