{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:56:56Z","timestamp":1792695416262,"version":"4.5.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2019,8,3]],"date-time":"2019-08-03T00:00:00Z","timestamp":1564790400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,8,3]],"date-time":"2019-08-03T00:00:00Z","timestamp":1564790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Urol Rep"],"published-print":{"date-parts":[[2019,9]]},"DOI":"10.1007\/s11934-019-0917-1","type":"journal-article","created":{"date-parts":[[2019,8,3]],"date-time":"2019-08-03T02:13:55Z","timestamp":1564798435000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: What Is the Role and Significance of Inflammation?"],"prefix":"10.1007","volume":"20","author":[{"given":"Granville L.","family":"Lloyd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Marks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Ricke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,8,3]]},"reference":[{"key":"917_CR1","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1136\/bmj.39377.617269.55","volume":"335","author":"JN Armitage","year":"2007","unstructured":"Armitage JN, Sibanda N, Cathcart PJ, Emberton M, van der Meulen JHP. Mortality in men admitted to hospital with acute urinary retention: database analysis. BMJ. 2007;335:1199\u2013202.","journal-title":"BMJ."},{"key":"917_CR2","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1046\/j.1464-410x.1999.00157.x","volume":"84","author":"R Asplund","year":"1999","unstructured":"Asplund R. Mortality in the elderly in relation to nocturnal micturition. BJU Int. 1999;84:297\u2013301.","journal-title":"BJU Int"},{"key":"917_CR3","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1016\/S0022-5347(01)66779-X","volume":"154","author":"SA Kaplan","year":"1995","unstructured":"Kaplan SA, Te AE, Pressler LB, Olsson CA. Transition zone index as a method of assessing benign prostatic hyperplasia: correlation with symptoms, urine flow and detrusor pressure. J Urol. 1995;154:1764\u20139.","journal-title":"J Urol"},{"key":"917_CR4","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.1016\/S0022-5347(01)67448-2","volume":"153","author":"CJ Girman","year":"1995","unstructured":"Girman CJ, Jacobsen SJ, Guess HA, Oesterling JE, Chute CG, Panser LA, et al. Natural history of prostatism: relationship among symptoms, prostate volume and peak urinary flow rate. J Urol. 1995;153:1510\u20135.","journal-title":"J Urol"},{"key":"917_CR5","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1111\/j.1464-410X.2012.11395.x","volume":"111","author":"J Teng","year":"2013","unstructured":"Teng J, Zhang D, Li Y, Yin L, Wang K, Cui X, et al. Photoselective vaporization with the green light laser vs transurethral resection of the prostate for treating benign prostate hyperplasia: a systematic review and meta-analysis. BJU Int. 2013;111:312\u201323.","journal-title":"BJU Int"},{"key":"917_CR6","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.eururo.2014.06.017","volume":"67","author":"JN Cornu","year":"2015","unstructured":"Cornu JN, Ahyai S, Bachmann A, de la Rosette J, Gilling P, Gratzke C, et al. A systematic review and meta-analysis of functional outcomes and complications following transurethral procedures for lower urinary tract symptoms resulting from benign prostatic obstruction: an update. Eur Urol. 2015;67:1066\u201396.","journal-title":"Eur Urol"},{"key":"917_CR7","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1046\/j.1464-410x.1999.00352.x","volume":"84","author":"JC Nickel","year":"1999","unstructured":"Nickel JC, Downey J, Young I, Boag S. Asymptomatic inflammation and\/or infection in benign prostatic hyperplasia. BJU Int. 1999;84:976\u201381.","journal-title":"BJU Int"},{"key":"917_CR8","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/S0302-2838(02)00548-1","volume":"43","author":"F Di Silverio","year":"2003","unstructured":"Di Silverio F, Gentile V, De Matteis A, Mariotti G, Giuseppe V, Luigi PA, et al. Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: a retrospective analysis. Eur Urol. 2003;43:164\u201375.","journal-title":"Eur Urol"},{"key":"917_CR9","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1016\/S0022-5347(17)36966-5","volume":"148","author":"MJ Barry","year":"1992","unstructured":"Barry MJ, Fowler FJ, O\u2019Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American Urological Association symptom index for benign prostatic hyperplasia. The measurement Committee of the American Urological Association. J Urol. 1992;148:1549\u201357.","journal-title":"J Urol"},{"key":"917_CR10","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/S0022-5347(17)56980-3","volume":"121","author":"PW Kohnen","year":"1979","unstructured":"Kohnen PW, Drach GW. Patterns of inflammation in prostatic hyperplasia: a histologic and bacteriologic study. J Urol. 1979;121:755\u201360.","journal-title":"J Urol"},{"key":"917_CR11","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1016\/j.juro.2008.01.034","volume":"179","author":"NB Delongchamps","year":"2008","unstructured":"Delongchamps NB, de la Roza G, Chandan V, Jones R, Sunheimer R, Threatte G, et al. Evaluation of prostatitis in autopsied prostates\u2013is chronic inflammation more associated with benign prostatic hyperplasia or cancer? J Urol. 2008;179:1736\u201340.","journal-title":"J Urol"},{"issue":"10","key":"917_CR12","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1002\/pros.23518","volume":"78","author":"So Inamura","year":"2018","unstructured":"Inamura S, Ito H, Shinagawa T, Tsutsumiuchi M, Taga M, Kobayashi M, et al. Prostatic stromal inflammation is associated with bladder outlet obstruction in patients with benign prostatic hyperplasia. The Prostate. 2018;78:743\u201352 The authors retrospectively analyzed the prostate specimens of 179 men undergoing BPH surgery. Uniquely, they found that stromal inflammation was associated with a significant increase in prostate volume (63\u00a0mL vs 53\u00a0mL) and the existence of acute urinary retention (36.1% vs 11.4%).","journal-title":"The Prostate"},{"issue":"2","key":"917_CR13","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.juro.2015.03.103","volume":"194","author":"Kathleen C. Torkko","year":"2015","unstructured":"Torkko KC, Wilson RS, Smith EE, Kusek JW, van Bokhoven A, Lucia MS. Prostate biopsy markers of inflammation are associated with risk of clinical progression of benign prostatic hyperplasia: findings from the MTOPS study. J Urol. 2015;194:454\u201361 980 men in the MTOPS study were part of a subset requiring baseline biopsy. Men diagnosed with cancer were excluded. Inflammatory markers (CD-4, CD-8, CD-45, CD-68) in the transition zone biopsy cores were analyzed and compared with their prospectively collected clinical variables. CD-4 was associated with BPH progression as defined by IPSS progression of 4 points (HR\u2009=\u20091.86 (1.16, 2.98)). CD-4, CD-8, and CD-68 was associated with an increased risk of developing acute urinary retention.","journal-title":"Journal of Urology"},{"key":"917_CR14","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1093\/aje\/kwp406","volume":"171","author":"JM Schenk","year":"2010","unstructured":"Schenk JM, Kristal AR, Neuhouser ML, Tangen CM, White E, Lin DW, et al. Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol. 2010;171:571\u201382.","journal-title":"Am J Epidemiol"},{"key":"917_CR15","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1046\/j.1464-410x.2001.02193.x","volume":"87","author":"JC Nickel","year":"2001","unstructured":"Nickel JC, True LD, Krieger JN, Berger RE, Boag AH, Young ID. Consensus development of a histopathological classification system for chronic prostatic inflammation. BJU Int. 2001;87:797\u2013805.","journal-title":"BJU Int"},{"key":"917_CR16","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1056\/NEJMoa030656","volume":"349","author":"JD McConnell","year":"2003","unstructured":"McConnell JD, Roehrborn CG, Bautista OM, Andriole GL, Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349:2387\u201398.","journal-title":"N Engl J Med"},{"key":"917_CR17","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1056\/NEJMoa0908127","volume":"362","author":"GL Andriole","year":"2010","unstructured":"Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362:1192\u2013202.","journal-title":"N Engl J Med"},{"key":"917_CR18","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1016\/j.eururo.2007.11.026","volume":"54","author":"JC Nickel","year":"2008","unstructured":"Nickel JC, Roehrborn CG, O\u2019Leary MP, Bostwick DG, Somerville MC, Rittmaster RS. The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial. Eur Urol. 2008;54:1379\u201384.","journal-title":"Eur Urol"},{"key":"917_CR19","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/S0022-5347(18)35422-3","volume":"173","author":"CG Roehrborn","year":"2005","unstructured":"Roehrborn CG, Kaplan SA, Noble WD, Lucia MS, Slawin KM, McVary KT, et al. 1277: the impact of acute or chronic inflammation in baseline biopsy on the risk of clinical progression of BPH: results from the MTOPS study. J Urol. 2005;173:346.","journal-title":"J Urol"},{"key":"917_CR20","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1016\/S0022-5347(01)66780-6","volume":"154","author":"MJ Barry","year":"1995","unstructured":"Barry MJ, Williford WO, Chang Y, Machi M, Jones KM, Walker-Corkery E, et al. Benign prostatic hyperplasia specific health status measures in clinical research: how much change in the American Urological Association symptom index and the benign prostatic hyperplasia impact index is perceptible to patients? J Urol. 1995;154:1770\u20134.","journal-title":"J Urol"},{"key":"917_CR21","first-page":"264","volume":"21","author":"F Cantiello","year":"2014","unstructured":"Cantiello F, Cicione A, Salonia A, Autorino R, Ucciero G, Tucci L, et al. Metabolic syndrome correlates with peri-urethral fibrosis secondary to chronic prostate inflammation: evidence of a link in a cohort of patients undergoing radical prostatectomy. Int J Urol Off J Jpn Urol Assoc. 2014;21:264\u20139.","journal-title":"Int J Urol Off J Jpn Urol Assoc"},{"key":"917_CR22","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1016\/j.urology.2013.01.053","volume":"81","author":"F Cantiello","year":"2013","unstructured":"Cantiello F, Cicione A, Salonia A, Autorino R, Tucci L, Madeo I, et al. Periurethral fibrosis secondary to prostatic inflammation causing lower urinary tract symptoms: a prospective cohort study. Urology. 2013;81:1018\u201323.","journal-title":"Urology."},{"key":"917_CR23","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1016\/j.juro.2012.06.007","volume":"188","author":"J Ma","year":"2012","unstructured":"Ma J, Gharaee-Kermani M, Kunju L, Hollingsworth JM, Adler J, Arruda EM, et al. Prostatic fibrosis is associated with lower urinary tract symptoms. J Urol. 2012;188:1375\u201381.","journal-title":"J Urol"},{"key":"917_CR24","doi-asserted-by":"publisher","first-page":"109","DOI":"10.4111\/kju.2012.53.2.109","volume":"53","author":"JH Chung","year":"2012","unstructured":"Chung JH, Yu JH, Sung LH, Noh CH, Chung JY. Effect of prostatitis on lower urinary tract symptoms: retrospective analysis of prostate biopsy tissue. Korean J Urol. 2012;53:109\u201313.","journal-title":"Korean J Urol"},{"issue":"Suppl 3","key":"917_CR25","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/j.1464-410X.2008.07497.x","volume":"101","author":"CG Roehrborn","year":"2008","unstructured":"Roehrborn CG. BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU Int. 2008;101(Suppl 3):17\u201321.","journal-title":"BJU Int"},{"key":"917_CR26","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1464-410X.2007.06910.x","volume":"100","author":"VC Mishra","year":"2007","unstructured":"Mishra VC, Allen DJ, Nicolaou C, Sharif H, Hudd C, Karim OM, et al. Does intraprostatic inflammation have a role in the pathogenesis and progression of benign prostatic hyperplasia? BJU Int. 2007;100:327\u201331.","journal-title":"BJU Int"},{"key":"917_CR27","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/j.juro.2016.06.090","volume":"196","author":"JC Nickel","year":"2016","unstructured":"Nickel JC, Roehrborn CG, Castro-Santamaria R, Freedland SJ, Moreira DM. Chronic prostate inflammation is associated with severity and progression of benign prostatic hyperplasia, lower urinary tract symptoms and risk of acute urinary retention. J Urol. 2016;196:1493\u20138.","journal-title":"J Urol"},{"key":"917_CR28","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.prnil.2017.12.003","volume":"6","author":"SS Cakir","year":"2018","unstructured":"Cakir SS, Polat EC, Ozcan L, Besiroglu H, \u00d6tunctemur A, Ozbek E. The effect of prostatic inflammation on clinical outcomes in patients with benign prostate hyperplasia. Prostate Int. 2018;6:71\u20134.","journal-title":"Prostate Int"},{"key":"917_CR29","doi-asserted-by":"publisher","first-page":"F299","DOI":"10.1152\/ajprenal.00297.2013","volume":"306","author":"FM Hughes","year":"2014","unstructured":"Hughes FM, Vivar NP, Kennis JG, Pratt-Thomas JD, Lowe DW, Shaner BE, et al. Inflammasomes are important mediators of cyclophosphamide-induced bladder inflammation. Am J Physiol Renal Physiol. 2014;306:F299\u2013308.","journal-title":"Am J Physiol Renal Physiol"},{"key":"917_CR30","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1016\/j.juro.2015.12.068","volume":"195","author":"FM Hughes","year":"2016","unstructured":"Hughes FM, Hill HM, Wood CM, Edmondson AT, Dumas A, Foo W-C, et al. The NLRP3 inflammasome mediates inflammation produced by bladder outlet obstruction. J Urol. 2016;195:1598\u2013605 This rat model elucidates the inflammatory mechanism by which bladder outlet obstruction leads to histologic changes in the bladder. Bladder outlet obstruction led to an increase in the NLRP3 inflammasome. This was associated with increased inflammation and bladder hypertrophy. Targeted inhibition of the inflammasome led to improvements in urodynamics and bladder hypertrophy.","journal-title":"J Urol"},{"key":"917_CR31","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1093\/aje\/kwj258","volume":"164","author":"JL St Sauver","year":"2006","unstructured":"St Sauver JL, Jacobson DJ, McGree ME, Lieber MM, Jacobsen SJ. Protective association between nonsteroidal antiinflammatory drug use and measures of benign prostatic hyperplasia. Am J Epidemiol. 2006;164:760\u20138.","journal-title":"Am J Epidemiol"},{"key":"917_CR32","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1001\/archinte.165.13.1547","volume":"165","author":"KM Verhamme","year":"2005","unstructured":"Verhamme KM, Dieleman JP, Van Wijk MA, van der Lei J, Bosch JL, Stricker BH, et al. Nonsteroidal anti-inflammatory drugs and increased risk of acute urinary retention. Arch Intern Med. 2005;165:1547\u201351.","journal-title":"Arch Intern Med"},{"key":"917_CR33","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1093\/aje\/kwr524","volume":"176","author":"JM Schenk","year":"2012","unstructured":"Schenk JM, Calip GS, Tangen CM, Goodman P, Parsons JK, Thompson IM, et al. Indications for and use of nonsteroidal antiinflammatory drugs and the risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. Am J Epidemiol. 2012;176:156\u201363.","journal-title":"Am J Epidemiol"},{"key":"917_CR34","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1002\/pros.23359","volume":"77","author":"LH Nyg\u00e5rd","year":"2017","unstructured":"Nyg\u00e5rd LH, Talala K, Taari K, Tammela TLJ, Auvinen A, Murtola TJ. The effect of non-steroidal anti-inflammatory drugs on risk of benign prostatic hyperplasia. Prostate. 2017;77:1029\u201335.","journal-title":"Prostate"},{"key":"917_CR35","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1111\/j.1464-410X.2011.10867.x","volume":"110","author":"S Sutcliffe","year":"2012","unstructured":"Sutcliffe S, Grubb Iii RL, Platz EA, Ragard LR, Riley TL, Kazin SS, et al. Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the prostate, lung, colorectal, and ovarian cancer screening trial. BJU Int. 2012;110:1050\u20139.","journal-title":"BJU Int"},{"key":"917_CR36","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.eururo.2004.08.024","volume":"47","author":"F Di Silverio","year":"2005","unstructured":"Di Silverio F, Bosman C, Salvatori M, Albanesi L, Proietti Pannunzi L, Ciccariello M, et al. Combination therapy with rofecoxib and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Eur Urol. 2005;47:72\u20138.","journal-title":"Eur Urol"},{"key":"917_CR37","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.urology.2009.01.088","volume":"74","author":"I Ozdemir","year":"2009","unstructured":"Ozdemir I, Bozkurt O, Demir O, Aslan G, Esen AA. Combination therapy with doxazosin and tenoxicam for the management of lower urinary tract symptoms. Urology. 2009;74:431\u20135.","journal-title":"Urology."},{"key":"917_CR38","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1111\/j.1464-410X.2012.11559.x","volume":"111","author":"A Kahokehr","year":"2013","unstructured":"Kahokehr A, Vather R, Nixon A, Hill AG. Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in benign prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials. BJU Int. 2013;111:304\u201311.","journal-title":"BJU Int"},{"key":"917_CR39","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1016\/j.urology.2011.04.076","volume":"78","author":"CH Liao","year":"2011","unstructured":"Liao CH, Chung SD, Kuo HC. Serum C-reactive protein levels are associated with residual urgency symptoms in patients with benign prostatic hyperplasia after medical treatment. Urology. 2011;78:1373\u20138.","journal-title":"Urology."},{"key":"917_CR40","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1002\/pros.20110","volume":"62","author":"S Rohrmann","year":"2005","unstructured":"Rohrmann S, De Marzo AM, Smit E, Giovannucci E, Platz EA. Serum C-reactive protein concentration and lower urinary tract symptoms in older men in the third national health and nutrition examination survey (NHANES III). Prostate. 2005;62:27\u201333.","journal-title":"Prostate."},{"key":"917_CR41","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1093\/aje\/kwp085","volume":"169","author":"JL St Sauver","year":"2009","unstructured":"St Sauver JL, Sarma AV, Jacobson DJ, McGree ME, Lieber MM, Girman CJ, et al. Associations between C-reactive protein and benign prostatic hyperplasia\/lower urinary tract symptom outcomes in a population-based cohort. Am J Epidemiol. 2009;169:1281\u201390.","journal-title":"Am J Epidemiol"},{"key":"917_CR42","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1016\/j.urology.2008.12.012","volume":"73","author":"V Kupelian","year":"2009","unstructured":"Kupelian V, McVary KT, Barry MJ, Link CL, Rosen RC, Aiyer LP, et al. Association of C-reactive protein and lower urinary tract symptoms in men and women: results from Boston Area Community Health survey. Urology. 2009;73:950\u20137.","journal-title":"Urology."},{"issue":"105","key":"917_CR43","first-page":"e1","volume":"12","author":"H Tarhan","year":"2016","unstructured":"Tarhan H, Ekin RG, Can E, Cakmak O, Yavascan O, Mutlubas Ozsan F, et al. C-reactive protein levels in girls with lower urinary tract symptoms. J Pediatr Urol. 2016;12(105):e1\u20134.","journal-title":"J Pediatr Urol"},{"key":"917_CR44","doi-asserted-by":"crossref","unstructured":"Peixoto CA,dos Gomes SFO. The role of phosphodiesterase-5 inhibitors in prostatic inflammation: a review. J Inflamm Lond Engl [Internet]. 2015 [cited 2019 Mar 10];12. Available from: \n                      https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4570643\/","DOI":"10.1186\/s12950-015-0099-7"},{"key":"917_CR45","doi-asserted-by":"crossref","unstructured":"Zhang W, Zang N, Jiang Y, Chen P, Wang X, Zhang X. Upregulation of phosphodiesterase type 5 in the hyperplastic prostate. Sci Rep [Internet]. 2015 [cited 2019 Mar 10];5. Available from: \n                      https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4674741\/","DOI":"10.1038\/srep17888"},{"key":"917_CR46","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/j.eururo.2012.09.006","volume":"63","author":"F Giuliano","year":"2013","unstructured":"Giuliano F, \u00dcckert S, Maggi M, Birder L, Kissel J, Viktrup L. The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol. 2013;63:506\u201316.","journal-title":"Eur Urol"},{"key":"917_CR47","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1002\/pros.22686","volume":"73","author":"L Vignozzi","year":"2013","unstructured":"Vignozzi L, Gacci M, Cellai I, Morelli A, Maneschi E, Comeglio P, et al. PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS. Prostate. 2013;73:1391\u2013402.","journal-title":"Prostate"},{"key":"917_CR48","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1002\/pros.22584","volume":"73","author":"A Morelli","year":"2013","unstructured":"Morelli A, Comeglio P, Filippi S, Sarchielli E, Vignozzi L, Maneschi E, et al. Mechanism of action of phosphodiesterase type 5 inhibition in metabolic syndrome-associated prostate alterations: an experimental study in the rabbit. Prostate. 2013;73:428\u201341.","journal-title":"Prostate"},{"key":"917_CR49","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1002\/pros.23514","volume":"78","author":"K Okamoto","year":"2018","unstructured":"Okamoto K, Kurita M, Yamaguchi H, Numakura Y, Oka M. Effect of tadalafil on chronic pelvic pain and prostatic inflammation in a rat model of experimental autoimmune prostatitis. Prostate. 2018;78:707\u201313.","journal-title":"Prostate"},{"key":"917_CR50","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1002\/pros.23750","volume":"79","author":"H Yamaguchi","year":"2019","unstructured":"Yamaguchi H, Kurita M, Okamoto K, Kotera T, Oka M. Voiding behavior and chronic pelvic pain in two types of rat nonbacterial prostatitis models: attenuation of chronic pelvic pain by repeated administration of tadalafil. The Prostate. 2019;79:446\u201353 Using rat non-bacterial prostatitis models, the authors demonstrated that chronic pelvic pain was increased after induction of the model. However, bladder function as measured by cystometric changes was not affected. Six-week administration of tadalafil attenuated the chronic pelvic pain.","journal-title":"The Prostate"},{"key":"917_CR51","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1016\/j.eururo.2012.02.033","volume":"61","author":"M Gacci","year":"2012","unstructured":"Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA, et al. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with \u03b1-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012;61:994\u20131003.","journal-title":"Eur Urol"},{"key":"917_CR52","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s00345-018-2370-z","volume":"37","author":"J Zhang","year":"2019","unstructured":"Zhang J, Li X, Yang B, Wu C, Fan Y, Li H. Alpha-blockers with or without phosphodiesterase type 5 inhibitor for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review and meta-analysis. World J Urol. 2019;37:143\u201353.","journal-title":"World J Urol"},{"key":"917_CR53","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1196\/annals.1351.021","volume":"1069","author":"M Schmidt","year":"2006","unstructured":"Schmidt M, Naumann H, Weidler C, Schellenberg M, Anders S, Straub RH. Inflammation and sex hormone metabolism. Ann N Acad Sci. 2006;1069:236\u201346.","journal-title":"Ann N Acad Sci"},{"key":"917_CR54","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1210\/jcem.86.2.7219","volume":"86","author":"SM Harman","year":"2001","unstructured":"Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Aging BLS of longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86:724\u201331.","journal-title":"J Clin Endocrinol Metab"},{"key":"917_CR55","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1530\/JOE-12-0142","volume":"214","author":"L Vignozzi","year":"2012","unstructured":"Vignozzi L, Cellai I, Santi R, Lombardelli L, Morelli A, Comeglio P, et al. Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells. J Endocrinol. 2012;214:31\u201343.","journal-title":"J Endocrinol"},{"key":"917_CR56","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/pros.22623","volume":"73","author":"L Vignozzi","year":"2013","unstructured":"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;73:789\u2013800.","journal-title":"Prostate"},{"issue":"12","key":"917_CR57","doi-asserted-by":"publisher","first-page":"549","DOI":"10.3390\/jcm7120549","volume":"7","author":"Abdulmaged Traish","year":"2018","unstructured":"Traish A, Bolanos J, Nair S, Saad F, Morgentaler A. Do androgens modulate the pathophysiological pathways of inflammation? Appraising the contemporary evidence. J Clin Med. 2018;7.","journal-title":"Journal of Clinical Medicine"},{"key":"917_CR58","doi-asserted-by":"crossref","unstructured":"Ry\u0142 A, Rotter I, Grzywacz A, Ma\u0142ecka I, Skonieczna-\u017bydecka K, Grzesiak K, et al. Molecular analysis of the SRD5A1 and SRD5A2 genes in patients with benign prostatic hyperplasia with regard to metabolic parameters and selected hormone levels. Int J Environ Res Public Health. 2017;14 This study analyzed the relationships between the incidence of metabolic diseases and the genotypes of the 5\ud6c2-reductase enzyme polymorphisms in patients with BPH. 299 patients who presented for TURP had their blood drawn preoperatively. This found that certain polymorphisms of the SDR5A2 loci were associated with MetS.","DOI":"10.3390\/ijerph14111318"},{"key":"917_CR59","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.ajpath.2014.11.020","volume":"185","author":"R Ge","year":"2015","unstructured":"Ge R, Wang Z, Bechis SK, Otsetov AG, Hua S, Wu S, et al. DNA methyl transferase 1 reduces expression of SRD5A2 in the aging adult prostate. Am J Pathol. 2015;185:870\u201382.","journal-title":"Am J Pathol"},{"key":"917_CR60","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/j.eururo.2013.02.038","volume":"63","author":"RL Muller","year":"2013","unstructured":"Muller RL, Gerber L, Moreira DM, Andriole G, Hamilton RJ, Fleshner N, et al. Obesity is associated with increased prostate growth and attenuated prostate volume reduction by dutasteride. Eur Urol. 2013;63:1115\u201321.","journal-title":"Eur Urol"},{"key":"917_CR61","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1002\/pros.23320","volume":"77","author":"S Mizoguchi","year":"2017","unstructured":"Mizoguchi S, Mori K, Wang Z, Liu T, Funahashi Y, Sato F, et al. Effects of estrogen receptor \u03b2 stimulation in a rat model of non-bacterial prostatic inflammation. Prostate. 2017;77:803\u201311.","journal-title":"Prostate."},{"issue":"6","key":"917_CR62","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.molcel.2016.07.025","volume":"63","author":"Boyu Zhang","year":"2016","unstructured":"Zhang B, Kwon OJ, Henry G, Malewska A, Wei X, Zhang L, et al. Non-cell-autonomous regulation of prostate epithelial homeostasis by androgen receptor. Mol Cell. 9(63):976\u201389.","journal-title":"Molecular Cell"},{"key":"917_CR63","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.2353\/ajpath.2009.081107","volume":"175","author":"SJ Ellem","year":"2009","unstructured":"Ellem SJ, Wang H, Poutanen M, Risbridger GP. Increased endogenous estrogen synthesis leads to the sequential induction of prostatic inflammation (prostatitis) and prostatic pre-malignancy. Am J Pathol. 2009;175:1187\u201399.","journal-title":"Am J Pathol"},{"issue":"1","key":"917_CR64","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3390\/diagnostics9010021","volume":"9","author":"Marouane Kdadra","year":"2019","unstructured":"Kdadra M, H\u00f6ckner S, Leung H, Kremer W, Schiffer E. Metabolomics biomarkers of prostate cancer: a systematic review. Diagn Basel Switz. 2019;9.","journal-title":"Diagnostics"},{"key":"917_CR65","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.molmet.2018.03.001","volume":"15","author":"KB Rubinow","year":"2018","unstructured":"Rubinow KB. An intracrine view of sex steroids, immunity, and metabolic regulation. Mol Metab. 2018;15:92\u2013103.","journal-title":"Mol Metab"},{"key":"917_CR66","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/nrurol.2015.301","volume":"13","author":"L Vignozzi","year":"2016","unstructured":"Vignozzi L, Gacci M, Maggi M. Lower urinary tract symptoms, benign prostatic hyperplasia and metabolic syndrome. Nat Rev Urol. 2016;13:108\u201319 This review explores the pathogenic relationships between LUTS, metabolic syndrome and its components, inflammation, and sex steroid imbalance in men. They conclude that various metabolic insult lead to inflammation and alter the natural history of BPH and LUTS. More studies are needed to investigate lifestyle modifications to mitigate to progression of this disease process.","journal-title":"Nat Rev Urol"},{"key":"917_CR67","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3109\/13685538.2015.1028353","volume":"18","author":"GI Russo","year":"2015","unstructured":"Russo GI, Cimino S, Morgia G. Benign prostatic hyperplasia and metabolic syndrome: the expanding evidences of a new disease of aging male. Aging Male Off J Int Soc Study Aging Male. 2015;18:133\u20134.","journal-title":"Aging Male Off J Int Soc Study Aging Male"},{"key":"917_CR68","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1530\/JOE-11-0289","volume":"212","author":"L Vignozzi","year":"2012","unstructured":"Vignozzi L, Morelli A, Sarchielli E, Comeglio P, Filippi S, Cellai I, et al. Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit. J Endocrinol. 2012;212:71\u201384.","journal-title":"J Endocrinol"},{"key":"917_CR69","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/bju.12728","volume":"115","author":"M Gacci","year":"2015","unstructured":"Gacci M, Corona G, Vignozzi L, Salvi M, Serni S, De Nunzio C, et al. Metabolic syndrome and benign prostatic enlargement: a systematic review and meta-analysis. BJU Int. 2015;115:24\u201331.","journal-title":"BJU Int"},{"key":"917_CR70","first-page":"219","volume":"10","author":"BM Inouye","year":"2018","unstructured":"Inouye BM, Hughes FM, Jin H, L\u00fctolf R, Potnis KC, Routh JC, et al. Diabetic bladder dysfunction is associated with bladder inflammation triggered through hyperglycemia, not polyuria. Res Rep Urol. 2018;10:219\u201325.","journal-title":"Res Rep Urol"},{"key":"917_CR71","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1113\/JP277452","volume":"597","author":"Y Funahashi","year":"2019","unstructured":"Funahashi Y, Takahashi R, Mizoguchi S, Suzuki T, Takaoka E, Ni J, et al. Bladder overactivity and afferent hyperexcitability induced by prostate-to-bladder cross-sensitization in rats with prostatic inflammation. J Physiol. 2019;597:2063\u201378.","journal-title":"J Physiol"},{"key":"917_CR72","first-page":"764","volume":"76","author":"Y Chen","year":"2010","unstructured":"Chen Y, Wu X, Liu J, Tang W, Zhao T, Zhang J. Distribution of convergent afferents innervating bladder and prostate at dorsal root Ganglia in rats. Urology. 2010;76:764\u2013e1\u20136.","journal-title":"Urology"}],"container-title":["Current Urology Reports"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11934-019-0917-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11934-019-0917-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11934-019-0917-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T19:24:14Z","timestamp":1596309854000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11934-019-0917-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,3]]},"references-count":72,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["917"],"URL":"https:\/\/doi.org\/10.1007\/s11934-019-0917-1","relation":{},"ISSN":["1527-2737","1534-6285"],"issn-type":[{"value":"1527-2737","type":"print"},{"value":"1534-6285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,3]]},"assertion":[{"value":"3 August 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"Granville L. Lloyd, Jeffrey M. Marks, and William A. Ricke each declare no potential conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}],"article-number":"54"}}