Effects of low-dose oral and transdermal estrogen replacement therapy on hemostatic factors in healthy postmenopausal women: A randomized placebo-controlled study

Post, Marinka S.; Mooren, M.J. van der; Baal, W.M. van; Blankenstein, Marinus A.; Merkus, Hans M.W.M.; Kroeks, M. V. A. M.; Franke, H; Kenemans, P.; Stehouwer, Coen D.A.

doi:10.1067/s0002-9378(03)00599-4

Cited by 58 publications

(71 citation statements)

References 28 publications

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“…17,18,25,31,32 The route of administration also determines the effect of HRT on the fibrinolytic system. In this regard, transdermal HRT avoids the first-pass effect of estrogen in the liver and decreases PAI-1 and t-PA antigen to a lesser extent than oral HRT.…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women

et al. 2008

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Abstract-Angiotensin-converting enzyme inhibition potentiates basal and bradykinin-stimulated tissue-type plasminogen activator (t-PA) release to a greater extent in women than in men. This study tested the hypothesis that 17␤-estradiol enhances the effect of angiotensin-converting enzyme inhibition on t-PA release in young postmenopausal women. We conducted a double-blind, prospective, crossover study in 14 young postmenopausal women (mean age 48.2Ϯ2.3 years) who were randomized to receive 17␤-estradiol (1 mg/d) or matching placebo for 4 weeks. At the end of each treatment period, we measured the effect of intraarterial infusion of bradykinin, methacholine, and nitroprusside on forearm blood flow and net t-PA release, before and during intraarterial enalaprilat (0.33 g/min/100 mL forearm volume Key Words: estradiol Ⅲ angiotensin-converting enzyme inhibition Ⅲ postmenopausal women Ⅲ plasminogen activator Ⅲ bradykinin E strogen deficiency of menopause causes vascular and metabolic changes that increase the risk for cardiovascular disease. 1,2 In contrast to observational studies that suggest that hormone replacement therapy (HRT) reduces the risk of coronary heart disease (CHD), 3-5 recent randomized controlled trials indicate that treatment with conjugated estrogen plus progestin increases the risk of pulmonary emboli, CHD, and stroke, whereas treatment with conjugated estrogen alone increases risk of stroke without affecting embolic events or risk of CHD. 6 -8 This discrepancy in results has been attributed to the type of HRT used, the timing of intervention of HRT after menopause, 9,10 or the route of administration. 11 For example, the Heart and Estrogen/progestin Replacement Study (HERS) 8 and the Women's Health Initiative (WHI) 6,7 study assessed the effect of treatment with conjugated equine estrogens, a mixture of estrogens extracted from horse urine that also contains progestins and androgens, whereas estradiol is the major endogenous estrogen. 12 Differences in the outcomes of epidemiological studies and clinical trials are best interpreted in the context of an understanding of the biological effects of estrogen. On the one hand, oral HRT increases circulating fibrin split products (FSP), concentrations of inflammatory cytokines, and C-reactive protein. [13][14][15] On the other, estradiol exerts many salutary effects on the vasculature, including improving endothelial-dependent vasodilation, 16 decreasing fibrinogen and plasminogen activator inhibitor (PAI)-1 (PAI-1), [17][18][19] increasing the secretion of nitric oxide from intact platelets, 20 and attenuating platelet-derived growth factor (PDGF) receptor-activated smooth muscle cell migration and proliferation. 21 HRT decreases circulating t-PA antigen in parallel with PAI-1 antigen, to which it is complexed. Circulating t-PA antigen does not reflect the capacity of the vasculature to release t-PA, however, and the effect of HRT or estrogen on endothelial fibrinolytic function has not been studied exten-

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Section: Discussionmentioning

confidence: 99%

17β-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women

et al. 2008

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“…A limited number of studies have reported con icting results regarding brinolytic activity in human and rats [27][28][29][30][31][32][33][34][35][36]. Additionally, no report on the in uence of norethisterone acetate and drospirenone on the tPA and PAI-1 levels in liver and brain tissue of rats has been published to date.…”

Section: Discussionmentioning

confidence: 99%

“…Higher levels of PAI-1:Ag were found in women who used transdermal postmenopausal hormonal therapy than in those who received oral postmenopausal hormonal therapy. Other studies [30][31][32][33][34][35][36] demonstrated that oral postmenopausal hormonal therapy signi cantly reduced the levels of PAI-1 (by up to 50%); however, no such signi cant change was associated with transdermal postmenopausal hormonal therapy.…”

Section: Discussionmentioning

confidence: 99%

“…HRT caused a decrease in the brinolytic activity rates in both plasma and liver tissue of ovariectomized rats. It seems clear that drospirenone decreases the PAI levels of liver tissue more e ectively than norethister- [36] showed that oral use of postmenopausal hormonal therapy resulted in stimulation of the synthesis of many proteins in the liver (including t-PA and PAI-1) and increased clearance in hepatocytes. Our results are consistent with those of Post et al [36].…”

Section: Discussionmentioning

confidence: 99%

“…It seems clear that drospirenone decreases the PAI levels of liver tissue more e ectively than norethister- [36] showed that oral use of postmenopausal hormonal therapy resulted in stimulation of the synthesis of many proteins in the liver (including t-PA and PAI-1) and increased clearance in hepatocytes. Our results are consistent with those of Post et al [36]. Coagulation and brinolysis may also in uence cardiovascular risk; however, the relationship of the lipid pro le to these processes in menopause is unclear.…”

Section: Discussionmentioning

confidence: 99%

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

Topçuoğlu¹,

Albayrak²,

Erman³

et al. 2014

CIM

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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.

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HT: Pharmacology Tailored to Women’s Health

Skouby

2019

ISGE Series

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Effects of low-dose oral and transdermal estrogen replacement therapy on hemostatic factors in healthy postmenopausal women: A randomized placebo-controlled study

Cited by 58 publications

References 28 publications

17β-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women

17β-Estradiol Increases Basal but Not Bradykinin-Stimulated Release of Active t-PA in Young Postmenopausal Women

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

HT: Pharmacology Tailored to Women’s Health

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