Cardiovascular Toxicities of Androgen Deprivation Therapy

Challa, Azariyas A.; Calaway, Adam; Cullen, Jennifer; García, Jorge A.; Desai, Nihar R.; Weintraub, Neal L.; Deswal, Anita; Kutty, Shelby; Vallakati, Ajay; Baliga, Ragavendra R.; Campbell, Courtney; Guha, Avirup

doi:10.1007/s11864-021-00846-z

Cited by 37 publications

(35 citation statements)

References 101 publications

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“…including a direct effect on the activation of monocytes and T lymphocytes in the immune system and indirect effects, such as reducing circulating testosterone. 3,4,35 The association between use of GnRH agonists and increased risk of type 2 diabetes has also been established and is also supported by several proposed underlying mechanisms, such as the low testosterone level induced by GnRH agonists. 11,12 The US Food and Drug Administration issued a safety warning, requiring labeling on GnRH agonists warning of the increased risk of diabetes.…”

Section: Jama Network Open | Oncologymentioning

confidence: 89%

Association of Gonadotropin-Releasing Hormone Agonists for Prostate Cancer With Cardiovascular Disease Risk and Hypertension in Men With Diabetes

et al. 2022

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IMPORTANCEMen with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD. OBJECTIVE To evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS This nationwide population-based cohort study identified men with type 2 diabetes by use of data in the Prostate Cancer Data Base Sweden version 4.1 and the Swedish National Diabetes Register, with longitudinal data from 2006 to 2016. These data were used to create 2 cohorts, 1 including men with and without PCa and the other including men with PCa who received and did not receive GnRH agonists. Data analysis was conducted from January 2006 to December 2016. EXPOSURES Treatment with GnRH agonists and PCa diagnosis were the primary exposures. MAIN OUTCOMES AND MEASURES Primary outcome was a 10% increase in predicted 5-year CVD risk score. Secondary outcome was worsening hypertension as defined by the European Society of Hypertension Guidelines. Cox proportional hazards regression models were used to analyze the association. RESULTS The PCa exposure cohort included 5714 men (median [IQR] age, 72.0 [11.0]), and the non-PCa cohort included 28 445 men without PCa (median [IQR] age, 72.0 [11.0]). The GnRH agonist-exposure cohort included 692 men with PCa who received a GnRH agonist, compared with 3460 men with PCa who did not receive a GnRH agonist. Men with PCa receiving GnRH agonists had an increased estimated 5-year CVD risk score compared with men without PCa (hazard ratio [HR],1.25; 95% CI, 1.16-1.36) and compared with men with PCa not receiving GnRH agonists (HR, 1.53; 95% CI, 1.35-1.74). Men receiving GnRH agonists had decreased blood pressure compared with men without PCa (HR, 0.70; 95% CI, 0.61-0.80) and compared with men with PCa not receiving GnRH agonists (HR, 0.68; 95% CI, 0.56-0.82). CONCLUSIONS AND RELEVANCEIn this population-based cohort study, there was an increased risk of CVD in men with type 2 diabetes who received a GnRH agonist for PCa. These findings highlight the need to closely control CVD risk factors in men with type 2 diabetes treated with GnRH agonists. The association between GnRH agonist use and decreased blood pressure levels warrants further study.

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Section: Jama Network Open | Oncologymentioning

confidence: 89%

Association of Gonadotropin-Releasing Hormone Agonists for Prostate Cancer With Cardiovascular Disease Risk and Hypertension in Men With Diabetes

et al. 2022

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“…Low levels of testosterone in aging men are linked with high inflammatory markers such as IL-6 and increased risk of lung damage after pneumonia ( 89 ). In addition, androgen deprivation therapy has been associated with adverse cardiovascular events ( 90 ), endothelial dysfunction, thrombosis and defective immune response ( 91 ). Consistently, the testicle expresses high levels of ACE2, making it a target of SARS-CoV-2, which could account for the low testosterone and high luteinizing hormone levels in COVID-19 males ( 86 ).…”

Section: Covid-19 and Endocrine Activitymentioning

confidence: 99%

Potential of Endogenous Oxytocin in Endocrine Treatment and Prevention of COVID-19

et al. 2022

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Coronavirus disease 2019 or COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant threat to the health of human beings. While wearing mask, maintaining social distance and performing self-quarantine can reduce virus spreading passively, vaccination actively enhances immune defense against COVID-19. However, mutations of SARS-CoV-2 and presence of asymptomatic carriers frustrate the effort of completely conquering COVID-19. A strategy that can reduce the susceptibility and thus prevent COVID-19 while blocking viral invasion and pathogenesis independent of viral antigen stability is highly desirable. In the pathogenesis of COVID-19, endocrine disorders have been implicated. Correspondingly, many hormones have been identified to possess therapeutic potential of treating COVID-19, such as estrogen, melatonin, corticosteroids, thyroid hormone and oxytocin. Among them, oxytocin has the potential of both treatment and prevention of COVID-19. This is based on oxytocin promotion of immune-metabolic homeostasis, suppression of inflammation and pre-existing comorbidities, acceleration of damage repair, and reduction of individuals’ susceptibility to pathogen infection. Oxytocin may specifically inactivate SARS-COV-2 spike protein and block viral entry into cells via angiotensin-converting enzyme 2 by suppressing serine protease and increasing interferon levels and number of T-lymphocytes. In addition, oxytocin can promote parasympathetic outflow and the secretion of body fluids that could dilute and even inactivate SARS-CoV-2 on the surface of cornea, oral cavity and gastrointestinal tract. What we need to do now is clinical trials. Such trials should fully balance the advantages and disadvantages of oxytocin application, consider the time- and dose-dependency of oxytocin effects, optimize the dosage form and administration approach, combine oxytocin with inhibitors of SARS-CoV-2 replication, apply specific passive immunization, and timely utilize efficient vaccines. Meanwhile, blocking COVID-19 transmission chain and developing other efficient anti-SARS-CoV-2 drugs are also important. In addition, relative to the complex issues with drug applications over a long term, oxytocin can be mobilized through many physiological stimuli, and thus used as a general prevention measure. In this review, we explore the potential of oxytocin for treatment and prevention of COVID-19 and perhaps other similar pathogens.

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“…Em relação aos casos mais graves e metastáticos, os principais achados incluem o edema de membros inferiores e a dor óssea. Contudo, a neoplasia de próstata ainda é considerada uma forma indolente de câncer, estimando-se a ocorrência de um óbito a cada cada 41 casos diagnosticados, estando o índice de mortalidade diretamente relacionado ao avanço da idade (Challa, et al, 2021).…”

Section: Introductionunclassified

“…Conforme os dados divulgados pelo programa de Vigilância, Epidemiologia e Resultados Finais do Instituto do Câncer -também conhecido por Surveillance, Epidemiology, and End Results (SEER) -a doença cardiovascular se configura como a principal causa de óbito e de comprometimento da qualidade de vida em pacientes diagnosticados com câncer de próstata (Davey & Alexandrou, 2021). As evidências científicas também apontam que homens de origem afrodescendente apresentam 2,5 vezes mais chances de evoluírem ao óbito por CaP, comparativamente às populações caucasianas, hispânicas, asiáticas e pertencentes às ilhas do Pacífico (Challa, et al, 2021). Desse modo, a literatura demonstrou que homens negros, ainda que em idade não avançada, são mais suscetíveis aos piores desfechos clínicos, mesmo quando submetidos às terapias de tratamento medicamentoso e cirúrgico propostas para o controle dessa doença.…”

Section: Introductionunclassified

Doença cardiovascular associada às terapias de supressão androgênica utilizadas para o tratamento do câncer de próstata: uma revisão de escopo

Santos¹,

Lima²,

Souza

et al. 2022

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No mundo, o câncer de próstata (CaP) representa a segunda principal causa de morte por neoplasia na população masculina, e compartilha de muitos dos fatores de risco que também predispõem ao surgimento das doenças cardiovasculares (DCV´s). O tratamento consagrado para o CaP envolve o uso das terapias de privação androgênica, embora essa estratégia sabidamente possa induzir a injúria miocárdica. O objetivo do presente texto é discorrer sobre a associação entre as DCV´s e as terapias de supressão androgênica utilizadas para o CaP. Para essa Revisão de Escopo, realizada através das plataformas PubMed e Science Direct entre 2020 e 2022, os descritores eleitos foram ‘’Heart’’, ‘’Therapy’’, ‘’Androgen’’ e ''Prostate Cancer’’, associados ao operador booleano ‘’AND’’. Os critérios de inclusão consistiram em 1) ensaios clínicos, testes controlados e aleatórios, revisões e meta-análises; 2) trabalhos sobre a associação entre as DCV´s e as terapias de supressão androgênica 3) estudos que avaliaram os danos da cardiotoxicidade, assim como seu manejo e seguimento e 4) artigos m inglês, espanhol e português. Os critérios de exclusão consistiram em inadequações ao tema, relatos de casos e estudos com animais, além de textos fora do limite temporal. Observou-se que o uso da privação androgênica para o CaP pode induzir a repercussões cardiovasculares adversas, como a hipertensão arterial sistêmica, a insuficiência cardíaca, o infarto agudo do miocárdio e o acidente vascular cerebral. A descontinuação desses medicamentos e os consensos sobre o limiar de toxicidade para essas drogas ainda são tópicos controversos, assim como a escolha das terapias de cardioproteção.

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Cardiovascular Toxicities of Androgen Deprivation Therapy

Cited by 37 publications

References 101 publications

Association of Gonadotropin-Releasing Hormone Agonists for Prostate Cancer With Cardiovascular Disease Risk and Hypertension in Men With Diabetes

Association of Gonadotropin-Releasing Hormone Agonists for Prostate Cancer With Cardiovascular Disease Risk and Hypertension in Men With Diabetes

Potential of Endogenous Oxytocin in Endocrine Treatment and Prevention of COVID-19

Doença cardiovascular associada às terapias de supressão androgênica utilizadas para o tratamento do câncer de próstata: uma revisão de escopo

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