Experimental arterial thrombosis regulated by androgen and its receptor via modulation of platelet activation

Li, Shijun; Li, Xiaoying; Li, Jian; Deng, Xinli; Li, Yan; Yu, Cong

doi:10.1016/j.thromres.2007.03.008

Cited by 42 publications

(35 citation statements)

References 26 publications

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“…treatment with testosterone has not been associated with an increased rate of VTE (21). Moreover, in vitro studies indicate that testosterone in physiological doses may actually have beneficial effects on the haemostatic system through enhancement of anticoagulant activity in endothelial cells (22) and via modulation of platelet activation (23). The latter experimental studies support the notion that physiological levels of testosterone would be superior to low testosterone levels in protecting against thrombosis, however, our results in men from a general population do not support this thesis.…”

Section: Discussionmentioning

confidence: 99%

Endogenous sex hormone levels in men are not associated with risk of venous thromboembolism: the Tromsø study

Svartberg

Brækkan

Laughlin

et al. 2009

European Journal of Endocrinology

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Objectives: Low testosterone levels in men have been associated with cardiovascular risk factors and atherosclerosis and lately also an increased risk of both cardiovascular disease (CVD) and all-cause mortality. As arterial CVDs and venous thromboembolism (VTE) have been shown to share common risk factors, the purpose of the present study was to determine the impact of endogenous sex hormone levels on the incidence of VTE in a cohort of men. Design: A prospective, population-based study. Methods: Sex hormone measurements were available in 1350 men, aged 50-84, participating in the Tromsø study in 1994-1995. First, lifetime VTE-events during the follow-up were registered up to September 1 2007. Results: There were 63 incident VTE-events (4.5 per 1000 person-years) during a mean of 10.4 years of follow-up. Age was significantly associated with increased risk of VTE; men 70 years or older had a 2.5-fold higher risk of VTE (HR 2.47, 95% CI 1.19-5.12), compared with those between 50 and 60 years of age. In age-adjusted analyses, endogenous sex hormones levels were not associated with risk of VTE; for each S.D. increase, hazards ratios (95% CI) were 1.06 (0.83-1.35) for total testosterone, 1.02 (0.79-1.33) for free testosterone, and 1.27 (0.94-1.71) for ln-estradiol. In dichotomized analyses comparing men in the lowest total and free testosterone quartile with men in the higher quartiles, hypoandrogenemia was not associated with risk of VTE. Conclusions: In this population-based study of middle-aged and older men, endogenous sex hormone levels were not associated with 10-year risk of VTE.

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Section: Discussionmentioning

confidence: 99%

Endogenous sex hormone levels in men are not associated with risk of venous thromboembolism: the Tromsø study

Svartberg

Brækkan

Laughlin

et al. 2009

European Journal of Endocrinology

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“…Extensive researches have proclaimed that an artery to the brain may be blocked by a clot which aggravate the artery occurs, and then ischemia and anoxia of cerebra take place. Therefore, anti-platelet therapy is considered to be one of valid ways to ameliorate cerebral ischemic injury [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Antiplatelet activity of 3-butyl-6-bromo-1(3H)-isobenzofuranone on rat platelet aggregation

Gao

Qiao

et al. 2011

J Thromb Thrombolysis

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This study aimed to explore the impact of 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) on rat platelet aggregation induced by arachidonic acid (AA). Anti-platelet activities in vitro and ex vivo in rat platelets and the possible mechanism were also investigated. The 50% inhibitory concentration (IC(50)) of Br-NBP was 84 μM in washed platelet added AA (final concentration, 780 μM) in vitro, meanwhile intravenous injection of Br-NBP also potently inhibited platelet aggregation ex vivo. Br-NBP significantly restrained thromboxane B(2) formation and Ca(2+) mobilization caused by AA, but failed to regulate 6-keto-prostaglandin F(1α) production and malonaldehyde content. Treatment of Br-NBP improved cAMP, cGMP levels and NO synthesis but prevented serotonin secretion and PF(4) release. Results suggested that Br-NBP inhibited rat platelet aggregation and that the anti-platelet activity was related to both arachidonic acid cascade and cGMP-NO signal path.

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“…16 This finding suggests that the mechanism is unlikely to be solely via diabetes and atherosclerosis, although plaque progression and instability may still contribute. 15 For venous thromboembolism, the increased risk was not evident until at least five months of therapy, and we actually observed fewer venous thromboembolic events in the first months after therapy. Although we attempted to minimize bias, this could be a result of unobserved confounding if men with risk factors for VTE, such as hospitalization, for example, are not started on GnRH agonist therapy until after other medical conditions have stabilized.…”

Section: Discussionmentioning

confidence: 53%

“…Androgen deprivation therapy is also commonly used following biochemical recurrence after primary treatment with radical prostatectomy or radiation therapy, 14 another setting where data are lacking to support improved outcomes. However, androgen deprivation may cause atherosclerotic plaque progression and instability, 15 and its use has been associated with an increased risk of coronary heart disease. [16][17][18][19][20] Consistent with evidence that aging 21 and cancer 22 are associated with an increased risk of venous thromboembolism (i.e., pulmonary embolism and deep venous thrombosis), a population-based study of the Swedish National Prostate Cancer Register demonstrated that prostate cancer was associated with an increased risk of venous thromboembolism, and men with prostate cancer treated with androgen deprivation therapy were at greatest risk for venous thrmoboembolism.…”

Section: Introductionmentioning

confidence: 99%

170 Androgen Deprivation Therapy for Non-Metastatic Prostate Cancer Is Associated With an Increased Risk of Peripheral Arterial Disease and Venous Thromboembolism

Williams¹,

O’Malley

Smith

et al. 2012

Journal of Urology

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Background-Previous studies demonstrate that androgen deprivation therapy with gonodotropin-releasing hormone (GnRH) agonists and orchiectomy for prostate cancer is associated with cardiovascular disease. However, few studies have examined its effect on the peripheral vascular system.Objective-To study the risk of peripheral arterial disease and venous thromboembolism associated with androgen deprivation therapy for prostate cancer.Design, Settings and Participants-Population-based observational study of 182,757 U.S. men aged 66 years and older who were diagnosed with loco-regional prostate cancer from 1992 to 2007, of whom 47.8% received GnRH agonists and 2.2% orchiectomy.Measurements-We used Cox proportional hazards models with time-varying treatment variables to assess whether treatment with GnRH agonists or orchiectomy was associated with peripheral arterial disease and/or venous thromboembolism.Results and limitations-Overall, 47.8% of men received a GnRH agonist during follow-up and 2.2% underwent orchiectomy. GnRH agonist use was associated with an increased risk of incident peripheral arterial disease (adjusted hazard ratio [HR], 1.15, 95% confidence interval [CI] 1.11-1.19) and incident venous thromboembolism (adjusted HR, 1.1, 95% CI 1.04-1.16). In addition, orchiectomy was associated with an increased risk of peripheral arterial disease (adjusted HR, 1.14, 95% CI 1.03-1.27) and venous thromboembolism (adjusted HR, 1.22, 95% CI 1.07-1.40). Limitations include the observational study design, inability to assess the use of oral antiandrogens as monotherapy or combined androgen deprivation.Conclusions-Androgen deprivation therapy for loco-regional prostate cancer is associated with an increased risk of peripheral artery disease and venous thromboembolism. Additional research is needed to better understand the potential risks and benefits, so that these treatments can be targeted to patients where the benefits are most clear.

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Experimental arterial thrombosis regulated by androgen and its receptor via modulation of platelet activation

Cited by 42 publications

References 26 publications

Endogenous sex hormone levels in men are not associated with risk of venous thromboembolism: the Tromsø study

Endogenous sex hormone levels in men are not associated with risk of venous thromboembolism: the Tromsø study

Antiplatelet activity of 3-butyl-6-bromo-1(3H)-isobenzofuranone on rat platelet aggregation

170 Androgen Deprivation Therapy for Non-Metastatic Prostate Cancer Is Associated With an Increased Risk of Peripheral Arterial Disease and Venous Thromboembolism

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