The cardiovascular risk of gonadotropin releasing hormone agonists in men with prostate cancer: An unresolved controversy

Conteduca, Vincenza; Lorenzo, Giuseppe Di; Tartarone, Alfredo; Aieta, Michele

doi:10.1016/j.critrevonc.2012.09.008

Cited by 52 publications

(51 citation statements)

References 77 publications

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“…In consequence, the US Food and Drug Administration issued a safety warning in May 2010 recognizing the risk of cardiovascular disease in patients treated with GnRH agonists [15]. While the evidence suggests that ADT-related cardiovascular morbidity applies to all men, including those without pre-existing cardiac disease [11], the relationship between ADT and cardiovascular disease remains controversial [16,17]. While a recent meta-analysis published by Nguyen et al [17] did not show an association between ADT and the risk of cardiovascular death, Carneiro et al [18], evaluating randomized controlled trials and large cohort studies, showed that ADT resulted in a significant increase in cardiovascular morbidity.…”

Section: Introductionmentioning

confidence: 99%

Dose‐dependent effect of androgen deprivation therapy for localized prostate cancer on adverse cardiac events

et al. 2015

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ObjectivesTo investigate the dose-dependent effect of androgen deprivation therapy (ADT) on adverse cardiac events in elderly men with non-metastatic prostate cancer (PCa) stratified according to life expectancy. Patients and MethodsA total of 50 384 men diagnosed with localized PCa between 1992 and 2007 were identified within the Surveillance, Epidemiology, and End Results registry areas. We compared those who received ADT within 2 years of PCa diagnosis with those who did not, calculated as monthly equivalent doses of GnRH agonists (<8, ≥8 doses), or orchiectomy. Men were further stratified according to life expectancy (<5 years, 5-10 years and >10 years). Adjusted Cox hazard models assessed the risk of new-onset coronary heart disease (CHD), acute myocardial infarction (AMI), sudden cardiac death (SCD) and cardiac-related interventions, as well as any of these events. ResultsOverall, patients receiving GnRH agonists were more likely to experience a cardiac event, with the most pronounced effect among those receiving ≥8 doses (hazard ratio [HR] <8 doses: 1.13, 95% confidence interval [CI] 1.09-1.16, and HR ≥8 doses: 1.18, 95% CI 1.14-1.22; both P < 0.001). The effect of prolonged (≥8 doses) GnRH agonist use on cardiac events was sustained across all strata of life expectancy; however, there was no effect among men with a life expectancy of <5 years and when use of GnRH agonists was limited to <8 doses (HR 0.99, 95% CI 0.67-1.46; P = 0.964). The use of GnRH agonists was associated with a higher risk of CHD (HR <8 doses: 1.13, 95% CI 1.09-1.17 and HR ≥8 doses: 1.17, 95% CI 1.13-1.21; both P < 0.001). Conversely, the use of GnRH was generally not associated with an increased risk of AMI or SCD, except for men who received ≥8 doses of GnRH agonists and had a life expectancy of ≥5 years, who were at a significantly higher risk of SCD (HR for life expectancy 5-10 years: 1.19, 95% CI 1.06-1.33; P = 0.003 and HR for life expectancy >10 years: 1.16, 95% CI 1.04-1.29; P = 0.006). Finally, orchiectomy was not associated with overall cardiac events, AMI or SCD, and was protective with regard to cardiac-related interventions (HR 0.78, 95% CI 0.68-0.90, P = 0.001). ConclusionExposure to ADT with GnRH agonists is associated with an increased risk of cardiac events in elderly men with localized PCa and a decent life expectancy. Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged life expectancy. Routine screening and lifestyle interventions are warranted in at-risk subpopulations treated with ADT.

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Section: Introductionmentioning

confidence: 99%

Dose‐dependent effect of androgen deprivation therapy for localized prostate cancer on adverse cardiac events

et al. 2015

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“…Les modifications biologiques générées par la castration, notamment en termes d'équilibre glycémique et de profil lipidique, pourraient modifier le risque cardiovasculaire d'un patient donné après instauration d'une castration [28]. Les conséquences métaboliques de l'hypogonadisme induit par la castration sont notamment la résistance à l'insuline, la dyslipidémie, l'hyperglycémie et une hausse tensionnelle, intégrés ou non dans le cadre du syndrome métabolique.…”

Section: Effets Secondaires Cardiovasculairesunclassified

“…Cette déstabilisation est causée par la dégradation du tissu endothélial par des macrophages, eux-mêmes activés par des lymphocytes T (Th1) pro-inflammatoires [48]. L'action agoniste sur le récepteur à la GnRH lymphocytaire stimule la sécrétion de cytokines pro-inflammatoires, qui vont secondairement activer les lymphocytes T et favoriser leur différenciation en lymphocytes Th1 [28,47]. Cette cascade d'activation pouvant conduire in fine à la déstabilisation de la plaque d'athérome, même rapidement après instauration d'une castration par agonistes.…”

Section: Troisième Hypothèse : Rôle Des Récepteurs De La Gnrhunclassified

“…Cette hypothèse immunitaire distinguant deux voies d'activation peut donc participer à la compréhension des profils d'effets secondaires cardiovasculaire différents entre agonistes et antagoniste, et entre agonistes et castration chirurgicale [29,34]. Il existe également des récepteurs à la GnRH sur le muscle cardiaque, dépendants de la protéine kinase A, et l'hypothèse de diminution de la contractilité cardiaque par stimulation de ces récepteurs a été évoquée [28,34].…”

Section: Troisième Hypothèse : Rôle Des Récepteurs De La Gnrhunclassified

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Modalités de castration dans la prise en charge du cancer de la prostate : sont-elles toutes équivalentes ?

Ploussard

Bruyère

Culine³

et al. 2016

Progrès en Urologie

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“…tamoxifen and toremifene control estragon's effect by preventing estrogen binding to receptors. 44 Cardiac complications induced by breast cancer hormonal therapy in women are very rare and the mechanism is also unclear. In men with prostate cancer; the incidence of cardiac toxicity is even low 0.5-2.5%.…”

Section: 21mentioning

confidence: 99%

Breast Cancer and the Heart: Burden on the Chest

Singh¹,

Harish

Devasia

et al. 2018

JCDR

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Breast cancer survivors after successful treatment face various complications in their life. These problems are related to their psycho-social life and/or related to altered body image or may be because of the side effects of breast cancer therapy. Different types of treatment show various hemodynamic/physiological changes on one or more organ/systems. Cardiovascular is the mainly affected system after breast cancer treatment. Radiation-induced heart diseases (RIHD) involve a broad cardiac pathology comprising myocardial fibrosis and cardiomyopathies, pericardial disease, valvular heart diseases, arrhythmias and coronary artery diseases. Chemotherapy induced cardiotoxicity (CIC) affects the morbidity and mortality in breast cancer survivors. Regardless of cancer prognosis; it impacts the quality of life and overall survival with major limitations in life. Conventional diagnostic procedures and biomarkers can be used to detect RIHD and CIC. Cardio-oncology helps in filling the gap between cardiologist and oncologist to reduce the future cardiac risk in survivors.

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The cardiovascular risk of gonadotropin releasing hormone agonists in men with prostate cancer: An unresolved controversy

Cited by 52 publications

References 77 publications

Dose‐dependent effect of androgen deprivation therapy for localized prostate cancer on adverse cardiac events

Dose‐dependent effect of androgen deprivation therapy for localized prostate cancer on adverse cardiac events

Modalités de castration dans la prise en charge du cancer de la prostate : sont-elles toutes équivalentes ?

Breast Cancer and the Heart: Burden on the Chest

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