The influence of metabolic syndrome on the development and clinical manifestations of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) — one of the most common urological diseases that lead to the development of symptoms of the lower urinary tract (SLUT). BPH-multifactorial disease, in which a significant role is given to increase the activity of the enzyme 5a-reductase and hormonal imbalance associated with the exchange of testosterone and dihydrotestosterone. However, to date, not all aspects of the etiology and pathogenesis of this condition have been studied. The results of numerous studies indicate a significant role of complex metabolic disorders included in the modern concept of "metabolic syndrome" (MS), the development and progression of BPH/SLUT. The main pathogenetic factors leading to the formation of BPH and concomitant urination disorders are considered to be a violation of the balance of sex hormones, the development of chronic ischemia of the pelvic organs, a violation of carbohydrate and lipid metabolism. The relationship between BPH and MS is one of the most urgent problems of modern medicine. Different components of MS independently from each other can influence more pronounced progression of BPH/SLUT in comparison with development of this disease in men without metabolic disorders that is the reason of lower efficiency of surgical and medical treatment of this group of patients.

1. Wei JT, Calhoun E, Jacobsen SJ. Urologic diseases in America project: benign prostatic hyperplasia. J Urol. 2008 May;179 (5 Suppl): S75—80. DOI: 10.1016/j.juro.2008.03.141.

2. Apolikhin OI, Sivkov AV, Moskaleva NG, Solntseva TV, Komarova VA. Analysis of the uronephrological morbidity and mortality in the Russian Federation during the 10-year period (2002-2012) according to the official statistics. Experimental and Clinical Urology. 2014; (2):4-10. (In Russian).

3. Kalinchenko SYu, Tyuzikov IA, Grekov EA, Vorslov LO, Fomin AM, Tishova YuA. Metabolicheskii sindrom i dobrokachestvennaya giperplaziya predstatel'noi zhelezy: edinstvo patofiziologicheski-kh mekhanizmov i novye perspektivy patogeneticheskoi terapii. Consilium Medicum. 2012;14 (7):19-24. (In Russian).

4. Hammarsten J, Hogstedt B. Hyperinsulinemia as a risk factor for developing benign prostatic hyperplasia. Eur Urol. 2001 Feb;39 (2):151-8. DOI: 10.1159/000052430

5. Golden SH, Robinson KA, Saldanha I, Anton B, Laden-son PW. Clinical review: prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab. 2009 Jun;94 (6):1853-78. DOI: 10.1210/jc.2008-2291.

6. Kondratyeva LV, Popkova TV, Nasonov EL. Metabolic syndrome in rheumatoid arthritis. Rheumatology Science and Practice. 2013;51 (3):302-12. (In Russian).

7. Gorbachinsky I. Metabolic Syndrome and Urological Deseases. Rev Urol. 2010;12 (4):157-80.

8. Niskanen L, Laaksonen DE, Punnonen K, Mustajoki P, Kaukua J, Rissanen A. Changes in sex hormonebinding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab. 2004 May;6 (3):208-15. DOI: 10.1111/j.1462-8902.2004.00335.x

9. Srikanthan P, Karlamangla AS. Relative Muscle Mass Is Inversely Associated with Insulin Resistance and Prediabetes. Findings from The Third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab. 2011 Sep;96 (9):2898-903. DOI: 10.1210/jc.2011-0435

10. Vignozzi L, Gacci M, Maggi M. Lower urinary tract symptoms, benign prostatic hyperplasia and metabolic syndrome. Nat Rev Urol. 2016 Feb;13 (2):108-19. DOI: 10.1038/nrurol.2015.301.

11. Tyuzikov IA, Grekov EA, Kalinchenko SYu. Features of clinical course and morphometric parameters of benign prostatic hyperplasia in men with metabolic syndrome and androgen deficiency. Urology. 2015;5:66-9. (In Russian).

12. Zhang X, Zong X, Liu Y, Dong L, Zhao X, Qu X. Impact of metabolic syndrome on benign prostatic hyperplasia in elderly Chinese men. Urol Int. 2014;93 (2):214-9. DOI: 10.1159/000357760.

13. Yin Z, Yang JR, Rao JM, Song W, Zhou KQ. Association between benign prostatic hyperplasia, body mass index and metabolic syndrome in Chinese men. Asian J Androl. 2015 Sep-Oct;17 (5):826-30. DOI: 10.4103/1008-682X.148081.

14. Hammarsten J, Hogstedt B, Holthuis N, Mellstrom D. Components of metabolic syndrome — risk factors for the development of benign prostatic hyperplasia. Prostate Cancer Prostatic Dis. 1998 Mar;1 (3):157-162. DOI: 10.1038/sj.pcan.4500221

15. Ryl A, Rotter I, Miazgowski T, Slojewski M, Dolegowska B, et al. Metabolic syndrome and benign prostatic hyperplasia: association or coincidence? Diabetol Metab Syndr. 2015 Oct 29;7:94. DOI: 10.1186/s13098-015-0089-1

16. Wang JE, Fu YY, Kang DY. The association between metabolic syndrome and characteristics of benign prostatic hyperplasia. A systematic review and metaanalysis. Medicine (Baltimore). 2016 May;95 (19) :e3243. DOI: 10.1097/MD.0000000000003243.

17. Loeb S, Kettermann A, Carter HB, Ferrucci L, Mettr EJ, Walsh PC. Prostate volume changes over time: results from the Baltimore Longitudinal Study of Aging. J Urol. 2009 Oct;182 (4):1458-62. DOI: 10.1016/j.juro.2009.06.047.

18. Pan JH, Jiang C, Luo R, Zhou X. Association of metabolic syndrome and benign prostatic hyperplasia in Chinese patients of different age decades. Urol Int. 2014;93 (1):10-6. DOI: 10.1159/000354026.

19. Zhao S, Chen C, Chen Z, Xia M, Tang J, Shao S, Yan Y. Relationship between metabolic syndrome and predictors for clinical benign prostatic hyperplasia progression and International Prostate Symptoms Score in patients with moderate to severe lower urinary tract symptoms. Urol J. 2016 Jun 28;13 (3):2717-26.

20. Kirpatovskiy VI, Frolova EV, Nadtochiy ON, Chochuev OS, Kazachenko AV. Androgen deficiency and progression of benign prostatic hyperplasia in patients with metabolic syndrome: is there any controversy? Andrology and Genital Surgery. 2017;18 (3):10-9. DOI: 10.17650/2070-9781-2017-18-3-10-19 (In Russian).

21. Yang TK, Hsieh JT, Chen SC. Metabolic syndrome associated with reduced lower urinary tract symptoms in middle-aged men receiving health checkup. Urology. 2012 Nov;80 (5):1093-7. DOI: 10.1016/j.urology.2012.08.002.

22. Laven BA, Orsini N, Andersson SO, Johansson JE, Gerber GS, Wolk A. Birth weight, abdominal obesity and the risk of lower urinary tract symptoms in a population based study of Swedish men. J Urol. 2008 May;179 (5):1891-5; discussion 1895-6. DOI: 10.1016/j.juro.2008.01.029

23. Hadhsheno MA, Mellstrom D, Peeter R, Hammarsten J, Lorent-zon M, Sundh V, et al. Lower urinary tract symptoms are associated with low level of serum serotonin, high level af adiponectin and fasting glucose and benign prostatic enlargement. Scand J Urol 2015; 49 (2):155-161. DOI: 10.3109/21681805.2014.936405.

24. Telli O, Demirbas A, Kabar M, Karagoz MA, Sarici H, Resor-lu B. Does metabolic syndrome or its components correlate with lower urinary tract symptoms in benign prostatic hyperplasia patients? Nephrourol Mon. 2015 May 23;7 (3 ):e27253. DOI: 10.5812/numonthly.7 (3)2015.27253.

25. Pashootan P, Ploussard G, Cocaul A, Gouvello A, Desgrand-champs F. Association between metabolic syndrome and severity lower urinary tract symptoms (LUTS): an observation study in a 4666 European men cohort. BJU Int. 2015 Jul;116 (1):124-30. DOI: 10.1111/bju.12931.

26. Gacci M, Corona G, Vignozzi L, Salvi M, Serni S, De Nunzio C, et al. Metabolic syndrome and benign prostatienlargement: a systematic review and metaanalisys. BJU Int. 2015 Jan;115 (1):24-31. DOI: 10.1111/bju.12728.

27. Oelke M, Bachmann A, Descazeaud A, et al. Guideline on management of male low urinary tract symptoms (LUTS), incl. benign prostatic obstruction (BPO). EAU 2012, 74 p.

28. DiBello JR, Ioannou C, Rees J, Challacombe B, Maskell J, Choudhury N, Kastner C, Kirby M. The prevalence of metabolic syndrome and its components amongst men with and without clinical benign prostatic hyperplasia: a large, cross-sectional, UK epidemiological study. BJU Int 2016; 17 (5):801-8. DOI: 10.1111/bju.13334

29. Ryl A, Rotter I, Slojewski M, Dolegowska B, Grabowska M, Baranowska-Bosiacka I, Laszczynska M. Hormone concentration, metabolic disorders and immunoexpression of androgen and estrogen-alpha receptors in men with benign prostatic hyperplasia and testosterone deficiency syndrome. Folia Histochem Cytobiol. 2015;53 (3):227-35. DOI: 10.5603/fhc.a2015.0026

30. He Q, Wang Z, Liu G, Daneshgari F, MacLennan GT, Gupta S. Metabolic syndrome, inflammation and lower urinary tract symptoms: possible translational risks. Prostate Cancer Prostatic Dis. 2016 Mar;19 (1):7-13. DOI: 10.1038/pcan.2015.43

31. Dogan Y, Urug F, Aras B, §ahin A, Kivrak M, Urkmez A, Guner ND, Aydin S. The relationships between metabolic syndrome, erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia. Turk J Urol. 2015 Mar;41 (1):7-12. DOI: 10.5152/tud.2015.99997

32. Zou C, Gong D, Fang N, Fan Y. Meta-analysis of metabolic syndrome and benign prostatic hyperplasia in Chinese patients. World J Urol. 2016 Feb;34 (2):281-9. DOI: 10.1007/s00345-015-1626-0

33. Tyuzikov IA, Bratchikov OI, Michajlov DV, Schumakova EA, Churaev SA. The role of age-related androgen deficiency in the pathogenesis of prostate adenoma. Pacific Medical Journal. 2016;1 (63):14-18. (In Russian).

34. Corona G, Vignozzi L, Rastrelli G et al. Benign prostatic hyperplasia: a new metabolic disease of the aging male and its correlation with sexual dysfunctions. Int J Endocrinol. 2014;2014:329456. DOI: 10.1155/2014/329456.

35. Kirpatovskiy VI, Chochuev OS, Golovanov SA, Drozhzheva VV, Kudryavtseva LV, Frolova EV, Kazachenko AV. Experimentally induced metabolic syndrome in rats: the pathogenesis of the development of benign prostatic hyperplasia and urination disorders. Experimental and Clinical Urology. 2016;4:32-7. (In Russian).

36. Shibata Y, Kashiwagi B, Ono Y, Fukabori Y, Suzuki K, Honma S, Yamanaka H. The evaluation of rat prostate blood flow using a laser speckle flowmetry: a comparative study using the microsphere method in castrated and androgen-replenished rats. Urol Res. 2004 Feb;32 (1):44-8. DOI: 10.1007/s00240-003-0375-5

37. Navarro-Dorado J, Orensanz LM, Recio P, Bustamante S, Ben-edito S, Martinez AC, et al. Mechanisms involved in testosterone-induced vasodilatation in pig prostatic small arteries. Life Sci. 2008 Oct 10;83 (15-16):569-73. DOI: 10.1016/j.lfs.2008.08.009.

38. Vignozzi L, Morelli A, Sarchielli E, Comeglio P, Filippi S, et al. Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit. J Endocrinol. 2012 Jan;212 (1):71-84. DOI: 10.1530/JOE-11-0289

39. Azadzoi KM, Radisavljevic ZM, Golabek T, Yalla SV, Siroky MB. Oxidative modification of mitochondrial integrity and nerve fiber density in the ischemic overactive bladder. J Urol. 2010 Jan;183 (1):362-9. DOI: 10.1016/j.juro.2009.08.103.

40. Azzouni F, Godoy A, Li Y, Mohler J. The 5 alpha-reductase isozyme famil: a review of basic biology and their role in human diseases. Adv Urol. 2012;2012:530121. DOI: 10.1155/2012/530121.

41. Vikram A, Jena G, Ramarao P. Insulin-resistance and benign prostatic hyperplasia: the connection. Eur J Pharmacol. 2010 Sep 1;641 (2-3):75-81. DOI: 10.1016/j.ejphar.2010.05.042.

42. Balhara B, Burkart A, Topcu V, Lee YK, Cowan C, Kahn CR, Patti ME. Severe insulin resistance alters metabolism in mesenchymal progenitor cells. Endocrinology. 2015 Jun;156 (6):2039-48. DOI: 10.1210/en.2014-1403

43. Wang Z, Olumi AF. Diabetes, growth hormone-insulin-like growth factor pathways and association to benign prostatic hyperplasia. Differentiation. 2011 Nov-Dec;82 (4-5):261-71. DOI: 10.1016/j.diff.2011.04.004.

44. Ceylan C, Serel A, Doluoglu OG, Armagan A, Yiiksel S. Prostatic fluid free insulin-like growth factor-1 in relation to benign prostatic hyperplasia: a controlled study. Urol J. 2014 Jan 4;10 (4):1067-71.

45. Kupelian V, McVary KT, Kaplan SA. Association of lower urinary tract symptoms and the metabolic syndrome: results from the Boston Area Community Health Survey. J Urol. 2009 Aug;182 (2):616-24; discussion 624-5. DOI: 10.1016/j.juro.2009.04.025.

46. Nicholson TM, Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: past, present and future. Differentiation. 2011 Nov-Dec;82 (4-5):184-99. DOI: 10.1016/j.diff.2011.04.006.

47. Wu JH, Jiang XR, Liu GM, Liu XY, He GL, Sun ZY. Oral exposure to low-dose bisphenol Aaggravates testosterone-induced benign hyperplasia prostate in rats. Toxicol Ind Health. 2011 Oct;27 (9):810—9. DOI: 10.1177/0748233711399310

48. McLaren ID, Jerde TJ, Bushman W. Role of interleukins, IGF and stem cells in BPH. Differentiation. 2011 Nov-Dec;82 (4-5):237—43. DOI: 10.1016/j.diff.2011.06.001

49. Vignozzi L, Gacci M, Cellai I, Santi R, Corona G, Morelli A, et al. Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation. Prostate. 2013 Jun;73 (8):789—800. DOI: 10.1002/pros.22623

50. Gacci M, Vignozzi L, Sebastianelli A, Salvi M, Giannessi C, De Nunzio C, et al. Metabolic syndrome and lower urinary tract symptoms: the role of inflammation. P Prostate Cancer Prostatic Dis. 2013 Mar;16 (1):101-6. DOI: 10.1038/pcan.2012.44

51. Azadzoi KM, Chen BG, Radisavljevic ZM, Siroku MB. Molecular reactions and ultrastructural damage in the chronically ischemic bladder. J Urol. 2011 Nov;186 (5):2115-22. DOI: 10.1016/j. juro.2011.06.047.

52. Cyrus A, Kabir A, Goodarzi D, Talaei A, Moradi A, Rafiee M, et al. Impact of metabolic syndrome on response to medical treatment of benign prostatic hyperplasia. Korean J Urol. 2014 Dec;55 (12):814—20. DOI: 10.4111/kju.2014.55.12.814.

53. Espinosa G, Esposito R, Kazzazi A, Djavan B. Vitamin D and benign prostatic hyperplasia. Can J Urol. 2013 Aug;20 (4):6820-5.

54. Corona G, Vignozzi L, Rastrelli G, Loffi F, Cipriani S, Mag-gi M. Benign prostatic hyperplasia: a new metabolic disease of the aging male and its correlation with sexual dysfunctions. Int J Endocrinol. 2014;2014:329456. DOI: 10.1155/2014/329456

55. Demir O, Akgul K, Akar Z. Association between severity of lower urinary tract symptoms, erectile dysfunction and metabolic syndrome. Aging Male. 2009 Mar;12 (1):29-34. DOI: 10.1080/13685530902777425.

56. Sener NC, Zengin K, Ozturk U, Bas O, Ercil H, Ekici M, Evliyao-glu Y, Imamoglu MA. The impact of metabolic syndrome on the outcomes of transurethral resection of the prostate. J Endourol. 2015 Mar;29 (3):340-3. DOI: 10.1089/end.2014.0562

57. Tyuzikov IA, Martov AG, Grekov EA. The correlation of metabolic syndrome components and hormonal disorders in prostate diseases pathogenesis. Experimental and Clinical Urology. 2012;3:39-47. (In Russian).