Table of Contents Author Guidelines Submit a Manuscript
International Journal of Endocrinology
Volume 2014, Article ID 329456, 14 pages
http://dx.doi.org/10.1155/2014/329456
Review Article

Benign Prostatic Hyperplasia: A New Metabolic Disease of the Aging Male and Its Correlation with Sexual Dysfunctions

1Endocrinology Unit, Medical Department, Azienda Usl, Maggiore-Bellaria Hospital, Bologna, Italy
2Sexual Medicine Andrology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy

Received 26 October 2013; Accepted 5 December 2013; Published 13 February 2014

Academic Editor: Antonio Aversa

Copyright © 2014 Giovanni Corona et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. Salvioli, D. Monti, C. Lanzarini et al., “Immune system, cell senescence, aging and longevity—inflamm-aging reappraised,” Current Pharmaceutical Design, vol. 19, no. 9, pp. 1675–1679, 2013. View at Google Scholar
  2. G. Corona, G. Rastrelli, A. Morelli, L. Vignozzi, E. Mannucci, and M. Maggi, “Hypogonadism and metabolic syndrome,” Journal of Endocrinological Investigation, vol. 34, no. 7, pp. 557–567, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. G. Corona, G. Rastrelli, and M. Maggi, “Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes,” Best Practice & Research Clinical Endocrinology & Metabolism, vol. 27, no. 7, pp. 557–579, 2013. View at Google Scholar
  4. M. Gacci, L. Vignozzi, A. Sebastianelli et al., “Metabolic syndrome and lower urinary tract symptoms: the role of inflammation,” Prostate Cancer and Prostatic Diseases, vol. 16, no. 1, pp. 101–106, 2013. View at Google Scholar
  5. S. W. Hayward and G. R. Cunha, “The prostate: development and physiology,” Radiologic Clinics of North America, vol. 38, no. 1, pp. 1–14, 2000. View at Google Scholar · View at Scopus
  6. G. R. Cunha and W. A. Ricke, “A historical perspective on the role of stroma in the pathogenesis of benign prostatic hyperplasia,” Differentiation, vol. 82, no. 4-5, pp. 168–172, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. J. M. Shannon and G. R. Cunha, “Characterization of androgen binding and deoxyribonucleic acid synthesis in prostate-like structures induced in the urothelium of testicular feminized (Tfm/Y) mice,” Biology of Reproduction, vol. 31, no. 1, pp. 175–183, 1984. View at Google Scholar · View at Scopus
  8. G. R. Cunha and L. W. K. Chung, “Stromal-epithelial interactions. I. Induction of prostatic phenotype in urothelium of testicular feminized (Tfm/y) mice,” Journal of Steroid Biochemistry, vol. 14, no. 12, pp. 1317–1324, 1981. View at Publisher · View at Google Scholar · View at Scopus
  9. P. C. Haughney, S. W. Hayward, R. Dahiya, and G. R. Cunha, “Species-specific detection of growth factor gene expression in developing murine prostatic tissue,” Biology of Reproduction, vol. 59, no. 1, pp. 93–99, 1998. View at Publisher · View at Google Scholar · View at Scopus
  10. S. O. Lee, J. Tian, C. K. Huang et al., “Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells,” Journal of Endocrinology, vol. 213, no. 2, pp. 173–182, 2012. View at Google Scholar
  11. G. Corona, E. Baldi, and M. Maggi, “Androgen regulation of prostate cancer: where are we now?” Journal of Endocrinological Investigation, vol. 34, no. 3, pp. 232–243, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. S. J. Berry, D. S. Coffey, P. C. Walsh, and L. L. Ewing, “The development of human benign prostatic hyperplasia with age,” The Journal of Urology, vol. 132, no. 3, pp. 474–479, 1984. View at Google Scholar · View at Scopus
  13. P. C. Walsh and J. D. Wilson, “The induction of prostatic hypertrophy in the dog with androstanediol,” Journal of Clinical Investigation, vol. 57, no. 4, pp. 1093–1097, 1976. View at Google Scholar · View at Scopus
  14. P. Abrams, “LUTS, BPH, BPE, BPO: a plea for the logical use of correct terms,” Reviewsin Urology, vol. 1, no. 2, p. 65, 1999. View at Google Scholar
  15. C.-C. Liu, S.-P. Huang, W.-M. Li et al., “Relationship between serum testosterone and measures of benign prostatic hyperplasia in aging men,” Urology, vol. 70, no. 4, pp. 677–680, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Martin, K. Lange, M. T. Haren, A. W. Taylor, and G. Witter, “Risk factors for progression and improvement of lower urinary tract symptoms (LUTS) in a prospective cohort of men,” The Journal of Urology, vol. 191, no. 1, pp. 130–137, 2013. View at Publisher · View at Google Scholar
  17. F. C. W. Wu, A. Tajar, S. R. Pye et al., “Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European male aging study,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 7, pp. 2737–2745, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. J. S. Tenover, “Effects of testosterone supplementation in the aging male,” Journal of Clinical Endocrinology and Metabolism, vol. 75, no. 4, pp. 1092–1098, 1992. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Holmäng, P. Mårin, G. Lindstedt, and H. Hedelin, “Effect of long-term oral testosterone undecanoate treatment on prostate volume and serum prostate-specific antigen concentration in eugonadal middle-aged men,” Prostate, vol. 23, no. 2, pp. 99–106, 1993. View at Google Scholar · View at Scopus
  20. K. Shigehara, K. Sugimoto, H. Konaka et al., “Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study,” Aging Male, vol. 14, no. 1, pp. 53–58, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Haider, L. J. Gooren, P. Padungtod, and F. Saad, “Concurrent improvement of the metabolic syndrome and lower urinary tract symptoms upon normalisation of plasma testosterone levels in hypogonadal elderly men,” Andrologia, vol. 41, no. 1, pp. 7–13, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Kalinchenko, E. L. Vishnevskiy, A. N. Koval, G. J. Mskhalaya, and F. Saad, “Beneficial effects of testosterone administration on symptoms of the lower urinary tract in men with late-onset hypogonadism: a pilot study,” Aging Male, vol. 11, no. 2, pp. 57–61, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. J. A. Pearl, D. Berhanu, N. François et al., “Testosterone supplementation does not worsen lower urinary tract symptoms,” The Journal of Urology, vol. 190, no. 5, pp. 1828–1833, 2013. View at Google Scholar
  24. Y. H. Ko, G. Moon du, and K. H. Moon, “Testosterone replacement alone for testosterone deficiency syndrome improves moderate lower urinary tract symptoms: one year follow-up,” The World Journal of Men's Health, vol. 31, no. 1, pp. 47–52, 2013. View at Google Scholar
  25. S. Karazindiyanoǧlu and S. Çayan, “The effect of testosterone therapy on lower urinary tract symptoms/bladder and sexual functions in men with symptomatic late-onset hypogonadism,” Aging Male, vol. 11, no. 3, pp. 146–149, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. P. Comeglio, A. Morelli, I. Cellai et al., “Opposite effects of tamoxifen on metabolic syndrome induced bladder and prostate alterations: a role for GPR30/GPER?” Prostate, vol. 74, no. 1, pp. 10–28, 2014. View at Publisher · View at Google Scholar
  27. T. M. Nicholson and W. A. Ricke, “Androgens and estrogens in benign prostatic hyperplasia: past, present and future,” Differentiation, vol. 82, no. 4-5, pp. 184–199, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. A. K. Chavalmane, P. Comeglio, A. Morelli et al., “Sex steroid receptors in male human bladder: expression and biological function,” Journal of Sexual Medicine, vol. 7, no. 8, pp. 2698–2713, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. J. Marmorston, L. J. Lombardo Jr., S. M. Myers, H. Gierson, E. Stern, and C. E. Hopkins, “Urinary excretion of estrone, estradiol and estriol by patients with prostatic cancer and benign prostate hypertrophy,” The Journal of Urology, vol. 93, no. 2, pp. 287–295, 1965. View at Google Scholar · View at Scopus
  30. A. W. Partin, J. E. Oesterling, J. I. Epstein, R. Horton, and P. C. Walsh, “Influence of age and endocrine factors on the volume of benign prostatic hyperplasia,” The Journal of Urology, vol. 145, no. 2, pp. 405–409, 1991. View at Google Scholar · View at Scopus
  31. A. W. Meikle, R. A. Stephenson, W. P. McWhorter, M. H. Skolnick, and R. G. Middleton, “Effects of age, sex steroids, and family relationships on volumes of prostate zones in men with and without prostate cancer,” Prostate, vol. 26, no. 5, pp. 253–259, 1995. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Hammarsten, J.-E. Damber, M. Karlsson et al., “Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia,” Prostate Cancer and Prostatic Diseases, vol. 12, no. 2, pp. 160–165, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. Y. Miwa, T. Kaneda, and O. Yokoyama, “Association between lower urinary tract symptoms and serum levels of sex hormones in men,” Urology, vol. 72, no. 3, pp. 552–555, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. J. L. St. Sauver, D. J. Jacobson, M. E. McGree et al., “Associations between longitudinal changes in serum estrogen, testosterone, and bioavailable testosterone and changes in benign urologic outcomes,” American Journal of Epidemiology, vol. 173, no. 7, pp. 787–796, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. P. Abrams, L. Cardozo, M. Fall et al., “The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society,” Urology, vol. 61, no. 1, pp. 37–49, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. C. de Nunzio, W. Aronson, S. J. Freedland, E. Giovannucci, and J. K. Parsons, “The correlation between metabolic syndrome and prostatic diseases,” European Urology, vol. 61, no. 3, pp. 560–570, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. J. B. Bourke and J. P. Griffin, “Diabetes mellitus in patients with benign prostatic hyperplasia,” British Medical Journal, vol. 4, no. 629, pp. 492–493, 1968. View at Google Scholar · View at Scopus
  38. J. Hammarsten and B. Högstedt, “Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplasia,” European Urology, vol. 39, no. 2, pp. 151–158, 2001. View at Publisher · View at Google Scholar · View at Scopus
  39. M. C. Michel, L. Mehlburger, H. Schumacher, H.-U. Bressel, and M. Goepel, “Effect of diabetes on lower urinary tract symptoms in patients with benign prostatic hyperplasia,” The Journal of Urology, vol. 163, no. 6, pp. 1725–1729, 2000. View at Google Scholar · View at Scopus
  40. M. A. Joseph, S. D. Harlow, J. T. Wei et al., “Risk factors for lower urinary tract symptoms in a population-based sample of African-American men,” American Journal of Epidemiology, vol. 157, no. 10, pp. 906–914, 2003. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Seim, C. Hoyo, T. Østbye, and L. Vatten, “The prevalence and correlates of urinary tract symptoms in Norwegian men: the HUNT Study,” British Journal of Urology International, vol. 96, no. 1, pp. 88–92, 2005. View at Publisher · View at Google Scholar · View at Scopus
  42. H. Nandeesha, B. C. Koner, L. N. Dorairajan, and S. K. Sen, “Hyperinsulinemia and dyslipidemia in non-diabetic benign prostatic hyperplasia,” Clinica Chimica Acta, vol. 370, no. 1-2, pp. 89–93, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. F. Lotti, G. Corona, L. Vignozzi et al., “Metabolic syndrome and prostate abnormalities in male subjects of infertile couples,” Asian Journal of Andrology, 2014. View at Google Scholar
  44. A. Vikram, G. Jena, and P. Ramarao, “Insulin-resistance and benign prostatic hyperplasia: the connection,” European Journal of Pharmacology, vol. 641, no. 2-3, pp. 75–81, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. J. C. Kim, J.-Y. Lee, J. H. Kim et al., “Effects of obesity on lower urinary tract symptoms in Korean BPH patients,” Asian Journal of Andrology, vol. 11, no. 6, pp. 663–668, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. J. K. Parsons, “Benign prostatic hyperplasia and male lower urinary tract symptoms: epidemiology and risk factors,” Current Bladder Dysfunction Reports, vol. 5, no. 4, pp. 212–218, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. J. M. Kim, P. H. Song, H. T. Kim, and K. H. Moon, “Effect of obesity on prostate-specific antigen, prostate volume, and international prostate symptom score in patients with benign prostatic hyperplasia,” Korean Journal of Urology, vol. 52, no. 6, pp. 401–405, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. J. B. Bourke and J. P. Griffin, “Hypertension, diabetes mellitus, and blood groups in benign prostatic hypertrophy,” British Journal of Urology, vol. 38, no. 1, pp. 18–23, 1966. View at Google Scholar · View at Scopus
  49. S. E. Dahle, A. P. Chokkalingam, Y.-T. Gao, J. Deng, F. Z. Stanczyk, and A. W. Hsing, “Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia,” The Journal of Urology, vol. 168, no. 2, pp. 599–604, 2002. View at Google Scholar · View at Scopus
  50. R. J. Glynn, E. W. Campion, G. R. Bouchard, and J. E. Silbert, “The development of benign prostatic hyperplasia among volunteers in the normative aging study,” American Journal of Epidemiology, vol. 121, no. 1, pp. 78–90, 1985. View at Google Scholar · View at Scopus
  51. S. Sidney, C. P. Quesenberry Jr., M. C. Sadler, H. A. Guess, E. G. Lydick, and E. V. Cattolica, “Incidence of surgically treated benign prostatic hypertrophy and of prostate cancer among blacks and whites in a prepaid health care plan,” American Journal of Epidemiology, vol. 134, no. 8, pp. 825–829, 1991. View at Google Scholar · View at Scopus
  52. S. Wang, Q. Mao, Y. Lin et al., “Body mass index and risk of BPH: a meta-analysis,” Prostate Cancer and Prostatic Diseases, vol. 15, no. 3, pp. 265–272, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. F. Lotti, G. Corona, G. M. Colpi et al., “Elevated body mass index correlates with higher seminal plasma interleukin 8 levels and ultrasonographic abnormalities of the prostate in men attending an andrology clinic for infertility,” Journal of Endocrinological Investigation, vol. 34, no. 10, pp. 336–342, 2011. View at Google Scholar · View at Scopus
  54. M. R. Freeman and K. R. Solomon, “Cholesterol and prostate cancer,” Journal of Cellular Biochemistry, vol. 91, no. 1, pp. 54–69, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. G. Swyer, “Cholesterol content of normal and enlarged prostates,” Cancer Research, vol. 2, pp. 372–375, 1942. View at Google Scholar
  56. H. Nandeesha, B. C. Koner, L. N. Dorairajan, and S. K. Sen, “Hyperinsulinemia and dyslipidemia in non-diabetic benign prostatic hyperplasia,” Clinica Chimica Acta, vol. 370, no. 1-2, pp. 89–93, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Gupta, S. Gupta, M. Pavuk, and C. G. Roehrborn, “Anthropometric and metabolic factors and risk of benign prostatic hyperplasia: a prospective cohort study of Air Force veterans,” Urology, vol. 68, no. 6, pp. 1198–1205, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. M. Lekili, T. Müezzinoǧlu, B. S. Uyanik, and C. Büyüksu, “Serum lipid levels in benign prostatic hyperplasia,” World Journal of Urology, vol. 24, no. 2, pp. 210–213, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Zucchetto, A. Tavani, L. Dal Maso et al., “History of weight and obesity through life and risk of benign prostatic hyperplasia,” International Journal of Obesity, vol. 29, no. 7, pp. 798–803, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. J. K. Parsons, J. Bergstrom, and E. Barrett-Connor, “Lipids, lipoproteins and the risk of benign prostatic hyperplasia in community-dwelling men,” British Journal of Urology International, vol. 101, no. 3, pp. 313–318, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. J. B. Bourke and J. P. Griffin, “Hypertension, diabetes mellitus, and blood groups in benign prostatic hypertrophy,” British Journal of Urology, vol. 38, no. 1, pp. 18–23, 1966. View at Google Scholar · View at Scopus
  62. P. H. Gann, C. H. Hennekens, C. Longcope, W. Verhoek-Oftedahl, F. Grodstein, and M. J. Stampfer, “A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia,” Prostate, vol. 26, no. 1, pp. 40–49, 1995. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Seim, C. Hoyo, T. Østbye, and L. Vatten, “The prevalence and correlates of urinary tract symptoms in Norwegian men: the HUNT Study,” British Journal of Urology International, vol. 96, no. 1, pp. 88–92, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Rohrmann, E. Smit, E. Giovannucci, and E. A. Platz, “Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey (NHANES III),” International Journal of Obesity, vol. 29, no. 3, pp. 310–316, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. M. A. Joseph, S. D. Harlow, J. T. Wei et al., “Risk factors for lower urinary tract symptoms in a population-based sample of African-American men,” American Journal of Epidemiology, vol. 157, no. 10, pp. 906–914, 2003. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Hammarsten, B. Högstedt, N. Holthuis, and D. Mellström, “Components of the metabolic syndrome—risk factors for the development of benign prostatic hyperplasia,” Prostate Cancer and Prostatic Diseases, vol. 1, no. 3, pp. 157–162, 1998. View at Google Scholar · View at Scopus
  67. C. Ozden, O. L. Ozdal, G. Urgancioglu, H. Koyuncu, S. Gokkaya, and A. Memis, “The correlation between metabolic syndrome and prostatic growth in patients with benign prostatic hyperplasia,” European Urology, vol. 51, no. 1, pp. 199–206, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. H. K. Park, H. W. Lee, K. S. Lee et al., “Relationship between lower urinary tract symptoms and metabolic syndrome in a community-based elderly population,” Urology, vol. 72, no. 3, pp. 556–560, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. S. J. Yim, Y. S. Cho, and K. J. Joo, “Relationship between metabolic syndrome and prostate volume in korean men under 50 years of age,” Korean Journal of Urology, vol. 52, no. 6, pp. 390–395, 2011. View at Publisher · View at Google Scholar · View at Scopus
  70. J. H. Jeong, E. T. Kim, and D. K. Kim, “Association of metabolic syndrome and benign prostate enlargement in young Korean males,” Korean Journal of Urology, vol. 52, no. 11, pp. 757–762, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. H. K. Byun, Y. H. Sung, W. Kim, J. H. Jung, J. M. Song, and H. C. Chung, “Relationships between prostate-specific antigen, prostate volume, and components of metabolic syndrome in healthy Korean men,” Korean Journal of Urology, vol. 53, no. 11, pp. 774–778, 2011. View at Google Scholar
  72. T. K. Yang, J. T. Hsieh, S. C. Chen, H. C. Chang, H. J. Yang, and K. H. Huang, “Metabolic syndrome associated with reduced lower urinary tract symptoms in middle-aged men receiving health checkup,” Urology, vol. 80, no. 5, pp. 1093–1097, 2012. View at Google Scholar
  73. Y. W. Park, S. B. Kim, H. Kwon et al., “The relationship between lower urinary tract symptoms/benign prostatic hyperplasia and the number of components of metabolic syndrome,” Urology, vol. 82, no. 3, pp. 674–679, 2013. View at Google Scholar
  74. G. Corona, E. Mannucci, L. Petrone et al., “A comparison of NCEP-ATPIII and IDF metabolic syndrome definitions with relation to metabolic syndrome-associated sexual dysfunction,” Journal of Sexual Medicine, vol. 4, no. 3, pp. 789–796, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. G. Corona, G. Rastrelli, L. Vignozzi, E. Mannucci, and M. Maggi, “Testosterone, cardiovascular disease and the metabolic syndrome,” Best Practice and Research, vol. 25, no. 2, pp. 337–353, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. V. Kupelian, K. T. McVary, S. A. Hall et al., “Association of lower urinary tract symptoms and the metabolic syndrome: results from the Boston Area Community Health Survey,” The Journal of Urology, vol. 189, no. 1, pp. S107–S114, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. F. Lotti, G. Corona, E. Maseroli et al., “Clinical implications of measuring prolactin levels in males of infertile couples,” Andrology, vol. 1, no. 5, pp. 764–771, 2013. View at Google Scholar
  78. M. S. Litwin, M. McNaughton-Collins, F. J. Fowler Jr. et al., “The National Institutes of Health chronic prostatitis symptom index: development and validation of a new outcome measure,” The Journal of Urology, vol. 162, no. 2, pp. 369–375, 1999. View at Publisher · View at Google Scholar · View at Scopus
  79. C. G. Roehrborn, J. G. Nuckolls, J. T. Wei, and W. Steers, “The benign prostatic hyperplasia registry and patient survey: study design, methods and patient baseline characteristics,” British Journal of Urology International, vol. 100, no. 4, pp. 813–819, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. J. C. Nickel, C. G. Roehrborn, M. P. O'Leary, D. G. Bostwick, M. C. Somerville, and R. S. Rittmaster, “The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial,” European Urology, vol. 54, no. 6, pp. 1379–1384, 2008. View at Publisher · View at Google Scholar · View at Scopus
  81. F. di Silverio, V. Gentile, A. de Matteis et al., “Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: a retrospective analysis,” European Urology, vol. 43, no. 2, pp. 164–175, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. J. M. Schenk, A. R. Kristal, M. L. Neuhouser et al., “Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial,” American Journal of Epidemiology, vol. 171, no. 5, pp. 571–582, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. L. Vignozzi, G. Rastrelli, G. Corona, M. Gacci, G. Forti, and M. Maggi, “Benign prostatic hyperplasia: a new metabolic disease?” Journal of Endocrinological Investigation, 2014. View at Google Scholar
  84. L. Adorini, G. Penna, B. Fibbi, and M. Maggi, “Vitamin D receptor agonists target static, dynamic, and inflammatory components of benign prostatic hyperplasia: annals of the New York Academy of Sciences,” Annals of the New York Academy of Sciences, vol. 1193, pp. 146–152, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. G. Penna, B. Fibbi, S. Amuchastegui et al., “Human benign prostatic hyperplasia stromal cells as inducers and targets of chronic immuno-mediated inflammation,” Journal of Immunology, vol. 182, no. 7, pp. 4056–4064, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. L. Vignozzi, I. Cellai, R. Serni et al., “Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells,” Journal of Endocrinology, vol. 214, no. 1, pp. 31–43, 2012. View at Publisher · View at Google Scholar · View at Scopus
  87. L. Vignozzi, M. Gacci, I. Cellai et al., “Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation,” Prostate, vol. 73, no. 8, pp. 789–800, 2013. View at Google Scholar
  88. L. Vignozzi, M. Gacci, I. Cellai et al., “PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS,” Prostate, vol. 73, no. 13, pp. 1391–1402, 2013. View at Google Scholar
  89. G. Penna, N. Mondaini, S. Amuchastegui et al., “Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia,” European Urology, vol. 51, no. 2, pp. 524–533, 2007. View at Publisher · View at Google Scholar · View at Scopus
  90. G. Penna, B. Fibbi, S. Amuchastegui et al., “The vitamin D receptor agonist elocalcitol inhibits IL-8-dependent benign prostatic hyperplasia stromal cell proliferation and inflammatory response by targeting the RhoA/Rho kinase and NF-kB pathways,” Prostate, vol. 69, no. 5, pp. 480–493, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. B. Fibbi, G. Penna, A. Morelli, L. Adorini, and M. Maggi, “Chronic inflammation in the pathogenesis of benign prostatic hyperplasia,” International Journal of Andrology, vol. 33, no. 3, pp. 475–488, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. F. Lotti and M. Maggi, “Interleukin 8 and the male genital tract,” Journal of Reproductive Immunology, vol. 100, no. 1, pp. 54–65, 2013. View at Publisher · View at Google Scholar
  93. A. Morelli, P. Comeglio, S. Filippi et al., “Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 132, no. 1-2, pp. 80–92, 2012. View at Google Scholar
  94. S. Filippi, L. Vignozzi, A. Morelli et al., “Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome,” Journal of Sexual Medicine, vol. 6, no. 12, pp. 3274–3288, 2009. View at Publisher · View at Google Scholar · View at Scopus
  95. L. Vignozzi, A. Morelli, S. Filippi et al., “Farnesoid X receptor activation improves erectile function in animal models of metabolic syndrome and diabetes,” Journal of Sexual Medicine, vol. 8, no. 1, pp. 57–77, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. L. Vignozzi, A. Morelli, E. Sarchielli et al., “Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit,” Journal of Endocrinology, vol. 212, no. 1, pp. 71–84, 2012. View at Publisher · View at Google Scholar · View at Scopus
  97. A. Morelli, P. Comeglio, S. Filippi et al., “Mechanism of action of phosphodiesterase type 5 inhibition in metabolic syndrome-associated prostate alterations: an experimental study in the rabbit,” Prostate, vol. 73, no. 4, pp. 428–441, 2013. View at Google Scholar
  98. M. Oelke, A. Bachmann, A. Descazeaud et al., “EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction,” European Urology, vol. 64, no. 1, pp. 118–140, 2013. View at Google Scholar
  99. A. M. Mondul, E. Giovannucci, and E. A. Platz, “A prospective study of obesity and incidence and progression of lower urinary tract symptoms,” The Journal of Urology, pp. 05477–05479, 2013. View at Publisher · View at Google Scholar
  100. G. Corona, G. Rastrelli, M. Monami et al., “Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis,” European Journal of Endocrinology, vol. 168, no. 6, pp. 829–843, 2013. View at Google Scholar
  101. M. Hamer and Y. Chida, “Intake of fruit, vegetables, and antioxidants and risk of type 2 diabetes: systematic review and meta-analysis,” Journal of Hypertension, vol. 25, no. 12, pp. 2361–2369, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. L. Dauchet, P. Amouyel, S. Hercberg, and J. Dallongeville, “Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies,” Journal of Nutrition, vol. 136, no. 10, pp. 2588–2593, 2006. View at Google Scholar · View at Scopus
  103. F. J. He, C. A. Nowson, and G. A. MacGregor, “Fruit and vegetable consumption and stroke: meta-analysis of cohort studies,” The Lancet, vol. 367, no. 9507, pp. 320–326, 2006. View at Publisher · View at Google Scholar · View at Scopus
  104. S. Suzuki, E. A. Platz, I. Kawachi, W. C. Willett, and E. Giovannucci, “Intakes of energy and macronutrients and the risk of benign prostatic hyperplasia,” American Journal of Clinical Nutrition, vol. 75, no. 4, pp. 689–697, 2002. View at Google Scholar · View at Scopus
  105. A. R. Kristal, K. B. Arnold, J. M. Schenk et al., “Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the Prostate Cancer Prevention Trial,” American Journal of Epidemiology, vol. 167, no. 8, pp. 925–934, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. S. Rohrmann, E. Giovannucci, W. C. Willett, and E. A. Platz, “Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men,” American Journal of Clinical Nutrition, vol. 85, no. 2, pp. 523–529, 2007. View at Google Scholar · View at Scopus
  107. T. Liang and S. Liao, “Inhibition of steroid 5α-reductase by specific aliphatic unsaturated fatty acids,” Biochemical Journal, vol. 285, no. 2, pp. 557–562, 1992. View at Google Scholar · View at Scopus
  108. G. Block, M. Dietrich, E. P. Norkus et al., “Factors associated with oxidative stress in human populations,” American Journal of Epidemiology, vol. 156, no. 3, pp. 274–285, 2002. View at Publisher · View at Google Scholar · View at Scopus
  109. R. Tewari, S. Rajender, S. M. Natu et al., “Diet, obesity, and prostate health: are we missing the link?” Journal of Andrology, vol. 33, no. 5, pp. 763–776, 2012. View at Google Scholar
  110. E. A. Platz, I. Kawachi, E. B. Rimm et al., “Physical activity and benign prostatic hyperplasia,” Archives of Internal Medicine, vol. 158, no. 21, pp. 2349–2356, 1998. View at Google Scholar · View at Scopus
  111. J. K. Parsons and C. Kashefi, “Physical activity, benign prostatic hyperplasia, and lower urinary tract symptoms,” European Urology, vol. 53, no. 6, pp. 1228–1235, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. M. Gacci, G. Corona, M. Salvi et al., “A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia,” European Urology, vol. 61, no. 5, pp. 994–1003, 2012. View at Publisher · View at Google Scholar · View at Scopus
  113. K. T. McVary, W. Monnig, J. L. Camps Jr., J. M. Young, L.-J. Tseng, and G. van den Ende, “Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial,” The Journal of Urology, vol. 177, no. 3, pp. 1071–1077, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. K. T. McVary, C. G. Roehrborn, J. C. Kaminetsky et al., “Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia,” The Journal of Urology, vol. 177, no. 4, pp. 1401–1407, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. C. G. Stief, H. Porst, D. Neuser, M. Beneke, and E. Ulbrich, “A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia,” European Urology, vol. 53, no. 6, pp. 1236–1244, 2008. View at Publisher · View at Google Scholar · View at Scopus
  116. C. G. Roehrborn, K. T. McVary, A. Elion-Mboussa, and L. Viktrup, “Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study,” The Journal of Urology, vol. 180, no. 4, pp. 1228–1234, 2008. View at Publisher · View at Google Scholar · View at Scopus
  117. H. Porst, K. T. McVary, F. Montorsi et al., “Effects of once-daily tadalafil on erectile function in men with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia,” European Urology, vol. 56, no. 4, pp. 727–736, 2009, Corrigendum. European Urology. Vol. 59, no. 6, pp. 2082, 2011. View at Publisher · View at Google Scholar · View at Scopus
  118. N. A. M. Tamimi, I. Mincik, S. Haughie, J. Lamb, A. Crossland, and P. Ellis, “A placebo-controlled study investigating the efficacy and safety of the phosphodiesterase type 5 inhibitor UK-369,003 for the treatment of men with lower urinary tract symptoms associated with clinical benign prostatic hyperplasia,” British Journal of Urology International, vol. 106, no. 5, pp. 674–680, 2010. View at Publisher · View at Google Scholar · View at Scopus
  119. H. Porst, E. D. Kim, A. R. Casabé et al., “Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: results of an international randomized, double-blind, placebo-controlled trial,” European Urology, vol. 60, no. 5, pp. 1105–1113, 2011. View at Publisher · View at Google Scholar · View at Scopus
  120. R. B. Egerdie, S. Auerbach, C. G. Roehrborn et al., “Tadalafil 2.5 or 5mg administered once daily for 12 weeks in men with both erectile dysfunction and signs and symptoms of benign prostatic hyperplasia: results of a randomized, placebo-controlled, double-blind study,” Journal of Sexual Medicine, vol. 9, no. 1, pp. 271–281, 2012. View at Publisher · View at Google Scholar · View at Scopus
  121. M. Oelke, F. Giuliano, V. Mirone, L. Xu, D. Cox, and L. Viktrup, “Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial,” European Urology, vol. 61, no. 5, pp. 917–925, 2012. View at Publisher · View at Google Scholar · View at Scopus
  122. G. Brock, G. Broderick, C. G. Roehrborn, L. Xu, D. Wong, and L. Viktrup, “Tadalafil once daily in the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in men without erectile dysfunction,” British Journal of Urology International, vol. 112, no. 7, pp. 990–997, 2013. View at Google Scholar
  123. R. Dmochowski, C. Roehrborn, S. Klise, L. Xu, J. Kaminetsky, and S. Kraus, “Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-Week clinical trial,” The Journal of Urology, vol. 183, no. 3, pp. 1092–1097, 2010. View at Publisher · View at Google Scholar · View at Scopus
  124. O. Yokoyama, M. Yoshida, S. C. Kim et al., “Tadalafil once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a randomized placebo- and tamsulosin-controlled 12-week study in Asian men,” International Journal of Urology, vol. 20, no. 2, pp. 193–201, 2013. View at Google Scholar
  125. F. Giuliano, S. Ückert, M. Maggi, L. Birder, J. Kissel, and L. Viktrup, “The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia,” European Urology, vol. 63, no. 3, pp. 506–516, 2013. View at Google Scholar
  126. M. Gacci, I. Eardley, F. Giuliano et al., “Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia,” European Urology, vol. 60, no. 4, pp. 809–825, 2011. View at Publisher · View at Google Scholar · View at Scopus
  127. K.-E. Andersson, W. C. de Groat, K. T. McVary et al., “Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action,” Neurourology and Urodynamics, vol. 30, no. 3, pp. 292–301, 2011. View at Publisher · View at Google Scholar · View at Scopus
  128. B. Fibbi, A. Morelli, L. Vignozzi et al., “Characterization of phosphodiesterase Type 5 expression and functional activity in the human male lower urinary tract,” Journal of Sexual Medicine, vol. 7, no. 1, pp. 59–69, 2010. View at Publisher · View at Google Scholar · View at Scopus
  129. A. Morelli, E. Sarchielli, P. Comeglio et al., “Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats,” Journal of Sexual Medicine, vol. 8, no. 10, pp. 2746–2760, 2011. View at Publisher · View at Google Scholar · View at Scopus
  130. A. Morelli, S. Filippi, P. Sandner et al., “Vardenafil modulates bladder contractility through cGMP-mediated inhibition of RhoA/Rho kinase signaling pathway in spontaneously hypertensive rats,” Journal of Sexual Medicine, vol. 6, no. 6, pp. 1594–1608, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. S. Filippi, A. Morelli, P. Sandner et al., “Characterization and functional role of androgen-dependent PDE5 activity in the bladder,” Endocrinology, vol. 148, no. 3, pp. 1019–1029, 2007. View at Publisher · View at Google Scholar · View at Scopus
  132. L. Vignozzi, S. Filippi, P. Comeglio et al., “Tadalafil effect on metabolic syndrome-associated bladder alterations: an experimental study in a rabbit model,” Journal of Sexual Medicine, vol. 73, no. 4, pp. 428–441, 2013. View at Publisher · View at Google Scholar
  133. A. Morelli, S. Filippi, P. Comeglio et al., “Acute vardenafil administration improves bladder oxygenation in spontaneously hypertensive rats,” Journal of Sexual Medicine, vol. 7, no. 1, pp. 107–120, 2010. View at Publisher · View at Google Scholar · View at Scopus
  134. D. Behr-Roussel, S. Oger, S. Caisey et al., “Vardenafil decreases bladder afferent nerve activity in unanesthetized, decerebrate, spinal cord-injured rats,” European Urology, vol. 59, no. 2, pp. 272–277, 2011. View at Publisher · View at Google Scholar · View at Scopus
  135. M. Gacci, G. Vittori, N. Tosi et al., “A randomized, placebo-controlled study to assess safety and efficacy of Vardenafil 10mg and Tamsulosin 0.4mg vs. Tamsulosin 0.4mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia,” Journal of Sexual Medicine, vol. 9, no. 6, pp. 1624–1633, 2012. View at Publisher · View at Google Scholar · View at Scopus
  136. K. Kinsella and Y. Gist, Older Workers, Retirement, and Pensions. A Comparative International Chartbook. Washington, DC: U.S. Census Bureau and U.S. National Institute on Aging, and U.S. Census Bureau. International Data Base, 1995, http://www.census.gov/ipc/www/idbnew.html.
  137. J. K. Parsons, “Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms: new approaches to old problems,” The Journal of Urology, vol. 178, no. 2, pp. 395–401, 2007. View at Publisher · View at Google Scholar · View at Scopus
  138. A. Morelli, E. Sarchielli, P. Comeglio et al., “Metabolic syndrome induces inflammation and impairs gonadotropin-releasing hormone neurons in the preoptic area of the hypothalamus in rabbits,” Molecular and Cellular Endocrinology, vol. 382, no. 1, pp. 107–119, 2013. View at Google Scholar