Effects of hormone replacement therapy on plasma and tissue fibrinolytic activity in a rat model of surgically induced menopause

Clin Invest Med. 2014 Apr 1;37(2):E85-92. doi: 10.25011/cim.v37i2.21090.

Abstract

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 17β-estradiol (0.02 mg/kg/day) (E2) + norethisterone acetate (0.01 mg/kg/day), and (4) ovariectomy group followed by oral administration of daily 17β-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 fibrinolytic 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.

MeSH terms

  • Animals
  • Brain / metabolism
  • Female
  • Fibrinolysis / drug effects*
  • Hormone Replacement Therapy / methods*
  • Liver / metabolism
  • Menopause / blood*
  • Menopause / metabolism*
  • Ovariectomy
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Plasminogen Activator / blood
  • Tissue Plasminogen Activator / metabolism

Substances

  • Plasminogen Activator Inhibitor 1
  • Tissue Plasminogen Activator