Abstract
This review discusses the available evidence concerning the use of anticholinergic drugs, alone or in combination with α-adrenoceptor antagonists, in men with lower urinary tract symptoms due to benign prostatic hyperplasia, benign prostatic enlargement, or benign prostatic obstruction and concomitant overactive bladder syndrome. We emphasize the safety and efficacy of anticholinergic agents in treating men with benign prostatic obstruction. Several recent studies of men with an overactive bladder suggest that combination therapy of anticholinergic and α-adrenoceptor antagonists improves the symptoms effectively without increasing the incidence of acute urinary retention.
Similar content being viewed by others
References
Abrams P (1994) In support of pressure-flow studies for evaluating men with lower urinary tract symptoms. Urology 44:153–155
Abrams P (2001) Evidence for the efficacy and safety of tolterodine in the treatment of overactive bladder. Expert Opin Pharmacother 2:1685–1701
Abrams PH, Farrar DJ, Turner-Warwick RT, Whiteside CG, Feneley RC (1979) The results of prostatectomy: a symptomatic and urodynamic analysis of 152 patients. J Urol 121:640–642
Abrams P, Kelleher CJ, Kerr LA, Rogers RG (2000) Overactive bladder significantly affects quality of life. Am J Manag Care 6:S580–S590
Abrams P, Andersson KE, Buccafusco JJ, Chapple C, de Groat WC, Fryer AD, Kay G, Laties A, Nathanson NM, Pasricha PJ, Wein AJ (2006a) Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol 148:565–578
Abrams P, Kaplan S, De Koning Gans HJ, Millard R (2006b) Safety and tolerability of tolterodine for the treatment of overactive bladder in men with bladder outlet obstruction. J Urol 175:999–1004; discussion 1004
Andersson KE (2002) Alpha-adrenoceptors and benign prostatic hyperplasia: basic principles for treatment with alpha-adrenoceptor antagonists. World J Urol 19:390–396
Andersson KE, Gratzke C (2007) Pharmacology of alpha1-adrenoceptor antagonists in the lower urinary tract and central nervous system. Nat Clin Pract Urol 4:368–378
Andersson KE, Yoshida M (2003) Antimuscarinics and the overactive detrusor—which is the main mechanism of action? Eur Urol 43:1–5
Athanasopoulos A, Gyftopoulos K, Giannitsas K, Fisfis J, Perimenis P, Barbalias G (2003) Combination treatment with an alpha-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlled study. J Urol 169:2253–2256
Barry MJ, Cockett AT, Holtgrewe HL, McConnell JD, Sihelnik SA, Winfield HN (1993) Relationship of symptoms of prostatism to commonly used physiological and anatomical measures of the severity of benign prostatic hyperplasia. J Urol 150:351–358
Birder LA, Apodaca G, De Groat WC, Kanai AJ (1998) Adrenergic- and capsaicin-evoked nitric oxide release from urothelium and afferent nerves in urinary bladder. Am J Physiol 275:F226–F229
Braverman AS, Ruggieri MR Sr (2003) Hypertrophy changes the muscarinic receptor subtype mediating bladder contraction from M3 toward M2. Am J Physiol Regul Integr Comp Physiol 285:R701–R708
Braverman AS, Luthin GR, Ruggieri MR (1998) M2 muscarinic receptor contributes to contraction of the denervated rat urinary bladder. Am J Physiol 275:R1654–R1660
Castro D, Espuna M, Prieto M, Badia X (2005) [Prevalence of overactive bladder in Spain: a population-based study]. Arch Esp Urol 58:131–138
Chapple CR (2000) Muscarinic receptor antagonists in the treatment of overactive bladder. Urology 55:33–46
Chapple C (2006) Alpha antagonists-from initial concept to routine clinical practice. Eur Urol 50:635–642
Chapple CR, Carter P, Christmas TJ, Kirby RS, Bryan J, Milroy EJ, Abrams P (1994) A three month double-blind study of doxazosin as treatment for benign prostatic bladder outlet obstruction. Br J Urol 74:50–56
Chapple CR, Rechberger T, Al-Shukri S, Meffan P, Everaert K, Huang M, Ridder A (2004) Randomized, double-blind placebo- and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder. BJU Int 93(3):303–310
Corcos J, Schick E (2004) Prevalence of overactive bladder and incontinence in Canada. Can J Urol 11:2278–2284
Dickson A, Avelino A, Cruz F, Ribeiro-da-Silva A (2006) Peptidergic sensory and parasympathetic fiber sprouting in the mucosa of the rat urinary bladder in a chronic model of cyclophosphamide-induced cystitis. Neuroscience 141:1633–1647
Ehlert FJ, Griffin MT, Abe DM, Vo TH, Taketo MM, Manabe T, Matsui M (2005) The M2 muscarinic receptor mediates contraction through indirect mechanisms in mouse urinary bladder. J Pharmacol Exp Ther 313:368–378
Forray C, Bard JA, Wetzel JM, Chiu G, Shapiro E, Tang R, Lepor H, Hartig PR, Weinshank RL, Branchek TA et al (1994) The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol 45:703–708
Fusco F, Groutz A, Blaivas JG, Chaikin DC, Weiss JP (2001) Videourodynamic studies in men with lower urinary tract symptoms: a comparison of community based versus referral urological practices. J Urol 166:910–913
Gonzalez RR, Te AE (2003) Overactive bladder and men: indications for anticholinergics. Curr Urol Rep 4:429–435
Hampel C, Dolber PC, Smith MP, Savic SL, Throff JW, Thor KB, Schwinn DA (2002) Modulation of bladder alpha1-adrenergic receptor subtype expression by bladder outlet obstruction. J Urol 167:1513–1521
Harriss DR, Marsh KA, Birmingham AT, Hill SJ (1995) Expression of muscarinic M3-receptors coupled to inositol phospholipids hydrolysis in human detrusor smooth muscle cells. J Urol 154:1241–1245
Hedlund P, Streng T, Lee T, Andersson KE (2007) Effects of tolterodine on afferent neurotransmission in normal and resiniferatoxin treated conscious rats. J Urol 178:326–331
Hegde SS, Choppin A, Bonhaus D, Briaud S, Loeb M, Moy TM, Loury D, Eglen RM (1997) Functional role of M2 and M3 muscarinic receptors in the urinary bladder of rats in vitro and in vivo. Br J Pharmacol 120:1409–1418
Homma Y, Yamaguchi O, Hayashi K (2005) An epidemiological survey of overactive bladder symptoms in Japan. BJU Int 96:1314–1318
Ikemoto I, Kiyota H, Ohishi Y, Abe K, Goto H, Kishimoto K, Miki K (2003) Usefulness of tamsulosin hydrochloride and naftopidil in patients with urinary disturbances caused by benign prostatic hyperplasia: a comparative, randomized, two-drug crossover study. Int J Urol 10:587–594
Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S, Coyne K, Kelleher C, Hampel C, Artibani W, Abrams P (2006a) Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur Urol 50:1306–1314; discussion 1314–1315
Irwin DE, Milsom I, Reilly K, Hunskaar S, Coyne KS, Kopp Z, Herschorn S, Kelleher C, Hampel C, Artibani W, Abrams P (2006b) Men and women with overactive bladder symptoms report higher prevalence for depression and lower quality of life: results from the EPIC study. ICS 2006 Abstract 433
Irwin DE, Milsom I, Kopp Z, Abrams P, Cardozo L (2006c) Impact of overactive bladder symptoms on employment, social interactions and emotional well-being in six European countries. BJU Int 97:96–100
Jardin A (1998) Alpha-blockers in the treatment of BPH. Health Publication, Plymouth, pp 599–632
Jolleys JV, Donovan JL, Nanchahal K, Peters TJ, Abrams P (1994) Urinary symptoms in the community: how bothersome are they? Br J Urol 74:551–555
Jumadilova Z, Harris H, del Aguilla M, Wagner S, Boccuzzi S, Bavendam T (2005) Agent selection for overactive bladder patients with and without documented comorbid benign prostatic hyperplasia. Presented at: the 35th Annual Meeting of the International Continence Society; August 28-September 2, 2005; Montreal, Canada
Kaplan SA, Walmsley K, Te AE (2005) Tolterodine extended release attenuates lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol 174:2273–2275
Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z (2006) Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA 296:2319–2328
Kessler TM, Studer UE, Burkhard FC (2006) The effect of terazosin on functional bladder outlet obstruction in women: a pilot study. J Urol 176:1487–1492
Knutson T, Edlund C, Fall M, Dahlstrand C (2001) BPH with coexisting overactive bladder dysfunction—an everyday urological dilemma. Neurourol Urodyn 20:237–247
Ko DS, Fenster HN, Chambers K, Sullivan LD, Jens M, Goldenberg SL (1995) The correlation of multichannel urodynamic pressure-flow studies and American Urological Association symptom index in the evaluation of benign prostatic hyperplasia. J Urol 154:396–398
Kortmann BB, Floratos DL, Kiemeney LA, Wijkstra H, de la Rosette JJ (2003) Urodynamic effects of alpha-adrenoceptor blockers: a review of clinical trials. Urology 62:1–9
Lee JZ, Tillig B, Perkash I, Constantinou CE (1998) Effect of alpha1 adrenoceptor antagonist on the urodynamics of the upper and lower urinary tract of the male rat. Neurourol Urodyn 17:213–229
Lee JY, Kim HW, Lee SJ, Koh JS, Suh HJ, Chancellor MB (2004) Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder. BJU Int 94:817–820
Lee KS, Choo MS, Kim DY, Kim JC, Kim HJ, Min KS, Lee JB, Jeong HJ, Lee T, Park WH (2005) Combination treatment with propiverine hydrochloride plus doxazosin controlled release gastrointestinal therapeutic system formulation for overactive bladder and coexisting benign prostatic obstruction: a prospective, randomized, controlled multicenter study. J Urol 174:1334–1338
MacDiarmid S, Rogers A (2007) Male overactive bladder: the role of urodynamics and anticholinergics. Curr Urol Rep 8:66–73
MacDiarmid S, Chen A, Tu N, Peters KM (2006) Effects of tamsulosin and extended-release oxybutynin on lower urinary tract symptoms in men [abstract 1638]. Program and abstracts of the American Urological Association 2006 Annual Meeting. May 20–25, 2006; Atlanta, GA
Machino R, Kakizaki H, Ameda K, Shibata T, Tanaka H, Matsuura S, Koyanagi T (2002) Detrusor instability with equivocal obstruction: A predictor of unfavorable symptomatic outcomes after transurethral prostatectomy. Neurourol Urodyn 21:444–449
Malloy BJ, Price DT, Price RR, Bienstock AM, Dole MK, Funk BL, Rudner XL, Richardson CD, Donatucci CF, Schwinn DA (1998) Alpha1-adrenergic receptor subtypes in human detrusor. J Urol 160:937–943
Marshall I, Burt RP, Chapple CR (1995) Noradrenaline contractions of human prostate mediated by alpha 1A-(alpha 1c-) adrenoceptor subtype. Br J Pharmacol 115:781–786
Meigs JB, Barry MJ, Giovannucci E, Rimm EB, Stampfer MJ, Kawachi I (1999) Incidence rates and risk factors for acute urinary retention: The health professionals followup study. J Urol 162:376–382
Michel MC, Vrydag W (2006) Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br J Pharmacol 147(Suppl 2):S88–S119
Michelotti GA, Price DT, Schwinn DA (2000) Alpha 1-adrenergic receptor regulation: basic science and clinical implications. Pharmacol Ther 83:281–309
Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff J, Wein AJ (2001) How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 87:760–766
Moorthy P, Lapitan MC, Quek PL, Lim PH (2004) Prevalence of overactive bladder in Asian men: an epidemiological survey. BJU Int 93:528–531
Noble AJ, Chess-Williams R, Couldwell C, Furukawa K, Uchyiuma T, Korstanje C, Chapple CR (1997) The effects of tamsulosin, a high affinity antagonist at functional alpha 1A- and alpha 1D-adrenoceptor subtypes. Br J Pharmacol 120:231–238
Nomiya M, Yamaguchi O (2003) A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders. J Urol 170:649–653
Perlberg S, Caine M (1982) Adrenergic response of bladder muscle in prostatic obstruction. Its relation to detrusor instability. Urology 20:524–527
Peters TJ, Donovan JL, Kay HE, Abrams P, de la Rosette JJ, Porru D, Thuroff JW (1997) The International Continence Society “Benign Prostatic Hyperplasia” Study: the bothersomeness of urinary symptoms. J Urol 157:885–889
Pontari MA, Braverman AS, Luthin GR, Ruggieri MR Sr (2004) The M2 muscarinic receptor mediates in vitro bladder contractions from patients with neurogenic bladder dysfunction. Am J Physiol Regul Integr Comp Physiol 286:R874–R880
Robertson AS, Griffiths C, Neal DE (1996) Conventional urodynamics and ambulatory monitoring in the definition and management of bladder outflow obstruction. J Urol 155:506–511
Roehrborn CG, Schwinn DA (2004) Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol 171:1029–1035
Rossi C, Kortmann BB, Sonke GS, Floratos DL, Kiemeney LA, Wijkstra H, de la RJ (2001) Alpha-blockade improves symptoms suggestive of bladder outlet obstruction but fails to relieve it. J Urol 165:38–41
Ruggieri MR Sr, Braverman AS, Pontari MA (2005) Combined use of alpha-adrenergic and muscarinic antagonists for the treatment of voiding dysfunction. J Urol 174:1743–1748
Saito H, Yamada T, Oshima H, Morita T, Mizuo T, Takeuchi S, Ando M, Sekine H (1999) A comparative study of the efficacy and safety of tamsulosin hydrochloride alone and combination of propiverine hydrochloride and tamsulosin hydrochloride in the benign prostatic hypertrophy with pollakisuria and/or urinary incontinence. Jpn J Urol Surg 12:525–536
Schwinn DA, Michelotti GA (2000) alpha1-adrenergic receptors in the lower urinary tract and vascular bed: potential role for the alpha1d subtype in filling symptoms and effects of ageing on vascular expression. BJU Int 85:6–11
Sellers DJ, McKay N (2007) Developments in the pharmacotherapy of the overactive bladder. Curr Opin Urol 17:223–230
Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ (2003) Prevalence and burden of overactive bladder in the United States. World J Urol 20:327–336
Swierzewski SJ 3rd, Gormley EA, Belville WD, Sweetser PM, Wan J, McGuire EJ (1994) The effect of terazosin on bladder function in the spinal cord injured patient. J Urol 151:951–954
Temml C, Heidler S, Ponholzer A, Madersbacher S (2005) Prevalence of the overactive bladder syndrome by applying the International Continence Society definition. Eur Urol 48:622–627
Trevisani M, Campi B, Gatti R, Andre E, Materazzi S, Nicoletti P, Gazzieri D, Geppetti P (2007) The influence of alpha(1)-adrenoreceptors on neuropeptide release from primary sensory neurons of the lower urinary tract. Eur Urol 52(3):901–908
Witjes WP, de la Rosette JJ, Donovan JL, Peters TJ, Abrams P, Kay HE, Hofner K, Kinn AC, Walter S (1997) The International Continence Society “Benign Prostatic Hyperplasia” Study: international differences in lower urinary tract symptoms and related bother. J Urol 157:1295–1300
Yokoyama O, Yusup A, Miwa Y, Oyama N, Aoki Y, Akino H (2005) Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats. J Urol 174:2032–2036
Yokoyama O, Yusup A, Oyama N, Aoki Y, Miwa Y, Akino H (2007) Improvement in bladder storage function by tamsulosin depends on suppression of C-fiber urethral afferent activity in rats. J Urol 177:771–775
Yoshida M, Miyamae K, Iwashita H, Otani M, Inadome A (2004) Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urology 63:17–23
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, KS., Lee, H.W. & Han, D.H. Does anticholinergic medication have a role in treating men with overactive bladder and benign prostatic hyperplasia?. Naunyn-Schmied Arch Pharmacol 377, 491–501 (2008). https://doi.org/10.1007/s00210-007-0242-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-007-0242-y