Effects of Hormone Replacement Therapy on Plasma and Tissue Fibrinolytic Activity in a Rat Model of Surgically Induced Menopause

Abstract

Purpose: e purpose of this study was to analyze the e ects of estrogen de ciency and hormone replacement therapy (HRT) on brinolytic activity in a rat mode of surgicallyinduced 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 brinolysis in plasma and liver and brain tissue.Results: Compared with sham-operated rats, ovariectomized rats showed higher levels of brinolytic activity; however, the increased brinolytic activity in plasma and liver tissue was signi cantly reduced by HRT regimens. No change was observed in the levels of brinolytic activity in brain tissue.Conclusions: HRT showed bene cial e ects by decreasing brinolytic activity related to surgically-induced menopause. Short-term HRT treatment was associated with a shi in the procoagulant-anticoagulant balance toward a procoagulant state.

Sex dimorphisms in coagulation: Implications in trauma‐induced coagulopathy and trauma resuscitation

“…8,57,75 In a rat model examining the effects of surgically induced menopause on fibrinolysis, Topcuoglu et al demonstrate that ovariectomized rats have higher relative levels of fibrinolytic activity, which can then be reduced with hormonal treatment. 84 These same correlative changes are seen in humans-premenopausal females have higher circulating levels of PAI-1 as compared to their older, less hormonally active counterparts, 85 and in the setting of oral contraceptive therapy, there are robust increases in PAI-1 and subsequent decreases in endogenous fibrinolytic activity. 86,87 These associations with estrogen and an antifibrinolytic effect are also seen in vivo in patients after injury as well, with positive correlations between estrogen levels and fibrinogen, fibrin deposition and cross-linking, and clot strength.…”

“…Like other coagulation contributors, these sex dimorphisms appear to be at least partially driven by sex hormones, with estradiol provoking increased functional fibrinogen and increased fibrinogen contribution to clot strength in vitro and in vivo 8,57,75 . In a rat model examining the effects of surgically induced menopause on fibrinolysis, Topcuoglu et al demonstrate that ovariectomized rats have higher relative levels of fibrinolytic activity, which can then be reduced with hormonal treatment 84 . These same correlative changes are seen in humans—premenopausal females have higher circulating levels of PAI‐1 as compared to their older, less hormonally active counterparts, 85 and in the setting of oral contraceptive therapy, there are robust increases in PAI‐1 and subsequent decreases in endogenous fibrinolytic activity 86,87 …”

Effects of Contraception Pills and Hormone Replacement Therapy on Tissue Plasminogen Activator -1 and Plasminogen Activator Inhibitor-1 in Per and Postmenopausal Women

“…In regard of estrogen deficiency and hormone replacement therapy on blood coagulation particularly fibrinolytic system , previous experimental study was established on rats with induced surgical menopause (ovariectomy and then drenched with different doses of contraceptive (alone or compined ) then after levels of tissue plasminogen activator (TPA) and plasminogen activator inhibitor were estimated and their results showed a significant reductions in the TPA and fibrinolytic activity (11) .…”

Menopause and Ischemic Stroke: A Brief Review

“…The incidences of venous infarction [34] and ischemic stroke [34,35] are significantly higher in patients on HRT, especially when given to younger females. Experiments have shown that HRT decreases the fibrinolytic activity of tissue plasminogen activator (t-PA) in oophorectomized rats [36] whereas a randomized controlled study in healthy postmenopausal women shows a positive effect of HRT on the fibrinolytic system [37]. More validation of the usefulness of HRT is indeed required.…”