Association of Androgen Deprivation Therapy With Cardiovascular Death in Patients With Prostate Cancer

Nguyen, Paul L.; Je, Youjin; Schutz, Fabio A.B.; Hoffman, Karen E.; Hu, Jim C.; Parekh, Arti; Beckman, Joshua A.; Choueiri, Toni K.

doi:10.1001/jama.2011.1745

Cited by 405 publications

(249 citation statements)

References 39 publications

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“…Body composition changes in men undergoing ADT place them at increased risk not only for diminished physical capacity, but also for coronary artery disease, type II diabetes and the metabolic syndrome, 3 though a recent meta-analysis suggests no increase in cardiovascular mortality. 4 In addition, ADTassociated decreases in muscle and bone mass are thought to be associated with increased fracture risk, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

Storer¹,

Miciek²,

Travison³

2012

Asian J Androl

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Prostate cancer (PCa) is the most common visceral malignancy in men with androgen deprivation therapy (ADT) the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectiveness in lowering testosterone, ADT is associated with side effects including loss of muscle mass, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life. This review reports a survey of the literature with a focus on changes in muscle strength, physical function and body composition, due to short-term and long-term ADT. Studies in these areas are sparse, especially well-controlled, prospective randomized trials. Cross-sectional and longitudinal data (up to 2 years) for men with PCa treated with ADT as well as patients with PCa not receiving ADT and age-matched healthy men are presented when available. Based on limited longitudinal data, the adverse effects of ADT on muscle function, physical performance and body composition occur shortly after the onset of ADT and tend to persist and worsen over time. Exercise training is a safe and effective intervention for mitigating these changes and initial guidelines for exercise program design for men with PCa have been published by the American College of Sports Medicine. Disparities in study duration, types of studies and other patient-specific variables such as time since diagnosis, cancer stage and comorbidities may all affect an understanding of the influence of ADT on health, physical performance and mortality. Keywords: androgen deprivation therapy; androgen suppression; exercise prescription; exercise training; functional assessment; lean body mass; older men; prostate cancer INTRODUCTION Prostate cancer (PCa) is the most common visceral malignancy in men.1 Since the tumor is initially testosterone dependent, androgen deprivation therapy (ADT) is the preferred modality to suppress testosterone production in men with this disease. ADT has been extensively studied with surgical and chemical castration achieved via bilateral orchiectomy, use of a gonadotropin hormone-releasing hormone (GnRH) agonist or anti-androgens. Annually, about 500 000 men in the United States are treated with GnRH agonists.2 Though their effectiveness in lowering serum testosterone to castrate levels is well established, side effects are common.Testosterone and its metabolites are essential for the maintenance of muscle mass and bone mineral content. Body composition changes in men undergoing ADT place them at increased risk not only for diminished physical capacity, but also for coronary artery disease, type II diabetes and the metabolic syndrome, 3 though a recent meta-analysis suggests no increase in cardiovascular mortality. 4 In addition, ADTassociated decreases in muscle and bone mass are thought to be associated with increased fracture risk, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life (Figure 1).This narrative review focuses on changes in muscle strength, physi...

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Section: Introductionmentioning

confidence: 99%

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

Storer¹,

Miciek²,

Travison³

2012

Asian J Androl

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“…However, it is interesting to note that a meta-analysis of RCTs evaluating the impact of ADT on the risk of myocardial infarctions failed to detect a detrimental effect, perhaps because such patients comprise a relatively small percentage of the patients placed on such trials. 50 Despite the assurances provided by this meta-analysis, the authors pointed out that it is unknown whether these results can be applied to men with a prior history of congestive heart failure or myocardial infarction, thereby making stratification of future randomized trials by cardiovascular comorbidity necessary. Thus, caution may still be advisable in such patients.…”

Section: Comorbidity and The Benefits Of Adtmentioning

confidence: 96%

Current trends for the use of androgen deprivation therapy in conjunction with radiotherapy for patients with unfavorable intermediate‐risk, high‐risk, localized, and locally advanced prostate cancer

Roach

2014

Cancer

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Androgen deprivation therapy (ADT) is now a well‐established standard of care in combination with definitive radiotherapy for patients with unfavorable intermediate‐risk to high‐risk locally advanced prostate cancer. It is also well established that combination modality treatment with ADT and radiotherapy is superior to either of these modalities alone for the treatment of patients with high‐risk locally advanced disease. Current treatment guidelines for prostate cancer in the United States are based on the estimated risk of recurrence and death. This review examines the clinical evidence underpinning the use of ADT and radiotherapy among patients with high‐risk localized and locally advanced disease in the United States. This review also considers the rationale for moving from traditional luteinizing hormone‐releasing hormone agonists to more recently developed gonadotrophin‐releasing hormone antagonists. Cancer 2014;120:1620–1629. © 2014 American Cancer Society.

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“…There is concern that low testosterone in men treated with androgen deprivation for prostate cancer may contribute to an increase in CV events and mortality (25). However, a recent meta-analysis of eight prospective, randomized trials of androgen deprivation for nonmetastatic prostate cancer that reported CV events by study arm did not find evidence for an increase in CV risk (26). Admittedly, findings in men with castrate testosterone levels due to androgen deprivation may not be generalizable to older men with modest reductions in testosterone.…”

Section: Endogenous Testosterone In Older Menmentioning

confidence: 98%

Testosterone therapy and cardiovascular risk

Walsh

Kitchens

2015

Trends in Cardiovascular Medicine

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Endogenous testosterone levels are inversely associated with cardiovascular risk in older men and men with cardiovascular disease. Current data on cardiovascular outcomes of testosterone therapy include only observational studies and adverse event monitoring in short term trials that were not designed to measure cardiovascular outcomes. These studies have yielded conflicting results, and some have raised concerns that testosterone therapy may increase cardiovascular risk. A well designed, adequately powered, prospective trial will ultimately be required to clarify whether testosterone therapy impacts cardiovascular outcomes. This review describes the findings and limitations of recent studies of cardiovascular risk in older men on testosterone therapy and discusses some of the mechanisms through which testosterone may modify cardiovascular risk

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Association of Androgen Deprivation Therapy With Cardiovascular Death in Patients With Prostate Cancer

Abstract: In a pooled analysis of randomized trials in unfavorable-risk prostate cancer, ADT use was not associated with an increased risk of cardiovascular death but was associated with a lower risk of PCSM and all-cause mortality.

Cited by 405 publications

References 39 publications

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

Current trends for the use of androgen deprivation therapy in conjunction with radiotherapy for patients with unfavorable intermediate‐risk, high‐risk, localized, and locally advanced prostate cancer

Testosterone therapy and cardiovascular risk

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