{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:20Z","timestamp":1787028920769,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Lower urinary tract symptoms (LUTS) are highly prevalent among aging men and have traditionally been attributed primarily to benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO). However, growing evidence suggests that bladder-related mechanisms play a critical and often underrecognized role. This review aims to summarize current evidence on the contribution of the aging bladder to LUTS pathophysiology and to explore the therapeutic implications in men with BPH. Materials and Methods: A comprehensive literature search was conducted in PubMed\/MEDLINE, Scopus, and Web of Science for studies published between January 2010 and April 2025. Search terms included combinations of \u201caging bladder\u201d, \u201cdetrusor dysfunction\u201d, \u201cLUTS\u201d, \u201cBPH\u201d, \u201cbladder outlet obstruction\u201d, \u201cischemia\u201d, \u201coveractive bladder\u201d, and \u201cdetrusor underactivity\u201d. Eligible studies included narrative reviews, systematic reviews, meta-analyses, clinical studies, and translational research addressing bladder aging and its clinical implications. A narrative synthesis approach was used due to heterogeneity in study design and outcomes. Results: A total of 43 studies were included in the qualitative synthesis. The evidence indicates that LUTS in older men result from multifactorial processes involving not only prostatic enlargement but also bladder dysfunction. Aging-associated changes include detrusor remodeling, impaired compliance, neural alterations, and vascular insufficiency, particularly chronic ischemia and oxidative stress. These mechanisms contribute to both detrusor overactivity and underactivity, providing a unifying framework for storage and voiding symptoms. Importantly, the severity of LUTS does not consistently correlate with prostate size or degree of obstruction. Conclusions: LUTS in aging men should be considered a complex condition involving both bladder and outlet factors. A bladder-centered perspective may improve patient stratification and therapeutic outcomes. Integrating bladder-targeted therapies with conventional BPH management supports a more personalized and effective approach to care.<\/jats:p>","DOI":"10.3390\/medicina62040685","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:10:27Z","timestamp":1775448627000},"page":"685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of the Aging Bladder in Lower Urinary Tract Symptoms: Pathophysiology and Therapeutic Implications in Patients with Benign Prostatic Hyperplasia"],"prefix":"10.3390","volume":"62","author":[{"given":"Dimitrios","family":"Papanikolaou","sequence":"first","affiliation":[{"name":"General Hospital Papageorgiou, 2nd Urology Department, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Diamantopoulos","sequence":"additional","affiliation":[{"name":"General Hospital Papageorgiou, 2nd Urology Department, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1938-8004","authenticated-orcid":false,"given":"Ioannis","family":"Sokolakis","sequence":"additional","affiliation":[{"name":"General Hospital Papageorgiou, 2nd Urology Department, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merkourios","family":"Kolvatzis","sequence":"additional","affiliation":[{"name":"General Hospital Papageorgiou, 2nd Urology Department, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Antoniadis","sequence":"additional","affiliation":[{"name":"Urology Department, General Hospital of Larissa, 41221 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriakos","family":"Moysidis","sequence":"additional","affiliation":[{"name":"General Hospital Papageorgiou, 2nd Urology Department, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Hatzimouratidis","sequence":"additional","affiliation":[{"name":"General Hospital Papageorgiou, 2nd Urology Department, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9424-795X","authenticated-orcid":false,"given":"Michael","family":"Samarinas","sequence":"additional","affiliation":[{"name":"General Hospital Papageorgiou, 2nd Urology Department, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s11884-010-0067-2","article-title":"Benign prostatic hyperplasia and male lower urinary tract symptoms: Epidemiology and risk factors","volume":"5","author":"Parsons","year":"2010","journal-title":"Curr. Bladder Dysfunct. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.mcna.2010.08.013","article-title":"Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH)","volume":"95","author":"Roehrborn","year":"2011","journal-title":"Med. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.4111\/kju.2015.56.4.266","article-title":"A current perspective on geriatric lower urinary tract dysfunction","volume":"56","author":"Jung","year":"2015","journal-title":"Korean J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.4103\/tcmj.tcmj_3_17","article-title":"Current consensus and controversy on the diagnosis of male lower urinary tract symptoms\/benign prostatic hyperplasia","volume":"29","author":"Lee","year":"2017","journal-title":"Tzu Chi Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4103\/tcmj.tcmj_20_17","article-title":"Pathophysiology of benign prostate enlargement and lower urinary tract symptoms: Current concepts","volume":"29","author":"Lee","year":"2017","journal-title":"Tzu Chi Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E165","DOI":"10.5489\/cuaj.8139","article-title":"Prostatic zonal parameters and lower urinary tract symptoms as quantified via magnetic resonance imaging","volume":"17","author":"Moryousef","year":"2023","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1002\/nau.24313","article-title":"Are oxidative stress and ischemia significant causes of bladder damage leading to lower urinary tract dysfunction? Report from the ICI-RS 2019","volume":"39","author":"Speich","year":"2020","journal-title":"Neurourol. Urodyn."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yang, J.H., Choi, H.P., Niu, W., and Azadzoi, K.M. (2021). Cellular stress and molecular responses in bladder ischemia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111862"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.5213\/inj.2244190.095","article-title":"Oxidative stress and its relation to lower urinary tract symptoms","volume":"26","author":"Andersson","year":"2022","journal-title":"Int. Neurourol. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wu, Y.H., Chueh, K.S., Chuang, S.M., Long, C.Y., Lu, J.H., and Juan, Y.S. (2021). Bladder hyperactivity induced by oxidative stress and bladder ischemia: A review of treatment strategies with antioxidants. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116014"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.2147\/CIA.S174402","article-title":"Mirabegron in the treatment of overactive bladder: Safety and efficacy in the very elderly patient","volume":"15","author":"Makhani","year":"2020","journal-title":"Clin. Interv. Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4111\/icu.2016.57.4.249","article-title":"Progressive changes in detrusor function and micturition patterns with chroinc bladder ischemia","volume":"57","author":"Zhao","year":"2016","journal-title":"Investig. Clin. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1177\/1756287216675778","article-title":"The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction","volume":"9","author":"Andersson","year":"2017","journal-title":"Ther. Adv. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"129","DOI":"10.5213\/inj.2346028.014","article-title":"Role of Pelvic Ischemia in Human Lower Urinary Tract Symptoms and Sexual Function among Patients with Common Iliac Artery Obstruction Undergoing Revascularization Surgery","volume":"27","author":"Papaefstathiou","year":"2023","journal-title":"Int. Neurourol. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.eururo.2018.07.037","article-title":"Detrusor Underactivity and the Underactive Bladder: A Systematic Review of Preclinical and Clinical Studies","volume":"74","author":"Osman","year":"2018","journal-title":"Eur. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/nau.21097","article-title":"Detrusor underactivity: A plea for new approaches","volume":"30","author":"Vahabi","year":"2011","journal-title":"Neurourol. Urodyn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.2147\/IJWH.S372597","article-title":"Mirabegron in the Management of Overactive Bladder Syndrome","volume":"14","author":"Robinson","year":"2022","journal-title":"Int. J. Womens Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s40266-019-00674-9","article-title":"Relative Risk of Adverse Events and Treatment Discontinuations Between Older and Non-Older Adults Treated with Antimuscarinics for Overactive Bladder: A Systematic Review and Meta-Analysis","volume":"36","author":"Usmani","year":"2019","journal-title":"Drugs Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/j.1742-1241.2010.02611.x","article-title":"Antimuscarinics for treatment of storage lower urinary tract symptoms in men: A systematic review","volume":"65","author":"Kaplan","year":"2011","journal-title":"Int. J. Clin. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/JU.0000000000003077","article-title":"Role of Antimuscarinics Combined with Alpha-blockers in the Management of Urinary Storage Symptoms in Patients With Benign Prostatic Hyperplasia: An Updated Systematic Review and Meta-analysis","volume":"209","author":"Lenfant","year":"2023","journal-title":"J. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.eururo.2015.12.048","article-title":"Latest Evidence on the Use of Phosphodiesterase Type 5 Inhibitors for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia","volume":"70","author":"Gacci","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.eururo.2012.09.006","article-title":"The Mechanism of Action of Phosphodiesterase Type 5 Inhibitors in the Treatment of Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia","volume":"63","author":"Giuliano","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Cui, J., Cao, D., Bai, Y., Wang, J., Yin, S., Wei, W., Xiao, Y., Wang, J., and Wei, Q. (2021). Efficacy and Safety of 12-week Monotherapy With Once Daily 5 mg Tadalafil for Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: Evidence-based Analysis. Front. Med., 8.","DOI":"10.3389\/fmed.2021.744012"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.eururo.2013.03.004","article-title":"EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction","volume":"64","author":"Oelke","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1016\/j.juro.2012.11.021","article-title":"Evaluation and treatment of lower urinary tract symptoms in older men","volume":"189","author":"Abrams","year":"2013","journal-title":"J. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1089\/end.2022.0654","article-title":"Surgical Outcomes for Elderly Patients Undergoing Transurethral Resection of the Prostate for Chronic Urinary Retention and Proposal of a Management Algorithm","volume":"37","author":"Antoniou","year":"2023","journal-title":"J. Endourol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13643-024-02514-3","article-title":"Transurethral surgical treatment for benign prostatic hyperplasia with detrusor underactivity: A systematic review and meta-analysis","volume":"13","author":"Zou","year":"2024","journal-title":"Syst. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.1007\/s00345-023-04656-w","article-title":"The influence of preoperative urodynamic parameters on clinical results in patients with benign prostatic hyperplasia after transurethral resection of the prostate","volume":"41","author":"Yang","year":"2023","journal-title":"World J. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1001\/jama.2025.7045","article-title":"Lower urinary tract symptoms in men","volume":"334","author":"Wei","year":"2025","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1742-1241.2010.02341.x","article-title":"A stepwise approach to the treatment of the enlarged prostate","volume":"64","author":"Chapple","year":"2010","journal-title":"Int. J. Clin. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/nau.10052","article-title":"The standardisation of terminology of lower urinary tract function","volume":"21","author":"Abrams","year":"2002","journal-title":"Neurourol. Urodyn."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/nau.22195","article-title":"How does the urothelium affect bladder function in health and disease?","volume":"31","author":"Birder","year":"2012","journal-title":"Neurourol. Urodyn."},{"key":"ref_33","first-page":"64","article-title":"Mechanisms of lower urinary tract symptoms in pelvic ischemia","volume":"1","author":"Azadzoi","year":"2013","journal-title":"J. Biochem. Pharmacol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1540\/jsmr.60.23","article-title":"Association of detrusor underactivity with aging and metabolic syndrome: Suggestions from animal models","volume":"60","author":"Shimizu","year":"2024","journal-title":"J. Smooth Muscle Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e070","DOI":"10.1097\/j.pbj.0000000000000070","article-title":"Understanding underactive bladder: A review of the contemporary literature","volume":"5","author":"Charrua","year":"2020","journal-title":"Porto Biomed. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"195","DOI":"10.4103\/tcmj.tcmj_83_18","article-title":"Individualizing medical treatment of overactive bladder","volume":"30","author":"Kuo","year":"2018","journal-title":"Tzu Chi Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.eururo.2012.02.033","article-title":"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","volume":"61","author":"Gacci","year":"2012","journal-title":"Eur. Urol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/phar.1243","article-title":"Tadalafil: A Phosphodiesterase-5 Inhibitor for Benign Prostatic Hyperplasia","volume":"33","author":"Cantrell","year":"2013","journal-title":"Pharmacotherapy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1743-6109.2011.02504.x","article-title":"Tadalafil 2.5 or 5 mg 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","volume":"9","author":"Egerdie","year":"2012","journal-title":"J. Sex. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"193","DOI":"10.5534\/wjmh.2013.31.3.193","article-title":"Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (BPH) and LUTS\/BPH with Erectile Dysfunction in Asian Men: A Systematic Review Focusing on Tadalafil","volume":"31","author":"Park","year":"2013","journal-title":"World J. Mens. Health"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.eururo.2014.12.038","article-title":"EAU Guidelines on the Assessment of Non-neurogenic Male Lower Urinary Tract Symptoms including Benign Prostatic Obstruction","volume":"67","author":"Gratzke","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lombardo, R., Ghezzo, N., Sarcinelli, L., Turchi, B., Zammitti, F., Franco, A., Nacchia, A., Cicione, A., Tema, G., and Pastore, A.L. (2024). Post-Voided Residual Ratio Does Not Predict Trifecta Outcome after Transurethral Resection of Prostate. Life, 14.","DOI":"10.3390\/life14040445"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101097JU0000000000004975","DOI":"10.1097\/JU.0000000000004975","article-title":"BladderSpan: Years Lived With Optimal Detrusor Function","volume":"19","author":"Kuang","year":"2026","journal-title":"J. Urol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1097\/CU9.0000000000000299","article-title":"Tackling the progression of benign prostatic hyperplasia\/benign prostatic obstruction progression: Deobstructing within the \u201cwindow of curability\u201d (a hypothesis-generating review)","volume":"19","author":"Kuang","year":"2025","journal-title":"Curr. Urol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41391-023-00747-2","article-title":"When you say \u201cProstate\u201d, don\u2019t forget to say \u201cBladder\u201d!","volume":"27","author":"Cindolo","year":"2024","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_46","unstructured":"Cornu, J.N., Gacci, M., Hashim, H., Herrmann, T.R.W., Malde, S., Netsch, C., De Nunzio, C., Rieken, M., Sakalis, V., and Tutolo, M. (2024). EAU Guidelines on Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS), European Association of Urology. EAU Guidelines."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/685\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:56:01Z","timestamp":1775451361000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["medicina62040685"],"URL":"https:\/\/doi.org\/10.3390\/medicina62040685","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]}}}