Key Points
-
The aetiology and pathophysiology of detrusor underactivity (DUA) are poorly understood—multiple aetiological factors and pathogenic mechanisms are likely to be involved
-
Definite aetiologies include injuries or diseases of the nervous system and diabetes mellitus. Bladder outlet obstruction and normal ageing can, at present, only be considered likely causes of DUA
-
Aetiological factors probably cause DUA by interrupting processes that are essential for the generation of an efficient voiding contraction
-
Pathophysiological mechanisms can be classified as myogenic (affecting detrusor myocytes or their surrounding matrix) or neurogenic (affecting central neural control mechanisms governing the voiding reflex or afferent and/or efferent nerves)
-
To develop new effective treatments, a better understanding of the mechanism underlying the generation of a normal voiding contraction and which abnormalities cause DUA is required
Abstract
Detrusor underactivity (DUA) is a poorly understood, yet common, bladder dysfunction, referred to as underactive bladder, which is observed in both men and women undergoing urodynamic studies. Despite its prevalence, no effective therapeutic approaches exist for DUA. Exactly how the contractile function of the detrusor muscle changes with ageing is unclear. Data from physiological studies in animal and human bladders are contradictory, as are the results of the limited number of clinical studies assessing changes in urodynamic parameters with ageing. The prevalence of DUA in different patient groups suggests that multiple aetiologies are involved in DUA pathogenesis. Traditional concepts focused on either efferent innervation or myogenic dysfunction. By contrast, contemporary views emphasize the importance of the neural control mechanisms, particularly the afferent system, which can fail to potentiate detrusor contraction, leading to premature termination of the voiding reflex. In conclusion, the contemporary understanding of the aetiology and pathophysiology of DUA is limited. Further elucidation of the underlying mechanisms is needed to enable the development of new and effective treatment approaches.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Abarbanel, J. & Marcus, E. L. Impaired detrusor contractility in community-dwelling elderly presenting with lower urinary tract symptoms. Urology 69, 436–440 (2007).
Nitti, V. W., Lefkowitz, G., Ficazzola, M. & Dixon, C. M. Lower urinary tract symptoms in young men: videourodynamic findings and correlation with noninvasive measures. J. Urol. 168, 135–138 (2002).
Resnick, N. M., Brandeis, G. H., Baumann, M. M., DuBeau, C. E. & Yalla, S. V. Misdiagnosis of urinary incontinence in nursing home women: prevalence and a proposed solution. Neurourol. Urodyn. 15, 599–613; discussion 613–618 (1996).
Abrams, P. et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol. Urodyn. 21, 167–178 (2002).
Chancellor, M. B. & Kaufman, J. Case for pharmacotherapy development for underactive bladder. Urology 72, 966–967 (2008).
Chapple, C. Overactive bladder and underactive bladder: a symptom syndrome or urodynamic diagnosis? Neurourol. Urodyn. 32, 305–307 (2013).
Miyazato, M., Yoshimura, N. & Chancellor, M. B. The other bladder syndrome: underactive bladder. Rev. Urol. 15, 11–22 (2013).
Osman, N. I. et al. Detrusor underactivity and the underactive bladder: a new clinical entity? A review of current terminology, definitions, epidemiology, aetiology, and diagnosis. Eur. Urol. 65, 389–398 (2014).
van Koeveringe, G. A., Vahabi, B., Andersson, K. E., Kirschner-Herrmans, R. & Oelke, M. Detrusor underactivity: a plea for new approaches to a common bladder dysfunction. Neurourol. Urodyn. 30, 723–728 (2011).
Zhao, W. et al. Impaired bladder function in aging male rats. J. Urol. 184, 378–385 (2010).
Munro, D. D. & Wendt, I. R. Contractile and metabolic properties of longitudinal smooth muscle from rat urinary bladder and the effects of aging. J. Urol. 150, 529–536 (1993).
Wilfehrt, H. M., Carson, C. C. 3rd & Marson, L. Bladder function in female rats: effects of aging and pregnancy. Physiol. Behav. 68, 195–203 (1999).
Longhurst, P. A., Eika, B., Leggett, R. E. & Levin, R. M. Comparison of urinary bladder function in 6 and 24 month male and female rats. J. Urol. 148, 1615–1620 (1992).
Pagala, M. K., Tetsoti, L., Nagpal, D. & Wise, G. J. Aging effects on contractility of longitudinal and circular detrusor and trigone of rat bladder. J. Urol. 166, 721–727 (2001).
Gomez-Pinilla, P. J., Pozo, M. J. & Camello, P. J. Aging differentially modifies agonist-evoked mouse detrusor contraction and calcium signals. Age (Dordr.) 33, 81–88 (2011).
Ordway, G. A., Esbenshade, T. A., Kolta, M. G., Gerald, M. C. & Wallace, L. J. Effect of age on cholinergic muscarinic responsiveness and receptors in the rat urinary bladder. J. Urol. 136, 492–496 (1986).
Lluel, P. et al. Functional and morphological modifications of the urinary bladder in aging female rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278, R964–R972 (2000).
Lluel, P. et al. Increased adrenergic contractility and decreased mRNA expression of NOS III in aging rat urinary bladders. Fundam. Clin. Pharmacol. 17, 633–641 (2003).
Yu, H. I., Wein, A. J. & Levin, R. M. Contractile responses and calcium mobilization induced by muscarinic agonists in the rat urinary bladder: effects of age. Gen. Pharmacol. 28, 623–628 (1997).
Saito, M., Kondo, A., Gotoh, M., Kato, K. & Levin, R. M. Age-related changes in the response of the rat urinary bladder to neurotransmitters. Neurourol. Urodyn. 12, 191–200 (1993).
Saito, M., Gotoh, M., Kato, K. & Kondo, A. Influence of aging on the rat urinary bladder function. Urol. Int. 47 (Suppl. 1), 39–42 (1991).
Saito, M., Kondo, A., Gotoh, M. & Kato, K. Age-related changes in the rat detrusor muscle: the contractile response to inorganic ions. J. Urol. 146, 891–894 (1991).
Chun, A. L., Wallace, L. J., Gerald, M. C., Wein, A. J. & Levin, R. M. Effects of age on urinary bladder function in the male rat. J. Urol. 141, 170–173 (1989).
Lieu, P. K., Sa'adu, A., Orugun, E. O. & Malone-Lee, J. G. The influence of age on isometric and isotonic rat detrusor contractions. J. Gerontol. A Biol. Sci. Med. Sci. 52, M94–M96 (1997).
Kageyama, S. et al. Effect of age on the responses of rat bladder detrusor strips to adenosine triphosphate. BJU Int. 85, 899–904 (2000).
Lin, A. T., Yang, C. H. & Chang, L. S. Impact of aging on rat urinary bladder fatigue. J. Urol. 157, 1990–1994 (1997).
Fry, C. H., Bayliss, M., Young, J. S. & Hussain, M. Influence of age and bladder dysfunction on the contractile properties of isolated human detrusor smooth muscle. BJU Int. 108, E91–E96 (2011).
Yoshida, M. et al. Age-related changes in cholinergic and purinergic neurotransmission in human isolated bladder smooth muscles. Exp. Gerontol. 36, 99–109 (2001).
Mark, S. D. et al. Detrusor contractility: Age related correlation with urinary flow rate in asymptomatic males [abstract 13]. Neurourol. Urodyn. 11, 315–317 (1992).
Lepor, H., Sunaryadi, I., Hartanto, V. & Shapiro, E. Quantitative morphometry of the adult human bladder. J. Urol. 148, 414–417 (1992).
Holm, N. R., Horn, T. & Hald, T. Detrusor in ageing and obstruction. Scand. J. Urol. Nephrol. 29, 45–49 (1995).
Gosling, J. A. Modification of bladder structure in response to outflow obstruction and ageing. Eur. Urol. 32 (Suppl. 1), 9–14 (1997).
Elbadawi, A., Hailemariam, S., Yalla, S. V. & Resnick, N. M. Structural basis of geriatric voiding dysfunction. VI. Validation and update of diagnostic criteria in 71 detrusor biopsies. J. Urol. 157, 1802–1813 (1997).
Andersson, K. E. & Arner, A. Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol. Rev. 84, 935–986 (2004).
Lowalekar, S. K., Cristofaro, V., Radisavljevic, Z. M., Yalla, S. V. & Sullivan, M. P. Loss of bladder smooth muscle caveolae in the aging bladder. Neurourol. Urodyn. 31, 586–592 (2012).
Cristofaro, V., Peters, C. A., Yalla, S. V. & Sullivan, M. P. Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions. Neurourol. Urodyn. 26, 71–80 (2007).
Sadegh, M. K. et al. Biomechanical properties and innervation of the female caveolin-1-deficient detrusor. Br. J. Pharmacol. 162, 1156–1170 (2011).
Lai, H. H. et al. Loss of caveolin-1 expression is associated with disruption of muscarinic cholinergic activities in the urinary bladder. Neurochem. Int. 45, 1185–1193 (2004).
Pfisterer, M. H., Griffiths, D. J., Schaefer, W. & Resnick, N. M. The effect of age on lower urinary tract function: a study in women. J. Am. Geriatr. Soc. 54, 405–412 (2006).
Schäfer, W. Analysis of bladder-outlet function with the linearized passive urethral resistance relation, linPURR, and a disease-specific approach for grading obstruction: from complex to simple. World J. Urol. 13, 47–58 (1995).
Smith, A. L. et al. Urodynamic trends in the female aging population: detrusor overactivity with impaired contractility, two conditions or one? 39th Annual Meeting of the International Continence Society (San Francisco, CA) [online], (2009).
Valentini, F. A., Robain, G. & Marti, B. G. Urodynamics in women from menopause to oldest age: what motive? What diagnosis? Int. Braz. J. Urol. 37, 100–107 (2011).
Karram, M. M., Partoll, L., Bilotta, V. & Angel, O. Factors affecting detrusor contraction strength during voiding in women. Obstet. Gynecol. 90, 723–726 (1997).
Madersbacher, S. et al. The aging lower urinary tract: a comparative urodynamic study of men and women. Urology 51, 206–212 (1998).
Madersbacher, S. et al. Age related urodynamic changes in patients with benign prostatic hyperplasia. J. Urol. 156, 1662–1667 (1996).
Levin, R. M. et al. Studies on experimental bladder outlet obstruction in the cat: long-term functional effects. J. Urol. 148, 939–943 (1992).
Saito, M., Yokoi, K., Ohmura, M. & Kondo, A. Effects of partial outflow obstruction on bladder contractility and blood flow to the detrusor: comparison between mild and severe obstruction. Urol. Int. 59, 226–230 (1997).
Levin, R. M., Haugaard, N., Levin, S. S., Buttyan, R., Chen, M.-W., Monson, F. C., Wein, A. J. in Muscle, matrix, and bladder function (ed. Zderic, S. A.) 7–19 (Plenum Press, 1995).
Greenland, J. E. & Brading, A. F. Urinary bladder blood flow changes during the micturition cycle in a conscious pig model. J. Urol. 156, 1858–1861 (1996).
Erdem, E., Leggett, R., Dicks, B., Kogan, B. A. & Levin, R. M. Effect of bladder ischaemia/reperfusion on superoxide dismutase activity and contraction. BJU Int. 96, 169–174 (2005).
Zhao, Y., Levin, S. S., Wein, A. J. & Levin, R. M. Correlation of ischemia/reperfusion or partial outlet obstruction-induced spectrin proteolysis by calpain with contractile dysfunction in rabbit bladder. Urology 49, 293–300 (1997).
Bauer, V. et al. Reactive oxygen species induced smooth muscle responses in the intestine, vessels and airways and the effect of antioxidants. Life Sci. 65, 1909–1917 (1999).
Schröder, A. et al. Effect of chronic bladder outlet obstruction on blood flow of the rabbit bladder. J. Urol. 165, 640–646 (2001).
Thomas, A. W., Cannon, A., Bartlett, E., Ellis-Jones, J. & Abrams, P. The natural history of lower urinary tract dysfunction in men: minimum 10-year urodynamic follow-up of untreated bladder outlet obstruction. BJU Int. 96, 1301–1306 (2005).
George, N. J., O'Reilly, P. H., Barnard, R. J. & Blacklock, N. J. High pressure chronic retention. Br. Med. J. (Clin. Res. Ed.) 286, 1780–1783 (1983).
Djavan, B., Madersbacher, S., Klingler, C. & Marberger, M. Urodynamic assessment of patients with acute urinary retention: is treatment failure after prostatectomy predictable? J. Urol. 158, 1829–1833 (1997).
Lifford, K. L., Curhan, G. C., Hu, F. B., Barbieri, R. L. & Grodstein, F. Type 2 diabetes mellitus and risk of developing urinary incontinence. J. Am. Geriatr. Soc. 53, 1851–1857 (2005).
Lee, W. C. et al. Effects of diabetes on female voiding behavior. J. Urol. 172, 989–992 (2004).
Hill, S. R., Fayyad, A. M. & Jones, G. R. Diabetes mellitus and female lower urinary tract symptoms: a review. Neurourol. Urodyn. 27, 362–367 (2008).
Fedele, D. Therapy Insight: sexual and bladder dysfunction associated with diabetes mellitus. Nat. Clin. Pract. Urol. 2, 282–290; quiz 309 (2005).
Sasaki, K. et al. Diabetic cystopathy correlates with a long-term decrease in nerve growth factor levels in the bladder and lumbosacral dorsal root ganglia. J. Urol. 168, 1259–1264 (2002).
Hellweg, R., Raivich, G., Hartung, H. D., Hock, C. & Kreutzberg, G. W. Axonal transport of endogenous nerve growth factor (NGF) and NGF receptor in experimental diabetic neuropathy. Exp. Neurol. 130, 24–30 (1994).
Longhurst, P. A. & Belis, J. A. Abnormalities of rat bladder contractility in streptozotocin-induced diabetes mellitus. J. Pharmacol. Exp. Ther. 238, 773–777 (1986).
Waring, J. V. & Wendt, I. R. Effects of streptozotocin-induced diabetes mellitus on intracellular calcium and contraction of longitudinal smooth muscle from rat urinary bladder. J. Urol. 163, 323–330 (2000).
Daneshgari, F., Liu, G., Birder, L., Hanna-Mitchell, A. T. & Chacko, S. Diabetic bladder dysfunction: current translational knowledge. J. Urol. 182 (Suppl. 6), S18–S26 (2009).
Burney, T. L., Senapati, M., Desai, S., Choudhary, S. T. & Badlani, G. H. Acute cerebrovascular accident and lower urinary tract dysfunction: a prospective correlation of the site of brain injury with urodynamic findings. J. Urol. 156, 1748–1750 (1996).
Araki, I., Kitahara, M., Oida, T. & Kuno, S. Voiding dysfunction and Parkinson's disease: urodynamic abnormalities and urinary symptoms. J. Urol. 164, 1640–1643 (2000).
Stocchi, F. et al. Urodynamic and neurophysiological evaluation in Parkinson's disease and multiple system atrophy. J. Neurol. Neurosurg. Psychiatry 62, 507–511 (1997).
Yamamoto, T. et al. Time-dependent changes and gender differences in urinary dysfunction in patients with multiple system atrophy. Neurourol. Urodyn. 33, 516–523 (2014).
Bloch, F. et al. Urodynamic analysis in multiple system atrophy: characterisation of detrusor-sphincter dyssynergia. J. Neurol. 257, 1986–1991 (2010).
Litwiller, S. E., Frohman, E. M. & Zimmern, P. E. Multiple sclerosis and the urologist. J. Urol. 161, 743–757 (1999).
Plotti, F. et al. Update on urodynamic bladder dysfunctions after radical hysterectomy for cervical cancer. Crit. Rev. Oncol. Hematol. 80, 323–329 (2011).
Zanolla, R., Campo, B., Ordesi, G. & Martino, G. Bladder urethral dysfunction after abdominoperineal resection of the rectum for ano-rectal cancer. Tumori 70, 555–559 (1984).
Maurer, C. A. et al. Total mesorectal excision preserves male genital function compared with conventional rectal cancer surgery. Br. J. Surg. 88, 1501–1505 (2001).
Elbadawi, A., Atta, M. A., Hanno, A. G.-E. Intrinsic neuromuscular defects in the neurogenic bladder: VIII. Effects of unilateral pelvic and pelvic plexus neurectomy on ultrastructure of the feline bladder base. Neurourol. Urodyn. 7, 77–92 (1988).
Brierly, R. D., Hindley, R. G., McLarty, E., Harding, D. M. & Thomas, P. J. A prospective controlled quantitative study of ultrastructural changes in the underactive detrusor. J. Urol. 169, 1374–1378 (2003).
Elbadawi, A., Yalla, S. V. & Resnick, N. M. Structural basis of geriatric voiding dysfunction. II. Aging detrusor: normal versus impaired contractility. J. Urol. 150, 1657–1667 (1993).
Elbadawi, A., Yalla, S. V. & Resnick, N. M. Structural basis of geriatric voiding dysfunction. III. Detrusor overactivity. J. Urol. 150, 1668–1680 (1993).
Elbadawi, A., Yalla, S. V. & Resnick, N. M. Structural basis of geriatric voiding dysfunction. IV. Bladder outlet obstruction. J. Urol. 150, 1681–1695 (1993).
Hindley, R. G., Brierly, R. D., McLarty, E., Harding, D. M. & Thomas, P. J. A qualitative ultrastructural study of the hypocontractile detrusor. J. Urol. 168, 126–131 (2002).
Sullivan, M. P. & Yalla, S. V. Detrusor contractility and compliance characteristics in adult male patients with obstructive and nonobstructive voiding dysfunction. J. Urol. 155, 1995–2000 (1996).
Schroder, A., Uvelius, B., Capello, S. A. & Longhurst, P. A. Regional differences in bladder enlargement and in vitro contractility after outlet obstruction in the rabbit. J. Urol. 168, 1240–1246 (2002).
de Groat, W. C. et al. Developmental and injury induced plasticity in the micturition reflex pathway. Behav. Brain Res. 92, 127–140 (1998).
Sugaya, K. et al. Ascending and descending brainstem neuronal activity during cystometry in decerebrate cats. Neurourol. Urodyn. 22, 343–350 (2003).
Sugaya, K., Nishijima, S., Miyazato, M. & Ogawa, Y. Central nervous control of micturition and urine storage. J. Smooth Muscle Res. 41, 117–132 (2005).
Blok, B. F., Willemsen, A. T. & Holstege, G. A PET study on brain control of micturition in humans. Brain 120, 111–121 (1997).
Kim, Y. H. et al. The correlation of urodynamic findings with cranial magnetic resonance imaging findings in multiple sclerosis. J. Urol. 159, 972–976 (1998).
Gilpin, S. A., Gilpin, C. J., Dixon, J. S., Gosling, J. A. & Kirby, R. S. The effect of age on the autonomic innervation of the urinary bladder. Br. J. Urol. 58, 378–381 (1986).
Feber, J. L., van Asselt, E. & van Mastrigt, R. Neurophysiological modeling of voiding in rats: urethral nerve response to urethral pressure and flow. Am. J. Physiol. 274, R1473–R1481 (1998).
Bump, R. C. The urethrodetrusor facilitative reflex in women: results of urethral perfusion studies. Am. J. Obstet. Gynecol. 182, 794–802; discussion 802–804 (2000).
Pfisterer, M. H., Griffiths, D. J., Rosenberg, L., Schaefer, W. & Resnick, N. M. Parameters of bladder function in pre-, peri-, and postmenopausal continent women without detrusor overactivity. Neurourol. Urodyn. 26, 356–361 (2007).
Griffiths, D., Tadic, S. D., Schaefer, W. & Resnick, N. M. Cerebral control of the bladder in normal and urge-incontinent women. Neuroimage 37, 1–7 (2007).
Smith, P. P. Aging and the underactive detrusor: a failure of activity or activation? Neurourol. Urodyn. 29, 408–412 (2010).
Resnick, N. M. & Yalla, S. V. Detrusor hyperactivity with impaired contractile function. An unrecognized but common cause of incontinence in elderly patients. JAMA 257, 3076–3081 (1987).
Fowler, C. J. et al. Abnormal electromyographic activity of the urethral sphincter, voiding dysfunction, and polycystic ovaries: a new syndrome? BMJ 297, 1436–1438 (1988).
Osman, N. I. & Chapple, C. R. Fowler's syndrome—a cause of unexplained urinary retention in young women? Nat. Rev. Urol. 11, 87–98 (2014).
Panicker, J. N., DasGupta, R., Elneil, S. & Fowler, C. J. in Pelvic organ dysfunction in neurological disease: Clinical management and rehabilitation (eds Fowler, C. J., Panicker, J. N. & Emmanuel, A.) 293–306 (Cambridge University Press, 2010).
de Groat, W. C. et al. Neural control of the urethra. Scand. J. Urol. Nephrol. Suppl. 35, 35–43; discussion 106–125 (2001).
Fowler, C. J. Neurological disorders of micturition and their treatment. Brain 122, 1213–1231 (1999).
DasGupta, R. & Fowler, C. J. The management of female voiding dysfunction: Fowler's syndrome—a contemporary update. Curr. Opin. Urol. 13, 293–299 (2003).
Haylen, B. T. et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol. Urodyn. 29, 4–20 (2010).
Carlson, K. V., Rome, S. & Nitti, V. W. Dysfunctional voiding in women. J. Urol. 165, 143–147; discussion 147–148 (2001).
Author information
Authors and Affiliations
Contributions
Both authors contributed equally to all aspects of the article (researching the data for the article, discussing content, writing the article and reviewing/editing the manuscript before submission).
Corresponding author
Ethics declarations
Competing interests
C.R.C. is a consultant and researcher for Allergan, Astellas, Pfizer and Recordati. N.I.O. declares no competing interests.
Rights and permissions
About this article
Cite this article
Osman, N., Chapple, C. Contemporary concepts in the aetiopathogenesis of detrusor underactivity. Nat Rev Urol 11, 639–648 (2014). https://doi.org/10.1038/nrurol.2014.286
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrurol.2014.286
This article is cited by
-
When you say “Prostate”, don’t forget to say “Bladder”!
Prostate Cancer and Prostatic Diseases (2024)
-
Detrusor underactivity is associated with metabolic syndrome in aged primates
Scientific Reports (2023)
-
Management of Elevated Post-Void Residual Volume
Current Bladder Dysfunction Reports (2023)
-
Detrusor underactivity prevalence and risk factors according to different definitions in women attending urogynecology clinic
International Urogynecology Journal (2022)
-
A Preclinical Study of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells for Treating Detrusor Underactivity by Chronic Bladder Ischemia
Stem Cell Reviews and Reports (2021)