Differential effect of the ultra-low dose and standard estrogen plus dydrogesterone therapy on thrombin generation and fibrinolysis in postmenopausal women

Abstract

Introduction: The objective of this study was to estimate the effects of different doses of oral hormone therapy (HT) on thrombin generation and fibrinolytic activity in postmenopausal women after 12 months of treatment. Material and methods: Thrombin generation, fibrinolysis activators and inhibitors were determined before and after 12 months of treatment. Participants (180) were assigned (1:1:1) as follows: (1) standard HT group, 17β-estradiol (1 mg/day) with dydrogesterone (5 mg/day); (2) ultra-low dose HT group, 17β-estradiol (0.5 mg/day) with dydrogesterone (2.5 mg/day); (3) control group, no treatment. Results: The standard HT led to a higher concentration of prothrombin 1 + 2 fragment (by 5.8%) with lower antithrombin activity (by 6.1%). Compared with baseline, we observed a reduction in mean antithrombin activity in the standard HT group and increases in mean levels of prothrombin 1 + 2 fragment in two HT groups. We found decreases after treatment in both standard and ultra-low dose HT groups in plasminogen activator inhibitor-1 (PAI-1) activity (−32.4% and −19.6%, respectively) and PAI-1 antigen (−9.9% and −7.8%, respectively). Intergroup analysis revealed reduction in both mean PAI-1 activities and PAI-1 antigen levels in the two treatment groups when compared with the control. Conclusion: Contrary to the standard estrogen plus dydrogesterone treatment, ultra-low dose HT revealed positive effects on hemostasis by intensifying fibrinolysis through a decrease in both PAI-1 activity and antigen levels, and with no impact on thrombin generation.