Lipoprotein(a) Levels and Isoforms and Fibrinolytic Activity in Postmenopause – Influence of Hormone Replacement Therapy

SummaryEpidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in postmenopausal women via several mechanisms, including modifications in the fibrinolytic system and lipoprotein(a) [Lp(a)] levels. The aim of this study was to examine the influence of the levels and isoforms of Lp(a) on fibrinolytic activity in 91 postmenopausal women in comparison with premenopause and analyze the effect of HRT on those parameters. In postmenopause, an increase in plasma Lp(a) and plasminogen activator inhibitor-1 (PAI-1) levels was found. A significant inverse correlation was observed between Lp(a) or PAI-1 levels and plasmin generation. Plasma samples with low molecular weight (MW) apo(a) isoforms showed higher plasmin inhibition than plasmas with high MW apo(a) isoforms and similar levels of total Lp(a) and PAI-1. HRT induced a significant decrease in Lp(a) and PAI-1 levels and an increase in estradiol levels, as well as an increase in fibrinolytic activity. A significant correlation was found between the percentages of variation in Lp(a) levels and in plasmin generation and between the percentages of variation in PAI-1 levels and in the euglobulin lysis time under HRT. In conclusion, the increase in fibrinolytic activity observed in women under HRT could be explained by two independent mechanisms: (a) the decrease in PAI-1 and (b) the decrease in the inhibition of plasmin generation due to the decrease in Lp(a) levels.

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

Indian Journal of Forensic Medicine & Toxicology ◽

10.37506/ijfmt.v15i3.16248 ◽

2021 ◽

Keyword(s):

Hormone Replacement Therapy ◽

Replacement Therapy ◽

Postmenopausal Women ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Hormone Replacement ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Tissue Plasminogen ◽

Activator Inhibitor

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The effect of hormone replacement therapy and tibolone on lipoprotein (a) concentrations in postmenopausal women: a systematic review and meta-analysis of randomized controlled studies

Endocrine Abstracts ◽

10.1530/endoabs.49.ep1084 ◽

2017 ◽

Author(s):

Panagiotis Anagnostis ◽

Petros Galanis ◽

Vasileia Chatzistergiou ◽

John Stevenson ◽

Ian Godsland ◽

...

Keyword(s):

Systematic Review ◽

Hormone Replacement Therapy ◽

Replacement Therapy ◽

Postmenopausal Women ◽

Meta Analysis ◽

Hormone Replacement ◽

Lipoprotein A ◽

Randomized Controlled ◽

Randomized Controlled Studies

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

Clinical & Investigative Medicine ◽

10.25011/cim.v37i2.21090 ◽

2014 ◽

Vol 37 (2) ◽

pp. 85 ◽

Cited By ~ 1

Author(s):

Ata Topcuoglu ◽

Mustafa Albayrak ◽

Hayriye Erman ◽

Huriye Balci ◽

Mesut Karakus ◽

...

Keyword(s):

Hormone Replacement Therapy ◽

Oral Administration ◽

Replacement Therapy ◽

Plasminogen Activator ◽

Brain Tissue ◽

Fibrinolytic Activity ◽

Hormone Replacement ◽

17Β Estradiol ◽

Surgically Induced ◽

Pai 1

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.

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Impact of hormone replacement therapy on postprandial lipoproteins and lipoprotein(a) in normolipidemic postmenopausal women

The Clinical Investigator ◽

10.1007/bf00207478 ◽

1994 ◽

Vol 72 (7) ◽

Cited By ~ 13

Author(s):

U. Julius ◽

H. Fritsch ◽

W. Fritsch ◽

E. Rehak ◽

K. F�cker ◽

...

Keyword(s):

Hormone Replacement Therapy ◽

Replacement Therapy ◽

Postmenopausal Women ◽

Hormone Replacement ◽

Lipoprotein A

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Effects of simvastatin or hormone replacement therapy, or both, on fibrinogen, factor VII, and plasminogen activator inhibitor levels in postmenopausal women with proven coronary artery disease

The American Journal of Cardiology ◽

10.1016/s0002-9149(00)00831-6 ◽

2000 ◽

Vol 86 (1) ◽

pp. 80-83 ◽

Cited By ~ 11

Author(s):

Eftihia Sbarouni ◽

Efthimia Melissari ◽

Zenon S Kyriakides ◽

Dimitrios Th Kremastinos

Keyword(s):

Coronary Artery Disease ◽

Hormone Replacement Therapy ◽

Coronary Artery ◽

Replacement Therapy ◽

Postmenopausal Women ◽

Hormone Replacement ◽

Plasminogen Activator Inhibitor ◽

Factor Vii ◽

Artery Disease ◽

Activator Inhibitor

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Haemostatic Variables and Menopausal Status: Influence of Hormone Replacement Therapy

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649632 ◽

1993 ◽

Vol 70 (04) ◽

pp. 584-587 ◽

Cited By ~ 69

Author(s):

Pierre-Yves Scarabin ◽

Geneviève Plu-Bureau ◽

Lucienne Bara ◽

Claire Bonithon-Kopp ◽

Louis Guize ◽

...

Keyword(s):

Hormone Replacement Therapy ◽

Replacement Therapy ◽

Postmenopausal Women ◽

Randomized Clinical Trials ◽

Hormone Replacement ◽

Menopausal Status ◽

Premenopausal Women ◽

Plasminogen Activator Inhibitor ◽

Factor Vii ◽

Clotting Factors

SummaryLarge cohort studies have shown that postmenopausal estrogen use was associated with a reduction in the risk of coronary heart disease, This putative beneficial effect of hormone replacement therapy (HRT) may be partly mediated through changes in clotting factors and fibrinolytic system. We have measured haemostatic variables in 293 consecutive healthy women aged 45-54 years who attended a health check-up centre in Paris (IPC). Premenopausal women taking hormonal therapy were excluded (n = 34). Most women using HRT were given 17-β estradiol in combination with progestin. Mean levels (m ± sd) of plasma fibrinogen, factor VII coagulant activity and plasminogen activator inhibitor (PAI) were significantly higher in postmenopausal women not taking HRT (n = 99) than in premenopausal women (n = 139) within the same decade (319 ± 52 mg/dl vs 304 ± 60 mg/dl, 107 ± 17% vs 96 ± 16%, 9.73 ± 5.71 U/ml vs 7.61 ± 4.36 U/ml respectively). Allowance for main cardiovascular risk factors made no substantial differences to the results, although the effect of the menopause on fibrinogen was no longer significant. HRT (n = 21) significantly reversed the menopause-related changes in factor VII (94 ± 15%), even after adjustment for confounding factors. The same trend in both fibrinogen (294 ± 46 mg/dl) and PAI (8.22 ± 5.51 U/ml) was observed. Similar results were found in women using oral or percutaneous estrogen. Our findings suggest that 17-β estradiol in combination with progestins may protect against an increased thrombotic tendency in postmenopausal women. Randomized clinical trials are urgently needed for a better understanding of HRT effect on atherothrombotic process.

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Topical Progesterone Cream Does Not Increase Thrombotic and Inflammatory Factors in Postmenopausal Women.

Blood ◽

10.1182/blood.v104.11.5318.5318 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5318-5318 ◽

Cited By ~ 1

Author(s):

Kenna Stephenson ◽

Carol Price ◽

Anna Kurdowska ◽

Pierre Neuenschwander ◽

John Stephenson ◽

...

Keyword(s):

Hormone Replacement Therapy ◽

Replacement Therapy ◽

Postmenopausal Women ◽

Factor Viia ◽

Hormone Replacement ◽

Menopausal Symptoms ◽

Inflammatory Factors ◽

Factor V ◽

Pai 1 ◽

Placebo Cream

Abstract Postmenopausal women have an increased risk of cardiovascular disease, and heart disease is the leading cause of death in postmenopausal American women. Conventional hormone replacement therapy has been shown to result in an increase in thrombotic events in large prospective clinical trials including HERS I, and the recently halted Women’s Health Initiative. One possible mechanism for this observed increase is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory factors. An estimated 50 million American women are peri or postmenopausal and clinical therapies for menopausal symptoms remain a significant challenge in light of the known thrombotic risks. In this prospective blinded study, we examined the short-term effect of topical progesterone cream on menopausal symptom relief in 30 healthy postmenopausal women. Potential adverse effects of topical progesterone on hemostatic and inflammatory factors and cortisol levels were also examined. Subjects were randomized to first receive either 20 mg of topical progesterone cream or placebo cream for 4 weeks. Following a subsequent 4-week washout period, subjects were crossed over to either placebo cream or active drug for an additional 4-week period. In each case, progesterone and cortisol levels were monitored by salivary sampling. Baseline values, 4-week follow-up values and end-of-study values were also obtained for the Greene Climacteric Scale, total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin, PAI-1, CRP, TNFα, and IL-6. For subjects receiving 20 mg of topical progesterone cream for 4 weeks, Greene Climacteric Scale scores were consistently and significantly improved (decreased) over baseline, demonstrating significant relief from menopausal symptoms. In addition, in a subpopulation of hypercortisolemic women, topical progesterone was associated with a favorable decrease in nocturnal cortisol. Surprisingly, and in sharp contrast to earlier studies with conventional hormone replacement therapy, topical progesterone had no effect on any of the hemostatic components examined: total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin, and PAI-1 levels were all unchanged. Levels of CRP, TNFα and IL-6 also remained unchanged. From this study we conclude that administration of topical progesterone cream at a daily dose of 20 mg significantly relieves menopausal symptoms in postmenopausal women without adversely altering prothrombotic potential. Since the thrombotic complications that are typically observed with conventional hormone replacement therapy do not seem to occur with topical progesterone, this treatment should be seriously considered as an effective and safe alternative clinical therapy for women suffering from menopausal symptoms.

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