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

Abstract

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...

Muscle, fat and performance during androgen deprivation for prostate cancer

“…In support of our limitations when muscle strength was assessed, 40% of men in a cohort of 62 men commencing ADT (mean age, 68 years) were unable to complete at least one of three assessment of handgrip strength over a 12-month follow-up [28] . Moreover, given the average annual gain of total body fat mass exceeds 11% in ADT-treated men [198] and the known limitations of DXA scan acquisition in those with obesity [76] , the missing 186 Chapter 6 data in our study appears to be in line with current limitations of these tools. However, our findings suggest that researchers should consider the feasibility of data collection when designing trials with clinical populations groups with multiple comorbidities, such as men treated with ADT for PCa.…”

“…Previous studies in men treated with ADT have reported mixed results in terms of muscle strength when compared to both PCa and healthy controls [198] . Consistent with our findings, Joly et al [26] reported no difference in handgrip strength between 57 men treated with ADT (mean age, 73 years) and 51 healthy age-matched controls.…”

“…Therefore, research is required to examine changes in muscle CSA via CT measures at various sites, whilst also accounting for confounding variables, such as age, disease status and treatment modality. Men treated with ADT were observed to experience a continuous increase in fat mass (Table 2.4), with the average annual gain exceeding 11% [198] . These annual gains contrast and exceed the plateau in fat mass accumulation commonly observed in older men [142] .…”

Patient-Reported Outcomes in Prostate Cancer: Prospective Changes Analysis for Prognosis Prediction

“…Therapy for PC often promotes loss of muscle mass, diminished muscle strength, increases fat mass and central adiposity, improving the loss of physical performance and earlier fatigue [28] [29]. These findings may explain worse HRQoL, affecting particularly the physical function and the fatigue symptom.…”

Muscle and bone effects of androgen deprivation therapy: current and emerging therapies

“…The studies of the effects of ADT on muscle mass, muscle strength, and physical performance have yielded variable results and are summarized below. Well-designed, controlled, prospective studies in this area are lacking (Storer et al 2012). Muscle mass decreases consistently; however, when muscle strength outcomes are assessed, results have not all been concordant.…”