Commentary on Tolterodine for Men With Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms

Commentary on Tolterodine for Men With Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms ow often has the practicing urologist been presented with the following scenario? A middle-aged man presents with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). He is treated with an alpha-blocker and/or a 5␣-reductase inhibitor with some improvement in stream hesitancy and flow (obstructive symptoms) but little change in urgency, frequency and nocturia (irritative symptoms). If this patient were a female, there would be little hesitation to make a diagnosis of overactive bladder and prescribe an anticholinergic. However in males conventional wisdom has held that these drugs are contraindicated for this condition. As recently as 2004 we were warned that “the use of anticholinergic agents as primary therapy for BPH/LUTS or combined with alpha blockers cannot be recommended for routine use in the absence of an adequate published evidence base.”1 Shortly thereafter the preceding article by Kaplan et al was published. Although the number of patients was small (43 men) and followup was short (6 months), these authors were among the first to question the long held belief that treating symptoms of detrusor instability was contraindicated in the presence of obstruction. This study demonstrated a significant decrease in AUA symptom score (⫺6.1) as well as a modest improvement in post-void residual (PVR) and maximum flow rate (Qmax) with no urinary retention. It is tempting to conclude from this study that antimuscarinics improve bladder compliance which results in improved symptoms. However, a recent meta-analysis of anticholinergics in men with BPH revealed no change in Qmax and a slight (11 cc) increase in PVR with no increase in episodes of acute urinary retention.2 Similarly, Abrams et al reported on a 12-week randomized, placebo controlled trial of tolterodine in 221 men with overactive bladder and bladder outlet obstruction, and found improved maximum cystometric capacity and increased bladder volume with little change in voiding pressure or Qmax.3 In another study by

Kaplan et al men with LUTS were treated with a combination of tolterodine and the alpha-blocker tamsulosin compared to monotherapy or placebo.4 Irritative symptoms were significantly improved with combination therapy compared to monotherapy or placebo. Based on the preceding article as well as subsequent studies, what then can we conclude about the use of anticholinergics in men with BPH/LUTS? Men with irritative symptoms, minimal obstructive symptoms and low PVRs can be treated with an anticholinergic alone such as oxybutynin, tolterodine, darifenacin, solifenacin or trospium. Men with a combination of bladder outlet obstruction and overactive bladder can be safely and effectively treated with an anticholinergic and an alpha-blocker such as tamsulosin, alfuzosin, terazocin or doxazocin provided they do not have a significantly increased PVR. For men with an increased PVR, the bladder outlet obstruction should be treated first.

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0022-5347/08/1795-0086/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION

Michael P. O’Leary Department of Surgery, Division of Urology Brigham and Women’s Hospital Boston, Massachusetts 1.

Chapple CR: Pharmacological therapy of benign prostatic hyperplasia/lower urinary tract symptoms: an overview for the practicing clinician. BJU Int 2004; 94: 738. 2. Blake-James BT, Rashidian A, Ipeda Y and Emberton M: The role of anticholinergics in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a systematic review and meta-analysis. BJU Int 2004; 99: 85. 3. Abrams P, Kaplan S, DeKoning Gans HJ and Millard R: Safety and tolerability of tolterodine for the treatment of overactive bladder in men with bladder outlet obstruction. J Urol 2006; 175: 999. 4. Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T and Guan Z: Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA 2006; 296: 2319.

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Vol. 179, S86, May 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.03.012