A Shifted Paradigm for the Further Understanding, Evaluation, and Treatment of Lower Urinary Tract Symptoms in Men: Focus on the Bladder

The Royal Hallamshire Hospital, Sheffield, UK.
European Urology (Impact Factor: 13.94). 05/2006; 49(4):651-8. DOI: 10.1016/j.eururo.2006.02.018
Source: PubMed


Lower urinary tract symptoms (LUTS) are highly prevalent among older men and have a negative impact on health-related quality of life. Frequent comorbidity with potential prostatic disease adds complexity to the management of male LUTS. In this review, we discuss the pathophysiological conditions that underlie male LUTS, and examine the relationship between symptoms and urodynamic findings. The contribution of bladder dysfunction to male LUTS, with a particular emphasis on overactive bladder (OAB) symptoms, is explored. We also consider pharmacotherapeutic options for male LUTS. Pharmacotherapies that target the prostate (alpha1-receptor antagonists and 5alpha-reductase inhibitors) often fail to alleviate OAB symptoms, and may not be the most appropriate therapy for men with storage LUTS. Multiple studies have suggested that antimuscarinic therapy alone or in combination with alpha1-receptor antagonists improve OAB symptoms in men with and without bladder outlet obstruction. Although these agents may represent appropriate first-line therapies for men with OAB symptoms, the therapeutic potential of antimuscarinics alone or in combination with alpha1-receptor antagonists in this population should be evaluated in large-scale, well-designed clinical trials.

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    • "LUTS consist of storage, voiding and post-micturition symptoms, with the storage symptoms being the most frequent among these [3], [4]. For the treatment of storage symptoms anti-muscarinic agents are effective [5], [6]. However, there are issues associated with these drugs including a high burden of economic cost and significant adverse effects including dry mouth and constipation [7], [8], [9]. "
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    ABSTRACT: Lower urinary tract symptoms (LUTS) include storage, voiding and post-micturition symptoms, featuring many urological diseases. Storage symptoms are the most frequent among these and associated with overactive bladder and non-bacterial bladder inflammation such as interstitial cystitis/bladder pain syndrome (IC/BPS). Gap junction, a key regulator of hyperactive conditions in the bladder, has been reported to be involved in pathological bladder inflammation. Here we report involvement of gap junction in the etiology of storage symptoms in bladder inflammation. In this study, cyclophosphamide-induced cystitis was adapted as a model of bladder inflammation. Cyclophosphamide-treated mice showed typical storage symptoms including increased urinary frequency and reduced bladder capacity, with concurrent up-regulation of connexin 43 (GJA1), one of the major gap junction proteins in the bladder. In isometric tension study, bladder smooth muscle strips taken from the treated mice showed more pronounced spontaneous contraction than controls, which was attenuated by carbenoxolone, a gap junction inhibitor. In voiding behavior studies, the storage symptoms in the treated mice characterized by frequent voiding were alleviated by 18α-glycyrrhetinic acid, another gap junction inhibitor. These results demonstrate that cyclophosphamide-induced mouse model of cystitis shows clinical storage symptoms related with bladder inflammation and that gap junction in the bladder may be a key molecule of these storage symptoms. Therefore, gap junction in the bladder might be an alternative therapeutic target for storage symptoms in bladder inflammation.
    PLoS ONE 08/2014; 9(8):e104216. DOI:10.1371/journal.pone.0104216 · 3.23 Impact Factor
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    • "LUTS in men are often treated first with agents that target the prostate or bladder outlet obstruction (BOO; dynamic obstruction), such as 5-alpha reductase inhibitors (5-ARIs) and alpha receptor antagonists [9]. Men with LUTS/OAB are usually treated with BPH drugs rather than those specific for OAB, despite the high prevalence of coexistent storage symptoms in men with LUTS [10]. "
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    ABSTRACT: Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) are highly prevalent in older men. The storage subcategory of LUTS is synonymous with overactive bladder (OAB) syndrome, which is an empirical diagnosis. Traditionally, alpha-blockers are widely prescribed to manage the LUTS of BPH, although storage symptoms may persist in many men despite treatment. Therefore, because therapies that target the prostate often fail to alleviate storage symptoms, they may not be the appropriate therapy for OAB. In past years, most physicians appeared to give more weight in elderly men to voiding symptoms than to storage symptoms and to be more concerned with initial treatment with anticholinergics for males with storage symptoms. Considering the recent increase in data on the efficacy and safety of combination treatment with alpha receptor antagonists and antimuscarinic agents, the standard pharmacologic treatment of patients with LUTS combined with OAB should be an alpha receptor antagonist and an antimuscarinic agent. Beta-3 adrenoreceptor agonists may also potentially be useful for the treatment of male LUTS combined with OAB.
    06/2014; 2(2):43-9. DOI:10.12954/PI.14045
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    • "This association suggests that we should consider other strategies for treating these conditions. The lack of efficacy of α-blockers and 5-α-reductase inhibitors in improving such urinary symptoms contrary to the efficacious effect of anticholinergics is a main rationale for considering the likely affected function of the bladder to control storage symptoms after TURP or prostatectomy [14]. "
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    ABSTRACT: To evaluate the effect of tolterodine on early storage symptoms following transurethral resection of the prostate. Seventy patients over 55 years of age who underwent transurethral resection of the prostate owing to benign prostatic hyperplasia were randomly assigned to receive either 2 mg of tolterodine twice daily (treatment group) or matched placebo during a 1-month study period. Before and 1 month after the procedure, they were asked to complete the International Prostate Symptom Score (IPSS) questionnaire and quality of life subscale to assess their symptoms. Also, analgesic use and adverse drug events were determined at follow-up. Of 70 allocated patients, 64 patients (91.4%), including 33 in the treatment group and 31 in the placebo group, completed the study. The mean age of the patients was 67 years. None of the patients' basic clinical characteristics were significantly different. At the end of the follow-up period, the total IPSS and quality of life score had significantly improved in the patients receiving tolterodine compared with those receiving placebo (p=0.001 and p=0.036, respectively). The treatment group compared with placebo demonstrated significant improvements in frequency and urgency but not in nocturia. The amount of consumed painkiller was also significantly lower in the tolterodine group than in the placebo group (p=0.0001). The rate of side effects was not significantly different between the groups. Administering 2 mg of tolterodine twice daily is an effective and well-tolerated regimen to relieve early storage symptoms, quality of life, and the amount of analgesic consumption following transurethral resection of the prostate.
    Korean journal of urology 04/2014; 55(4):260-4. DOI:10.4111/kju.2014.55.4.260
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