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Papet J, Cornu JN, Dupuis H. Combination Pharmacotherapy for Benign Prostatic Hyperplasia: Evaluation of Existing Literature on Combination Therapies for Lower Urinary Tract Symptoms Associated with BPH. Drugs Aging 2025:10.1007/s40266-025-01198-1. [PMID: 40316889 DOI: 10.1007/s40266-025-01198-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/02/2025] [Indexed: 05/04/2025]
Abstract
OBJECTIVE Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) significantly impact quality of life in aging men. While monotherapies, including alpha-blockers, 5-alpha reductase inhibitors (5-ARI), or phosphodiesterase type 5 inhibitors (PDE5i), are widely used, the potential benefits and risks of combination pharmacotherapies remain less well-documented. This study reviews and assesses the current evidence regarding the use of combination pharmacotherapies in the management of BPH-related LUTS to provide a comprehensive overview of their efficacy and safety profiles. METHODS A literature search was conducted in PubMed, including randomized controlled trials (RCTs) published up to June 2024. Studies were selected on the basis of predefined inclusion criteria, focusing on clinical outcomes such as International Prostate Symptom Score (IPSS), urinary flow rate (Qmax), and quality of life. Data from 22 eligible studies were analyzed and summarized. RESULTS Combination therapies, particularly those involving alpha-blockers and 5-ARI, demonstrated significant reductions in clinical progression, improvements in urinary flow, and symptom relief compared with monotherapies. Therapies combining alpha-blockers with anticholinergics, beta-3 agonists, or phytotherapeutic agents showed potential for targeting mixed symptoms, though evidence remains limited. Triple therapy studies are scarce, with benefits observed only in highly symptomatic or refractory cases. CONCLUSIONS Combination therapies for LUTS/BPH offer superior efficacy over monotherapy in certain cases, particularly with alpha-blockers and 5-ARI, which significantly reduce disease progression and symptoms. Other combinations, including alpha-blockers with anticholinergics, beta-3 agonists, or PDE5 inhibitors, provide potential benefits for patients with mixed symptom profiles, though evidence remains heterogeneous. The level of evidence among studies varies significantly, ranging from high-quality RCTs to lower-level observational data, requiring careful interpretation. While combination treatments improve outcomes, they also present challenges in adherence and side effects. A personalized and evidence-based approach is essential to optimize treatment selection and balance efficacy with tolerability.
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Affiliation(s)
- Joséphine Papet
- Department of Urology, Charles Nicolle University Hospital (CHU de Rouen), 37 Boulevard Gambetta, 76000, Rouen, France
| | - Jean-Nicolas Cornu
- Department of Urology, Charles Nicolle University Hospital (CHU de Rouen), 37 Boulevard Gambetta, 76000, Rouen, France
| | - Hugo Dupuis
- Department of Urology, Charles Nicolle University Hospital (CHU de Rouen), 37 Boulevard Gambetta, 76000, Rouen, France.
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Winograd J, Venishetty N, Codelia-Anjum A, Bhojani N, Elterman D, Zorn KC, Te A, Chughtai B. Emerging drugs for the treatment of benign prostatic hyperplasia: a 2023 update. Expert Opin Emerg Drugs 2024; 29:205-217. [PMID: 38841744 DOI: 10.1080/14728214.2024.2363213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 05/30/2024] [Indexed: 06/07/2024]
Abstract
INTRODUCTION Benign prostatic hyperplasia (BPH) is a condition that affects over 50% of men as they enter their fifth decade of life, often leading to lower urinary tract symptoms (LUTS). Primary treatment options include alpha blockers, 5-alpha reductase inhibitors, and phosphodiesterase-5 inhibitors. However, these medications can have some side effects, and there is a noticeable dearth of information addressing the long-term use of these medications. Thus, the exploration of all treatment modalities helps ensure patients receive personalized and effective care. Consequently, the primary objective of this review is to identify potential emerging medications for the treatment of BPH. AREAS COVERED We conducted an extensive review of articles discussing pharmacotherapy for BPH spanning the last 15 years. Our information gathering process involved Scopus, PubMed-MEDLINE, Cochrane, Wiley Online Library Google Scholar, ClinicalTrials.gov, and the PharmaProjects database. This approach ensures that readers gain an in-depth knowledge of the existing therapeutic agents as well as promising avenues for managing BPH. EXPERT OPINION BPH treatment targets a patient's specific constellation of symptoms. Therefore, a broad knowledge base encompassing various treatment options is paramount in ensuring optimal treatment. Looking forward, the emphasis on personalization promises to reshape the landscape of BPH treatment and improve patient outcomes.
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Affiliation(s)
- Joshua Winograd
- Department of Urology, Weill Cornell Medicine, New York, NY, USA
| | - Nikit Venishetty
- Paul L. Foster School of Medicine, Texas Tech Health Sciences Center, El Paso, TX, USA
| | | | - Naeem Bhojani
- Division of Urology, University of Montreal, Montreal, Québec, Canada
| | - Dean Elterman
- Division of Urology, University of Toronto, Toronto, Ontario, Canada
| | - Kevin C Zorn
- Division of Urology, University of Montreal, Montreal, Québec, Canada
| | - Alexis Te
- Department of Urology, Weill Cornell Medicine, New York, NY, USA
| | - Bilal Chughtai
- Department of Urology, Weill Cornell Medicine, New York, NY, USA
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Herschorn S, Tarcan T, Jiang YH, Chung E, Abdul Hadi F, Steup A, Sumarsono B. Safety and efficacy of an α 1 -blocker plus mirabegron compared with an α 1 -blocker plus antimuscarinic in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and overactive bladder: A systematic review and network meta-analysis. Neurourol Urodyn 2024; 43:604-619. [PMID: 38291827 DOI: 10.1002/nau.25399] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 12/04/2023] [Accepted: 01/08/2024] [Indexed: 02/01/2024]
Abstract
AIM Antimuscarinics and the β3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α1 -adrenoreceptor antagonists (α1 -blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an α1 -blocker plus mirabegron with an α1 -blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations. METHODS Included records had to be from a parallel-group, randomized clinical trial that was ≥8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an α1 -blocker plus OAB agent with an α1 -blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Qmax ). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis. RESULTS Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the α1 -blocker plus mirabegron and α1 -blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the α1 -blocker plus mirabegron group compared with the α1 -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Qmax . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α1 -blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation. CONCLUSION This systematic review and meta-analysis showed that an α1 -blocker plus mirabegron and an α1 -blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting.
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Affiliation(s)
- Sender Herschorn
- Department of Surgery/Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
| | - Tufan Tarcan
- Department of Urology, School of Medicine, Marmara University, Istanbul, Turkey
- Department of Urology, School of Medicine, Koç University, Istanbul, Turkey
| | - Yuan-Hong Jiang
- Department of Urology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan
| | - Eric Chung
- Department of Urology, Princess Alexandra Hospital, The University of Queensland, Brisbane, Queensland, Australia
| | | | - Achim Steup
- Astellas Pharma Global Development Inc., Northbrook, Illinois, USA
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Tahmasbi F, Salehi-Pourmehr H, Naseri A, Ghaderi S, Javadi-Farid F, Hajebrahimi S, Sedigh O, Soleimanzadeh F. Effects of posterior tibial nerve stimulation (PTNS) on lower urinary tract dysfunction: An umbrella review. Neurourol Urodyn 2024; 43:494-515. [PMID: 38153131 DOI: 10.1002/nau.25343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/26/2023] [Accepted: 11/16/2023] [Indexed: 12/29/2023]
Abstract
BACKGROUND Lower urinary tract dysfunction (LUTD) is a common, troublesome condition that often negatively affects patients' quality of life. Current literature has long been interested in how posterior tibial nerve stimulation (PTNS) can affect this condition. AIM To extensively and systematically explore how PTNS affects LUTD based on the most recent systematic reviews. METHODS A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All the systematic reviews, with or without meta-analysis that assessed the effects of PTNS on LUTD were retrieved. The quality of the included studies was assessed using the Joanna Briggs Institute tool, and analysis was conducted using the Comprehensive Meta-Analysis version 3 tool. RESULTS From a total of 3077 citations, 20 systematic reviews entered this study, and 13 of them included meta-analysis. The population of studies varied vastly, for instance, some studies included only children or women while other focused on a specific pathology like multiple sclerosis-induced neurogenic LUTD. The majority of included studies reported an overall improvement in LUTD following percutaneous PTNS, although admitting that these results were derived from moderate to low-quality evidence. CONCLUSION The findings of this thorough umbrella review showed that the positive benefits of PTNS in treating LUTD are currently supported by low-quality evidence, and it is crucial to interpret them with great care.
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Affiliation(s)
- Fateme Tahmasbi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A JBI Centre of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hanieh Salehi-Pourmehr
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A JBI Centre of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amirreza Naseri
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A JBI Centre of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Fatemeh Javadi-Farid
- Department of Urology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sakineh Hajebrahimi
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A JBI Centre of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Omid Sedigh
- Department of Urology and Reconstructive Andrology, Humanitas Gradenigo Hospital, Torino, Italy
| | - Farzin Soleimanzadeh
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A JBI Centre of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
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Gravas S, Gacci M, Gratzke C, Herrmann TRW, Karavitakis M, Kyriazis I, Malde S, Mamoulakis C, Rieken M, Sakalis VI, Schouten N, Speakman MJ, Tikkinen KAO, Cornu JN. Summary Paper on the 2023 European Association of Urology Guidelines on the Management of Non-neurogenic Male Lower Urinary Tract Symptoms. Eur Urol 2023; 84:207-222. [PMID: 37202311 DOI: 10.1016/j.eururo.2023.04.008] [Citation(s) in RCA: 84] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 04/06/2023] [Indexed: 05/20/2023]
Abstract
CONTEXT Lower urinary tract symptoms (LUTS) are common, often bothersome, and have multifactorial aetiology. OBJECTIVE To present a summary of the 2023 version of the European Association of Urology guidelines on the management of male LUTS. EVIDENCE ACQUISITION A structured literature search from 1966 to 2021 selected the articles with the highest certainty evidence. The Delphi technique consensus approach was used to develop the recommendations. EVIDENCE SYNTHESIS The assessment of men with LUTS should be practical. A careful medical history and physical examination are essential. Validated symptom scores, urine test, uroflowmetry, and postvoid urine residual, as well as frequency-volume charts for patients with nocturia or predominately storage symptoms should be used. Prostate-specific antigen should be ordered if a diagnosis of prostate cancer changes the treatment plan. Urodynamics should be performed for selected patients. Men with mild symptoms are candidates for watchful waiting. Behavioural modification should be offered to men with LUTS prior to, or concurrent with, treatment. The choice of medical treatment depends on the assessment findings, predominant type of symptoms, ability of the treatment to change the findings, and the expectations to be met in terms of the speed of onset, efficacy, side effects, and disease progression. Surgery is reserved for men with absolute indications, and for patients who fail or prefer not to receive medical therapy. Surgical management has been divided into five sections: resection, enucleation, vaporisation, and alternative ablative and nonablative techniques. The choice of surgical technique depends on patient's characteristics, expectations, and preferences; surgeon's expertise; and availability of modalities. CONCLUSIONS The guidelines provide an evidence-based approach for the management of male LUTS. PATIENT SUMMARY A clinical assessment should identify the cause(s) of symptoms and define the clinical profile and patient's expectations. The treatment should aim to ameliorate symptoms and reduce the risk of complications.
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Affiliation(s)
- Stavros Gravas
- Department of Urology, Medical School, University of Cyprus, Nicosia, Cyprus
| | - Mauro Gacci
- Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Christian Gratzke
- Department of Urology, University Hospital Freiburg, Freiburg, Germany
| | | | - Markos Karavitakis
- Department of Urology, University General Hospital of Heraklion, University of Crete Medical School, Heraklion, Crete, Greece
| | - Iason Kyriazis
- Department of Urology, General University Hospital of Patras, Patras, Greece
| | - Sachin Malde
- Department of Urology, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Charalampos Mamoulakis
- Department of Urology, University General Hospital of Heraklion, University of Crete Medical School, Heraklion, Crete, Greece
| | | | - Vasileios I Sakalis
- Department of Urology, Hippokrateion General Hospital, Thessaloniki, Greece.
| | - Natasha Schouten
- European Association of Urology Guidelines Office, Arnhem, The Netherlands
| | - Mark J Speakman
- Department of Urology, Taunton & Somerset Hospital, Taunton, UK
| | - Kari A O Tikkinen
- Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Surgery, South Karelia Central Hospital, Lappeenranta, Finland
| | - Jean-Nicolas Cornu
- Department of Urology, CHU Hôpitaux de Rouen - Hôpital Charles Nicolle, Rouen, France
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Fan Z, Shi H, Zhang J, Wang H, Wang J. Comparative Efficacy of Different Drugs for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Bayesian Network Meta-Analysis. Front Pharmacol 2022; 13:763184. [PMID: 35330833 PMCID: PMC8940212 DOI: 10.3389/fphar.2022.763184] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 02/17/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are common in middle-aged and elderly men. The current drugs for treating this disease include α1-adrenoceptor antagonists (ABs), muscarinic receptor antagonists (MRAs), phosphodiesterase five inhibitors (PDE5-Is), and β3-adrenoceptor agonists (B3As). However, direct comparative studies analyzing different therapies are limited; therefore, we conducted a network meta-analysis (NMA) to evaluate the efficacy of different drug regimens for treating BPH/LUTS. Methods: The PubMed, EMbase, Web of Science, and Cochrane Library databases were searched to collect randomized controlled trials (RCTs) of different drug treatments for BPH/LUTS from January 2000 to April 2021. The NMA was performed using R 4.1 software. Results: Fifty-five RCTs were included among a total of 1639 trials. ① ABs + PDE5-Is, ABs + B3As, ABs + MRAs, ABs, and PDE5-IS were superior to the placebo in improving the total International Prostate Symptom Score (IPSS), IPSS-Voiding, and IPSS-storage. ② For increasing the maximum flow rate (Qmax), ABs + PDE5-Is, ABs + MRAs, and ABs were more effective than the placebo. ③ Regarding reducing post-void residual urine (PVR), none of the six treatment plans had significant effects. Conclusion: Combination therapy showed greater efficacy than monotherapy, and ABs + PDE5-Is was the most successful treatment for improving the overall IPSS score. ABs are a primary therapeutic measure to increase Qmax, and ABs + PDE5-I may be a more suitable choice for enhancing Qmax. The combination of MRA and AB+ MRA may lead to an increase in PVR. Systematic Review Registration: [website], identifier [registration number].
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Affiliation(s)
- Zhinan Fan
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Hongjin Shi
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jinsong Zhang
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Haifeng Wang
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jiansong Wang
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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Singh I, Behera DP, T K A, Gupta S. Efficacy and safety of tamsulosin vs its combination with mirabegron in the management of lower urinary tract non-neurogenic overactive bladder symptoms (OABS) because of Benign Prostatic Enlargement (BPE)-An open label randomised controlled clinical study. Int J Clin Pract 2021; 75:e14184. [PMID: 33780106 DOI: 10.1111/ijcp.14184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 03/22/2021] [Accepted: 03/25/2021] [Indexed: 11/30/2022] Open
Abstract
PURPOSE The efficacy and safety of βeta-3 agonists (Mirabegron 50 mg) have been sparingly assessed in the published English literature. We aim to do an efficacy-safety analysis of Mirabegron-Tamsulosin combination therapy vs tamsulosin-placebo monotherapy in a select subset of medication virgin Benign Prostatic Enlargement (BPE) patients with coexisting predominant non-neurogenic overactive bladder symptoms (OABS). METHODS After prior written informed consent and IEC, 80 patients of uncomplicated BPE with coexisting non-neurogenic OABS and IPSS of >7 without contraindications to drug therapy were computer randomised/allocated to receive either[50 mg Mirabegron plus Tamsulosin 0.4 mg (Intervention arm-I)]or [Tamsulosin 0.4 mg plus capsule lactobacillus (Comparator arm-II)] once daily for 8 weeks. Efficacy was evaluated using the OABS Score (OABSS), mean change in nocturnal frequency (NF), PVR and IPSS, while safety was assessed by recording treatment emergent adverse events (TEAE). Follow-up visits were performed at second, fourth and eighth week. RESULTS Patient data in both groups were generally comparable with the exception of NF and IPSS storage sub score (IPSS-ss). Significant improvements were visualised in the eighth week primary endpoint total OABS sub score (OABSS-ss) in the combination group (P < .001).Similar significant improvements were seen with most secondary parameters such as the mean change in NF, IPSS, IPSS-ss, OABS-ss, voided volume, Qmax, and Quality of life index (QOL) (P < .001). No significant increase in PVR was observed in the Mirabegron arm and no patient developed urinary retention. The TEAE were minor, self-limiting and managed symptomatically without drug discontinuity. CONCLUSION Mirabegron can be significantly efficacious and safe in ameliorating non-neurogenic OABS induced by BPE vs placebo by initiating combination therapy from the start as opposed to the usual 'add on therapy' protocol. This combination appeared to be superior in terms of overall safety, minimal side effects, better compliance and tolerability vs Tamsulosin monotherapy in select BPE patients with predominant non-neurogenic OABS.
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Affiliation(s)
- Iqbal Singh
- Department of Surgery (Urology), University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi, India
| | - Dibya P Behera
- Department of Surgery, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi, India
| | - Aravind T K
- Department of Surgery, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi, India
| | - Sanjay Gupta
- Department of Surgery, University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi, India
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Pang R, Zhou XY, Wang X, Wang B, Yin XL, Bo H, Jung JH. Anticholinergics combined with alpha-blockers for treating lower urinary tract symptoms related to benign prostatic obstruction. Cochrane Database Syst Rev 2021; 2:CD012336. [PMID: 33567116 PMCID: PMC8094929 DOI: 10.1002/14651858.cd012336.pub2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in men. Alpha-blockers are widely used as first-line therapy for men with LUTS secondary to BPO, but up to one third of men report no improvement in their LUTS after taking alpha-blockers. Anticholinergics used in addition to alpha-blockers may help improve symptoms but it is uncertain how effective they are. OBJECTIVES: To assess the effects of combination therapy with anticholinergics and alpha-blockers in men with LUTS related to BPO. SEARCH METHODS We performed a comprehensive search of medical literature, including the Cochrane Library, MEDLINE, Embase, and trials registries, with no restrictions on the language of publication or publication status. The date of the latest search was 7 August 2020. SELECTION CRITERIA We included randomized controlled trials. Inclusion criteria were men with LUTS secondary to BPO, ages 40 years or older, and a total International Prostate Symptom Score of 8 or greater. We excluded trials of men with a known neurogenic bladder due to spinal cord injury, multiple sclerosis, or central nervous system disease, and those examining medical therapy for men who were treated with surgery for BPO. We performed three comparisons: combination therapy versus placebo, combination therapy versus alpha-blockers monotherapy, and combination therapy versus anticholinergics monotherapy. DATA COLLECTION AND ANALYSIS Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model and interpreted data according to the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE approach to rate the certainty of evidence. MAIN RESULTS We included 23 studies with 6285 randomized men across three comparisons. The mean age of participants ranged from 54.4 years to 73.9 years (overall mean age 65.7 years). Of the included studies, 12 were conducted with a single-center setting, while 11 used a multi-center setting. We only found short-term effect (12 weeks to 12 months) of combination therapy based on available evidence. Combination therapy versus placebo: based on five studies with 2369 randomized participants, combination therapy may result in little or no difference in urologic symptom scores (mean difference (MD) -2.73, 95% confidence interval (CI) -5.55 to 0.08; low-certainty evidence). We are very uncertain about the effect of combination therapy on quality of life (QoL) (MD -0.97, 95% CI -2.11 to 0.16; very low-certainty evidence). Combination therapy likely increases adverse events (risk ratio (RR) 1.24, 95% CI 1.04 to 1.47; moderate-certainty evidence); based on 252 adverse events per 1000 participants in the placebo group, this corresponds to 61 more adverse events (95% CI 10 more to 119 more) per 1000 participants treated with combination therapy. Combination therapy versus alpha-blockers alone: based on 22 studies with 4904 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -2.04, 95% CI -3.56 to -0.52; very low-certainty evidence) and QoL (MD -0.71, 95% CI -1.03 to -0.38; very low-certainty evidence). Combination therapy may result in little or no difference in adverse events rate (RR 1.10, 95% CI 0.90 to 1.34; low-certainty evidence); based on 228 adverse events per 1000 participants in the alpha-blocker group, this corresponds to 23 more adverse events (95% CI 23 fewer to 78 more) per 1000 participants treated with combination therapy. Combination therapy compared to anticholinergics alone: based on three studies with 1218 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -3.71, 95% CI -9.41 to 1.98; very low-certainty evidence). Combination therapy may result in an improvement in QoL (MD -1.49, 95% CI -1.88 to -1.11; low-certainty evidence). Combination therapy likely results in little to no difference in adverse events (RR 1.26, 95% CI 0.81 to 1.95; moderate-certainty evidence); based on 115 adverse events per 1000 participants in the anticholinergic alone group, this corresponds to 4 fewer adverse events (95% CI 7 fewer to 13 more) per 1000 participants treated with combination therapy. AUTHORS' CONCLUSIONS Based on the findings of the review, combination therapy with anticholinergics and alpha-blockers are associated with little or uncertain effects on urologic symptom scores compared to placebo, alpha-blockers, or anticholinergics monotherapy. However, combination therapy may result in an improvement in quality of life compared to anticholinergics monotherapy, but an uncertain effect compared to placebo, or alpha-blockers. Combination therapy likely increases adverse events compared to placebo, but not compared to alpha-blockers or anticholinergics monotherapy. The findings of this review were limited by study limitations, inconsistency, and imprecision. We were unable to conduct any of the predefined subgroup analyses.
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Affiliation(s)
- Ran Pang
- Department of Urology, Guang An Men Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xin-Yao Zhou
- Internal Medicine & Outpatients Management Office, Guang An Men Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiangling Wang
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
| | - Bin Wang
- China Academy of Chinese Medical Sciences, Beijing, China
| | - Xue-Lai Yin
- Department of Urology, Guang An Men Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hai Bo
- Department of Urology, Guang An Men Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jae Hung Jung
- Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea, South
- Center of Evidence Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, Korea, South
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Johnson TM, Goode PS, Hammontree L, Markland AD, Vaughan CP, Ouslander JG, Falk K, McGwin G, Burgio KL. An Exploratory Analysis of Tamsulosin for Overactive Bladder (OAB) in Men With Varying Voiding Symptom Burden. Urology 2021; 153:42-48. [PMID: 33482134 DOI: 10.1016/j.urology.2021.01.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 12/17/2020] [Accepted: 01/11/2021] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To evaluate tamsulosin (α-blocker therapy) for male overactive bladder (OAB) and to examine if indicators of concomitant benign prostatic hyperplasia are associated with OAB symptom improvement. MATERIALS AND METHODS This was a planned, exploratory analysis of a 4-week, α-blocker (tamsulosin 0.4 mg) run-in phase of the Male Overactive Bladder Trial in Veterans (MOTIVE). Participants with urinary urgency and urinary frequency (> 8 voids/24 hours) completed bladder diaries, answered symptom questionnaires (AUA-7 SI), and had post-void residual and noninvasive uroflowmetry measurement. RESULTS A total of 116 male Veterans aged 42-88 years with OAB participated. There were statistically significant reductions in voiding frequency (11.3 > 10.0 voids/24 hours, P < .0001), urgency scores (mean 2.5-2.2 points, P < .0001), and nightly nocturia (2.1 > 1.8, P < .001). Only baseline AUA-7 SI total and voiding subscale categories (mild, moderate, severe) were associated with significant reduction in AUA-7 SI total score. For continuous variables, only AUA-7 SI baseline total score was associated with AUA-7 SI storage symptom changes. No other baseline measures were associated with changes in urgency, frequency, or nocturia. CONCLUSION Initiation of short course tamsulosin therapy in men was associated with statistical reduction in OAB symptoms. Baseline post-void residual, uroflow rate, and the voiding symptom subscore of the AUA-7 SI were not predictive of OAB symptom improvement with tamsulosin. These findings merits further exploration.
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Affiliation(s)
- Theodore M Johnson
- Birmingham/Atlanta Department of Veterans Affairs Geriatric Research, Education, and Clinical Center (GRECC), Birmingham, AL, and Decatur, GA; Emory University, Atlanta, GA.
| | - Patricia S Goode
- Birmingham/Atlanta Department of Veterans Affairs Geriatric Research, Education, and Clinical Center (GRECC), Birmingham, AL, and Decatur, GA; University of Alabama at Birmingham, Birmingham, AL
| | | | - Alayne D Markland
- Birmingham/Atlanta Department of Veterans Affairs Geriatric Research, Education, and Clinical Center (GRECC), Birmingham, AL, and Decatur, GA; University of Alabama at Birmingham, Birmingham, AL
| | - Camille P Vaughan
- Birmingham/Atlanta Department of Veterans Affairs Geriatric Research, Education, and Clinical Center (GRECC), Birmingham, AL, and Decatur, GA; Emory University, Atlanta, GA
| | - Joseph G Ouslander
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Miami, FL
| | | | - Gerald McGwin
- Birmingham/Atlanta Department of Veterans Affairs Geriatric Research, Education, and Clinical Center (GRECC), Birmingham, AL, and Decatur, GA; University of Alabama at Birmingham, Birmingham, AL
| | - Kathryn L Burgio
- Birmingham/Atlanta Department of Veterans Affairs Geriatric Research, Education, and Clinical Center (GRECC), Birmingham, AL, and Decatur, GA; University of Alabama at Birmingham, Birmingham, AL
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Phé V, Gamé X. [Male non-neurogenic overactive bladder]. Prog Urol 2020; 30:880-886. [PMID: 33220816 DOI: 10.1016/j.purol.2020.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 08/10/2020] [Accepted: 09/04/2020] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Male lower urinary tract symptoms (LUTS) and in particular overactive bladder (OAB) are a frequent reason for consultation in urology and have a significant functional impact in patients. OBJECTIVE To synthesize current knowledge on non-neurogenic OAB in male patients. METHOD A systematic literature review based on Pubmed, Embase, Google Scholar was conducted in June 2020. RESULTS The prevalence of OAB and benign prostatic hyperplasia increases with age. Symptoms of OAB, on the one hand, and symptoms of prostatic bladder outlet obstruction, on the other hand, can be concomitant and the causal link between the two types of symptoms is difficult to establish. In case of mixed symptoms, it is recommended to treat the most troublesome type of symptoms first and to inform the patient of the risks of failure or deterioration. Indeed, many patients remain symptomatic after prostate surgery and the predictive factors for failure remain to be defined. Thus, preoperative urodynamics is not routinely performed even in case of OAB. De novo detrusor overactivity after radical prostatectomy can reach 77% and persists in the majority of cases. The overall relative risk of storage symptoms after radiotherapy and brachytherapy is higher than that after prostatectomy. The etiology of OAB after prostate surgery is multifactorial. While drug treatments have proven to be effective, little data exists on second-line treatments for OAB after prostate surgery. CONCLUSION OAB in men is often linked to a prostatic bladder outlet obstruction. It is essential to inform patients about the possibility of persistence, deterioration, or occurrence of OAB after prostate surgery while the predictors of surgical failure are not clearly defined.
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Affiliation(s)
- V Phé
- Sorbonne université, hôpital Pitié-Salpêtrière, service d'urologie, assistance publique-hôpitaux de Paris, Paris, France.
| | - X Gamé
- Département d'urologie, transplantation rénale et andrologie, CHU Rangueil, université Paul-Sabatier, Toulouse, France
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11
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Shin DG, Kim HW, Yoon SJ, Song SH, Kim YH, Lee YG, Joo KJ, Bae JH, Kang TW, Jeong SJ, Woo SH, Yoo ES, Son H, Koo KC, Kim SW. Mirabegron as a treatment for overactive bladder symptoms in men (MIRACLE study): Efficacy and safety results from a multicenter, randomized, double-blind, placebo-controlled, parallel comparison phase IV study. Neurourol Urodyn 2018; 38:295-304. [PMID: 30311691 DOI: 10.1002/nau.23852] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 09/12/2018] [Indexed: 11/06/2022]
Abstract
AIMS To evaluate the efficacy and safety of mirabegron in males with overactive bladder (OAB) symptoms. METHODS In total, 464 males with OAB symptoms were enrolled from 14 institutes and were sorted into either the mirabegron 50 mg (n = 310) or placebo (n = 154) groups. The change in (i) the mean number of 24-h micturition episodes; (ii) OAB Symptom Scale (OABSS); and (iii) International Prostate Symptom Score (IPSS) from baseline to 12 weeks of treatment were compared between the two groups. Safety assessments included treatment-emergent adverse events, blood pressure, pulse rate, postvoid residual volume, and maximum urinary flow rate. After 12 weeks, the study was extended for 14 additional weeks by administering mirabegron 50 mg to both groups. RESULTS The reduction in the mean number of 24-h micturition episodes from baseline to 12 weeks of treatment was similar between the two groups. However, significantly greater changes from baseline to 12 weeks were observed in total OABSS, OABSS urgency incontinence score (Q4), IPSS storage subscore (Q2 + Q4 + Q7), and IPSS urgency score (Q4) in the mirabegron group (P = 0.01 for all). According to the extended study, the changes of all efficacy variables from baseline to 26 weeks were similar between both groups. The safety assessment results were also similar between the two groups at 12 and 26 weeks. CONCLUSION A daily 50 mg dose of mirabegron for 12 weeks reduced OAB symptoms in men, and no significant adverse events compared to the placebo group were noted.
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Affiliation(s)
| | | | - Sang Jin Yoon
- Gacheon University Gil Medical Center, Incheon, Korea
| | | | - Young Ho Kim
- Soon Chun Hyang University Bucheon Hospital, Bucheon, Korea
| | - Young Goo Lee
- Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
| | | | | | - Taek Won Kang
- Chonnam National University Hospital, Gwangju, Korea
| | | | | | - Eun Sang Yoo
- Kyungpook National University Hospital, Daegu, Korea
| | - Hwancheol Son
- Seoul National University Boramae Medical Center, Seoul, Korea
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12
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Antimuscarinic Use in Men Treated With Bladder Outlet Obstruction Medication Therapy. Urology 2018; 122:76-82. [PMID: 30205105 DOI: 10.1016/j.urology.2018.08.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 08/01/2018] [Accepted: 08/28/2018] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To assess changes over time in the use of antimuscarinics (AM) among visits in adult men treated with bladder outlet obstruction (BOO) medication therapy (ie, alpha blocker and 5-alpha reductase inhibitors). METHODS We used the National Ambulatory Medicare Care Survey database (2006-2014) to identify men aged 40 or older, who initiated or continued on BOO medication therapy. Among these visits, we assessed the percentage of AM and evaluated trends of AM use across between 2006 and 2014 using multivariable logistic regression. RESULTS Overall, there were 7561 patient visits in men aged 40 or older, who were treated with BOO medication therapy between 2006 and 2014 which equates to approximately 158 million visits in the United States after incorporating National Ambulatory Medicare Care Survey weights. Overall, AM was used in 3.7% of visits, among those who were treated with BOO medication therapy; use of AM increased with age. In the multivariable analysis, there was no increasing trend in the use of AM in 2006 relative to subsequent years through 2014 (P = .8104). CONCLUSION Despite a previous study that showed an increasing trend in antimuscarinic use among patients coded for lower urinary tract symptoms or benign prostatic hyperplasia between 1993 and 2010, several recent randomized-controlled trials, and a recommendation in a clinical practice guideline in 2010, we found no increasing trend in antimuscarinic use among visits in men who were treated with BOO medication therapy in 2006 compared to subsequent years. This suggests the potential undertreatment of antimuscarinics and an area for improved prescribing.
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Combination treatment for male lower urinary tract symptoms with anticholinergic and alpha-blockers. Curr Opin Urol 2018; 28:277-283. [PMID: 29432226 DOI: 10.1097/mou.0000000000000489] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Although alpha-adrenergic antagonists (α-blockers) are effective for relieving voiding lower urinary tract symptoms (LUTS) in men, storage symptoms often persist. The aim of this manuscript is to evaluate the efficacy and safety of combination therapy with α-blockers and muscarinic receptor antagonists (anticholinergics). RECENT FINDINGS High-quality evidence confirms that the addition of an anticholinergic improves micturition diary parameters, such as daytime and nocturnal frequency and urgency incontinence episodes, as well as total and storage subset scores on the International Prostate Symptom Score. Most studies demonstrate a statistically significant improvement over α-blocker monotherapy. Both, incidence of urinary retention and study withdrawal because of treatment-related adverse events with combination therapy, are low. Urodynamic indices, such as maximum flow rate and postvoid residual volume, are also minimally impacted by combination therapy. Outcomes on validated questionnaires and quality-of-life (QoL) indices also indicate a significant improvement. SUMMARY The addition of an anticholinergic to an α-blocker in men with storage and voiding LUTS is an effective practice in reducing both categories of symptoms. The addition of anticholinergic is associated with a low rate of urinary retention and the impact on efficient bladder emptying is minimal. Not unexpectedly, QoL is improved.
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14
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Ng KK, Ng FC. The use of antimuscarinics, phosphodiesterase type V inhibitors and phytotherapy for lower urinary tract symptoms in men. Asian J Urol 2017; 4:191-194. [PMID: 29264230 PMCID: PMC5717977 DOI: 10.1016/j.ajur.2017.05.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 03/10/2017] [Accepted: 03/13/2017] [Indexed: 11/25/2022] Open
Abstract
Besides the mainstay of α-blockers and 5α-reductase inhibitors, other forms of medical therapy complete the armamentarium in the treatment of lower urinary tract symptoms (LUTS) in men. These treatments can target specific symptoms as well as associated symptoms that would affect the quality of life of the patients. Many patients are bothered by storage symptoms, more so than the voiding symptoms. Antimuscarinics are efficacious and safe, provided the patients do not have high post void residual urine. Many patients with LUTS also have erectile dysfunction, and phosphodiesterase type V inhibitors are effective in relieving both LUTS as well as erectile dysfunction for such patients. Phytotherapy provides a popular and safe treatment for LUTS, however, the efficacy of the treatment has not been proven in well conducted prospective randomized controlled studies.
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Affiliation(s)
- Kok Kit Ng
- Department of Urology, Changi General Hospital, Singapore
| | - Foo Cheong Ng
- Department of Urology, Changi General Hospital, Singapore
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15
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Cho S, Kwon SS, Lee KW, Yoo TK, Shin DG, Kim SW, Bae JH, Choi H, Kim YH. A multicenter real-life study of the efficacy of an alpha-blocker with or without anticholinergic agent (imidafenacin) treatment in patients with lower urinary tract symptoms/benign prostatic hyperplasia and storage symptoms. Int J Clin Pract 2017; 71. [PMID: 28508455 DOI: 10.1111/ijcp.12938] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Accepted: 02/14/2017] [Indexed: 01/16/2023] Open
Abstract
AIMS To evaluate the efficacy and safety of combination therapy comprising a short-acting anticholinergic, imidafenacin and an alpha-blocker compared with monotherapy with an alpha-blocker only in men with lower urinary tract symptoms (LUTS) and storage symptoms. METHODS The 12-week, prospective, double-blind, randomised trial enrolled men with LUTS and storage symptom. The inclusion criteria were a total International Prostate Symptom Score (IPSS) ≥12, an IPSS question 4 score ≥2, ≥8 micturitions in 24 hours, and a prostate volume >20 mL. The primary outcome was a change in the micturition number from baseline. Bladder diary variables, Patient Perception of Intensity of Urgency Scale (PPIUS) scores, IPSS and safety were assessed. RESULTS Of 260 patients screened, 221 completed the study. Patients were randomly assigned to receive an alpha-blocker only (n=111, group 1) or combination therapy comprising an alpha-blocker and an anticholinergic (n=110, group 2) for 12 weeks. Group 1 and 2 showed significant improvement in their 24-hour micturition numbers (-1.87 and -2.08, respectively), nocturia episodes (-0.48 and -0.53, respectively), total IPSS (-9.9 and -8.8, respectively), and PPIUS scores (-0.19 and -0.24, respectively). Micturition number per 24 hours, daytime frequency, urgency, the PPIUS score, the IPSS question 4 score and IPSS QoL score improved significantly in the combination therapy group, but changes in total IPSS, nocturia episodes, and safety outcomes did not differ significantly between the groups. CONCLUSIONS AND CLINICAL IMPLICATIONS Compared with treatment with an alpha-blocker alone, combination therapy comprising an anticholinergic and an alpha-blocker showed superior efficacy and its safety was similar in patients with LUTS and storage symptoms.
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Affiliation(s)
- Seok Cho
- The Department of Urology, Ilsanpaik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Soon-Sun Kwon
- The Department of Mathematics, College of Natural Sciences, Ajou University, Suwon, Korea
| | - Kwang Woo Lee
- The Department of Urology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Tag Keun Yoo
- The Department of Urology, Ulji University Nowon Hospital, Ulji University College of Medicine, Daejeon, Korea
| | - Dong Gil Shin
- The Department of Urology, Busan University Hospital, Busan University College of Medicine, Busan, Korea
| | - Soo Woong Kim
- The Department of Urology, Seoul University Hospital, Seoul University College of Medicine, Seoul, Korea
| | - Jae Hyun Bae
- The Department of Urology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Hoon Choi
- The Department of Urology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Young Ho Kim
- The Department of Urology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
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Abstract
The etiology of men's lower urinary tract storage and voiding symptoms involves a contribution from both detrusor and outlet. As such, treatment of benign prostatic enlargement (BPE) ± benign prostatic obstruction (BPO) with standard alpha-adrenergic blockade and 5-alpha reductase inhibitor therapy may leave a population of men with persistent and bothersome urinary storage symptoms. An abundance of adequately powered, randomized, placebo-controlled trials indicate that the use of antimuscarinics and beta-3 adrenergic agonists, either alone or in combination with standard BPE/BPO therapy, leads to improvement in storage symptoms. At the same time, metrics associated with urinary emptying, such as maximum flow rate, post-void residual urinary volume, and incidence of treatment-associated urinary retention, appear to be stable and not significantly impacted by the addition of antimuscarinics.
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Affiliation(s)
- Matthew C Moss
- Department of Urology, Louisiana State University Health - Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA
| | - Tameem Rezan
- Department of Urology, Louisiana State University Health - Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA
| | - Umar R Karaman
- Department of Urology, Louisiana State University Health - Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA
| | - Alex Gomelsky
- Department of Urology, Louisiana State University Health - Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA.
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[S2e guideline of the German urologists: Conservative and pharmacologic treatment of benign prostatic hyperplasia]. Urologe A 2016; 55:184-94. [PMID: 26518303 DOI: 10.1007/s00120-015-3984-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
This report summarizes the relevant aspects of the S2e guideline of the German Urologists for the conservative and pharmacological treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Recommendations are given regarding watchful waiting, behavioral therapy, phytotherapy and pharmacological mono- and combination therapy. The influence of the different therapeutic options on bladder outlet obstruction (BOO) is described in detail.
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18
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Dahm P, Brasure M, MacDonald R, Olson CM, Nelson VA, Fink HA, Rwabasonga B, Risk MC, Wilt TJ. Comparative Effectiveness of Newer Medications for Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: A Systematic Review and Meta-analysis. Eur Urol 2016; 71:570-581. [PMID: 27717522 DOI: 10.1016/j.eururo.2016.09.032] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 09/16/2016] [Indexed: 12/14/2022]
Abstract
CONTEXT Alpha-blockers (ABs) and 5-alpha reductase inhibitors have an established role in treating male lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH). Recently, newer drugs have shown promise for this indication. OBJECTIVE To assess the comparative effectiveness and adverse effects (AEs) of newer drugs to treat LUTS attributed to BPH through a systematic review and meta-analysis. EVIDENCE ACQUISITION Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and Ovid Embase bibliographic databases (through June 2016) were hand searches for references of relevant studies. Eligible studies included randomized controlled trials published in English of newer ABs, antimuscarinics, a beta-3 adrenoceptor agonist, phosphodiesterase type-5 inhibitors, or combination therapy with one of these medications as an active comparator. Observational studies of the same agents with a duration ≥1 yr that reported AEs were also included. EVIDENCE SYNTHESIS We synthesized evidence from 43 randomized controlled trials as well as five observational studies. Based on improvement of mean International Prostate Symptom Score and quality of life scores, the effectiveness of the newer ABs was not different from the older ABs (moderate strength of evidence [SOE]), but had more AEs (low SOE). Antimuscarinics/AB combination therapy had similar outcomes as AB monotherapy (all moderate SOE), but often had more AEs. Phosphodiesterase type-5 inhibitors alone or in combination with ABs had similar or inferior outcomes than ABs alone. Evidence was insufficient for the beta-3 adrenoceptor agonist. For all newer agents, the evidence was generally insufficient to assess long-term efficacy, prevention of symptom progression, or AEs. CONCLUSIONS None of the drugs or drug combinations newly used to treat LUTS attributed to BPH showed outcomes superior to traditional AB treatment. Given the lack of superior outcomes, the studies' short time-horizon, and less assurance of their safety, their current value in treating LUTS attributable to BPH appears low. PATIENT SUMMARY In this paper, we reviewed the evidence of newer drugs to treat men with urinary problems attributable to an enlarged prostate. We found none of the new drugs to be better but there was more concern about side effects.
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Affiliation(s)
- Philipp Dahm
- Minneapolis VA Health Care System, Minneapolis, MN, USA.
| | - Michelle Brasure
- Division of Health Policy and Management, University of Minnesota, School of Public Health, Minneapolis, MN, USA
| | | | - Carin M Olson
- Division of Health Policy and Management, University of Minnesota, School of Public Health, Minneapolis, MN, USA
| | - Victoria A Nelson
- Division of Health Policy and Management, University of Minnesota, School of Public Health, Minneapolis, MN, USA
| | - Howard A Fink
- Geriatric Research Education and Clinical Center, Minneapolis Veterans Affairs Healthcare System, Minneapolis, MN, USA
| | - Bruce Rwabasonga
- Division of Health Policy and Management, University of Minnesota, School of Public Health, Minneapolis, MN, USA
| | - Michael C Risk
- Minneapolis VA Health Care System, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA
| | - Timothy J Wilt
- Minneapolis Veterans Affairs Healthcare System, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA
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Albisinni S, Biaou I, Marcelis Q, Aoun F, De Nunzio C, Roumeguère T. New medical treatments for lower urinary tract symptoms due to benign prostatic hyperplasia and future perspectives. BMC Urol 2016; 16:58. [PMID: 27629059 PMCID: PMC5024450 DOI: 10.1186/s12894-016-0176-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 09/08/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lower Urinary Tract Symptoms (LUTS) in men are a common clinical problem in urology and have been historically strictly linked to benign prostatic hyperplasia (BPH), which may lead to bladder outlet obstruction (BOO). New molecules have been approved and have entered the urologists' armamentarium, targeting new signaling pathways and tackling specific aspects of LUTS. Objective of this review is to summarize the evidence regarding the new medical therapies currently available for male non-neurogenic LUTS, including superselective α1-antagonists, PDE-5 inhibitors, anticholinergic drugs and intraprostatic onabotulinum toxin injections. METHODS The National Library of Medicine Database was searched for relevant articles published between January 2006 and December 2015, including the combination of "BPH", "LUTS", "medical" and "new". Each article's title, abstract and text were reviewed for their appropriateness and their relevance. One hundred forty eight articles were reviewed. RESULTS Of the 148 articles reviewed, 92 were excluded. Silodosin may be considered a valid alternative to non-selective α1-antagonists, especially in the older patients where blood pressure alterations may determine major clinical problems and ejaculatory alterations may be not truly bothersome. Tadalafil 5 mg causes a significant decrease of IPSS score with an amelioration of patients' QoL, although with no significant increase in Qmax. Antimuscarinic drugs are effective on storage symptoms but should be used with caution in patients with elevated post-void residual. Intraprostatic injections of botulinum toxin are well-tolerated and effective, with a low rate of adverse events; however profound ameliorations were seen also in the sham arms of RCTs evaluating intraprostatic injections. CONCLUSION New drugs have been approved in the last years in the medical treatment of BPH-related LUTS. Practicing urologists should be familair with their pharmacodynamics and pharmacokinetics.
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Affiliation(s)
- Simone Albisinni
- Urology Department, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium.
| | - Ibrahim Biaou
- Urology Department, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium
| | - Quentin Marcelis
- Urology Department, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium
| | - Fouad Aoun
- Urology Department, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium
| | - Cosimo De Nunzio
- Department of Urology, Ospedale Sant'Andrea, University "La Sapienza", Roma, Italy
| | - Thierry Roumeguère
- Urology Department, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium
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Pang R, Zhou XY, Wang XL, Wang B, Yin XL, Bo H. Anticholinergics combined with alpha-blockers for treating lower urinary tract symptoms related to benign prostatic obstruction. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2016. [DOI: 10.1002/14651858.cd012336] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Ran Pang
- Guang An Men Hospital, China Academy of Chinese Medical Sciences; Department of Urology; No.5 Bei Xian Ge Street, Xicheng District Beijing China 100053
| | - Xin-Yao Zhou
- Guang An Men Hospital, China Academy of Chinese Medical Sciences; Internal Medicine & Outpatients Management Office; No. 5 Bei Xian Ge Street, Xicheng District Beijing China 100053
| | - Xiang-ling Wang
- Mayo Clinic; Division of Nephrology and Hypertension; 200 First Street SW Rochester Minnesota USA 55905
| | - Bin Wang
- China Academy of Chinese Medical Sciences; No.16 Dong Zhi Men Nei Nan Xiao Street, Dongcheng District Beijing China 100700
| | - Xue-Lai Yin
- Guang An Men Hospital, China Academy of Chinese Medical Sciences; Department of Urology; No.5 Bei Xian Ge Street, Xicheng District Beijing China 100053
| | - Hai Bo
- Guang An Men Hospital, China Academy of Chinese Medical Sciences; Department of Urology; No.5 Bei Xian Ge Street, Xicheng District Beijing China 100053
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Osman NI, Aldamanhori R, Mangera A, Chapple CR. Antimuscarinics, β-3 Agonists, and Phosphodiesterase Inhibitors in the Treatment of Male Lower Urinary Tract Symptoms. Urol Clin North Am 2016; 43:337-49. [DOI: 10.1016/j.ucl.2016.04.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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22
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Benign prostatic hyperplasia and lower urinary tract symptoms. A review of current evidence. Actas Urol Esp 2016; 40:288-94. [PMID: 26823069 DOI: 10.1016/j.acuro.2015.12.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 12/14/2015] [Accepted: 12/15/2015] [Indexed: 02/07/2023]
Abstract
CONTEXT The treatment of benign prostatic hyperplasia (BPH) is changing due to a greater understanding of the disease and the development of the functional concept of lower urinary tract symptoms (LUTS). OBJECTIVES To describe the current state of BPH and the diagnosis and treatment of LUTS. ACQUISITION OF EVIDENCE We summarise the issues presented and debated by a group of expert urologists during the First UROVI Congress, sponsored by the Spanish Urological Association. SUMMARY OF THE EVIDENCE LUTS encompasses filling, voiding and postvoiding symptoms that affect patients' quality of life. The aetiological diagnosis is an important element in starting the most ideal treatment. For this reason, new alternative therapies (both pharmacological and surgical) are needed to help individually address the symptoms in the various patient profiles. There is now a new combination of drugs (6mg of solifenacin and 0.4mg of the tamsulosin oral controlled absorption system) for treating moderate to severe filling symptoms and emptying symptoms associated with BPH in patients who do not respond to monotherapy. Furthermore, new surgical techniques that are increasingly less invasive help provide surgical options for older patients and those with high comorbidity. CONCLUSIONS The availability of drugs that can act on the various LUTS helps integrate the pathophysiological paradigm into the functional one, providing more appropriate treatment for our patients.
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Burden H, Abrams P. Urinary incontinence in men: current and developing therapy options. Expert Opin Pharmacother 2016; 17:715-26. [PMID: 26800277 DOI: 10.1517/14656566.2016.1145662] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Urinary incontinence in men is a significant and often underappreciated problem. Men can have urgency and or stress incontinence. Urgency incontinence as part of the overactive bladder (OAB) syndrome and can often coexist with benign prostatic obstruction (BPO) in men and the initial treatment of this is conservative lifestyle changes and then medical therapy. AREAS COVERED This literature review aims to cover synthetic drugs currently utilised to treat urinary incontinence in men that are phase III and onwards. Neurological incontinence and surgical treatment options for male urinary incontinence are beyond the scope of this review. EXPERT OPINION The most common form of urinary incontinence in men is urgency incontinence secondary to an OAB, which often co-exists in men, with bladder outflow obstruction (BOO). The pharmacotherapy options to treat OAB include antimuscarinics, β3 agonists and phosphodiesterase inhibitors. Antimuscarinics and β3 agonists are effective in treating OAB, and have been found to have no increased urinary retention risk in the group of patients with co-existing BPO. Emerging medications include the alternative β3 agonists - solabegron and ritobegron. The future may include novel combinations of these therapies.
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Affiliation(s)
| | - Paul Abrams
- b Head of Teaching and Research, Bristol Urological Institute, Chair, International Consultation on Urological Diseases, Bristol Urological Institute , Southmead Hospital , Bristol, UK
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Oelke M, Speakman MJ, Desgrandchamps F, Mamoulakis C. Acute Urinary Retention Rates in the General Male Population and in Adult Men With Lower Urinary Tract Symptoms Participating in Pharmacotherapy Trials: A Literature Review. Urology 2015; 86:654-65. [DOI: 10.1016/j.urology.2015.06.025] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 06/08/2015] [Accepted: 06/18/2015] [Indexed: 11/26/2022]
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Mangera A, Chapple C. Update summarising the conclusions of the international consultation on male lower urinary tract symptoms. World J Clin Urol 2015; 4:83-91. [DOI: 10.5410/wjcu.v4.i2.83] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 10/07/2014] [Accepted: 05/11/2015] [Indexed: 02/05/2023] Open
Abstract
The International Consultation on Urological Disease have recently published comprehensive conclusions, based on evidence reviewed by eight committees, on aspects of male lower urinary tract symptoms (LUTS). In this review, we summarise the conclusions from four of the committees, namely, the evidence regarding the epidemiology of male LUTS, patient assessment, nocturia and medical management. It is indisputable that with an expanding and ageing global population the prevalence of male LUTS is likely to increase. Therefore symptom prevention and preservation of quality of life (QoL) feature highly in the guidelines. There are now a number of different medical options, proven to lead to significant improvements in symptom scores, flow rate and QoL available to men with LUTS. Meta-analyses have shown the benefits for alpha blockers, antimuscarinics, 5-α reductase and phosphodiesterase-5 inhibitors. High level evidence also exists for combinations of all of the above with alpha blockers and so men with concomitant storage symptoms, prostate volume > 30 mL, PSA > 1.4 or erectile dysfunction may be considered for combination treatment of an alpha blocker with an antimuscarinic, 5-α reductase inhibitor or phosphodiesterase-5 inhibitor respectively. In an era of personalised medicine, appropriate patient selection is likely to provide the key to the most effective clinical management strategy.
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Descazeaud A, Barry Delongchamps N, Cornu JN, Azzouzi A, Buchon D, Benchikh A, Coloby P, Dumonceau O, Fourmarier M, Haillot O, Lebdai S, Mathieu R, Misrai V, Saussine C, de La Taille A, Robert G. Guide de prise en charge en médecine générale des symptômes du bas appareil urinaire de l’homme liés à une hyperplasie bénigne de la prostate. Prog Urol 2015; 25:404-12. [DOI: 10.1016/j.purol.2015.02.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2015] [Revised: 02/17/2015] [Accepted: 02/26/2015] [Indexed: 11/25/2022]
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Lee HN, Lee KS, Kim JC, Chung BH, Kim CS, Lee JG, Kim DK, Park CH, Park JK, Hong SJ. Rate and associated factors of solifenacin add-on after tamsulosin monotherapy in men with voiding and storage lower urinary tract symptoms. Int J Clin Pract 2015; 69:444-453. [PMID: 25363606 DOI: 10.1111/ijcp.12581] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Accepted: 09/29/2014] [Indexed: 11/27/2022] Open
Abstract
AIM To explore the rate of add-on therapy with solifenacin in men with voiding and storage lower urinary tract symptoms (LUTS) after tamsulosin monotherapy and to explore predictive factors for starting solifenacin add-on therapy. METHODS Men aged ≥ 45 years with IPSS ≥ 12 and symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 2/24 h) were enrolled to receive tamsulosin 0.2 mg once daily. After 4 weeks, men with residual symptoms of OAB and reported 'dissatisfied' or 'a little satisfied' were received solifenacin 5 mg in combination with tamsulosin monotherapy. Subjects completed an IPSS, a Quality of life (QoL) index, OAB V8, and an International Consultation of Incontinence Questionnaire (ICIQ)-Male LUTS, and patient perception of bladder condition (PPBC) at baseline and week 4. RESULTS Of a total of 305 patients, 254 patients completed 4 weeks of tamsulosin treatment. For 176 patients, solifenacin was added (69.3%). Significant predictive factors of solifenacin add-on therapy included long LUTS duration, high IPSS, number of micturitions per 24 h, more urgency episodes, high urgency severity score in a voiding diary and high OAB V8 score. Based on multivariable analysis, potential predictive factors of solifenacin add-on therapy included long LUTS duration (OR = 1.008, 95% CI: 1.001-1.014), high serum PSA (OR = 1.543, 95% CI: 1.136-2.095) and small prostate size (OR = 0.970, 95% CI: 0.947-0.994) (p < 0.05). IPSS, daytime micturitions and urgency episodes, OAB V8 scores, ICIQ and PPBC were improved after tamsulosin monotherapy. CONCLUSIONS Two thirds of men with voiding and storage LUTS needed to add anticholinergics after 4 weeks of tamsulosin monotherapy. Patients with longer lasting symptoms and storage symptoms with small prostate volume may require the anticholinergic add-on.
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Affiliation(s)
- H N Lee
- Department of Urology, Seoul Seonam Hospital, Ewha Womans University, Seoul, Korea
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Liao CH, Kuo HC. How to choose first-line treatment for men with predominant storage lower urinary tract symptoms: a prospective randomised comparative study. Int J Clin Pract 2015; 69:124-30. [PMID: 25495719 DOI: 10.1111/ijcp.12488] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
AIMS To compare the therapeutic effects and identify predictors of successful treatment of first-line antimuscarinic and α-blocker monotherapy for men with predominant storage lower urinary tract symptoms (LUTS). METHODS This prospective randomised comparative study included men aged ≥ 40 years with a total IPSS ≥ 8, IPSS storage subscore (IPSS-S) ≥ voiding subscore (IPSS-V) and PVR ≤ 250 ml. Subjects were randomised to receive tolterodine 4 mg or doxazosin 4 mg daily for 12 weeks. The primary end-point included changes of total IPSS, IPSS subscore and global response assessment (GRA) after treatment. The secondary end-points included comparisons of baseline parameters between patients with a GRA ≥ 1 and GRA < 1. All adverse events were also recorded. RESULTS This study was completed by 163 patients. The IPSS-T, IPSS-S and quality of life index decreased significantly in both groups. An improved outcome (GRA ≥ 1) at 4 weeks was reported in 51/74 patients (68.9%) receiving doxazosin and 69/89 patients (77.5%) receiving tolterodine. The rate of improved outcome in patients with a TPV < 40 ml was significantly higher in tolterodine group (73.3% vs. 57.6%, p = 0.040). Patients with tolterodine treatment failure (GRA < 1) had higher baseline IPSS-V and IPSS intermittency domain, whereas patients with doxazosin treatment failure had a higher baseline IPSS urgency domain. CONCLUSIONS The rate of improved outcome was comparable between first-line tolterodine and doxazosin monotherapy for male storage LUTS. Antimuscarinic monotherapy was suggested for men with smaller prostate volume and higher urgency symptom scores, whereas α-blocker monotherapy was suggested for those with higher voiding symptom scores.
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Affiliation(s)
- C-H Liao
- Department of Urology, Cardinal Tien Hospital and School of Medicine, Fu-Jen Catholic University, Hualien, Taiwan
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Abstract
The medical management of lower urinary tract symptoms (LUTS) is aimed at addressing voiding and storage symptoms in patients with benign prostate hyperplasia (BPH) symptoms with or without an over-active bladder (OAB). Current available options for BPH include alpha-blockers, 5-alpha reductase inhibitors and phosphodiesterase type 5 inhibitors. For OAB, options include antimuscarinics, with or without an alpha-blocker, the beta-3-adrenergic agonist mirabegron and the synthetic diuretic desmopressin. With the availability of numerous options and combinations available for the treatment of LUTS, individual patient assessment is the key to optimal symptom control and management of adverse effects.
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Affiliation(s)
- Sidney B Radomski
- Professor of Surgery (Urology), University of Toronto, Toronto Western Hospital, Toronto, ON
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Wang X, Wang X, Li S, Meng Z, Liu T, Zhang X. Comparative effectiveness of oral drug therapies for lower urinary tract symptoms due to benign prostatic hyperplasia: a systematic review and network meta-analysis. PLoS One 2014; 9:e107593. [PMID: 25216271 PMCID: PMC4162615 DOI: 10.1371/journal.pone.0107593] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 08/12/2014] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are common in elder men and a number of drugs alone or combined are clinically used for this disorder. But available studies investigating the comparative effects of different drug therapies are limited. This study was aimed to compare the efficacy of different drug therapies for LUTS/BPH with network meta-analysis. MATERIALS AND METHODS An electronic search of PubMed, Cochrane Library and Embase was performed to identify randomized controlled trials (RCTs) comparing different drug therapies for LUTS/BPH within 24 weeks. Comparative effects were calculated using Aggregate Data Drug Information System. Consistency models of network meta-analysis were created and cumulative probability was used to rank different therapies. RESULTS A total 66 RCTs covering seven different therapies with 29384 participants were included. We found that α-blockers (ABs) plus phosphodiesterase 5 inhibitors (PDE5-Is) ranked highest in the test of IPSS total score, storage subscore and voiding subscore. The combination therapy of ABs plus 5α-reductase inhibitors was the best for increasing maximum urinary flow rate (Qmax) with a mean difference (MD) of 1.98 (95% CI, 1.12 to 2.86) as compared to placebo. ABs plus muscarinic receptor antagonists (MRAs) ranked secondly on the reduction of IPSS storage subscore, although monotherapies including MRAs showed no effect on this aspect. Additionally, PDE5-Is alone showed great effectiveness for LUTS/BPH except Qmax. CONCLUSIONS Based on our novel findings, combination therapy, especially ABs plus PDE5-Is, is recommended for short-term treatment for LUTS/BPH. There was also evidence that PDE5-Is used alone was efficacious except on Qmax. Additionally, it should be cautious when using MRAs. However, further clinical studies are required for longer duration which considers more treatment outcomes such as disease progression, as well as basic research investigating mechanisms involving PDE5-Is and other pharmacologic agents alleviate the symptoms of LUTS/BPH.
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Affiliation(s)
- Xinghuan Wang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan city, Hubei province, P.R.China
| | - Xiao Wang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan city, Hubei province, P.R.China
| | - Sheng Li
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan city, Hubei province, P.R.China
| | - Zhe Meng
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan city, Hubei province, P.R.China
| | - Tao Liu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan city, Hubei province, P.R.China
| | - Xinhua Zhang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan city, Hubei province, P.R.China
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Corman A. Les troubles urinaires du bas appareil (TUBA) dans la pratique du médecin sexologue : comment mieux prendre en charge nos patients. SEXOLOGIES 2014. [DOI: 10.1016/j.sexol.2014.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Lee SH, Lee JY. Current role of treatment in men with lower urinary tract symptoms combined with overactive bladder. Prostate Int 2014; 2:43-9. [PMID: 25032191 PMCID: PMC4099395 DOI: 10.12954/pi.14045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Accepted: 04/07/2014] [Indexed: 12/04/2022] Open
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.
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Affiliation(s)
- Seung Hwan Lee
- Department of Urology, Severance Hospital, Yonsei University Health System, Seoul, Korea
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Abstract
OBJECTIVES To review the use of non-hormonal pharmacotherapies in the treatment of lower urinary tract symptoms (LUTS) due to presumed benign prostatic hyperplasia (BPH). MATERIALS AND METHODS A search of the PUBMED database was conducted for the terms BPH, LUTS, bladder outlet obstruction, alpha-adrenoceptor blockers, anti-muscarinics, and phosphodiesterase-5-inhibitors. RESULTS Medical therapy has long been established as the accepted standard of care in the treatment of male LUTS. The aim of treatment is improvement in symptoms and quality of life whilst minimizing adverse effects. The agents most widely used as 1(st) line therapy are alpha-blockers (AB), as a standalone or in combination with 2 other classes of drug; 5-α reductase inhibitors and anti-muscarinics. AB have rapid efficacy, improving symptoms and flow rate in a matter of days, these effects are then maintained over time. AB do not impact on prostate size and do not prevent acute urinary retention or the need for surgery. Anti-mucarinics, alone or in combination with an AB are safe and efficacious in the treatment of bothersome storage symptoms associated with LUTS/BPH. Phosphodiesterase-5 inhibitors are an emerging treatment option that improve LUTS without improving flow rates. CONCLUSIONS AB are the most well-established pharmacotherapy in the management of men with LUTS/BPH. The emergence of different classes of agent offers the opportunity to target underlying pathophysiologies driving symptoms and better individualize treatment.
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Affiliation(s)
- Nadir I. Osman
- Department of Urology, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
| | - Altaf Mangera
- Department of Urology, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
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Efficacy and safety of muscarinic antagonists as add-on therapy for male lower urinary tract symptoms. Sci Rep 2014; 4:3948. [PMID: 24492830 PMCID: PMC3912477 DOI: 10.1038/srep03948] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Accepted: 01/15/2014] [Indexed: 02/05/2023] Open
Abstract
Alpha-adrenoceptor antagonists (alpha-blockers) are widely prescribed to treat lower urinary tract symptoms (LUTS) in men but fail to ameliorate LUTS sufficiently, especially the storage symptoms related to frequency, urgency and nocturia. We performed a meta-analysis of randomised controlled trials (RCTs) comparing an alpha-blocker plus muscarinic antagonist with an alpha-blocker alone in male LUTS patients who were treated with alpha-blocker prior to randomisation. The review contained six randomised controlled trials (RCTs) that included a total of 2,208 male patients who were randomised to receive alpha-blocker plus muscarinic antagonist or alpha-blocker alone. The add-on group experienced significantly greater improvement in both total IPSS (International Prostate Symptom Score) and storage IPSS. Adverse events (AEs) were commonly experienced by both groups (41.6 vs. 33.3%) though they were not severe. Our meta-analysis indicated that muscarinic antagonists as add-on therapy alleviate LUTS, especially storage symptoms. The add-on therapy demonstrated safety and tolerability comparable with alpha-blocker monotherapy in male with LUTS.
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Hao N, Tian Y, Liu W, Wazir R, Wang J, Liu L, Wang K, Li H. Antimuscarinics and α-blockers or α-blockers monotherapy on lower urinary tract symptoms--a meta-analysis. Urology 2013; 83:556-62. [PMID: 24361007 DOI: 10.1016/j.urology.2013.10.034] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Revised: 10/13/2013] [Accepted: 10/24/2013] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To assess the clinical efficiency and safety of combination pharmacotherapy of antimuscarinics and α-blockers vs α-blockers monotherapy on patients with moderate to severe lower urinary tract symptoms (LUTS). METHODS We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the Cochrane Database of Systematic Review, and Web of Science from their inception until June 2013 to identify all eligible studies that compare the 2 pharmacotherapy strategies on LUTS. The Cochrane Collaboration's RevMan 5.2 software was used for data analysis, and the fixed or the random effect model was selected depending on the proportion of heterogeneity. RESULTS Eighteen eligible randomized controlled trials were included in this systematic review, including 2106 (51.57%) in cotherapy group and 1978 (48.43%) in monotherapy group. Synthetic data showed that there were significant improvements on Storage International Prostate Symptom Score (mean difference [MD] = -1.51; 95% confidence interval [CI] -2.10 to -0.91, P <.00001), quality of life score (MD = -0.53; 95% CI -0.89 to -0.17, P = .004), micturitions per 24 hours (MD = -1.14; 95% CI -1.84 to -0.45, P = .001), and urgency episodes per 24 hours (MD = -0.99; 95% CI -1.46 to -0.51, P <.0001) in the cotherapy group. There were no significant difference regarding maximum flow rate (MD = -0.05; 95% CI -0.27 to 0.17, P = .64), Total International Prostate Symptom Score (TIPSS) (MD = -0.88; 95% CI -1.64 to -0.12, P = .02), and Voiding International Prostate Symptom Score (VIPSS) (MD = 0.40; 95% CI -0.34 to 1.15, P = .29). As to postvoid residual volume, however, a worse condition was showed in the cotherapy group (MD = -6.53; 95% CI 3.06-10.00, P <.0002). CONCLUSION Antimuscarinics could and should be added to the drug regimen for patients with LUTS attributed to benign prostatic hyperplasia/bladder outlet obstruction, particularly are dominated by storage symptoms. For patients with increased acute urinary retention risk, they should be carefully monitored.
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Affiliation(s)
- Nan Hao
- Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Ye Tian
- Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Wei Liu
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Romel Wazir
- Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Jianzhong Wang
- Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Liangren Liu
- Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Kunjie Wang
- Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
| | - Hong Li
- Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
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Filson CP, Hollingsworth JM, Clemens JQ, Wei JT. The efficacy and safety of combined therapy with α-blockers and anticholinergics for men with benign prostatic hyperplasia: a meta-analysis. J Urol 2013; 190:2153-60. [PMID: 23727412 PMCID: PMC3884517 DOI: 10.1016/j.juro.2013.05.058] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/23/2013] [Indexed: 01/19/2023]
Abstract
PURPOSE We performed a meta-analysis to compare treatment with α-blockers and anticholinergics (ie combination therapy) to α-blocker monotherapy to clarify the efficacy and safety of this treatment approach among men with storage urinary symptoms related to benign prostatic hyperplasia. MATERIALS AND METHODS We searched for trials of men with benign prostatic hyperplasia/lower urinary tract symptoms that were randomized to combination treatment or α-blockers alone. We pooled data from 7 placebo controlled trials meeting inclusion criteria. Primary outcomes of interest included changes in International Prostate Symptom Score (storage subscores) and urinary frequency. We also assessed post-void residual volume, maximal flow rate and the incidence of urinary retention. Data were pooled using random effects models for continuous outcomes and the Peto method to generate odds ratios for acute urinary retention. RESULTS Combination therapy had a significantly greater reduction in International Prostate Symptom Score storage subscores (Δ -0.73, 95% CI -1.09 - -0.37) and voiding frequency (Δ -0.69 voids, 95% CI -0.97 - -0.41). There was also a greater reduction in maximal urinary flow rate (Δ -0.59 ml per second, 95% CI -1.04 - -0.14) and increase in post-void residual urine volume (Δ 11.60 ml, 95% CI 8.50-14.70) with combination therapy. The number needed to treat with combination therapy to cause 1 acute urinary retention episode was 101 (95% CI 60-267). CONCLUSIONS Combination treatment with α-blockers and anticholinergics significantly improved storage voiding parameters compared to men treated with α-blocker therapy alone. This treatment approach is safe with a minimal risk of increased post-void residual urine volume, decreased maximal urinary flow rate or acute urinary retention.
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Affiliation(s)
- Christopher P Filson
- Division of Health Services Research, Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan
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Xin Z, Huang Y, Lu J, Zhang Q, Chen C. Addition of Antimuscarinics to Alpha-blockers for Treatment of Lower Urinary Tract Symptoms in Men: A Meta-analysis. Urology 2013; 82:270-7. [DOI: 10.1016/j.urology.2013.04.045] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2012] [Revised: 04/23/2013] [Accepted: 04/26/2013] [Indexed: 11/26/2022]
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Cambronero J, Arlandis S, Errando C, Mora A. Profile of lower urinary tract symptoms in the male and their impact on quality of life. Actas Urol Esp 2013; 37:401-7. [PMID: 23411069 DOI: 10.1016/j.acuro.2012.11.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Accepted: 11/27/2012] [Indexed: 10/27/2022]
Abstract
OBJECTIVES Following current European Guidelines, Lower Urinary Tract Symptoms (LUTS) are produced by several causes and, thus, thorough clinical assessment should be undertaken for a correct therapeutic management. This study was conducted in order to assess the symptoms profile and their impact on Health-Related Quality of Life (HRQL) of male patients attending urology outpatient clinics. MATERIAL AND METHODS Epidemiological, cross-sectional study including adult male patients (n=826) presenting with at least one de novo previously untreated LUTS. Socio-demographic and clinical variables were collected. Patients completed IPSS, Bladder Control Self-Assessment Questionnaire (B-SAQ) and SF-12 questionnaires. RESULTS Mean age (SD) was 65 (10) years. A combination of storage, voiding and post-micturition symptoms were present in 69% of subjects and 30% showed >2 urgency episodes and >6 micturitions daily (storage symptoms -SS- sub-population). Storage symptoms were the reason for consultation in 86%. Mean peak urinary flow (Q(max)) was 11.4 mL/s, in 44% of patients,prostate volume was 20-40 mL and 91% showed moderate or severe symptoms on IPSS with an overall mean (SD) score of 17 (7). SS sub-population had higher B-SAQ scores (6,9 vs 4,8 for symptoms; 7,8 vs 5,1 for bother), and worse HRQL (IPSS item 8). CONCLUSIONS These findings support the importance of addressing treatment adequately according to patient profile, bothersomeness and impact on HRQL.
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Osman NI, Chapple CR. Contemporary Combination Therapy in the Treatment of LUTS/BPH. CURRENT BLADDER DYSFUNCTION REPORTS 2013. [DOI: 10.1007/s11884-013-0173-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Brenes Bermúdez FJ, Cozar Olmo JM, Esteban Fuertes M, Fernández-Pro Ledesma A, Molero García JM. [Urine incontinence referral criteria for primary care]. Aten Primaria 2013; 45:263-73. [PMID: 23623519 PMCID: PMC6985511 DOI: 10.1016/j.aprim.2013.01.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Accepted: 01/29/2013] [Indexed: 11/06/2022] Open
Abstract
A pesar de la elevada incidencia de incontinencia urinaria (IU) existe una escasa sensibilización de los profesionales sanitarios hacia esta afección, que no es grave, pero que sí autolimita de forma importante la vida de las personas que la presentan. Las sociedades científicas de Atención Primaria (Sociedad Española de Médicos de Atención Primaria [SEMERGEN], Sociedad Española de Médicos Generales y de Familia [SEMG], Sociedad Española de Medicina de Familia y Comunitaria [semFYC]) y la Asociación Española de Urología [AEU]) han elaborado este documento de consenso con los objetivos de sensibilizar al médico de atención primaria y ayudarle a la evaluación diagnóstica, tratamiento y derivación al especialista de la IU. El primer objetivo desde atención primaria (AP) debe ser la detección de la IU, por lo que se recomienda realizar un cribado oportunista al menos, una vez a lo largo de la vida en mujeres asintomáticas > 40 años y en varones asintomáticos > 55 años. En la evaluación diagnóstica, basada en la anamnesis y la exploración física, se deberá determinar el tipo y gravedad de la IU con el objetivo de derivar al especialista los casos de IU complicada. Con excepción de la vejiga hiperactiva (VH), el tratamiento conservador no farmacológico constituye el abordaje principal de la IU no complicada, tanto en mujeres como en varones. En la IU de urgencia/VH (IUU/VH), los antimuscarínicos son los únicos fármacos que han demostrado eficacia y seguridad. En el caso de los varones con síntomas mixtos, excluyendo los casos de obstrucción severa, se debe optar por un tratamiento combinado de alfa-bloqueantes y antimuscarínicos.
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Criterios de derivación en incontinencia urinaria para atención primaria. Semergen 2013; 39:197-207. [DOI: 10.1016/j.semerg.2012.11.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Accepted: 11/13/2012] [Indexed: 11/17/2022]
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Liao CH, Kuo YC, Kuo HC. Predictors of successful first-line antimuscarinic monotherapy in men with enlarged prostate and predominant storage symptoms. Urology 2013; 81:1030-3. [PMID: 23506731 DOI: 10.1016/j.urology.2013.01.018] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Revised: 01/02/2013] [Accepted: 01/11/2013] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To identify predictors of successful first-line antimuscarinic monotherapy for patients with enlarged prostate and predominant storage symptoms. METHODS Men aged ≥ 50 years with total International Prostate Symptom Score (IPSS-T) ≥ 8, total prostate volume (TPV) ≥ 20 mL, IPSS quality of life (QOL) index ≥ 2, IPSS voiding to storage (IPSS-V/S) subscore ratio ≤ 1, and post-void residual (PVR) ≤ 250 mL were recruited into a prospective open-label study. All men received tolterodine ER (4 mg) daily. Global response assessment (GRA) ≥ 1 after treatment was considered successful treatment and an indication for continued antimuscarinic monotherapy. RESULTS One hundred ninety-seven men aged 50-89 years (average TPV 44.4 mL) received first-line tolterodine monotherapy. Mean IPSS-T, IPSS storage (IPSS-S) subscore, and QOL improved significantly at 2, 4, and 12 weeks. Average PVR increased significantly; no patient developed acute urinary retention. One hundred thirty-six patients (69.0%) showed improvement (GRA ≥ 1) at both 2 and 4 weeks. Regression analysis showed that IPSS-S (P = .039) and maximum urine flow (Qmax, P = .033) were significant predictors of therapeutic success. Patients with smaller baseline TPV, higher IPSS-S, and higher Qmax had significantly higher treatment success rates. CONCLUSION First-line antimuscarinic monotherapy is safe and effective within 12 weeks in selected patients with benign prostatic hyperplasia (BPH) Higher baseline IPSS-S, higher baseline Qmax, and lower TPV were predictors of successful antimuscarinic monotherapy.
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Affiliation(s)
- Chun-Hou Liao
- Department of Urology, Cardinal Tien Hospital and School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
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Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, N'dow J, Nordling J, de la Rosette JJ. EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol 2013; 64:118-40. [PMID: 23541338 DOI: 10.1016/j.eururo.2013.03.004] [Citation(s) in RCA: 844] [Impact Index Per Article: 70.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Accepted: 03/01/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To present a summary of the 2013 version of the European Association of Urology guidelines on the treatment and follow-up of male lower urinary tract symptoms (LUTS). EVIDENCE ACQUISITION We conducted a literature search in computer databases for relevant articles published between 1966 and 31 October 2012. The Oxford classification system (2001) was used to determine the level of evidence for each article and to assign the grade of recommendation for each treatment modality. EVIDENCE SYNTHESIS Men with mild symptoms are suitable for watchful waiting. All men with bothersome LUTS should be offered lifestyle advice prior to or concurrent with any treatment. Men with bothersome moderate-to-severe LUTS quickly benefit from α1-blockers. Men with enlarged prostates, especially those >40ml, profit from 5α-reductase inhibitors (5-ARIs) that slowly reduce LUTS and the probability of urinary retention or the need for surgery. Antimuscarinics might be considered for patients who have predominant bladder storage symptoms. The phosphodiesterase type 5 inhibitor tadalafil can quickly reduce LUTS to a similar extent as α1-blockers, and it also improves erectile dysfunction. Desmopressin can be used in men with nocturia due to nocturnal polyuria. Treatment with an α1-blocker and 5-ARI (in men with enlarged prostates) or antimuscarinics (with persistent storage symptoms) combines the positive effects of either drug class to achieve greater efficacy. Prostate surgery is indicated in men with absolute indications or drug treatment-resistant LUTS due to benign prostatic obstruction. Transurethral resection of the prostate (TURP) is the current standard operation for men with prostates 30-80ml, whereas open surgery or transurethral holmium laser enucleation is appropriate for men with prostates >80ml. Alternatives for monopolar TURP include bipolar TURP and transurethral incision of the prostate (for glands <30ml) and laser treatments. Transurethral microwave therapy and transurethral needle ablation are effective minimally invasive treatments with higher retreatment rates compared with TURP. Prostate stents are an alternative to catheterisation for men unfit for surgery. Ethanol or botulinum toxin injections into the prostate are still experimental. CONCLUSIONS These symptom-oriented guidelines provide practical guidance for the management of men experiencing LUTS. The full version is available online (www.uroweb.org/gls/pdf/12_Male_LUTS.pdf).
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Affiliation(s)
- Matthias Oelke
- Department of Urology, Hannover Medical School, Hannover, Germany
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Spatafora S, Casarico A, Fandella A, Galetti C, Hurle R, Mazzini E, Niro C, Perachino M, Sanseverino R, Pappagallo GL. Evidence-based guidelines for the treatment of lower urinary tract symptoms related to uncomplicated benign prostatic hyperplasia in Italy: updated summary from AURO.it. Ther Adv Urol 2013. [PMID: 23205056 DOI: 10.1177/1756287212463112] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The first Italian national guidelines were developed by the Italian Association of Urologists and published in 2007. Since then, a number of new drugs or classes of drugs have emerged for the treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH), new data have emerged on medical therapy (monotherapies and combination therapies), new surgical techniques have come into practice, and our understanding of disease pathogenesis has increased. Consequently, a new update of the guidelines has become necessary. METHODS A structured literature review was conducted to identify relevant papers published between 1 August 2006 and 12 December 2010. Publications before or after this timeframe were considered only if they were recognised as important milestones in the field or if the literature search did not identify publications within this timeframe. The quality of evidence and strength of recommendations were determined according to the Grading of Recommendations Assessment, Development and Evaluation framework. MAIN FINDINGS Decisions on therapeutic intervention should be based on the impact of symptoms on quality of life (QoL) rather than the severity of symptoms (International Prostate Symptom Score (IPSS) score). A threshold for intervention was therefore based on the IPSS Q8, with intervention recommended for patients with a score of at least 4. Several differences in clinical recommendations have emerged. For example, combination therapy with a 5α-reductase inhibitor plus α blocker is now the recommended option for the treatment of patients at risk of BPH progression. Other differences include the warning of potential worsening of cognitive disturbances with use of anticholinergics in older patients, the distinction between Serenoa repens preparations (according to the method of extraction), and the clearly defined threshold of prostate size for performing open surgery (>80 g). While the recommendations included in these guidelines are evidence based, clinical decisions should also be informed by patients' clinical and physical circumstances, as well as patients' preferences and actions. CONCLUSIONS These guidelines are intended to assist physicians and patients in the decision-making process regarding the management of LUTS/BPH, and support the process of continuous improvement of the quality of care and services to patients.
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Affiliation(s)
- Sebastiano Spatafora
- Department of Surgery, Azienda Ospedaliera S. Maria Nuova, viale Risorgimento 80, 42100 Reggio Emilia, Italy
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Füllhase C, Chapple C, Cornu JN, De Nunzio C, Gratzke C, Kaplan SA, Marberger M, Montorsi F, Novara G, Oelke M, Porst H, Roehrborn C, Stief C, McVary KT. Systematic review of combination drug therapy for non-neurogenic male lower urinary tract symptoms. Eur Urol 2013; 64:228-43. [PMID: 23375241 DOI: 10.1016/j.eururo.2013.01.018] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Accepted: 01/15/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND Several drugs are approved for the treatment of lower urinary tract symptoms (LUTS) in men, but these are mostly used by clinicians as monotherapies. The combination of different compounds, each of which targets a different aspect of LUTS, seems appealing. However, only few clinical trials have evaluated the effects of combination therapies. OBJECTIVE This systematic review analyzes the efficacy and adverse events of combination therapies for male LUTS. EVIDENCE ACQUISITION PubMed and Cochrane databases were used to identify clinical trials and meta-analyses on male LUTS combination therapy. The search was restricted to studies of level of evidence ≥ 1b. A total of 49 papers published between January 1988 and March 2012 were identified. EVIDENCE SYNTHESIS The α1-adrenoceptor antagonist (α1-blocker)/5α-reductase inhibitor (5-ARI) combination provides the most data. This combination seems to be more efficacious in terms of several outcome variables in patients whose prostate volume is between 30 ml and 40 ml when treatment is maintained for >1 yr; when given for <1 yr, α1-blockers alone are just as effective. The combination of α1-blocker/5-ARI shows a slightly increased rate of adverse events. It remains unknown whether its safety and superiority over either drug as monotherapy are sustained after >6 yr. The α1-blocker/muscarinic receptor antagonist (antimuscarinic) combination was most frequently assessed as an add-on therapy to already existing α1-blocker therapy. Inconsistent data derive from heterogeneous study populations and different study designs. Currently, the α1-blocker/antimuscarinic combination appears to be a second-line add-on for patients with insufficient symptom relief after monotherapy. The combination seems to be safe in men with postvoid residual <200 ml. However, there are no trials >4 mo concerning safety and efficacy of this combination. The α1-blocker/phosphodiesterase type 5 inhibitor combination is a new treatment option with only preliminary reports. More studies are needed before definitive conclusions can be drawn. CONCLUSIONS An α1-blocker/5-ARI combination is beneficial for patients whose prostate volume is between 30 ml and 40 ml when medical treatment is intended for >1 yr. Based on short-term follow-up studies, add-on of antimuscarinics to α1-blockers is an option when postvoid residual is <200 ml.
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Affiliation(s)
- Claudius Füllhase
- Department of Urology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany
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Konstantinidis C, Samarinas M, Andreadakis S, Xanthis S, Skriapas K. Lower urinary tract symptoms associated with benign prostatic hyperplasia: combined treatment with fesoterodine fumarate extended-release and tamsulosin--a prospective study. Urol Int 2012; 90:156-60. [PMID: 23221480 DOI: 10.1159/000345050] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2012] [Accepted: 10/08/2012] [Indexed: 11/19/2022]
Abstract
OBJECTIVE To evaluate the efficacy and safety of fesoterodine extended-release (ER) plus tamsulosin in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS Men aged ≥50 years, with LUTS, prostate volume ≤60 ml and International Prostate Symptom Score (IPSS) ≥13 were enrolled in this study. 173 consecutive patients were treated initially with tamsulosin (0.4 mg) for 1 week. At the second visit, 47 patients out of the sample of 173 who were still experiencing inconvenient LUTS were randomized into two groups. The first group received a therapy with tamsulosin and fesoterodine combination (group 1, n = 24) while the second continued the therapy with the single administration of tamsulosin (group 2, n = 23) for an additional 4-week period. RESULTS There was no statistically significant difference in age, prostate volume, Q, and postvoid residual urine between the two groups. A statistical significance appeared in the combination group regarding the storage and the total IPSS values among the second and third visits (10.5 ± 1.4 to 8.5 ± 1.3 and 16.1 ± 1.8 to 13.7 ± 1.5 respectively). CONCLUSION Regarding bothersome LUTS and storage symptoms, fesoterodine ER and tamsulosin combination was significantly more effective than the single administration of tamsulosin.
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Hernández Fernández C, Brenes Bermúdez F, Moncada Iribarren I. [Update of the usefulness of α-blockers in the treatment of different urologic pathologies]. Med Clin (Barc) 2012; 139:582-7. [PMID: 22982131 DOI: 10.1016/j.medcli.2012.06.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2012] [Revised: 06/24/2012] [Accepted: 06/28/2012] [Indexed: 12/28/2022]
Abstract
OBJECTIVE To review the role of α-blockers in various urological conditions such as benign prostatic hyperplasia, overactive bladder, chronic prostatitis, and erectile dysfunction and as expulsive treatment of distal ureteral stones. MATERIAL AND METHODS We reviewed the latest scientific evidence in all the fields mentioned above, performing a critical analysis. CONCLUSION α-blockers are now considered first-line treatment in lower urinary tract symptoms secondary to benign prostatic hyperplasia, but the indications go beyond, and are able to improve, alone or in combination with other drugs, the previously mentioned pathologies. The uroselective properties of some α-blockers make them a highly safe medication.
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Descazeaud A, Robert G, Delongchamps N, Cornu JN, Saussine C, Haillot O, Devonec M, Fourmarier M, Ballereau C, Lukacs B, Dumonceau O, Azzouzi A, Faix A, Desgrandchamps F, de la Taille A. Bilan initial, suivi et traitement des troubles mictionnels en rapport avec hyperplasie bénigne de prostate : recommandations du CTMH de l’AFU. Prog Urol 2012. [DOI: 10.1016/j.purol.2012.10.001] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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