Effects of hormone replacement on hemostasis in spontaneous menopause

OBJECTIVE: To examine the effects of continuous combined estrogen-progesterone replacement therapy on coagulation and natural anticoagulant systems in spontaneous menopause. DESIGN: A randomized, double-blind, placebo-controlled study was conducted during a 6-month period to examine the effect of hormone replacement therapy (HRT) on blood coagulation parameters. One hundred-ten healthy postmenopausal women were randomized into two groups. Those in group 1 were given conjugated estrogen (0.625 mg/d, Premarin) and medroxyprogesterone acetate (5 mg/d, Farlutal), and those in group 2 were given identical tablets of placebo for 6 months. Serum levels of modified activated protein C resistance, antithrombin III, fibrinogen, factor VIIIa, factor VIII, factor IX, activated partial thromboplastin time, prothrombin time, thrombin time, and lipoprotein (a) were measured before and 6 months after the treatment and analyzed for changes in extrinsic and intrinsic coagulation parameters. RESULTS: At the end of the 6-month period, fibrinogen, lipoprotein (a), and activated protein C resistance levels were decreased significantly in the HRT group compared with the control group. Antithrombin III levels were increased, indicating antithrombin activity. Activated partial thromboplastin time, as a measure for intrinsic coagulation cascade, was prolonged in concert with decreased intrinsic coagulation factors, factor VIII, and factor IX (p < 0.05). In the extrinsic coagulation system, prothrombin time was significantly increased, although factor VIIa level was not changed (p > 0.05). CONCLUSION: Significant changes were observed in the coagulation parameters, which may further explain the cardioprotective effect of HRT.