Exercise as it relates to Disease/Exercise effects on prostate cancer patients undergoing androgen deprivation therapy

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Background
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Normal and Enlarged Prostate
Prostate Cancer[edit]

The prostate is part of the male reproductive system. The walnut sized organ is located below the bladder and in front of the bowel. Its primary function is to produce fluid to protect and enrich sperm[1]. The development of prostate cancer (PCa) occurs when the abnormal growth of cells mutate and form a tumour within the prostate. Left untreated, the tumour can spread to other areas of the body, including lymph nodes and bone, and can be life-threatening[1].
There are several symptoms associated with PCa, often dismissed as being a natural consequence of ageing[1][2]. See further readings for an indepth description of symptoms.

Prevalence[edit]

Prostate cancer has the highest level of incidence for men within Australian and New Zealand populations. Approximately 18,700 men are diagnosed each year, with an approximate 14.9% mortality rate (over a five year period) in Australian and New Zealand alone[3]. PCa is the second leading cause of cancer related deaths among the male population[1][3][4][5]. It is more common for PCa to impact men over 50 years of age. However younger individuals, with family history of PCa, have a greater risk of developing the cancer[1].

Androgens[edit]

Androgens are primarily produced in the form of testosterone by the Leydig cells in the testes [6]. It circulates in the blood where it binds with albumin and sex-hormone-binding-globulin[7]. When testosterone enters prostate cells, it get converted to dihydrotestosterone, enabling it to have a greater affinity with the androgen receptors (AR)[7]. The development of prostate cancer relies on AR for the growth of the cancerous cells to avoid apoptosis[6]. As a result, standard therapy for PCa is to deprive the cancerous cells of the androgens, i.e. through androgen deprivation therapy[7].

Androgen Deprivation Therapy
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Androgen deprivation therapy (ADT) is a widely utilised form of hormonal treatment for advanced prostate sufferers[8][9]. ADT can be achieved through either surgical castration or medicinal administration of luteinizing hormone-releasing hormone (LH-RH)[8][10]. LH-RH acts through blocking the androgen receptors, suppressing growth of the cancerous cells[9]. The main aim of ADT is to reduce the size of the tumor in the prostate[8], further increasing the survival rate by reducing the amount of testicular androgen production via LH-RH[8][9]. Studies have identified ADT to adversely be associated with significant morbidities, including an increase in body mass index, increased fat deposition, muscle atrophy, reduced strength, decreased insulin sensitivity, osteoporosis, fatigue, depression and loss of sexual functioning[4][9]. Many of these side effects may compromise a patient’s quality of life (QOL)[9], which can impair psychological wellbeing of the individual[2].

Exercise: An Intervention
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Pharmaceutical intervention is expensive and does not provide an intervention to improve physical functioning or quality of life[8]. Research has shown that men receiving ADT should undertake progressive resistance and aerobic training to alleviate the potential side effects of the treatment[11].
Exercise as an intervention aims to do the following:

Resistance Exercise Aerobic Exercise Impact on Quality of Life
Main Goal:
* Increase muscular strength[12]
* Reduce adiposity[13][14]
* Minimise effects of ADT[9]
* Improvements in motor control[9]
Main Goal:
* Improves cardiovascular fitness
* Improves musculoskeletal functioning[12]
* Improvements in overall health[9]
* Improvement in psychological functioning[13][14]
Main Goal:
* Improves ability to perform daily activities without the effects of fatigue[12]
* Reduces the effects of co-morbidities[13][14]
* Reduces potential sexual dysfunction[9]
* Improves overall self-efficacy and psychological wellbeing[13][14].

Recommendations
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Resistance Training[edit]

Initially, resistance exercises should incorporate training machines (to provide concentric muscle contractions)[13][14]. Exercises should altered as the individual progresses, incorporating an adequate warm up and warm down and general flexibility exercises[11].

Weight Intensity Exercise Examples
60-70% 1RM* 2-4sets
6-12repetitions
Leg extension, leg curl, chest press, lower back extension, calf raises, latissimus pull down, tricep extention, bicep curls, chin-up's (assisted).

*RM=repetition max, the maximum amount of weight that can be lifted at once[14]. To ensure safety to participants, all exercises should be supervised for correct technique.

Aerobic Training[edit]

Cardiovascular training should also be incorporated within the exercise program[14]. Initial aerobic exercises should be completed at a low intensity, increasing in intensity as the weeks progress[12].

Exercises: walking, cycling, jogging, or swimming.
Duration: 15 minutes (initially), and up to 45-60 minutes[12].
Intensity: 50-60% maximum effort, increasing to 75% maximum effort. Monitoring rate of perceived exertion and heart rate[14].

Further Readings
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References
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  1. a b c d e f Prostate Cancer Foundation of Australia. (2013). The Prostate – What is it? Retrieved from Prostate Cancer Foundation of Australia website: http://www.prostate.org.au/articleLive/pages/The-Prostate-%252d-What-is-it%3F.html
  2. a b Prostate Cancer Institute. (2012). Exercise and Diet. Retrieved from Prostate Cancer Institute website: http://www.prostatecancer.org.au/PCI/Exercise_%26_Diet.html
  3. a b World Health Organisation (2008). Globocan Fast Stats: Australia/New Zealand Cancer Statistics. Retrieved from WHO International Agency for Research on Cancer website: http://globocan.iarc.fr/factsheet
  4. a b Culos-Reed, S. N., Robinson, J. W., Lau, H., Stephenson, L., Keats, M., Norris, S., ... Faris, P. (2010). Physical activity for men receiving androgen deprivation therapy for prostate cancer: Benefits from a 16-week intervention. Support Care Cancer, 18, 591-599.
  5. Smith, M, R., Finkelstein, J.S., McGovern, F.J., Zeitman, A.L., Fallon, M., Schoenfeld, D.A. & Kantoff, P.W. (2002). Changes in body composition during androgen deprivation therapy for prostate cancer. The Journal of Clinical Endocrinology and Metabolism, 87(2), 599-603.
  6. a b Grossmann, M.E., Huang, H., & Tindall, D.J. (2001). Androgen receptor signalling in androgen-refactory prostate cancer. Journal of the National Cancer Institute, 93(22), 1687-1697.
  7. a b c Feldman, B.J., & Feldman, D. (2001). The development of androgen-independent prostate cancer. Nature Reviews Cancer, 1(1), 34-45.
  8. a b c d e Galvao, D.A., Nosaka, K., Taaffe, D.R., Peake, J., Spry, N., Suzuki, K., ... Newton, R.U. (2007). Endocrine and immune responses to resistance training in prostate cancer patients. Prostate Cancer and Prostatic Diseases, 1-6.
  9. a b c d e f g h i Tsai, H.K., D’Amico, A.V., Sadetsky, N., Chen, M.H. & Carroll, P.R. (2007). Androgen deprivation therapy for localised prostate cancer and the risk of cardiovascular mortality. Journal of the National Cancer Institute, 99(20), 1516-1524.
  10. Letsch, M., Schally, A.V., Stangelberger, A., Groot, K. & Varga, J.L. (2004). Antagonists of growth hormone-releasing hormone (GH-RH) enhance tumour growth inhabitation induced by androgen deprivation in human MDA-Pca-2b prostate cancers. European Journal of Cancer, 40, 436-444.
  11. a b Galvao, A, D., (2006). Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. School of Exercise, biomedical and health sciences Edith Cowan University. 5,64-73
  12. a b c d e Keogh, J, W. & McLeod, R.D. (2012). Body composition, physical fitness, functional performance, quality of life, and fatigue benefits of exercise for prostate cancer patients: A systematic review. Journal of Pain and Symptom Management, 43(1), 96-110).
  13. a b c d e Segal, R.J., Reid, R.D., Courneya, K.S., Malone, S.C., Parliament, M.B., Scott, C.G ... Wells, G.A. (2003). Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. Journal of Clinical Oncology, 21(9), 1653-1659.
  14. a b c d e f g h Segal, R.J., Reid, R.D., Courneya, K.S., Sigal, R.J., Kenny, G.P., Prud’Homme, D.G., ... D’Angelo, S. (2009). Randomised controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. Journal of Clinical Oncology, 27(3), 344-351.
  15. Allan, C. (2012). Fact sheet: Androgen deprivation therapy (ADT). Retrieved from Andrology Australia website: https://www.andrologyaustralia.org/wp-content/uploads/AA_Factsheet_ADT_v1.pdf