Androgen-Deprivation Therapy and the Risk of Stroke in Patients With Prostate Cancer

Azoulay, Laurent; Yin, Hui; Benayoun, Serge; Renoux, Christel; Boivin, Jean‐François; Suissa, Samy

doi:10.1016/j.eururo.2011.08.041

Cited by 101 publications

(83 citation statements)

References 21 publications

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“…Other studies have confirmed that this increase in risk applies not only to MI but also to peripheral artery disease and stroke [Azoulay et al 2011;Hu et al 2012].…”

Section: Risk Of Cvd In Men Treated With Adtmentioning

confidence: 82%

Androgen deprivation therapy and cardiovascular disease: what is the linking mechanism?

Zareba

Duivenvoorden

Leong

et al. 2015

Therapeutic Advances in Urology

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Abstract:The past decade has brought increased awareness of the potential adverse effects of androgen deprivation therapy (ADT) in men with prostate cancer. Arguably the most important and controversial of these is the increased risk of cardiovascular morbidity and mortality. Although multiple observational studies have shown that men treated with ADT are at increased risk of developing atherosclerotic cardiovascular disease, our understanding of the biological mechanisms that might underlie this phenomenon is still evolving. In this review, we discuss some of the mechanisms that have been proposed to date, including ADTinduced metabolic changes that promote the development and progression of atherosclerotic plaques as well as direct local effects of hormonal factors on plaque growth, rupture and thrombosis.

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“…Other studies have confirmed that this increase in risk applies not only to MI but also to peripheral artery disease and stroke [Azoulay et al 2011;Hu et al 2012].…”

Section: Risk Of Cvd In Men Treated With Adtmentioning

confidence: 82%

Androgen deprivation therapy and cardiovascular disease: what is the linking mechanism?

Zareba

Duivenvoorden

Leong

et al. 2015

Therapeutic Advances in Urology

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“…A recent population-based cohort study of 22 310 patients with PCa showed that ADT may increase risk of transient ischemic attacks and stroke. 32 Increased frequency of thromboembolic events have also been reported in androgen-deprived men. 33 ADT AND CVD: CONFLICTING DATA Although some studies do illustrate a relationship between ADT and increased risk of CV events, other studies have not confirmed this association.…”

Section: Cardio-metabolic Complications Of Adt L Collins and S Basarimentioning

confidence: 94%

Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications

Collins¹,

Basaria²

2012

Asian J Androl

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Prostate cancer (PCa) is the most common malignancy in men. Prostate being an androgen responsive tissue, androgen deprivation therapy (ADT) is used in the management of locally advanced (improves survival) and metastatic (improves pain and quality of life) PCa. Over the past two decades, the use of ADT has significantly increased as it is also being used in patients with localized disease and those experiencing biochemical recurrences, though without any evidence of survival advantage. Hypogonadism resulting from ADT is associated with decreased muscle mass and strength, increased fat mass, sexual dysfunction, vasomotor symptoms, decreased quality of life, anemia and bone loss. Insulin resistance, diabetes and cardiovascular disease have recently been added to the list of these complications. As the majority of men with PCa die of conditions other than their primary malignancy, recognition and management of these adverse effects is paramount. Here we review data evaluating metabolic and cardiovascular complications of ADT.

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“…However we cannot exclude the possibility of a small treatment effect on CVM or that an unidentified subset of patients (including those with prior CV comorbidity using a validated metric) are at risk for ADTrelated harm. Results from RTOG 08-15 will provide clarification on the role for ADT with Although population-based studies have associated ADT with coronary heart disease, myocardial infarction, stroke, and metabolic changes including weight gain, sarcopenia, dyslipidemia, insulin resistance, and DM, the magnitude of effect on CVD has been modest (eg, number needed to harm estimated at 384 for each additional myocardial infarction) [10,11,[23][24][25][26][27]. These studies often lack robust risk group stratification and are limited in design to prove cause-and-effect relationships including a causal role for ADT and CVM [28].…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular mortality following short-term androgen deprivation in clinically localized prostate cancer: An analysis of RTOG 94-08.

Efstathiou

Paulus

Smith

et al. 2012

JCO

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Background-Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease.Objective-We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase 3 trial.Design, setting, and participants-A total of 1979 men with clinically localized (T1b-2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin-releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors.Outcome measurements and statistical analysis-The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed disease-specific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA.Results and limitations-Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard ratio: 1.07; confidence interval, 0.81-1.42; p = 0.62). Increased CVM was not observed in patients at low risk of PCa death or at high risk of cardiac-related death.Conclusions-Data from patients enrolled in RTOG 94-08 support the hypothesis that ADT does not increase CVM risk in all men with clinically localized PCa treated with short-course GnRH agonist therapy. These data support ADT use in settings with proven survival benefit.Patient summary-We investigated the controversial relationship between hormone therapy and cardiovascular mortality in men with prostate cancer (PCa) treated with radiation in a large randomized trial. Our data suggest that hormone therapy does not increase the risk of cardiovascular death in patients with clinically localized PCa and support the use of such therapy in settings with proven survival benefit.

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Androgen-Deprivation Therapy and the Risk of Stroke in Patients With Prostate Cancer

Cited by 101 publications

References 21 publications

Androgen deprivation therapy and cardiovascular disease: what is the linking mechanism?

Androgen deprivation therapy and cardiovascular disease: what is the linking mechanism?

Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications

Cardiovascular mortality following short-term androgen deprivation in clinically localized prostate cancer: An analysis of RTOG 94-08.

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