DOI QR코드

DOI QR Code

In Search for a Common Pathway for Health Issues in Men - the Sign of a Holmesian Deduction

  • Aoun, Fouad (Urology, Universite libre de Bruxelles, Jules Bordet Institute) ;
  • Chemaly, Anthony Kallas (Urology, Universite libre de Bruxelles, Jules Bordet Institute) ;
  • Albisinni, Simone (Urology, Universite libre de Bruxelles, Jules Bordet Institute) ;
  • Zanaty, Marc (Urology, Universite libre de Bruxelles, Jules Bordet Institute) ;
  • Roumeguere, Thierry (Urology, Universite libre de Bruxelles, Jules Bordet Institute)
  • Published : 2016.02.05

Abstract

The evidence for the existence of a common pathway for health issues in men is presented in this review. Several epidemiological studies have shown that conditions like cardiovascular diseases (CVD), metabolic syndrome, diabetes, lower urinary tract symptom (LUTS), erectile dysfunction (ED), prostate cancer, hypogonadism, depression and suicide can be associated as risk factors for each other. Thus, the risk of CVD is significantly increased in men with metabolic syndrome, ED, hypogonadism, prostate cancer and/or LUTS. In addition, the above mentioned conditions are more prevalent in atherosclerotic patients. In addition, growing evidence indicates that low androgen levels can cause metabolic syndrome. In addition, obesity, dyslipidaemia and diabetes can further reduce androgen levels potentiating their adverse effect. Low testosterone levels are also associated with a higher incidence of aggressive prostate cancer on biopsy and on definitive pathology, and lower probability of abiraterone response in the metastatic setting. Several recent studies point towards diffuse endothelial dysfunction and dysregulated pro-inflammatory state as the biological link between all these disorders. Our current hypothesis is that oxidative stress caused by these dysfunctions explains the pathogenesis of each of these conditions.

Keywords

References

  1. Al Hayek AA, Khader YS, Jafal S, et al (2013). Prevalence of low testosterone levels in men with type 2 diabetes mellitus: a cross-sectional study. J Family Community Med, 20, 179-86. https://doi.org/10.4103/2230-8229.122006
  2. Albertsen PC, Klotz L, Tombal B, et al (2014). Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur Urol, 65, 565-73. https://doi.org/10.1016/j.eururo.2013.10.032
  3. Alkamel A, Shafiee A, Jalali A, et al (2014). The association between premature coronary artery disease and level of testosterone in young adult males. Arch Iran Med, 17, 545-50.
  4. Anitha B, Inamadar AC, Ragunatha S (2009). Finasteride-its impact on sexual function and prostate cancer. J Cutan Aesthet Surg, 2, 12-6. https://doi.org/10.4103/0974-2077.53093
  5. Araujo AB, Dixon JM, Suarez EA, et al (2011). Clinical review: Endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab, 96, 3007-19. https://doi.org/10.1210/jc.2011-1137
  6. Arrabal-Polo MA, Vera-Arroyo B, Lahoz-Garcia C, et al (2014). Erectile dysfunction, metabolic syndrome and arterial disease. Clinical-pathological relation by carotid ultrasonography. Actas Urol Esp, 38, 179-83. https://doi.org/10.1016/j.acuro.2013.09.005
  7. Azadzoi KM, Radisavljevic ZM, Siroky MB (2008). Effects of ischemia on tachykinin-containing nerves and neurokinin receptors in the rabbit bladder. Urol, 71, 979-83. https://doi.org/10.1016/j.urology.2007.11.012
  8. Bansal D, Bhansali A, Kapil G, et al (2013). Type 2 diabetes and risk of prostate cancer: a meta-analysis of observational studies. Prostate Cancer Prostatic Dis, 16, 151-8. https://doi.org/10.1038/pcan.2012.40
  9. Barqawi A, Crawford ED (2006). Testosterone replacement therapy and the risk of prostate cancer. Is there a link? Int J Impot Res, 18, 323-8. https://doi.org/10.1038/sj.ijir.3901418
  10. Bassil N, Alkaade S, Morley JE (2009). The benefits and risks of testosterone replacement therapy: a review. Prostate Cancer Prostatic Dis, 5, 427-48.
  11. Beatrice AM, Dutta D, Kumar M, et al (2014). Testosterone levels and type 2 diabetes in men: current knowledge and clinical implications. Diabetes Metab Syndr Obes, 7, 481-6.
  12. Beebe-Dimmer JL, Nock NL, Neslund-Dudas C, et al (2009). Racial differences in risk of prostate cancer associated with metabolic syndrome. Urol, 74, 185-90. https://doi.org/10.1016/j.urology.2009.03.013
  13. Berger AP, Bartsch G, Deibl M, et al (2006). Atherosclerosis as a risk factor for benign prostatic hyperplasia. BJU Int, 98, 1038-42. https://doi.org/10.1111/j.1464-410X.2006.06400.x
  14. Berger AP, Kofler K, Bektic J, et al (2003). Increased growth factor production in a human prostatic stromal cell culture model caused by hypoxia. Prostate, 57, 57-65. https://doi.org/10.1002/pros.10279
  15. Blumentals WA, Gomez-Caminero A, Joo S, et al (2004). Should erectile dysfunction be considered as a marker for acute myocardial infarction? Results from a retrospective cohort study. Int J Impot Res, 16, 350-3. https://doi.org/10.1038/sj.ijir.3901174
  16. Borst SE, Mulligan T (2007). Testosterone replacement therapy for older men. Clin Interv Aging, 2, 561-6.
  17. Botto H, Neuzillet Y, Lebret T, et al (2011). High incidence of predominant Gleason pattern 4 localized prostate cancer is associated with low serum testosterone. J Urol, 186, 1400-5. https://doi.org/10.1016/j.juro.2011.05.082
  18. Bouwman, II, Blanker MH, Schouten BW, et al (2015). Are lower urinary tract symptoms associated with cardiovascular disease in the Dutch general population? Results from the Krimpen study. World J Urol, 33, 669-76. https://doi.org/10.1007/s00345-014-1398-y
  19. Bouwman, II, Van Der Heide WK, Van Der Meer K, et al (2009). Correlations between lower urinary tract symptoms, erectile dysfunction, and cardiovascular diseases: are there differences between male populations from primary healthcare and Urol clinics? A review of the current knowledge. Eur J Gen Pract, 15, 128-35. https://doi.org/10.3109/13814780903329536
  20. Boyle P, Robertson C, Mazzetta C, et al (2003). The association between lower urinary tract symptoms and erectile dysfunction in four centres: the UrEpik study. BJU Int, 92, 719-25. https://doi.org/10.1046/j.1464-410X.2003.04459.x
  21. Braun M, Wassmer G, Klotz T, et al (2000). Epidemiology of erectile dysfunction: results of the 'cologne male survey'. Int J Impot Res, 12, 305-11. https://doi.org/10.1038/sj.ijir.3900622
  22. Cai X, Tian Y, Wu T, et al (2014). Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and metaanalysis of randomized controlled trials. Asian J Androl, 16, 146-52. https://doi.org/10.4103/1008-682X.122346
  23. Camacho EM, Huhtaniemi IT, O'Neill TW, et al (2013). Ageassociated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European male ageing study. Eur J Endocrinol, 168, 445-55. https://doi.org/10.1530/EJE-12-0890
  24. Caminiti G, Volterrani M, Iellamo F, et al (2009). Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol, 54, 919-27. https://doi.org/10.1016/j.jacc.2009.04.078
  25. Chang IH, Oh SY, Kim SC (2009). A possible relationship between testosterone and lower urinary tract symptoms in men. J Urol, 182, 215-20. https://doi.org/10.1016/j.juro.2009.02.123
  26. Colombo MG, Meisinger C, Amann U, et al (2015). Association of obesity and long-term mortality in patients with acute myocardial infarction with and without diabetes mellitus: results from the MONICA/KORA myocardial infarction registry. Cardiovasc Diabetol, 14, 24. https://doi.org/10.1186/s12933-015-0189-0
  27. Corona G, Lee DM, Forti G, et al (2010). Age-related changes in general and sexual health in middle-aged and older men: results from the European male ageing study (EMAS). J Sex Med, 7, 1362-80. https://doi.org/10.1111/j.1743-6109.2009.01601.x
  28. Corona G, Mannucci E, Schulman C, et al (2006). Psychobiologic correlates of the metabolic syndrome and associated sexual dysfunction. Eur Urol, 50, 595-604. https://doi.org/10.1016/j.eururo.2006.02.053
  29. Corona G, Rastrelli G, Monami M, et al (2011). Hypogonadism as a risk factor for cardiovascular mortality in men: a metaanalytic study. Eur J Endocrinol, 165, 687-701. https://doi.org/10.1530/EJE-11-0447
  30. Couillard C, Gagnon J, Bergeron J, et al (2000). Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: the HERITAGE Family Study. J Clin Endocrinol Metab, 85, 1026-31.
  31. Cutini PH, Campelo AE, Agriello E, et al (2012). The role of sex steroids on cellular events involved in vascular disease. J Steroid Biochem Mol Biol, 132, 322-30. https://doi.org/10.1016/j.jsbmb.2012.08.001
  32. Dal Pra A, Cury FL, Souhami L (2010). Combining radiation therapy and androgen deprivation for localized prostate cancer-a critical review. Curr Oncol, 17, 28-38.
  33. Dandona P, Dhindsa S (2011). Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab, 96, 2643-51. https://doi.org/10.1210/jc.2010-2724
  34. Davies JD, Carpenter KL, Challis IR, et al (2005). Adipocytic differentiation and liver x receptor pathways regulate the accumulation of triacylglycerols in human vascular smooth muscle cells. J Biol Chem, 280, 3911-9. https://doi.org/10.1074/jbc.M410075200
  35. De Nunzio C, Aronson W, Freedland SJ, et al (2012). The correlation between metabolic syndrome and prostatic diseases. Eur Urol, 61, 560-70. https://doi.org/10.1016/j.eururo.2011.11.013
  36. Dean RC, Lue TF (2005). Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am, 32, 379-95. https://doi.org/10.1016/j.ucl.2005.08.007
  37. English KM, Mandour O, Steeds RP, et al (2000a). Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J, 21, 890-4. https://doi.org/10.1053/euhj.1999.1873
  38. English KM, Steeds RP, Jones TH, et al (2000b). Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, doubleblind, placebo-controlled study. Circulat, 102, 1906-11. https://doi.org/10.1161/01.CIR.102.16.1906
  39. Esposito K, Giugliano F, Martedi E, et al (2005). High proportions of erectile dysfunction in men with the metabolic syndrome. Diabetes Care, 28, 1201-3. https://doi.org/10.2337/diacare.28.5.1201
  40. Filgueira FP, Lobato NS, DosSantos RA, et al (2012). Endogenous testosterone increases leukocyte-endothelial cell interaction in spontaneously hypertensive rats. Life Sci, 90, 689-94. https://doi.org/10.1016/j.lfs.2012.03.009
  41. Finkle WD, Greenland S, Ridgeway GK, et al (2014). Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One, 9, 85805. https://doi.org/10.1371/journal.pone.0085805
  42. Fisher WA, Rosen RC, Eardley I, et al (2005). Sexual experience of female partners of men with erectile dysfunction: the female experience of men's attitudes to life events and sexuality (FEMALES) study. J Sex Med, 2, 675-84. https://doi.org/10.1111/j.1743-6109.2005.00118.x
  43. Foradori CD, Weiser MJ, Handa RJ (2008). Non-genomic actions of androgens. Front Neuroendocrinol, 29, 169-81. https://doi.org/10.1016/j.yfrne.2007.10.005
  44. Frattaroli J, Weidner G, Dnistrian AM, et al (2008). Clinical events in prostate cancer lifestyle trial: results from two years of follow-up. Urol, 72, 1319-23. https://doi.org/10.1016/j.urology.2008.04.050
  45. Fukui M, Kitagawa Y, Nakamura N, et al (2003). Association between elevated testosterone and development of microalbuminuria during puberty in female subjects with type 1 diabetes: response to Amin et Al. Diabetes Care, 26, 2966-7.
  46. Gacci M, Eardley I, Giuliano F, et al (2011). Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol, 60, 809-25. https://doi.org/10.1016/j.eururo.2011.06.037
  47. Gandaglia G, Briganti A, Jackson G, et al (2014). A systematic review of the association between erectile dysfunction and cardiovascular disease. Eur Urol, 65, 968-78. https://doi.org/10.1016/j.eururo.2013.08.023
  48. Garcia-Cruz E, Leibar-Tamayo A, Romero-Otero J, et al (2014). Marked testosterone deficiency-related symptoms may be associated to higher metabolic risk in men with low testosterone levels. J Sex Med, 11, 2292-301. https://doi.org/10.1111/jsm.12615
  49. Garcia-Cruz E, Leibar-Tamayo A, Romero J, et al (2013). Metabolic syndrome in men with low testosterone levels: relationship with cardiovascular risk factors and comorbidities and with erectile dysfunction. J Sex Med, 10, 2529-38. https://doi.org/10.1111/jsm.12265
  50. Ghafar MA, Puchner PJ, Anastasiadis AG, et al (2002). Does the prostatic vascular system contribute to the development of benign prostatic hyperplasia? Curr Urol Rep, 3, 292-6. https://doi.org/10.1007/s11934-002-0051-2
  51. Giovambattista A, Suescun MO, Nessralla CC, et al (2003). Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats. Neuroendocrinol, 78, 270-9. https://doi.org/10.1159/000074448
  52. Gurbuz C, Canat L, Atis G, et al (2012). The role of serum testosterone to prostate-specific antigen ratio as a predictor of prostate cancer risk. Kaohsiung J Med Sci, 28, 649-53. https://doi.org/10.1016/j.kjms.2012.01.003
  53. Haider A, Gooren LJ, Padungtod P, et al (2009). Concurrent improvement of the metabolic syndrome and lower urinary tract symptoms upon normalisation of plasma testosterone levels in hypogonadal elderly men. Andrologia, 41, 7-13. https://doi.org/10.1111/j.1439-0272.2008.00880.x
  54. Haider A, Gooren LJ, Padungtod P, et al (2010). Improvement of the metabolic syndrome and of non-alcoholic liver steatosis upon treatment of hypogonadal elderly men with parenteral testosterone undecanoate. Exp Clin Endocrinol Diabetes, 118, 167-71. https://doi.org/10.1055/s-0029-1202774
  55. 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. https://doi.org/10.1038/sj.pcan.4500221
  56. Haring R, Baumeister SE, Volzke H, et al (2011). Prospective association of low total testosterone concentrations with an adverse lipid profile and increased incident dyslipidemia. Eur J Cardiovasc Prev Rehabil, 18, 86-96. https://doi.org/10.1097/HJR.0b013e32833c1a8d
  57. Haring R, Volzke H, Steveling A, et al (2010). Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20-79. Eur Heart J, 31, 1494-501. https://doi.org/10.1093/eurheartj/ehq009
  58. Ho T, Howard LE, Vidal AC, et al (2014). Smoking and risk of low- and high-grade prostate cancer: results from the REDUCE study. Clin Cancer Res, 20, 5331-8. https://doi.org/10.1158/1078-0432.CCR-13-2394
  59. Holmang S, Marin P, Lindstedt G, et al (1993). Effect of longterm oral testosterone undecanoate treatment on prostate volume and serum prostate-specific antigen concentration in eugonadal middle-aged men. Prostate, 23, 99-106. https://doi.org/10.1002/pros.2990230203
  60. Huncharek M, Haddock KS, Reid R, et al (2010). Smoking as a risk factor for prostate cancer: a meta-analysis of 24 prospective cohort studies. Am J Public Health, 100, 693-701. https://doi.org/10.2105/AJPH.2008.150508
  61. Hyde Z, Norman PE, Flicker L, et al (2012). Low free testosterone predicts mortality from cardiovascular disease but not other causes: the Health in Men Study. J Clin Endocrinol Metab, 97, 179-89. https://doi.org/10.1210/jc.2011-1617
  62. Isidori AM, Buvat J, Corona G, et al (2014). A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review. Eur Urol, 65, 99-112. https://doi.org/10.1016/j.eururo.2013.08.048
  63. Isidori AM, Giannetta E, Gianfrilli D, et al (2005). Effects of testosterone on sexual function in men: results of a metaanalysis. Clin Endocrinol, 63, 381-94. https://doi.org/10.1111/j.1365-2265.2005.02350.x
  64. Jackson G, Boon N, Eardley I, et al (2010). Erectile dysfunction and coronary artery disease prediction: evidence-based guidance and consensus. Int J Clin Pract, 64, 848-57. https://doi.org/10.1111/j.1742-1241.2010.02410.x
  65. Kalra S, Agrawal N, Kumar S, et al (2010). Testosterone replacement in male hypogonadism. Clin Pharmacol, 2, 149-53.
  66. Kapoor D, Aldred H, Clark S, et al (2007). Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity. Diabetes Care, 30, 911-7. https://doi.org/10.2337/dc06-1426
  67. Kapoor D, Goodwin E, Channer KS, et al (2006). Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol, 154, 899-906. https://doi.org/10.1530/eje.1.02166
  68. Kapoor D, Malkin CJ, Channer KS, et al (2005). Androgens, insulin resistance and vascular disease in men. Clin Endocrinol, 63, 239-50. https://doi.org/10.1111/j.1365-2265.2005.02299.x
  69. Karazindiyanoglu S, Cayan S (2008). The effect of testosterone therapy on lower urinary tract symptoms/bladder and sexual functions in men with symptomatic late-onset hypogonadism. Aging Male, 11, 146-9. https://doi.org/10.1080/13685530802290438
  70. Keating NL, O'Malley AJ, Smith MR (2006). Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol, 24, 4448-56. https://doi.org/10.1200/JCO.2006.06.2497
  71. Kenny AM, Kleppinger A, Annis K, et al (2010). Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc, 58, 1134-43. https://doi.org/10.1111/j.1532-5415.2010.02865.x
  72. Ketchandji M, Kuo YF, Shahinian VB, et al (2009). Cause of death in older men after the diagnosis of prostate cancer. J Am Geriatr Soc, 57, 24-30. https://doi.org/10.1111/j.1532-5415.2008.02091.x
  73. Khandrika L, Kumar B, Koul S, et al (2009). Oxidative stress in prostate cancer. Cancer Lett, 282, 125-36. https://doi.org/10.1016/j.canlet.2008.12.011
  74. Khaw KT, Dowsett M, Folkerd E, et al (2007). Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) prospective population study. Circulat, 116, 2694-701. https://doi.org/10.1161/CIRCULATIONAHA.107.719005
  75. Khera M, Crawford D, Morales A, et al (2014). A new era of testosterone and prostate cancer: from physiology to clinical implications. Eur Urol, 65, 115-23. https://doi.org/10.1016/j.eururo.2013.08.015
  76. Kim S, Jeong JY, Choi YJ, et al (2010). Association between lower urinary tract symptoms and vascular risk factors in aging men: the hallym aging Study. Korean J Urol, 51, 477-82. https://doi.org/10.4111/kju.2010.51.7.477
  77. Kirby M, Chapple C, Jackson G, et al (2013). Erectile dysfunction and lower urinary tract symptoms: a consensus on the importance of co-diagnosis. Int J Clin Pract, 67, 606-18. https://doi.org/10.1111/ijcp.12176
  78. Ko YH, Moon du G, Moon KH (2013). Testosterone replacement alone for testosterone deficiency syndrome improves moderate lower urinary tract symptoms: one year follow-up. World J Mens Health, 31, 47-52. https://doi.org/10.5534/wjmh.2013.31.1.47
  79. Koritsiadis G, Tyritzis SI, Koutalellis G, et al (2010). The effect of alpha-blocker treatment on bladder hypoxia inducible factor-1 alpha regulation during lower urinary tract obstruction. Int Braz J Urol, 36, 86-94. https://doi.org/10.1590/S1677-55382010000100013
  80. Kumar P, Kumar N, Thakur DS, et al (2010). Male hypogonadism: Symptoms and treatment. J Adv Pharm Technol Res, 1, 297-301. https://doi.org/10.4103/0110-5558.72420
  81. Kupelian V, Araujo AB, Chiu GR, et al (2010). Relative contributions of modifiable risk factors to erectile dysfunction: results from the boston area community health (BACH) survey. Prev Med, 50, 19-25. https://doi.org/10.1016/j.ypmed.2009.11.006
  82. 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.
  83. Lee RK, Chung D, Chughtai B, et al (2012). Central obesity as measured by waist circumference is predictive of severity of lower urinary tract symptoms. BJU Int, 110, 540-5. https://doi.org/10.1111/j.1464-410X.2011.10819.x
  84. Lee SH, Park TJ, Bae MH, et al (2013). Impact of treatment with statins on prostate-specific antigen and prostate volume in patients with benign prostatic hyperplasia. Korean J Urol, 54, 750-5. https://doi.org/10.4111/kju.2013.54.11.750
  85. Levin RM, O'Connor LJ, Leggett RE, et al (2003). Focal hypoxia of the obstructed rabbit bladder wall correlates with intermediate decompensation. Neurourol Urodyn, 22, 156-63. https://doi.org/10.1002/nau.10076
  86. Lin HJ, Weng SF, Yang CM, et al (2013). Risk of hospitalization for acute cardiovascular events among subjects with lower urinary tract symptoms: a nationwide population-based study. PLoS One, 8, 66661. https://doi.org/10.1371/journal.pone.0066661
  87. Liu Y, Hu F, Li D, et al (2011). Does physical activity reduce the risk of prostate cancer? A systematic review and metaanalysis. Eur Urol, 60, 1029-44. https://doi.org/10.1016/j.eururo.2011.07.007
  88. Lu YL, Kuang L, Zhu H, et al (2007). Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 5alphareductase inhibitor. Asian J Androl, 9, 843-7. https://doi.org/10.1111/j.1745-7262.2007.00327.x
  89. 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. https://doi.org/10.1093/aje/kwj284
  90. Malkin CJ, Pugh PJ, Morris PD, et al (2010). Low serum testosterone and increased mortality in men with coronary heart disease. Heart, 96, 1821-5. https://doi.org/10.1136/hrt.2010.195412
  91. Margel D, Urbach D, Lipscombe LL, et al (2013). Association between metformin use and risk of prostate cancer and its grade. J Natl Cancer Inst, 105, 1123-31. https://doi.org/10.1093/jnci/djt170
  92. Mayi TH, Daoudi M, Derudas B, et al (2012). Human adipose tissue macrophages display activation of cancer-related pathways. J Biol Chem, 287, 21904-13. https://doi.org/10.1074/jbc.M111.315200
  93. McEvoy JW, Nasir K, DeFilippis AP, et al (2015). Relationship of cigarette smoking with inflammation and subclinical vascular disease: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol, 35, 1002-10. https://doi.org/10.1161/ATVBAHA.114.304960
  94. McVary KT (2005). Erectile dysfunction and lower urinary tract symptoms secondary to BPH. Eur Urol, 47, 838-45. https://doi.org/10.1016/j.eururo.2005.02.001
  95. Mirone V, Imbimbo C, Fusco F, et al (2009). Androgens and morphologic remodeling at penile and cardiovascular levels: a common piece in complicated puzzles? Eur Urol, 56, 309-16. https://doi.org/10.1016/j.eururo.2008.12.037
  96. Mondul AM, Clipp SL, Helzlsouer KJ, et al (2010). Association between plasma total cholesterol concentration and incident prostate cancer in the CLUE II cohort. Cancer Causes Control, 21, 61-8. https://doi.org/10.1007/s10552-009-9434-8
  97. Montorsi P, Ravagnani PM, Galli S, et al (2006a). Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trial. Eur Heart J, 27, 2632-9. https://doi.org/10.1093/eurheartj/ehl142
  98. Montorsi P, Ravagnani PM, Galli S, et al (2006b). Association between erectile dysfunction and coronary artery disease: Matching the right target with the right test in the right patient. Eur Urol, 50, 721-31. https://doi.org/10.1016/j.eururo.2006.07.015
  99. Morgans AK, Fan KH, Koyama T, et al (2015). Influence of age on incident diabetes and cardiovascular disease in prostate cancer survivors receiving androgen deprivation therapy. J Urol, 193, 1226-31. https://doi.org/10.1016/j.juro.2014.11.006
  100. Morgentaler A, Lipshultz LI, Bennett R, et al (2011). Testosterone therapy in men with untreated prostate cancer. J Urol, 185, 1256-60. https://doi.org/10.1016/j.juro.2010.11.084
  101. Morgentaler A, Traish AM (2009). Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol, 55, 310-20. https://doi.org/10.1016/j.eururo.2008.09.024
  102. Morote J, Ropero J, Planas J, et al (2013). Metabolic syndrome increases the risk of aggressive prostate cancer detection. BJU Int, 111, 1031-6. https://doi.org/10.1111/j.1464-410X.2012.11406.x
  103. Muller RL, Gerber L, Moreira DM, et al (2012). Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the reduction by dutasteride of prostate cancer events trial. Eur Urol, 62, 757-64. https://doi.org/10.1016/j.eururo.2012.05.025
  104. Nehra A, Jackson G, Miner M, et al (2012). The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc, 87, 766-78. https://doi.org/10.1016/j.mayocp.2012.06.015
  105. Ng CF, Wong A, Li ML, et al (2007). The prevalence of cardiovascular risk factors in male patients who have lower urinary tract symptoms. Hong Kong Med J, 13, 421-6.
  106. Nock MK, Borges G, Bromet EJ, et al (2008). Suicide and suicidal behavior. Epidemiol Rev, 30, 133-54. https://doi.org/10.1093/epirev/mxn002
  107. Nomiya M, Burmeister DM, Sawada N, et al (2013). Prophylactic effect of tadalafil on bladder function in a rat model of chronic bladder ischemia. J Urol, 189, 754-61. https://doi.org/10.1016/j.juro.2012.07.141
  108. Olivan M, Rigau M, Colas E, et al (2015). Simultaneous treatment with statins and aspirin reduces the risk of prostate cancer detection and tumorigenic properties in prostate cancer cell lines. Biomed Res Int, 2015, 762178.
  109. Ozden C, Ozdal OL, Urgancioglu G, et al (2007). The correlation between metabolic syndrome and prostatic growth in patients with benign prostatic hyperplasia. Eur Urol, 51, 199-203. https://doi.org/10.1016/j.eururo.2006.05.040
  110. Paans N, van der Veen WJ, van der Meer K, et al (2011). Time spent in primary care for hip osteoarthritis patients once the diagnosis is set: a prospective observational study. BMC Fam Pract, 12, 48. https://doi.org/10.1186/1471-2296-12-48
  111. Parker AS, Thiel DD, Bergstralh E, et al (2013). Obese men have more advanced and more aggressive prostate cancer at time of surgery than non-obese men after adjusting for screening PSA level and age: results from two independent nested casecontrol studies. Prostate Cancer Prostatic Dis, 16, 352-6. https://doi.org/10.1038/pcan.2013.27
  112. Parsons JK (2010). Benign prostatic hyperplasia and male lower urinary tract symptoms: epidemiology and risk factors. Curr Bladder Dysfunct Rep, 5, 212-8. https://doi.org/10.1007/s11884-010-0067-2
  113. Parsons JK, Kashefi C (2008). Physical activity, benign prostatic hyperplasia, and lower urinary tract symptoms. Eur Urol, 53, 1228-35. https://doi.org/10.1016/j.eururo.2008.02.019
  114. Parsons JK, Messer K, White M, et al (2011). Obesity increases and physical activity decreases lower urinary tract symptom risk in older men: the Osteoporotic Fractures in Men study. Eur Urol, 60, 1173-80. https://doi.org/10.1016/j.eururo.2011.07.040
  115. Peairs KS, Barone BB, Snyder CF, et al (2011). Diabetes mellitus and breast cancer outcomes: a systematic review and metaanalysis. J Clin Oncol, 29, 40-6. https://doi.org/10.1200/JCO.2009.27.3011
  116. Pearl JA, Berhanu D, Francois N, et al (2013). Testosterone supplementation does not worsen lower urinary tract symptoms. J Urol, 190, 1828-33. https://doi.org/10.1016/j.juro.2013.05.111
  117. Perez-Hernandez AI, Catalan V, Gomez-Ambrosi J, et al (2014). Mechanisms linking excess adiposity and carcinogenesis promotion. Front Endocrinol, 5, 65.
  118. Pitteloud N, Hardin M, Dwyer AA, et al (2005). Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab, 90, 2636-41. https://doi.org/10.1210/jc.2004-2190
  119. Prezioso D, Iacono F, Russo U, et al (2014). Evaluation of penile cavernosal artery intima-media thickness in patients with erectile dysfunction. A new parameter in the diagnosis of vascular erectile dysfunction. Our experience on 59 cases. Arch Ital Urol Androl, 86, 9-14. https://doi.org/10.4081/aiua.2014.1.9
  120. Purushothaman KR, Meerarani P, Moreno PR (2007). Inflammation and neovascularization in diabetic atherosclerosis. Indian J Exp Biol, 45, 93-102.
  121. Rhoden EL, Morgentaler A (2003). Testosterone replacement therapy in hypogonadal men at high risk for prostate cancer: results of 1 year of treatment in men with prostatic intraepithelial neoplasia. J Urol, 170, 2348-51. https://doi.org/10.1097/01.ju.0000091104.71869.8e
  122. Rocha VZ, Libby P (2009). Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol, 6, 399-409. https://doi.org/10.1038/nrcardio.2009.55
  123. Roehrborn CG, Barkin J, Siami P, et al (2011). Clinical outcomes after combined therapy with dutasteride plus tamsulosin or either monotherapy in men with benign prostatic hyperplasia (BPH) by baseline characteristics: 4-year results from the randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) trial. BJU Int, 107, 946-54. https://doi.org/10.1111/j.1464-410X.2011.10124.x
  124. Rogers RS, Graziottin TM, Lin CS, et al (2003). Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats. Int J Impot Res, 15, 26-37. https://doi.org/10.1038/sj.ijir.3900943
  125. Rohrmann S, Smit E, Giovannucci E, et al (2005). Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey (NHANES III). Int J Obes, 29, 310-6. https://doi.org/10.1038/sj.ijo.0802881
  126. Rosen R, Altwein J, Boyle P, et al (2003). Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the Aging Male (MSAM-7). Eur Urol, 44, 637-49. https://doi.org/10.1016/j.eururo.2003.08.015
  127. Rosen RC, Fisher WA, Eardley I, et al (2004). The multinational Men's Attitudes to Life Events and Sexuality (MALES) study: I. Prevalence of erectile dysfunction and related health concerns in the general population. Curr Med Res Opin, 20, 607-17. https://doi.org/10.1185/030079904125003467
  128. Ryan CJ, Molina A, Li J, et al (2013). Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. J Clin Oncol, 31, 2791-8. https://doi.org/10.1200/JCO.2012.45.4595
  129. Ryu JK, Han JY, Chu YC, et al (2004). Expression of cavernous transforming growth factor-beta1 and its type II receptor in patients with erectile dysfunction. Int J Androl, 27, 42-9. https://doi.org/10.1046/j.0105-6263.2003.00447.x
  130. Schatzl G, Brossner C, Schmid S, et al (2000). Endocrine status in elderly men with lower urinary tract symptoms: correlation of age, hormonal status, and lower urinary tract function. the prostate study group of the austrian society of urology. Urol, 55, 397-402. https://doi.org/10.1016/S0090-4295(99)00473-2
  131. Seftel AD, de la Rosette J, Birt J, et al (2013). Coexisting lower urinary tract symptoms and erectile dysfunction: a systematic review of epidemiological data. Int J Clin Pract, 67, 32-45. https://doi.org/10.1111/ijcp.12044
  132. Selvin E, Feinleib M, Zhang L, et al (2007). Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care, 30, 234-8. https://doi.org/10.2337/dc06-1579
  133. Shigehara K, Sugimoto K, Konaka H, et al (2011). Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study. Aging Male, 14, 53-8. https://doi.org/10.3109/13685538.2010.518178
  134. Shiri R, Hakkinen J, Koskimaki J, et al (2007). Erectile dysfunction influences the subsequent incidence of lower urinary tract symptoms and bother. Int J Impot Res, 19, 317-20. https://doi.org/10.1038/sj.ijir.3901526
  135. Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
  136. Sih R, Morley JE, Kaiser FE, et al (1997). Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab, 82, 1661-7. https://doi.org/10.1210/jcem.82.6.3988
  137. Speakman MJ, Brading AF, Gilpin CJ, et al (1987). Bladder outflow obstruction--a cause of denervation supersensitivity. J Urol, 138, 1461-6. https://doi.org/10.1016/S0022-5347(17)43675-5
  138. St Sauver JL, Jacobsen SJ, Jacobson DJ, et al (2011). Statin use and decreased risk of benign prostatic enlargement and lower urinary tract symptoms. BJU Int, 107, 443-50. https://doi.org/10.1111/j.1464-410X.2010.09598.x
  139. Tarhan F, Kuyumcuoglu U, Kolsuz A, et al (1997). Cavernous oxygen tension in the patients with erectile dysfunction. Int J Impot Res, 9, 149-53. https://doi.org/10.1038/sj.ijir.3900270
  140. Tek M, Balli E, Cimen B, et al (2010). The effect of testosterone replacement therapy on bladder functions and histology in orchiectomized mature male rats. Urol, 75, 886-90. https://doi.org/10.1016/j.urology.2009.08.016
  141. Thom T, Haase N, Rosamond W, et al (2006). Heart disease and stroke statistics--2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulat, 113, 85-151. https://doi.org/10.1161/CIRCULATIONAHA.105.171600
  142. Tietge UJ (2014). Hyperlipidemia and cardiovascular disease: inflammation, dyslipidemia, and atherosclerosis. Curr Opin Lipidol, 25, 94-5. https://doi.org/10.1097/MOL.0000000000000051
  143. Torkler S, Wallaschofski H, Baumeister SE, et al (2011). Inverse association between total testosterone concentrations, incident hypertension and blood pressure. Aging Male, 14, 176-82. https://doi.org/10.3109/13685538.2010.529194
  144. Turhan S, Tulunay C, Gulec S, et al (2007). The association between androgen levels and premature coronary artery disease in men. Coron Artery Dis, 18, 159-62. https://doi.org/10.1097/MCA.0b013e328012a928
  145. Urushiyama T, Akutsu S, Miyazaki J, et al (2004). Change from a hard to soft diet alters the expression of insulin-like growth factors, their receptors, and binding proteins in association with atrophy in adult mouse masseter muscle. Cell Tissue Res, 315, 97-105. https://doi.org/10.1007/s00441-003-0787-0
  146. Vermeulen A (2001). Androgen replacement therapy in the Aging Male--a critical evaluation. J Clin Endocrinol Metab, 86, 2380-90.
  147. Vigen R, O'Donnell CI, Baron AE, et al (2013). Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA, 310, 1829-36. https://doi.org/10.1001/jama.2013.280386
  148. Vlachopoulos C, Aznaouridis K, Stefanadis C (2010). Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol, 55, 1318-27. https://doi.org/10.1016/j.jacc.2009.10.061
  149. Vlachopoulos C, Jackson G, Stefanadis C, et al (2013a). Erectile dysfunction in the cardiovascular patient. Eur Heart J, 34, 2034-46. https://doi.org/10.1093/eurheartj/eht112
  150. Vlachopoulos C, Rokkas K, Ioakeimidis N, et al (2005). Prevalence of asymptomatic coronary artery disease in men with vasculogenic erectile dysfunction: a prospective angiographic study. Eur Urol, 48, 996-1002. https://doi.org/10.1016/j.eururo.2005.08.002
  151. Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, et al (2013b). Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes, 6, 99-109. https://doi.org/10.1161/CIRCOUTCOMES.112.966903
  152. Wang C, Nieschlag E, Swerdloff RS, et al (2009). ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. Aging Male, 12, 5-12. https://doi.org/10.1080/13685530802389628
  153. Webb CM, McNeill JG, Hayward CS, et al (1999). Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulat, 100, 1690-6. https://doi.org/10.1161/01.CIR.100.16.1690
  154. Wehrberger C, Temml C, Gutjahr G, et al (2011). Is there an association between lower urinary tract symptoms and cardiovascular risk in men? A cross sectional and longitudinal analysis. Urol, 78, 1063-7. https://doi.org/10.1016/j.urology.2011.05.065
  155. Wein AJ, Coyne KS, Tubaro A, et al (2009). The impact of lower urinary tract symptoms on male sexual health: EpiLUTS. BJU Int, 103, 33-41.
  156. Yamaguchi O, Nomiya M, Andersson KE (2014). Functional consequences of chronic bladder ischemia. Neurourol Urodyn, 33, 54-8. https://doi.org/10.1002/nau.22517
  157. Yildiz O, Seyrek M (2007). Vasodilating mechanisms of testosterone. Exp Clin Endocrinol Diabetes, 115, 1-6. https://doi.org/10.1055/s-2007-949657
  158. Zitzmann M (2009). Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol, 5, 673-81. https://doi.org/10.1038/nrendo.2009.212

Cited by

  1. Relationship between oxidative stress and erectile function vol.51, pp.11-12, 2017, https://doi.org/10.1080/10715762.2017.1393074
  2. Oxidative stress and prostatic diseases vol.7, pp.5, 2017, https://doi.org/10.3892/mco.2017.1413