Reduced Muscle Strength And Functional Performance In Men With Prostate Cancer Undergoing Androgen Suppression: Cross-Sectional Investigation

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 08 Dec 2008 - 2:00 PST

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UroToday.com - It is becoming clearer that androgen suppression therapy (AST) is associated with undesirable side effects.¹ While the decline in bone and lean mass following AST has been consistently documented, ^{2, 3} 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, which can further compromise muscle strength, physical function, and independent living, particularly in older patients who may be approaching thresholds for disability. ⁴

This cross-sectional study examined the effects of AST on upper and lower body muscle strength and a range of direct measures of physical performance in 118 men (48 men undertaking AST for prostate cancer and 70 healthy aged-matched controls). Four important findings were reported:

(1) prostate cancer patients undergoing AST showed reduced performance in a range of physical tasks (e.g. 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 (i.e. reduced lean mass and greater fat mass), and

(4) whole body, hip, upper- and lower-limb bone mineral density (BMD) was markedly reduced in AST patients. These findings indicate that men on AST have not only compromised musculoskeletal status as previously reported^{2, 3} but poorer muscle strength and physical performance which may compromise their ability to perform daily tasks and, for the older old, difficulties with independent living.

Slow walking speed has been associated with reduced muscle strength, mobility limitation, disability and increased mortality. ⁵ AST patients had reduced walking speed compared to controls for all walking measures including usual, fast, and the long distance walk. Cardiorespiratory fitness, a strong predictor of cardiovascular disease measured by 400-m walk⁵, was significantly reduced in AST patients compared to controls. This reduction in cardiorespiratory fitness compounded with increases in fat mass and abdominal obesity following AST could substantially contribute to the increased incidence of cardiovascular and metabolic complications in men undergoing AST. ¹ Further, the reduction in muscle strength, dynamic balance (6-m backwards walk), and BMD places a greater risk for fracture following a fall, as risk of falling is strongly related to muscle strength and balance. ⁶

Currently, there is no established treatment to reverse the loss of lean mass and physical function during AST. Physical exercise, in particular resistance training, may be an important countermeasure against the reduction of lean mass and muscle strength that accompanies AST. ⁴ Resistance exercise can be safely undertaken by patients on AST without elevating testosterone⁷ and can significantly enhance upper and lower body muscle strength and improve physical performance. ⁸ Although long term studies using exercise are yet to be conducted, exercise may provide an important protective effect against fat mass gain and exacerbation of sarcopenia that can lead to loss of physical function and the increased risk for AST-associated cardiovascular diseases. ⁹

In summary, the study indicates 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. These 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. Currently, the undertaking of resistance exercise by men on AST appears to be the principal strategy to counter these AST-related adverse effects. ^{4, 8}

Written by:

Daniel A. Galvão, PhD; Dennis R. Taaffe, PhD; Nigel Spry, MD; David Joseph, MD; Darryl Turner, PhD; and Robert U. Newton, PhD; as part of Beyond the Abstract on UroToday.com

References:
1. Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006;24(27):4448-56.
2. 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(2):599-603.
3. 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(1):44-7.
4. 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(4):340-6.
5. 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(17):2018-26.
6. 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:64-7.
7. 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(2):160-5.
8. 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(12):2045-52.
9. 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(6):306-7.

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