Low-dose oral combination of 17β-estradiol and norethisterone acetate in postmenopausal women decreases factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1

Abstract

Objective Controversies still persist concerning hormone replacement therapy (HRT) and its effects upon blood coagulation and fibrinolysis. This study was carried out to evaluate possible effects of continuously administered low-dose 17β-estradiol (E₂) and norethisterone acetate (NETA) on coagulation and fibrinolytic factors.

Methods We conducted a randomized double-blind, placebo-controlled, 1-year study in 120 healthy postmenopausal women. The three groups consisted of a placebo group (n = 40), a group receiving oral continuous combined E₂ 1 mg and NETA 0.25 mg (n = 40) and a group receiving oral continuous combined E₂ 1 mg and NETA 0.5 mg (n = 40).

Results The two low doses of E₂-NETA induced significantly lower plasma levels of factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1 (PAI-1), compared with placebo treatment.

Conclusions Low-dose E₂ (1 mg) in combination with NETA resulted in favorable changes of factor VII activity and fibrinogen, compared with placebo. The lower plasma levels of PAI-1 may lead to increased fibrinolytic activity. These findings suggest a decreased risk of developing coronary heart disease. Antithrombin activity was also reduced, which may increase the risk of developing venous thromboembolism. The clinical significance of the lower levels of these factors remains to be clarified.

• HORMONE REPLACEMENT THERAPY
• FACTOR VII
• FIBRINOGEN
• ANTITHROMBIN
• PLASMINOGEN ACTIVATOR INHIBITOR