This study examined the effects of androgen suppression therapy (AST) on upper and lower body muscle strength and a range of direct measures of physical performance using a cross-sectional design with 118 men (48 men undertaking AST for prostate cancer and 70 healthy aged-matched controls) from a single tertiary center. Primary end points included muscle strength for the upper- and lower-body; functional performance—repeated chair rise, usual and fast 6-m walk, 6-m backwards walk and 400-m walk time; and dual-energy X-ray absorptiometry assessment—whole body, regional soft tissue composition and bone mineral density (BMD). Men on AST had significantly reduced muscle strength for the upper- and lower-body and impaired functional performance compared to controls (P<0.05). As expected, AST patients had significantly lower whole-body and hip BMD and higher percent of body fat than controls (P<0.05), and tended to have lower whole-body lean mass (−2.3 kg, P=0.077). Appendicular skeletal muscle was positively associated with upper-body (r=0.400–0.606, P<0.001) and lower-body (r=0.549–0.588, P<0.001) muscle strength, and strength was related to functional performance. Men undertaking AST were consistently impaired across a broad range of physical and functional musculoskeletal performance assessments compared with their age-matched normal controls. These findings are relevant for those patients considering AST for subclinical disease management, but whose physical reserve is marginal. Strategies to counter these adverse effects of AST need to be initiated so that independent living and quality of life can be maintained.
Prostate cancer is now the commonest cancer after skin cancer in Western men.1 Increased awareness about men's health and prostate cancer, combined with the widespread availability of the prostate-specific antigen (PSA) blood test has lead to much earlier diagnosis of prostate cancer. In the last 10–20 years, there has been a substantial increase in use of androgen suppression therapies (ASTs) in men with subclinical prostate cancer for the longer-term benefits of reduced relapse, and possible increased survival.2 However, it is becoming clearer that androgen suppression is associated with undesirable side effects3, 4, 5, 6, 7 and these need to be quantified in a meaningful way to assist informed decision-making, and direct research initiatives to minimize or address the more significant adverse consequences.
Although the decline in bone and lean mass (LM) following AST has been consistently documented,7, 8, 9 only scant information exists regarding the impact of testosterone suppression on muscle strength and physical performance. Such adverse alterations in body composition aggravates the age-related loss of muscle mass (termed sarcopenia), which can further compromise muscle strength, physical function and independent living, particularly in older patients who may be approaching thresholds for disability.10, 11 Further, older prostate cancer patients are normally already at a greater risk for other comorbid conditions and physical limitations (for example, cardiovascular disease, diabetes, osteoporosis, skeletal fractures)11, 12 that can dramatically affect their muscle and physical function. However, the development of effective counter strategies requires a detailed understanding of the consequences of AST on physical adverse effects.
In this cross-sectional study we compared upper- and lower-body muscle strength, and a range of direct physical performance measures in a cohort of older men with localized prostate cancer on AST to age-matched healthy controls. Further, we also examined the impact of AST on whole-body and regional body composition and bone mineral density (BMD).
A total of 118 men (48 prostate cancer patients undertaking AST and 70 healthy aged-matched controls) participating in an ongoing exercise intervention study of aerobic and resistance exercise (Australian Clinical Trial Registry—ACTRN12607000263493) served as participants. The eligibility criteria for the prostate cancer patients included: histologically documented prostate cancer, receiving AST in the form of GnRH agonists alone or GnRH agonists plus antiandrogens in the previous 2 months, no bone metastatic disease, absence of any musculoskeletal, cardiovascular or neurological disorder that could inhibit them from exercising, able to walk 400 m and to undertake upper- and lower-limb exercise, and no resistance training in the previous 12 months. The healthy aging cohort included aged-matched men with similar height and body weight. Eligibility criteria for controls included absence of any musculoskeletal, cardiovascular or neurological disorder that could inhibit them from exercising, able to walk 400 m and to undertake upper- and lower-limb exercise, and no resistance training in the previous 12 months. Further, controls did not present for prostate cancer nor were undergoing any form of testosterone suppression. The protocol was approved by the University Human Research Ethics Committee and all participants provided written informed consent.
Dynamic isotonic muscle strength and muscle endurance
Participants underwent one familiarization session that included instruction regarding correct exercise technique and practice on all four isotonic resistance machines (upper body: chest press and seated row, lower body: leg press and leg extension) before muscle strength was determined. Dynamic isotonic muscle strength for the four exercises was measured using 1-repetition maximum (1-RM), as described previously.13 The 1-RM is the maximal weight an individual can move through a full range of motion by using proper exercise technique and not changing body position other than that of the specific exercise motion. The coefficient of variation in our laboratory for repeated 1-RM measures performed approximately 1 week apart is 2.2–7.5%. Muscle endurance was measured using the maximal number of repetitions performed at 70% of 1-RM for the chest press and leg press exercises.14 The coefficients of variation for chest press and leg press muscle endurance are 6.3 and 6.8%, respectively.
A battery of tests was used to assess functional performance. Tests were performed in triplicate (except for the 400-m walk) with sufficient recovery time between trials.14 The fastest time recorded was used in the analyses.
Chair rise to standing
Subjects were seated in a hard-backed chair, with a seat height of 43 cm from the floor, with their arms folded across their chest. They were instructed to rise as fast as possible to a full standing position then return to a full sitting position five times.13, 14 The coefficient of variation in our laboratory for the repeated chair rise is 5.6%.
Two measures of gait speed were undertaken: usual pace, in which subjects were instructed to walk at a pace similar to which they may use during common daily activities; and a fast pace.15 Time taken was determined using electronic timing gates (Fitness Technology, South Australia). The coefficients of variation in our laboratory for usual and fast walk are 5.6 and 6.7%, respectively.
6-m backwards walk
As a measure of dynamic balance, subjects walked backwards 6 m placing one foot directly behind the heel of the other with the shoes touching.13, 15 Time taken was assessed using electronic timing gates. Subjects were spotted by an investigator and if they deviated from the line (lost their balance), they were instructed to move back to the line and continue the test, which increased the time required. The coefficient of variation in our laboratory for the backward walk is 9.4%.
Participants were required to walk 400 m, which consisted of 10 laps out and back over a 20-m course, as fast as they could at a pace they could maintain over the distance.14, 16 The 400-m walk has been shown to be a valid test to estimate cardiorespiratory fitness and walking endurance in older adults.17, 18, 19 The coefficient of variation in our laboratory for the 400-m walk is 2.5%.
Body composition and bone mineral density
BMD (g cm−2) of the hip and total body was assessed by dual-energy X-ray absorptiometry (Hologic Discovery A, Waltham, MA, USA). In addition, whole-body LM, fat mass (FM) and percent fat were derived from the whole-body scan. From the whole-body scan, upper limb, lower limb, and trunk LM and FM were derived by manipulating segmental lines according to anatomical landmarks.20 Upper limb LM (ULLM) and lower limb LM (LLLM) were then summed to derive appendicular skeletal muscle (ASM).21 Coefficients of variation (duplicate scans with repositioning) for WBLM, ULLM, LLLM and ASM were 0.3, 2.1, 0.8 and 0.3%, respectively.
Height and weight were determined by a stadiometer and electronic scale, respectively, and body mass index (BMI, kg m−2) was calculated from weight divided by the square of height. Self-rated health was based on a five-point scale of 1, excellent; 2, very good; 3, good; 4, fair and 5, poor. Number of prescription medications and comorbidities, and mild physical activity were assessed using a general health history questionnaire. For men on AST, GnRH agonists and/or antiandrogen medications and prostate cancer were not included as number of prescription medications or comorbidities. For mild physical activity, subjects were asked about their current level of activity and to provide details. Those reporting being physically active listed easy walking, easy bicycling, golf, bowling and gardening as their usual activities.
Data were analyzed using the SPSS statistical software package (SPSS Inc., Chicago, IL, USA). Normality of the distribution for the various measures was assessed using the Kolmogorov–Smirnov test. Analyses included standard descriptive statistics, unpaired Student's t-tests, χ2-test and Pearson's correlation test. All tests were two tailed and a P-value of <0.05 was required for significance. Results are given as the mean±s.d.
Patient characteristics are shown in Table 1. There was no difference between groups for age, height, weight or BMI, although the AST group had poorer perceived health than controls (P<0.001). There was no difference between groups for number of prescription medications taken or number of comorbidities. Both groups showed a similar rate for current mild physical exercise (AST, 85.4% active; controls, 89.9% active).
Men on AST had significantly reduced muscle strength for the chest press, seated row and leg extension compared to controls (Table 2; P<0.05). There were no differences between groups for either leg press strength or muscle endurance (P>0.05).
Men on AST performed poorer on the 6-m usual walk, 6-m fast walk, 6-m backwards walk, repeated chair rise and 400-m corridor walk than controls (Table 2; all Ps<0.05). The actual speed in meters per second (m s−1) for the 6-m usual and fast walk and the 400-m walk is shown in Figure 1. For all subjects, usual walk speed was correlated (P<0.001) with fast walk speed (r=0.660), backward walk (r=0.382), chair rise (r=0.430) and 400-m walk (r=0.416). Further, leg extension muscle strength was inversely associated (P<0.001) with 6-m usual walk (r=−320), 6-m fast walk (r=−346), 6-m backward walk (r=−308), chair rise (r=−352) and 400-m walk (r=−391) with higher quadriceps muscle strength associated with better functional performance.
Body composition and BMD
Men on AST had significantly lower whole-body, upper- and lower-limb, and hip BMD and higher percent of body fat than controls (Table 3; P<0.05). Further, whole-body FM tended to be higher (+2.2 kg, P=0.068) and whole-body LM lower (−2.3 kg, P=0.071) in AST patients. AST patients had ∼1 kg less ASM compared to controls although differences were not statistically significant (P>0.05). Further, there was a significant difference between groups for lower limb fat (P=0.012) but not for upper limb or trunk FM (P>0.05). In AST patients, ASM was positively associated with chest press (r=0.400, P<0.01), seated row (r=0.606, P<0.001), leg extension (r=0.549, P<0.001) and leg press (r=0.588, P<0.001) muscle strength.
There are four important findings from our cross-sectional analysis: (1) prostate cancer patients undergoing AST show reduced performance in a range of physical tasks (for example, gait speed, 400-m walk, chair rise) compared to healthy aged-matched controls, (2) upper- and lower-body muscle strength was reduced in patients on AST, (3) whole-body and regional soft tissue composition was compromised in patients on AST (that is, reduced LM and greater FM) and (4) whole-body, hip, upper- and lower-limb BMD was markedly reduced in AST patients. This indicates that men on AST have not only compromised musculoskeletal status but poorer muscle strength and physical performance, which may compromise their ability to perform daily tasks and, for the older ones, difficulties with independent living.
Slow walking speed has been associated with reduced muscle strength, mobility limitation, disability and increased mortality.18 In our cohort, AST patients had reduced walking speed compared to controls for all walking measures including usual, fast and the long-distance walk. These findings support a previous cross-sectional study indicating a reduction in usual walk speed of 0.18 m s−1 in AST patients compared to controls.22 Only scant information exists regarding the effect of long-term AST on functional performance outcomes. Levy et al.23 prospectively reported a reduction in usual walking speed ability in AST patients compared to controls. These results indicate that mobility is reduced following AST and may possibly lead to further deterioration in physical function by additional inactivity and musculoskeletal wasting.
Aerobic walking capacity (cardiorespiratory fitness) as measured by the 400-m walk has been shown to be a strong predictor of mortality, cardiovascular disease and mobility limitations in older adults.17, 18, 19 Moreover, even in individuals with well-known risk factors for cardiovascular disease (for example, hypertension, diabetes, smoking, high total cholesterol), it is clear that those with greater cardiorespiratory fitness are at lower risk for premature death than individuals with lower aerobic fitness (for example, sedentary) but without other risk factors for cardiovascular disease.24 We have observed that cardiorespiratory fitness was significantly reduced in AST patients compared to controls. This is a significant finding as the reduction in cardiorespiratory fitness compounded with increases in FM and abdominal obesity following AST could substantially contribute to the increased incidence of cardiovascular and metabolic complications in men undergoing AST.3, 4, 25, 26
We observed reduced muscle strength in men on AST compared to healthy aged-matched controls. Although the rapid loss of LM following AST is likely to negatively affect physical function, only limited information exists regarding the impact of AST on muscle function and strength. A previous cross-sectional study suggested that upper- (chest press) but not lower-limb muscle strength (leg press) was reduced following AST.27 Our study extends those findings indicating that quadriceps muscle strength using the leg extension exercise as well as chair rise ability, which incorporates lower limb muscle strength and endurance and also balance, was also reduced in AST patients. Further, we have demonstrated that elbow flexor as well as shoulder extensor muscle strength (seated row) was reduced. This is a significant finding given that the loss of upper- and lower-body muscle strength in AST patients can further compromise physical function and independent living, particularly in older patients who may be approaching thresholds for disability.10, 11
The loss of LM and BMD as well as an increase in FM following AST has been well documented.7, 8, 27, 28, 29 Our results confirm these findings and further indicate that ASM is positively associated with upper- and lower-body muscle strength. The reduction in BMD places the individual at a greater risk for fracture following a fall, and the risk of falling is strongly related to muscle strength and balance.30 Our men on AST had poorer strength, dynamic balance (as determined by the 6-m backwards walk test) and BMD, placing them at an increased risk for falls and subsequent fracture. As it has been reported31 that quality of life, morbidity and mortality following hip fracture in older people is particularly poor, this consequence of AST is also of great concern.
The associations we found among muscle mass, strength and physical performance suggest that preserving LM may protect against muscle strength loss and subsequent deterioration in physical function. Currently, there is no established treatment to reverse the loss of LM and physical function during AST. Physical exercise, in particular resistance training, may be an important countermeasure against the reduction of LM and muscle strength that accompanies AST.11 We have previously shown that resistance exercise can be safely undertaken by patients on AST without elevating testosterone32 and can significantly enhance upper and lower body muscle strength and improve physical performance.33 Although long-term studies using exercise are yet to be conducted, exercise may provide an important protective effect against FM gain and exacerbation of sarcopenia that can lead to loss of physical function and the increased risk for AST-associated cardiovascular diseases.34
Our study has several limitations. The cross-sectional nature of the study does not permit us to infer cause and effect. Therefore, prospective studies are required to confirm our findings. Further, we were unable to include data regarding testosterone and PSA as participants were drawn from an ongoing prospective study in which the blood sample data are not yet available; however the patients were undertaking standard AST programs that consistently achieve hypogonadal states. No patients were identified with active disease during or in the 3 months after completion of the study assessment period. Nevertheless, our study has several strengths including the comprehensive battery of functional tests, assessment of upper- and lower-body muscle strength, and measures of regional soft tissue composition. In addition, the healthy aged-matched controls did not differ for height or body weight to AST patients providing a strong comparison between the two groups. Further, all measures were conducted in a single center which reduces variation for the physical measures undertaken.
In summary, we found that men on AST have significantly worse musculoskeletal, physical and performance status compared with normal age-matched controls. These adverse outcomes could impair the ability to perform normal activities of daily living, an outcome of particular relevance to those with already marginal physical reserves such as some older, independent living prostate cancer patients. Our findings therefore have immediate clinical relevance for the informed consent process; elderly patients, with marginal physical reserve, might be less likely to complete AST for subclinical disease management. However, our primary aim was to examine a broad range of measures of musculoskeletal performance to better characterize the impact of AST. Only by understanding a process, can effective strategies be developed to address problems. Currently, the undertaking of resistance exercise by men on AST appears to be the principal strategy to counter these AST-related adverse effects.11, 33
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58: 71–96.
Cooperberg MR, Grossfeld GD, Lubeck DP, Carroll PR . National practice patterns and time trends in androgen ablation for localized prostate cancer. J Natl Cancer Inst 2003; 95: 981–989.
Keating NL, O’Malley AJ, Smith MR . Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006; 24: 4448–4456.
Tsai HK, D’Amico AV, Sadetsky N, Chen MH, Carroll PR . Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst 2007; 99: 1516–1524.
Smith MR, Boyce SP, Moyneur E, Duh MS, Raut MK, Brandman J . Risk of clinical fractures after gonadotropin-releasing hormone agonist therapy for prostate cancer. J Urol 2006; 175: 136–139; discussion 139.
Smith MR, Lee H, Nathan DM . Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 2006; 91: 1305–1308.
Galvão DA, Spry NA, Taaffe DR, Newton RU, Stanley J, Shannon T et al. Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer. BJU Int 2008; 102: 44–47.
Smith MR, Finkelstein JS, McGovern FJ, Zietman AL, Fallon MA, Schoenfeld DA et al. Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab 2002; 87: 599–603.
Greenspan SL, Coates P, Sereika SM, Nelson JB, Trump DL, Resnick NM . Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab 2005; 90: 6410–6417.
Rosenberg IH . Sarcopenia: origins and clinical relevance. J Nutr 1997; 127: 990S–991S.
Galvão DA, Taaffe DR, Spry N, Newton RU . Exercise can prevent and even reverse adverse effects of androgen suppression treatment in men with prostate cancer. Prostate Cancer Prostatic Dis 2007; 10: 340–346.
Yancik R, Ganz PA, Varricchio CG, Conley B . Perspectives on comorbidity and cancer in older patients: approaches to expand the knowledge base. J Clin Oncol 2001; 19: 1147–1151.
Taaffe DR, Duret C, Wheeler S, Marcus R . Once-weekly resistance exercise improves muscle strength and neuromuscular performance in older adults. J Am Geriatr Soc 1999; 47: 1208–1214.
Galvão DA, Taaffe DR . Resistance exercise dosage in older adults: single- versus multiset effects on physical performance and body composition. J Am Geriatr Soc 2005; 53: 2090–2097.
Fiatarone MA, Marks EC, Ryan ND, Meredith CN, Lipsitz LA, Evans WJ . High-intensity strength training in nonagenarians. Effects on skeletal muscle. JAMA 1990; 263: 3029–3034.
Taaffe DR, Simonsick EM, Visser M, Volpato S, Nevitt MC, Cauley JA et al. Lower extremity physical performance and hip bone mineral density in elderly black and white men and women: cross-sectional associations in the Health ABC Study. J Gerontol A Biol Sci Med Sci 2003; 58: M934–M942.
Simonsick EM, Fan E, Fleg JL . Estimating cardiorespiratory fitness in well-functioning older adults: treadmill validation of the long distance corridor walk. J Am Geriatr Soc 2006; 54: 127–132.
Newman AB, Simonsick EM, Naydeck BL, Boudreau RM, Kritchevsky SB, Nevitt MC et al. Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability. JAMA 2006; 295: 2018–2026.
Simonsick EM, Montgomery PS, Newman AB, Bauer DC, Harris T . Measuring fitness in healthy older adults: the Health ABC Long Distance Corridor Walk. J Am Geriatr Soc 2001; 49: 1544–1548.
Taaffe DR, Lewis B, Marcus R . Quantifying the effect of hand preference on upper limb bone mineral and soft tissue composition in young and elderly women by dual-energy X-ray absorptiometry. Clin Physiol 1994; 14: 393–404.
Heymsfield SB, Smith R, Aulet M, Bensen B, Lichtman S, Wang J et al. Appendicular skeletal muscle mass: measurement by dual-photon absorptiometry. Am J Clin Nutr 1990; 52: 214–218.
Clay CA, Perera S, Wagner JM, Miller ME, Nelson JB, Greenspan SL . Physical function in men with prostate cancer on androgen deprivation therapy. Phys Ther 2007; 87: 1325–1333.
Levy ME, Perera S, van Londen GJ, Nelson JB, Clay CA, Greenspan SL . Physical function changes in prostate cancer patients on androgen deprivation therapy: a 2-year prospective study. Urology 2008; 71: 735–739.
Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE . Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002; 346: 793–801.
Saigal CS, Gore JL, Krupski TL, Hanley J, Schonlau M, Litwin MS . Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer 2007; 110: 1493–1500.
D’Amico AV, Denham JW, Crook J, Chen MH, Goldhaber SZ, Lamb DS et al. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol 2007; 25: 2420–2425.
Basaria S, Lieb II J, Tang AM, DeWeese T, Carducci M, Eisenberger M et al. Long-term effects of androgen deprivation therapy in prostate cancer patients. Clin Endocrinol (Oxf) 2002; 56: 779–786.
Smith MR . Osteoporosis during androgen deprivation therapy for prostate cancer. Urology 2002; 60: 79–85.
Lee H, McGovern K, Finkelstein JS, Smith MR . Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma. Cancer 2005; 104: 1633–1637.
Wolfson L, Judge J, Whipple R, King M . Strength is a major factor in balance, gait, and the occurrence of falls. J Gerontol A Biol Sci Med Sci 1995; 50 (Spec No): 64–67.
Pande I, Scott DL, O’Neill TW, Pritchard C, Woolf AD, Davis MJ . Quality of life, morbidity, and mortality after low trauma hip fracture in men. Ann Rheum Dis 2006; 65: 87–92.
Galvão DA, Nosaka K, Taaffe DR, Peake J, Spry N, Suzuki K et al. Endocrine and immune responses to resistance training in prostate cancer patients. Prostate Cancer Prostatic Dis 2008; 11: 160–165.
Galvão DA, Nosaka K, Taaffe DR, Spry N, Kristjanson LJ, McGuigan MR et al. Resistance training and reduction of treatment side effects in prostate cancer patients. Med Sci Sports Exerc 2006; 38: 2045–2052.
Galvão DA, Newton RU, Taaffe DR, Spry N . Can exercise ameliorate the increased risk of cardiovascular disease and diabetes associated with ADT? Nat Clin Pract Urol 2008; 5: 306–307.
We thank The Cancer Council of Western Australia for their financial support in running the study. We also thank exercise physiologists Greg Levin, Kyle Smith and Zoe Gibbs, who contributed to the study.
Clinical Trial Registry: Resistance and aerobic exercise for reducing treatment side effects in men receiving androgen deprivation therapy for prostate cancer; ACTRN12607000263493; http://www.anzctr.org.au/trialSearch.aspx
About this article
Cite this article
Galvão, D., Taaffe, D., Spry, N. et al. Reduced muscle strength and functional performance in men with prostate cancer undergoing androgen suppression: a comprehensive cross-sectional investigation. Prostate Cancer Prostatic Dis 12, 198–203 (2009). https://doi.org/10.1038/pcan.2008.51
- androgen suppression
- skeletal muscle
- physical function
Mediterranean-style dietary pattern improves cancer-related fatigue and quality of life in men with prostate cancer treated with androgen deprivation therapy: A pilot randomised control trial
Clinical Nutrition (2020)
Incidence of the adverse effects of androgen deprivation therapy for prostate cancer: a systematic literature review
Supportive Care in Cancer (2020)
Oncology Nursing Forum (2020)
Timing of exercise for muscle strength and physical function in men initiating ADT for prostate cancer
Prostate Cancer and Prostatic Diseases (2020)
Physical exercise for bone health in men with prostate cancer receiving androgen deprivation therapy: a systematic review
Supportive Care in Cancer (2020)