Effects of hormone replacement therapy on plasma and tissue fibrinolytic activity in a rat model of surgically induced menopause
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Purpose: The purpose of this study was to analyze the effects of estrogen deficiency and hormone replacement therapy (HRT) on fibrinolytic activity in a rat mode of surgically induced menopause. Methods: Twelve-week-old, sexually mature female Sprague-Dawley rats, each weighing 200-250 g, were randomly divided into four groups: (1) sham- operated group, (2) ovariectomy group, (3) ovariectomy group followed by oral administration of daily 17 beta-estradiol (0.02 mg/kg/day) (E2) + norethisterone acetate (0.01 mg/kg/day), and (4) ovariectomy group followed by oral administration of daily 17 beta-estradiol (0.01 mg/kg/day) + drospirenone (0.02 mg/kg/day). Tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI- 1) antigen, and PAI-1/tPA levels were measured as markers of fibrinolysis in plasma and liver and brain tissue. Results: Compared with sham-operated rats, ovariectomized rats showed higher levels of fibrinolytic activity; however, the increased fibrinolytic activity in plasma and liver tissue was significantly reduced by HRT regimens. No change was observed in the levels of fi brinolytic activity in brain tissue. Conclusions: HRT showed beneficial effects by decreasing fibrinolytic activity related to surgically induced menopause. Short-term HRT treatment was associated with a shift in the procoagulant-anticoagulant balance toward a procoagulant state.