{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:13:53Z","timestamp":1791346433479,"version":"4.3.1"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["RC2 DK122379"],"award-info":[{"award-number":["RC2 DK122379"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>A critical appraisal of the literature regarding female urethral function and dysfunction is needed in light of recent evidence showing the urethra's role in causing stress and urge urinary incontinence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An evidence assessment was conducted using selected articles from the literature that contained mechanistic data on factors affecting urethral function and failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Maximal urethral closure pressure (MUCP) is 40% lower in stress urinary incontinence (SUI) than normal controls. Evidence from five women shows relatively equal contributions to MUCP from striated\/smooth muscle, vascular\u2010plexus, connective tissue. MUCP varies twofold in individuals of similar age and declines 15% per decade even in nulliparous women. Age explains 57% of the variance in MUCP. This parallels with striated\/smooth muscle loss and reduced nerve density. Factors influencing pressure variation minute\u2010to\u2010minute and decade\u2010to\u2010decade are poorly understood. Connective tissue changes have not been investigated. MUCP in <jats:italic>de novo<\/jats:italic> SUI persisting 9\u2010months postpartum is 25% less than in age and parity\u2010matched controls. Longitudinal studies do not show significant changes in urethral function after vaginal birth suggesting that changes in urethral support from birth may unmask pre\u2010existing sphincter weakness and precipitate SUI. Mechanisms of interaction between support injury, pre\u2010existing urethral weakness, and neuropathy are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Urethral failure is the predominant cause of SUI and a contributing factor for UUI; potentially explaining why mixed symptoms predominate in epidemiological studies. Age\u2010related striated muscle loss and differences between women of similar age are prominent features of poor urethral closure. Yet, connective tissue changes, vasculature function, and complex interactions among factors are poorly understood.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24760","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T18:32:00Z","timestamp":1630953120000},"page":"1869-1879","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Urethral function and failure: A review of current knowledge of urethral closure mechanisms, how they vary, and how they are affected by life events"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-8523","authenticated-orcid":false,"given":"Fernanda","family":"Pipitone","sequence":"first","affiliation":[{"name":"Pelvic Floor Research Group University of Michigan Ann Arbor Michigan USA"},{"name":"Hospital das Cl\u00ednicas da FMUSP University of S\u00e3o Paulo S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhina","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Division of Neurourology and Pelvic Reconstructive Surgery, Department of Urology University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John O. 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