Browse > Article
http://dx.doi.org/10.7314/APJCP.2012.13.1.001

Prostate Cancer and Metabolic Syndrome: Is there a link?  

McGrowder, Donovan A. (Department of Pathology, Faculty of Medical Sciences, The University of the West Indies)
Jackson, Lennox Anderson (Radiology West)
Crawford, Tazhmoye V. (Health Policy Department, Independent Health Policy Consultant)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.1, 2012 , pp. 1-13 More about this Journal
Abstract
Metabolic syndrome has become quite prevalent within our society. Over the past two decades, the prevalence of metabolic syndrome has sharply increased worldwide and it has become a major public health problem in several countries. It is associated with the global epidemic of obesity and diabetes mellitus and imposes numerous cardiovascular risks. Prostate cancer is the second most common cancer among men, surpassed only by non-melanoma skin cancer. A considerable body of evidence exists suggesting that some components of the metabolic syndrome have been associated with the risk of prostate cancer. These components include obesity, an abdominal fat distribution, and hyperinsulinemia. Androgen deprivation therapy (ADT) is the most widely used therapeutic modality in prostate cancer. It changed the body composition and lipid profile of men with prostate cancer. Androgen deficiency is associated with increased levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, increased production of proinflammatory factors, and increased thickness of the arterial wall and contributes to endothelial dysfunction. The aim of this review is to evaluate the association between metabolic syndrome and prostate cancer and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. A comprehensive literature search was carried out with the use of PubMed from 1980 through 2011, and relevant articles pertinent to metabolic syndrome and prostate cancer are evaluated and discussed.
Keywords
Metabolic syndrome; prostate cancer; hyperlipidemia; androgen deprivation; vitamin D;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Golden SH, Robinson KA, Saldanha I, et al (2009). Clinical review: prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab, 94, 1853-78.   DOI
2 Garnick MB (1986). Leuprolide versus diethylstilbestrol for previously untreated stage D2 prostate cancer. Results of a prospectively randomized trial. Urology, 27, 21-28.   DOI
3 Giovannucci E, Rimm EB, Liu Y, et al (2003). Body mass index and risk of prostate cancer in U.S. health professionals. J Natl Cancer Inst, 95, 1240-4.   DOI
4 Gronberg H (2003). Prostate cancer epidemiology. Lancet, 36, 859-64.   DOI
5 Grubb RL III, Black A, Izmirlian G, et al (2009). Serum prostatespecific antigen hemodilution among obese men undergoing screening in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiol Biomarkers Prev, 18, 748-51.   DOI
6 Grundy SM, Brewer HB Jr, Cleeman JI, et al (2004). Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol, 24, e13-e18.   DOI
7 Guay AT (2009). The emerging link between hypogonadism and metabolic syndrome. J Androl, 30, 370-6.   DOI
8 Gugliotta A, Ferreira U, Reis LO, et al (2008). Satisfaction analysis in men presenting with localized prostate cancer treated with radical prostatectomy or radiotherapy: psychological and social aspects. Actas Urol Esp, 32, 411-6.   DOI
9 Haffner S, Taegtmeyer H (2003). Epidemic Obesity and the Metabolic Syndrome. Circulation, 108, 1541-5   DOI
10 De Santana IA, Moura GS, Vieira NF (2008). Metabolic syndrome in patients with prostate cancer. Sao Paulo Med J, 126, 274-8.   DOI
11 Dunn SE, Kari FW, French J, et al (1997). Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53- deficient mice. Cancer Res, 57, 4667-72.
12 Eckel RH, Grundy SM, Zimmet PZ (2005). The metabolic syndrome. Lancet, 365, 1415-28.   DOI
13 Engeland A, Tretli S, Bjorge T (2003). Height, body mass index, and prostate cancer: a follow-up of 950000 Norwegian men. Br J Cancer, 89, 237-42.
14 Eri LM, Urdal P, Bechensteen AG (1995). Effects of the luteinizing hormone-releasing hormone agonist leuprolide on lipoproteins, fibrinogen and plasminogen activator inhibitor in patients with benign prostatic hyperplasia. J Urol, 154, 100-4.   DOI
15 Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (2001). Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, 285, 2486-97.   DOI
16 Ford ES, Giles WH, Dietz WH (2002). Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA, 287, 356-9.   DOI
17 Ford ES, Giles WH, Mokdad AH (2004). Increasing prevalence of the metabolic syndrome among U.S. adults. Diabetes Care, 27, 2444-9.   DOI
18 Freedland SJ, Platz EA (2007). Obesity and prostate cancer: making sense out of apparently conflicting data. Epidemiol Rev, 29, 88-97.   DOI
19 Freedland SJ, Platz EA, Presti JC Jr, et al (2006). Obesity, serum prostate specific antigen and prostate size: Implications for prostate cancer detection. J Urol, 175, 500-4.   DOI
20 Chrousos GP (1998). Stressors, stress, and neuroendocrine integration of the adaptive response. The 1997 Hans Selye Memorial Lecture. Ann NY Acad Sci, 851, 311-35.   DOI
21 Chun FK, Hutterer GC, Perrotte P, et al (2007). Distribution of prostate specific antigen (PSA) and percentage free PSA in a contemporary screening cohort with no evidence of prostate cancer. BJU Int, 100, 37-41.   DOI
22 Cohen PA, Kaufman JM, Deslypere JP, et al (1993). Attenuated luteinizing hormone (LH) pulse amplitude but normal pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab, 76, 1140-46.   DOI
23 Cohen P, Peehl DM, Lamson G, et al (1991). Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells. J Clin Endocrinol Metab, 73, 401-7.   DOI
24 Cohen PG (2008). Obesity in men: the hypogonadal-estrogen receptor relationship and its effect on glucose homeostasis. Med. Hypotheses, 70, 358-60.   DOI
25 Coman I, Cri-an N, Marian A, et al (2008). Prevalence of the metabolic syndrome in patients with prostate cancer. J Gastrointestin Liver Dis, 17, 237-8.
26 Cooperberg MR, Lubeck DP, Meng MV, et al (2004). The changing face of low-risk prostate cancer: trends in clinical presentation and primary management. J Clin Oncol, 22, 2141-9.   DOI
27 Cooperberg MR, Grossfeld GD, Lubeck DP, et al (2003). National practice patterns and time trends in androgen ablation for localized prostate cancer. J Natl Cancer Inst, 95, 981-9.   DOI
28 Corder EH, Guess HA, Hulka BS, et al (1993). Vitamin D and prostate cancer: A prediagnostic study with stored sera. Cancer Epidemiol Biomarkers Prev, 2, 467-72.
29 Beebe Dimmer JL, Nock NL, Neslund-Dudas C, et al (2009). Racial differences in risk of prostate cancer associated with metabolic syndrome. Urology, 74, 185-90.   DOI
30 Dandona P, Dhindsa S, Chaudhuri A, et al (2008). Hypogonadotrophic hypogonadism in type 2 diabetes. Aging Male, 11, 107-17.   DOI
31 Beebe Dimmer JL, Dunn RL, Sarma AV, et al (2007). Features of the metabolic syndrome and prostate cancer in African- American men. Cancer, 109, 875-81.   DOI
32 Bianchini F, Kaaks R, Vainio H (2002). Overweight, obesity, and cancer risk. Lancet Oncol, 3, 565-74.   DOI
33 Bolla B, Gonzalez D, Warde P, et al (1997). Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med, 337, 295-300.   DOI
34 Boyle BJ, Zhao XY, Cohen P, et al (2001). Insulin-like growth factor binding protein-3 mediates 1a,25-dihydroxyvitamin d(3) growth inhibition in the LNCaP prostate cancer cell line through p21/WAF1. J Urol, 165, 1319-24.   DOI
35 Braga Basaria M, Dobs AS, Muller DC, et al (2006b). Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy. J Clin Oncol, 24, 3979-83.   DOI
36 Braga-Basaria M, Muller DC, Carducci MA, et al (2006a). Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy. Int J Impot Res, 18, 494-8.   DOI
37 Bratt O (2002). Hereditary prostate cancer: clinical aspects. J Urol, 168, 906-13.   DOI
38 Bratt O, Rohrmann S, Landis PK, et al (2004). Association of prostate cancer risk with insulin, glucose, and anthropometry in the Baltimore longitudinal study of aging. Urology, 2, 253-8.
39 Chodak GW, Keane T, Klotz L (2002). Critical evaluation of hormonal therapy for carcinoma of the prostate. Urology, 60, 201-8.   DOI
40 Calle EE, Rodriguez C, Walker-Thurmond K, et al (2003). Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med, 348, 1625-38.   DOI
41 Attia N, Tamborlane WV, Heptulla R, et al (1998). The metabolic syndrome and insulin-like growth factor I regulation in adolescent obesity. J Clin Endocrinol Metab, 83, 1467-71.   DOI
42 Baillargeon J, Pollock BH, Kristal AR, et al (2005). The association of body mass index and prostate-specific antigen in a population-based study. Cancer, 103, 1092-95.   DOI
43 Baillargeon J, Rose DP (2006). Obesity, adipokines, and prostate cancer. Int J Oncol, 28, 737-45.
44 Balkau B, Charles MA, Drivsholm T, et al (2002). European Group for the Study of Insulin Resistance (EGIR). Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome. Diabetes Metab, 28, 364-76.
45 Bañez LL, Hamilton RJ, Partin AW, et al (2007). Obesity-related plasma hemodilution and PSA concentration among men with prostate cancer. JAMA, 298, 2275-80.   DOI
46 Barnard RJ, Aronson WJ, Tymchuk CN, et al (2002). Prostate cancer: another aspect of the insulin-resistance syndrome? Obes Rev, 3, 303-8.   DOI
47 Basaria S (2008). Androgen Deprivation Therapy, Insulin Resistance, and Cardiovascular Mortality: An Inconvenient Truth. J of Andrology, 29, 534-9.   DOI
48 Basaria S, Dobs AS (1999). Risks versus benefits of testosterone therapy in elderly men. Drugs Aging, 15, 131-42.   DOI
49 Basaria S, Lieb J 2nd, Tang AM, et al (2002). Longterm effects of androgen deprivation therapy in prostate cancer patients. Clin Endocrinol (Oxf), 56, 779-86.   DOI
50 Basaria S, Dobs AS (2001). Hypogonadism and androgen replacement therapy in elderly men. Am J Med, 110, 563-72.   DOI
51 Basaria S, Muller DC, Carducci MA, et al (2006). Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen deprivation therapy. Cancer, 106, 581-88.   DOI
52 Wallner LP, Morgenstern H, McGree ME, et al (2011). The effects of metabolic conditions on prostate cancer incidence over 15 years of follow-up: results from the Olmsted County Study. BJU Int, 107, 929-35.   DOI
53 Trevisan M, Liu J, Bahsas FB, et al (1998). Risk Factor and Life Expectancy Research Group. Syndrome X and mortality: a population based study. Am J Epidemiol, 148, 958-66.   DOI
54 Tuohimaa P, Tenkanen L, Ahonen M, et al (2004). Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer, 108, 104-8.   DOI
55 Tuohimaa P, Tenkanen L, Syvala H, et al (2007). Interaction of factors related to the metabolic syndrome and vitamin D on risk of prostate cancer. Cancer Epidemiol Biomarkers Prev, 16, 302-7.   DOI
56 Werny DM, Saraiya M, Gregg EW (2006). Prostate-specific antigen values in diabetic and non-diabetic US men, 2001- 2002. Am J Epidemiol, 164, 978-83.   DOI
57 World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus.
58 World Health Organization, 1999. Available from: http:// whqlibdoc.who.int/hq/1999/WHO_NCD_NCS_99.2.pdf.
59 Wilson PW, Kannel WB, Silbershatz H, et al (1999). Clustering of metabolic factors and coronary heart disease. Arch Intern Med, 159, 1104-9.   DOI
60 Yannucci J, Manola J, Garnick MB, et al (2006). The effect of androgen deprivation therapy on fasting serum lipid and glucose parameters. J Urol, 176, 520-5.   DOI
61 Zadshir A, Tareen N, Pan D, et al (2005). The prevalence of hypovitaminosis D among US adults: Data from the NHANES III. Ethn Dis, 15, 97-101.
62 Smith MR, Finkelstein JS, McGovern FJ, et al (2002). Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab, 87, 599-603.   DOI
63 Ahonen MH, Tenkanen L, Teppo L, et al (2000). Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control, 11, 847-52.   DOI
64 Andersson SO, Wolk A, Bergstrom R, et al (1997). Body size and prostate cancer: a 20-year follow-up study among 135006 Swedish construction workers. J Natl Cancer Inst, 89, 385- 9.   DOI
65 Araujo AB, O'Donnell AB, Brambilla DJ, et al (2004). Prevalence and incidence of androgen deficiency in middleaged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab, 89, 5920-26.   DOI
66 Smith M, Lee H, Nathan D (2006). Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab, 91, 1305-8.   DOI
67 Smith MR (2007). Androgen deprivation therapy for prostate cancer: new concepts and concerns. Curr Opin Endocrinol Diabetes Obes, 14, 247-54.   DOI
68 Sprenger CC, Peterson A, Lance R, et al (2001). Regulation of proliferation of prostate epithelial cells by 1,25-dihydroxyvitamin D3 is accompanied by an increase in insulin-like growth factor binding protein-3. J Endocrinol, 170, 609-18.   DOI
69 Stellato RK, Feldman HA, Hamdy O, et al (2000). Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care, 23, 490-4.   DOI
70 Stewart LV, Weigel NL (2004). Vitamin D and prostate cancer. Exp Biol Med (Maywood), 229, 277-84.   DOI
71 Svartberg J, von Muhlen D, Schirmer H, et al (2004). Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromso Study. Eur J Endocrinol, 150, 65-71.   DOI
72 Tande AJ, Platz EA, Folsom AR (2006). The metabolic syndrome is associated with reduced risk of prostate cancer. Am J Epidemiol, 164, 1094-102.   DOI
73 Teloken C, Da Ros CT, Caraver F, et al (2005). Low serum testosterone levels are associated with positive surgical margins in radical retropubic prostatectomy: hypogonadism represents bad prognosis in prostate cancer. J Urol, 174, 2178-80.   DOI
74 Rundle A, Richards C, Neugut AI (2009). Body composition, abdominal fat distribution, and prostate-specific antigen test results. Cancer Epidemiol Biomarkers Prev, 18, 331-6.   DOI
75 The Endocrine Society (2001). Summary from the 2nd Annual Andropause Consensus Meeting. The Endocrine Society, Chevy Chase, MD: The Endocrine Society Continuing Education Medical Services.
76 Rosmond R, Dallman MF, Bjorntorp P (1998). Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab, 83, 1853-9.   DOI
77 Rundle A, Neugut AI (2008). Obesity and screening PSA levels among men undergoing an annual physical exam. Prostate, 68, 373-80.   DOI
78 Sattar N, Gaw A, Scherbakova O, et al (2003). Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation, 108, 414-19.   DOI
79 Schröder LM, Schwartz, Woloshin S (2005). Prostate-specific antigen levels in the United States: implications of various definitions for abnormal. J Natl Cancer Inst, 97, 1132-7.   DOI
80 Schwartz GG (2005). Vitamin D and the epidemiology of prostate cancer. Semin Dial, 18, 276-89.   DOI
81 Schwartz GG, Hulka BS (1990). Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res, 10, 1307-11.
82 Severson RK, Grove JS, Nomura AM, et al (1988). Body mass and prostatic cancer: a prospective study. BMJ, 297, 713-5.   DOI
83 Sharifi N, Gulley JL, Dahut WL (2005). Androgen deprivation therapy for prostate cancer. JAMA, 294, 238-44.   DOI
84 Park SK, Sakoda LC, Kang D, et al (2006). Rising prostate cancer rates in South Korea. Prostate, 66, 1285-91.   DOI
85 Shulman AI, Mangelsdorf DJ (2005). Retinoid x receptor heterodimers in the metabolic syndrome. N Engl J Med, 353, 604-15.   DOI
86 Smith JC, Bennett S, Evans LM, et al (2001). The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J Clin Endocrinol Metab, 86, 4261-7.   DOI
87 Parekh N, Lin Y, Marcella S, et al (2008). Associations of lifestyle and physiologic factors with prostate-specific antigen concentrations: evidence from the National Health and Nutrition Examination Survey (2001-2004). Cancer Epidemiol Biomarkers Prev, 17, 2467-72.   DOI
88 Peehl DM, Feldman D (2003). The role of vitamin D and retinoids in controlling prostate cancer progression. Endocr Relat Cancer, 10, 131-140.   DOI
89 Phillips GB, Jing T, Heymsfield SB (2003). Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction. Metabolism, 52, 784-90.   DOI
90 Pischon T, Boeing H, Weikert S, et al (2008). Body size and risk of prostate cancer in the european prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev, 17, 3252-61.   DOI
91 Platz EA, Leitzmann MF, Rifai N, et al (2005). Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era. Cancer Epidemiol Biomarkers Prev, 14, 1262-9.   DOI
92 Pound CR, Partin AW, Eisenberger MA, et al (1999). Natural history of progression after PSA elevation following radical prostatectomy. JAMA, 281, 1591- 7.   DOI
93 Rodriguez C, Patel AV, Calle EE et al (2001). Body mass index, height, and prostate cancer mortality in two large cohorts of adult men in the United States. Cancer Epidemiol Biomarkers Prev, 10, 345-53.
94 Powell IJ (2007). Epidemiology and pathophysiology of prostate cancer in African-American men. J Urol, 177, 444-9.   DOI
95 Reaven GM (1988). Banting lecture 1988. Role of insulin resistance in human disease. Diabetes, 37, 1595-607.   DOI
96 Reis LO, Sasse AD, Matheus WE, et al (2009). Prostate cancer: evidence based clinical practice. Actas Urol Esp, 33, 344-50.   DOI
97 Mohile SG, Cooperberg MR, Elkin EP, et al (2003). Time trends and characteristics of men choosing watchful waiting for initial treatment of localized prostate cancer: results from CaPSURE. J Urol, 170, 1804-7.   DOI
98 Morley JE, Kaiser FE, Perry HM, et al. (1997). Longitudinal changes in testosterone, luteinizing hormone, and folliclestimulating hormone in healthy older men. Metabolism, 46, 410-3.   DOI
99 Morote J, Ramirez C, Gomez E, et al (2009). The relationship between total and free serum testosterone and the risk of prostate cancer and tumour aggressiveness. BJU Int, 104, 486-9.   DOI
100 Moyad MA (2002). Is obesity a risk factor for prostate cancer, and does it even matter? A hypothesis and different perspective. Urology, 59, 41-50.   DOI
101 Muller M, Grobbee DE, den Tonkelaar I, et al (2005). Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab, 90, 2618-23.   DOI
102 Mulligan T, Frick MF, Zuraw QZ, et al (2006). Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract, 60, 762-9.   DOI
103 Ogden C, Carroll M, McDowell M, et al (2007). Flegal K. Obesity Among Adults in the United States - No Change Since 2003-2004. Hyattsville, MD: National Center for Health Statistics.
104 National Cancer Institute Surveillance Epidemiology and End Results Program (2009). Retrieved from http://seer.cancer. gov/statfacts/html/prost.html.
105 Nelson WG, De Marzo AM, Isaacs WB (2003). Prostate cancer. Mechanisms of disease. N Engl J Med, 349, 366-81.   DOI
106 Nishiyama T, Ishizaki F, Anraku T, et al (2005). The influence of androgen deprivation therapy on metabolism in patients with prostate cancer. J Clin Endocrinol Metab, 90, 657-60.   DOI
107 O'Malley RL, Taneja SS (2006). Obesity and prostate cancer. Can J Urol, 13 (Suppl 2), 11-7.
108 Laukkanen JA, Laaksonen DE, Niskanen L, et al (2004). Metabolic syndrome and the risk of prostate cancer in Finnish men: a population - based study. Cancer Epidemiol Biomarkers Prev, 13, 1646-50.
109 Li H, Stampfer MJ, Hollis BW, et al (2007). A Prospective Study of Plasma Vitamin D Metabolites, Vitamin D Receptor Polymorphisms, and Prostate Cancer. PLoS Medicine, 4, e103.   DOI
110 Loblaw DA, Virgo KS, Nam R, et al (2007). Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol, 25, 1596-605.   DOI
111 Lund Haheim L, Wisloff TF, Holme I, et al (2006). Metabolic syndrome predicts prostate cancer in a cohort of middle-aged Norwegian men followed for 27 years. Am J Epidemiol, 164, 769-74.   DOI
112 MacInnis RJ, English DR (2006). Body size and composition and prostate cancer risk: systematic review and meta-regression analysis. Cancer Causes Control, 17, 989-1003.   DOI
113 Messing EM, Manola J, Sarosdy M, et al (1999). Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med, 341, 1781-8.   DOI
114 Malik S, Wong ND, Franklin SS, et al (2004). Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation, 110, 1245-50.   DOI
115 Malkin CJ, Pugh PJ, Jones RD, et al (2004). The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab, 89, 3313-8.   DOI
116 Martin RM, Vatten L, Gunnell D, et al (2009). Components of the metabolic syndrome and risk of prostate cancer: the HUNT 2 cohort, Norway. Cancer Causes Control, 20, 1181-92.   DOI
117 Jones JI, Clemmons DR (1995). Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev, 16, 3-34.
118 Kahn SE, Prigeon RL, Schwartz RS, et al (2001). Obesity, body fat distribution, insulin sensitivity and islet beta-cell function as explanations for metabolic diversity. J Nutr, 131, 354-60.   DOI
119 Kapoor D, Malkin CJ, Channer KS, et al (2005). Androgens, insulin resistance and vascular disease in men. Clin Endocrinol (Oxf), 63, 239-50.   DOI
120 Keating NL, O'Malley AJ, Smith MR (2006). Diabetes and cardiovascular disease during androgen deprivation for prostate cancer. J Clin Onco, 124, 4448-56.
121 Kim YJ, Cho YJ, Oh JE, et al (2008). The association between metabolic syndrome and prostate-specific antigen levels. Int J Urol, 15, 905-9.   DOI
122 Kim YJ, Han BK, Hong SK, et al (2007). Body mass index influences prostate-specific antigen in men younger than 60 years of age. Int J Uro, 14, 1009-12.   DOI
123 Lakka HM, Laaksonen DE, Lakka TA, et al (2002). The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA, 288, 2709-16.   DOI
124 Kristal AR, Chi C, Tangen CM, et al (2006). Associations of demographic and lifestyle characteristics with prostatespecific antigen (PSA) concentration and rate of PSA increase. Cancer, 106, 320-8.   DOI
125 Laaksonen DE, Lakka HM, Niskanen LK, et al (2002). Metabolic syndrome and development of diabetes mellitus: Application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol, 156, 1070-7.   DOI
126 Laaksonen DE, Niskanen L, Punnonen K, et al (2004). Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care, 27, 1036-41.   DOI
127 Hsing AW, Gao YT, Chua S Jr, et al (2003). Insulin resistance and prostate cancer risk. J Natl Cancer Inst, 95, 67-71.   DOI
128 Hsing AW, Sakoda LC, Chua S Jr (2007). Obesity, metabolic syndrome, and prostate cancer. Am J Clin Nutr, 86, 843-57.   DOI
129 Hsing AW, Tsao L, Devesa SS (2000). International trends and patterns of prostate cancer incidence and mortality. Int J Cancer, 85, 60-7.   DOI
130 Huang PL (2009). A comprehensive definition for metabolic syndrome. Dis Model Mech, 2, 231-7.   DOI
131 International Diabetes Federation (2005). The IDF consensus world-wide definition of the metabolic Syndrome Available from http://www.idf.org/webdata/docs/Metac_syndrome_ def.pdf.
132 Isomaa B, Almgren P, Tuomi T, et al (2001). Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care, 24, 683-9.   DOI
133 Jayachandran J, Hogstedt B (2005). Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. Eur J Cancer, 41, 2887-95.   DOI
134 Isom Batz G, Bianco FJ Jr, Kattan MW, et al (2005). Testosterone as a predictor of pathological stage in clinically localized prostate cancer. J Urol, 173, 1935-7.   DOI
135 Iwamura M, Sluss PM, Casamento JB, et al (1993). Insulinlike growth factor I: action and receptor characterization in human prostate cancer cell lines. Prostate, 22, 243-52.   DOI
136 Jayachandran J, Banez LL, Aronson WJ, et al (2009). Obesity as a predictor of adverse outcome across black and white race: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Cancer, 115, 5263-71.   DOI
137 Jemal A, Siegel R, Ward E, et al (2006). Cancer statistics. CA Cancer J Clin, 56, 106-30.   DOI
138 Jeong IG, Hwang SS, Kim HK, et al (2010). The Association of Metabolic Syndrome and Its Components with Serum Prostate-Specific Antigen Levels in a Korean-Screened Population. Cancer Epidemiol Biomarkers Prev, 19, 371-80.   DOI
139 Haffner SM, Mykkanen L, Valdez RA, et al (1993). Relationship of sex hormones to lipids and lipoproteins in non-diabetic men. J Clin Endocrinol Metab, 77, 1610-5.   DOI
140 Hakimian P, Blute M, Kashanian J, et al (2008). Metabolic and cardiovascular effects of androgen deprivation therapy. BJU Int, 102, 1509-14.   DOI
141 Hammarsten J, Hogstedt B (2001). Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplasia. Eur Urol, 39, 151-8.   DOI
142 Hammarsten J, Hogstedt B (2004). Clinical, haemodynamic, anthropometric, metabolic and insulin profile of men with high-stage and high-grade clinical prostate cancer. Blood Pressure, 13, 47-55.   DOI
143 Hanchette CL, Schwartz GG (1992). Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. Cancer, 70, 2861-9.   DOI
144 Hammarsten J, Hogstedt B (2005). Hyperinsulinaemia: A prospective risk factor for lethal clinical prostate cancer. Eur J Cancer, 41, 2887-95.   DOI
145 Hammarsten J, Hogstedt B, Holthuis N, et al (1998). Components of the metabolic syndrome-risk factors for the development of benign prostatic hyperplasia. Prostate Cancer Prostatic Dis, 1, 157-62.   DOI
146 Han JH, Chang IH, Ahn SH, et al (2008). Association between serum prostate- specific antigen level, liver function tests and lipid profile in healthy men. BJU Int, 102, 1097-101.   DOI
147 Hernandez J, Thompson IM (2004). Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker. Cancer, 101, 894-904.   DOI
148 Hsing AW, Chokkalingam AP (2006). Prostate cancer epidemiology. Front Biosci, 11, 1388-413.   DOI
149 Hsing AW, Devesa SS (2001). Trends and patterns of prostate cancer: what do they suggest? Epidemiol Rev, 23, 3-13.   DOI
150 Hsing AW, Devesa SS, Jin F, et al (1998). Rising incidence of prostate cancer in Shanghai, China. Cancer Epidemiol Biomarkers Prev, 7, 83-4.
151 Freedland SJ, Terris MK, Platz EA, et al (2005). Body mass index as a predictor of prostate cancer: Development versus detection on biopsy. Urology, 66, 108-13.
152 Gann PH, Hennekens CH, Ma J, et al (1996). Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst, 88, 1118-26.   DOI