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Bakr AM, El-Sakka AI. Effects of alpha-1 adrenergic receptor blockers on erectile function: a systematic review. Expert Opin Pharmacother 2025; 26:219-226. [PMID: 39709630 DOI: 10.1080/14656566.2024.2446628] [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: 10/30/2024] [Revised: 12/12/2024] [Accepted: 12/19/2024] [Indexed: 12/24/2024]
Abstract
INTRODUCTION Alpha-1 adrenergic receptor antagonists (α1-ARAs) are used in the well-established treatment for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS). Since BPH and erectile dysfunction (ED) are commonly concomitant conditions, the importance of addressing the potential role of α1-ARA in patients with ED is rising. METHODS We systemically reviewed literature for studies that assessed erectile function (EF) indices in relation to α1-ARA use. All types of comparisons were included. RESULTS Out of 1915 records, 21 articles have been included. All the articles suffered high risk of bias. α1-ARA showed a significant improvement in EF in comparison to baseline and placebo. Some α1-ARA are more erectogenic than others. Combined therapy with phosphodiesterase-5 inhibitors improved EF better than either alone. Factors like associated lower urinary symptoms, dose, and duration of therapy modify α1-ARA effects on EF. CONCLUSION Αlpha1-ARAs have a potential role in improving EF in subjective and objective scales. However, the available evidence is extracted from studies on patients with other indications for α1-ARAs, particularly BPH-related LUTS. Further investigations should target patients with ED only to precisely identify their clinical utility.
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Affiliation(s)
- Ahmed M Bakr
- Faculty of Medicine, Suez Canal University, Ismailia, Egypt
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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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ElHady AK, El-Gamil DS, Abdel-Halim M, Abadi AH. Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives. Pharmaceuticals (Basel) 2023; 16:1266. [PMID: 37765073 PMCID: PMC10536424 DOI: 10.3390/ph16091266] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 08/25/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
Phosphodiesterase 5 (PDE5) inhibitors presented themselves as important players in the nitric oxide/cGMP pathway, thus exerting a profound impact on various physiological and pathological processes. Beyond their well-known efficacy in treating male erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), a plethora of studies have unveiled their significance in the treatment of a myriad of other diseases, including cognitive functions, heart failure, multiple drug resistance in cancer therapy, immune diseases, systemic sclerosis and others. This comprehensive review aims to provide an updated assessment of the crucial role played by PDE5 inhibitors (PDE5-Is) as disease-modifying agents taking their limiting side effects into consideration. From a medicinal chemistry and drug discovery perspective, the published PDE5-Is over the last 10 years and their binding characteristics are systemically discussed, and advancement in properties is exposed. A persistent challenge encountered with these agents lies in their limited isozyme selectivity; considering this obstacle, this review also highlights the breakthrough development of the recently reported PDE5 allosteric inhibitors, which exhibit an unparalleled level of selectivity that was rarely achievable by competitive inhibitors. The implications and potential impact of these novel allosteric inhibitors are meticulously explored. Additionally, the concept of multi-targeted ligands is critically evaluated in relation to PDE5-Is by inspecting the broader spectrum of their molecular interactions and effects. The objective of this review is to provide insight into the design of potent, selective PDE5-Is and an overview of their biological function, limitations, challenges, therapeutic potentials, undergoing clinical trials, future prospects and emerging uses, thus guiding upcoming endeavors in both academia and industry within this domain.
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Affiliation(s)
- Ahmed K. ElHady
- School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo 11865, Egypt;
| | - Dalia S. El-Gamil
- Department of Chemistry, Faculty of Pharmacy, Ahram Canadian University, Cairo 12451, Egypt;
| | - Mohammad Abdel-Halim
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt;
| | - Ashraf H. Abadi
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt;
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AbdelRazek M, Abolyosr A, Mhammed O, Fathi A, Talaat M, Hassan A. Prospective comparison of tadalafil 5 mg alone, silodosin 8 mg alone, and the combination of both in treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. World J Urol 2022; 40:2063-2070. [PMID: 35773357 PMCID: PMC9279271 DOI: 10.1007/s00345-022-04071-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 06/01/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), will have deterioration in the quality of life. Likewise, BPH can be complicated by damage to bladder function, bladder stones formation, hematuria, and impaired kidney function. The goal of treatment is to avoid all those effects caused by BPH. OBJECTIVE To evaluate the efficacy of tadalafil alone, silodosin alone, and the combination of both in the treatment of LUTS associated with BPH. PATIENTS AND METHODS Patients in our department with BPH who had LUTS were assigned randomly to three groups: A (101 patients) received tadalafil, 5 mg; B (102 patients) received silodosin, 8 mg; and group C (105 patients) received the combination of tadalafil, 5 mg, and silodosin, 8 mg. For all participants, we asses changes in the maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) score, Post-voiding urine (PVR) and all results were recorded and analyzed with the (SPSS) and Microsoft Excel 2010. RESULTS Qmax, IPSS, PVR and IIEF score improved significantly more with the combination of tadalafil and silodosin than with either drug alone (p < 0.001). Three months after treatment, the mean Qmax values were 14.4 ml/sec in group A, 15.2 ml/sec in group B, and 15.8 ml/sec in group C; and the mean IPSSs were 17.6 in group A, 16.7 in group B, and 15.6 in group C (p < 0.001). CONCLUSION Tadalafil and silodosin are effective treatment options in men with BPH who have LUTS, but the combination of both is more effective and feasible in treating LUTS of BPH.
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Affiliation(s)
- Mostafa AbdelRazek
- Urology Department, Qena University Hospital, South Valley University, Qena, P.O: 83523, Egypt.
| | - Ahmad Abolyosr
- Urology Department, Qena University Hospital, South Valley University, Qena, P.O: 83523, Egypt
| | - Omar Mhammed
- Urology Department, Qena University Hospital, South Valley University, Qena, P.O: 83523, Egypt
| | - Atef Fathi
- Urology Department, Qena University Hospital, South Valley University, Qena, P.O: 83523, Egypt
| | - Mohammed Talaat
- Urology Department, Qena University Hospital, South Valley University, Qena, P.O: 83523, Egypt
| | - Ahmed Hassan
- Urology Department, Qena University Hospital, South Valley University, Qena, P.O: 83523, Egypt
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Leukes VN, Malherbe ST, Hiemstra A, Kotze LA, Roos K, Keyser A, De Swardt D, Gutschmidt A, Walzl G, du Plessis N. Sildenafil, a Type-5 Phosphodiesterase Inhibitor, Fails to Reverse Myeloid-Derived Suppressor Cell-Mediated T Cell Suppression in Cells Isolated From Tuberculosis Patients. Front Immunol 2022; 13:883886. [PMID: 35935981 PMCID: PMC9353143 DOI: 10.3389/fimmu.2022.883886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 06/24/2022] [Indexed: 11/13/2022] Open
Abstract
Successful TB treatment is hampered by increasing resistance to the two most effective first-line anti-TB drugs, namely isoniazid and rifampicin, thus innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for increasing treatment efficacy without inducing drug resistance. We assessed the ability of Sildenafil, a type-5 phosphodiesterase inhibitor, as a repurposed compound, to serve as HDT target, by counteracting the suppressive effects of myeloid-derived suppressor cells (MDSC) obtained from active TB cases on T-cell responsiveness. We confirm that MDSC suppress non-specific T-cell activation. We also show that Sildenafil treatment fails to reverse the MDSC-mediated suppression of T-cell functions measured here, namely activation and proliferation. The impact of Sildenafil treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted.
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Affiliation(s)
- Vinzeigh N. Leukes
- DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Stephanus T. Malherbe
- DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Andriette Hiemstra
- DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Leigh A. Kotze
- DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Kelly Roos
- DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Alana Keyser
- Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
| | - Dalene De Swardt
- Central Analytical Facility, Stellenbosch University, Cape Town, South Africa
| | - Andrea Gutschmidt
- DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Gerhard Walzl
- DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Nelita du Plessis
- DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa
- *Correspondence: Nelita du Plessis,
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Elama HS, Shalan SM, El-Shabrawy Y, Eid MI, Zeid AM. A synchronous spectrofluorometric technique for simultaneous detection of alfuzosin and tadalafil: applied to tablets and spiked biological samples. ROYAL SOCIETY OPEN SCIENCE 2022. [PMID: 35845851 DOI: 10.5061/dryad.7m0cfxpwq] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
A facile, accurate, eco-friendly and sensitive spectrofluorometric method was evolved to assay alfuzosin hydrochloride (AFH) and tadalafil (TDF) in different matrices. Such a co-administered combination is clinically used for the treatment of lower urinary tract symptoms. Both compounds are characterized by their native fluorescence spectra upon excitation at specific wavelengths. Their characteristic fluorescence spectra were used for sensitive assay of the studied analytes in tablets and human biological samples. The assay principle is based on first-order synchronous spectrofluorometric scan using Δλ = 60 nm in which AFH peaks were recorded at 366 nm. Meanwhile, TDF measurements were recorded at 293 nm in the same scans without overlap with AFH spectra. Recent analytical chemistry trends were implemented to lessen occupational and environmental perils, using ethanol as a diluting solvent for method optimization and application. Linearity ranges were 5.0-90.0 and 10.0-100.0 ng ml-1 for AFH and TDF, respectively in their raw materials with average % recoveries of 100.44% and 99.73% in raw materials, 100.15% and 100.20% in spiked plasma, and 97.14% and 99.99% in spiked urine. The proposed method was successfully applied to Prostetrol and Starkoprex commercial tablets with no interference with common tablet additives.
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Affiliation(s)
- Heba Samir Elama
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Shereen M Shalan
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Yasser El-Shabrawy
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Manal I Eid
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Abdallah M Zeid
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
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7
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Elama HS, shalan SM, El-Shabrawy Y, Eid MI, Zeid AM. A synchronous spectrofluorometric technique for simultaneous detection of alfuzosin and tadalafil: applied to tablets and spiked biological samples. ROYAL SOCIETY OPEN SCIENCE 2022; 9:220330. [PMID: 35845851 PMCID: PMC9277242 DOI: 10.1098/rsos.220330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 06/14/2022] [Indexed: 05/06/2023]
Abstract
A facile, accurate, eco-friendly and sensitive spectrofluorometric method was evolved to assay alfuzosin hydrochloride (AFH) and tadalafil (TDF) in different matrices. Such a co-administered combination is clinically used for the treatment of lower urinary tract symptoms. Both compounds are characterized by their native fluorescence spectra upon excitation at specific wavelengths. Their characteristic fluorescence spectra were used for sensitive assay of the studied analytes in tablets and human biological samples. The assay principle is based on first-order synchronous spectrofluorometric scan using Δλ = 60 nm in which AFH peaks were recorded at 366 nm. Meanwhile, TDF measurements were recorded at 293 nm in the same scans without overlap with AFH spectra. Recent analytical chemistry trends were implemented to lessen occupational and environmental perils, using ethanol as a diluting solvent for method optimization and application. Linearity ranges were 5.0-90.0 and 10.0-100.0 ng ml-1 for AFH and TDF, respectively in their raw materials with average % recoveries of 100.44% and 99.73% in raw materials, 100.15% and 100.20% in spiked plasma, and 97.14% and 99.99% in spiked urine. The proposed method was successfully applied to Prostetrol and Starkoprex commercial tablets with no interference with common tablet additives.
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Affiliation(s)
- Heba Samir Elama
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Shereen M. shalan
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Yasser El-Shabrawy
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Manal I. Eid
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Abdallah M. Zeid
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
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Bapir R, Bhatti KH, Eliwa A, García-Perdomo HA, Gherabi N, Hennessey D, Magri V, Mourmouris P, Ouattara A, Perletti G, Philipraj J, Trinchieri A, Buchholz N. Effect of alpha-adrenoceptor antagonists on sexual function. A systematic review and meta-analysis. Arch Ital Urol Androl 2022; 94:252-263. [PMID: 35775356 DOI: 10.4081/aiua.2022.2.252] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Alpha-adrenoreceptor antagonists or alpha-blockers are used in the treatment of hypertension, in the therapy of benign prostatic hyperplasia and in medical expulsive treatment of ureteral stones. These agents may affect the sexual function, with differences between drugs within the same class, depending on their selectivity for receptor subtypes. The aim of this review was to analyze the effects of alpha-blockers on sexual function. MATERIALS AND METHODS We conducted a systematic review and meta-analysis by searching PubMed, EMBASE and other databases for randomized controlled trials (RCTs) reporting sexual adverse effects in patients treated with alpha-blockers. Odds ratios for sexual dysfunction were calculated using random effects Mantel-Haenszel statistics. RESULTS Out of 608 records retrieved, 75 eligible RCTs were included in the meta-analysis. Compared with placebo, alphablockers were associated with increased odds of ejaculatory disorders both in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH) (OR: 7.53, 95% CI: 3.77-15.02, Z = 5.73, p < 0.00001, I2 = 55%) and in patients with ureteral stones (OR: 2.88, 95% CI: 1.50-5.44, Z = 3.19, p < 0.001, I2 = 31%). Uroselective alpha-blockers showed higher odds of ejaculatory disorders. Conversely, nonselective alpha-blockers were not associated with higher odds of ejaculatory dysfunction. Silodosin was associated with increased odds of ejaculatory dysfunction compared with tamsulosin (OR: 3.52, 95% CI: 2.18-5.68, 15 series, 1512 participants, Z = 5.15, p < 0.00001, I2 = 0%). Naftopidil and alfuzosin showed lower odds of ejaculatory dysfunction compared to uroselective alpha-blockers.No statistically significant differences in the odds of erectile dysfunction were observed when alpha-blockers were compared to placebo.
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Affiliation(s)
- Rawa Bapir
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Smart Health Tower, Sulaymaniyah, Kurdistan region.
| | - Kamran Hassan Bhatti
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Urology Department, HMC, Hamad Medical Corporation.
| | - Ahmed Eliwa
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Department of Urology, Zagazig University, Zagazig, Sharkia.
| | | | - Nazim Gherabi
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Faculty of Medicine Algiers 1, Algiers.
| | - Derek Hennessey
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Department of Urology, Mercy University Hospital, Cork.
| | - Vittorio Magri
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and ASST Nord Milano, Milan.
| | - Panagiotis Mourmouris
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and 2nd Department of Urology, National and Kapodistrian University of Athens, Sismanoglio Hospital, Athens.
| | - Adama Ouattara
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Division of Urology, Souro Sanou University Teaching Hospital, Bobo-Dioulasso.
| | - Gianpaolo Perletti
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Department of Biotechnology and Life Sciences, Section of Medical and Surgical Sciences, University of Insubria, Varese.
| | - Joseph Philipraj
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Department of Urology, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth, Puducherry.
| | - Alberto Trinchieri
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Urology School, University of Milan.
| | - Noor Buchholz
- U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; and Sobeh's Vascular and Medical Center, Dubai Health Care City, Dubai.
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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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10
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Naveed M, Changxing L, Ihsan AU, Shumzaid M, Kamboh AA, Mirjat AA, Saeed M, Baig MMFA, Zubair HM, Noreen S, Madni A, Xiaohui Z. Therapeutic interventions to urologic chronic pelvic pain syndrome and UPOINT system for clinical phenotyping: How far are we? Urologia 2022; 89:315-328. [PMID: 34978224 DOI: 10.1177/03915603211065301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The assessment and management of urologic chronic pelvic pain syndrome (UCPPS), is controversial. It is classified by voiding symptoms, pelvic pain, and bladder pain, which is weekly treated, weekly understood, and bothersome. In the aspect of clinical efforts and research to help people with this syndrome have been hampered by the deficiency of a widely reliable, accepted, and a valuable tool to evaluate the patient symptoms and quality of life (QoL) impact. However, the etiology comes into sight is multifactorial, and available treatment options have been imprecise considerably in present years. We compiled the published literature on the assessment of the syndrome, a tentative role of pharmacological and non-pharmacological (conservative, alternative, and invasive therapy) interventions in eradicating the disease as well as improving symptoms. The previously published literature on animal models has established the association of immune systems in the etiology, pathogenesis, and progression of the disease. The UPOINT system for clinical phenotyping of UCPPS patients has six predefined domains that direct multimodal therapy, which would lead to significant symptom improvement in the medical field. The narrative review aims to scrutinize the fluctuating scientist's views on the evaluation of patient and multimodal treatment of the UPOINT system.
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Affiliation(s)
- Muhammad Naveed
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Li Changxing
- Department of Human Anatomy, Medical College of Qinghai University, Xining, China
| | - Awais Ullah Ihsan
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Muhammad Shumzaid
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Pakistan
| | | | | | - Muhammad Saeed
- Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan
| | | | | | - Sobia Noreen
- Faculty of Pharmacy. The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Asadullah Madni
- Faculty of Pharmacy. The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Zhou Xiaohui
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
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Ziętek RJ, Ziętek ZM. Transurethral Microwave Thermotherapy (TUMT) in the Treatment of Benign Prostatic Hyperplasia: A Preliminary Report. Med Sci Monit 2021; 27:e931597. [PMID: 34234095 PMCID: PMC8276617 DOI: 10.12659/msm.931597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 04/18/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND One treatment option for benign prostatic hyperplasia (BPH) is transurethral microwave thermotherapy (TUMT). Unfortunately, TUMT has been increasingly marginalized recently. The aim of this study was to evaluate erectile function and urinary symptoms in patients after TUMT for BPH and compare the results with those of patients on pharmacological treatment for BPH. MATERIAL AND METHODS The study group consisted of 840 patients with BPH treated with TUMT and a control group consisting of 1040 patients who underwent pharmacotherapy. Erectile dysfunction was evaluated using the International Index of Erectile Function-5 questionnaire and the Individual Postoperative Erectile Assessment (IPEA) questionnaire, which was created by the authors for this study. Urinary symptoms were evaluated using the International Prostate Symptom Score (IPSS) questionnaire. RESULTS More than 50% of all patients experienced an improvement in urinary symptoms after TUMT, compared with only approximately 30% in the control group. Differences in each of the IPSS symptom scales between the TUMT and control groups were statistically significant (P<0.031, P<0.041, and P<0.025 for mild, moderate, and severe symptoms, respectively). Improvement in erectile dysfunction after TUMT was also statistically significant (P<0.0001, P<0.0001, P<0.05 for mild, moderate, and severe erectile dysfunction, respectively). Based on the IPEA questionnaire, approximately 24% of the TUMT group reported significant improvement in erectile function, while a decrease in erectile function was reported in the control group. CONCLUSIONS TUMT may still be a valuable option in the treatment of BPH. TUMT may be especially suitable for patients who expect to improve urinary symptoms without decreasing erectile function.
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Affiliation(s)
- Roger J. Ziętek
- Department of Urology, Hospital of the Ministry of Internal Affairs and Administration, Szczecin, Poland
| | - Zbigniew M. Ziętek
- Department of Urology, Hospital of the Ministry of Internal Affairs and Administration, Szczecin, Poland
- Department of Normal and Clinical Anatomy, Pomeranian Medical University, Szczecin, Poland
- Department of General Surgery and Transplantology, Pomeranian Medical University, Szczecin, Poland
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Mykoniatis I, Pyrgidis N, Sokolakis I, Ouranidis A, Sountoulides P, Haidich AB, van Renterghem K, Hatzichristodoulou G, Hatzichristou D. Assessment of Combination Therapies vs Monotherapy for Erectile Dysfunction: A Systematic Review and Meta-analysis. JAMA Netw Open 2021; 4:e2036337. [PMID: 33599772 PMCID: PMC7893498 DOI: 10.1001/jamanetworkopen.2020.36337] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
IMPORTANCE Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes. OBJECTIVE To assess whether different ED combination therapies were associated with improved outcomes compared with first-line ED monotherapy in various subgroups of patients with ED. DATA SOURCES Studies were identified through a systematic search in MEDLINE, Cochrane Library, and Scopus from inception of these databases to October 10, 2020. STUDY SELECTION Randomized clinical trials or prospective interventional studies of the outcomes of combination therapy vs recommended monotherapy in men with ED were identified. Only comparative human studies, which evaluated the change from baseline of self-reported erectile function using validated questionnaires, that were published in any language were included. DATA EXTRACTION AND SYNTHESIS Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. MAIN OUTCOMES AND MEASURES A meta-analysis was conducted that included randomized clinical trials that compared outcomes of combination therapy with phosphodiesterase type 5 (PDE5) inhibitors plus another agent vs PDE5 inhibitor monotherapy. Separate analyses were performed for the mean International Index of Erectile Function (IIEF) score change from baseline and the number of adverse events (AEs) by different treatment modalities and subgroups of patients. RESULTS A total of 44 studies included 3853 men with a mean (SD) age of 55.8 (11.9) years. Combination therapy compared with monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24; I2 = 77%; 95% PI, -0.56 to 4.08). Adding daily tadalafil, low-intensity shockwave therapy, vacuum erectile device, folic acid, metformin hydrochloride, or angiotensin-converting enzyme inhibitors was associated with a significant IIEF score improvement, but each measure was based on only 1 study. Specifically, the weighted mean difference (WMD) in IIEF score was 1.70 (95% CI, 0.79-2.61) for the addition of daily tadalafil, 3.50 (95% CI, 0.22-6.78) for the addition of low-intensity shockwave therapy, 8.40 (95% CI, 4.90-11.90) for the addition of a vacuum erectile device, 3.46 (95% CI, 2.16-4.76) for the addition of folic acid, 4.90 (95% CI, 2.82-6.98) for the addition of metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for the addition of angiotensin-converting enzyme inhibitors. The addition of α-blockers to PDE5 inhibitors was not associated with improvement in IIEF score (WMD, 0.80; 95% CI, -0.06 to 1.65; I2 = 72%). Compared with monotherapy, combination therapy was associated with improved IIEF score in patients with hypogonadism (WMD, 1.61; 95% CI, 0.99-2.23; I2 = 0%), monotherapy-resistant ED (WMD, 4.38; 95% CI, 2.37-6.40; I2 = 52%), or prostatectomy-induced ED (WMD, 5.47; 95% CI, 3.11-7.83; I2 = 53%). The treatment-related AEs did not differ between combination therapy and monotherapy (odds ratio, 1.10; 95% CI, 0.66-1.85; I2 = 78%). Despite multiple subgroup and sensitivity analyses, the levels of heterogeneity remained high. CONCLUSIONS AND RELEVANCE This study found that combination therapy of PDE5 inhibitors and antioxidants was associated with improved ED without increasing the AEs. Treatment with PDE5 inhibitors and daily tadalafil, shockwaves, or a vacuum device was associated with additional improvement, but this result was based on limited data. These findings suggest that combination therapy is safe, associated with improved outcomes, and should be considered as a first-line therapy for refractory, complex, or difficult-to-treat cases of ED.
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Affiliation(s)
- Ioannis Mykoniatis
- Department of Urology, Faculty of Medicine, Aristotle University of Thessaloniki School of Health Sciences, Thessaloniki, Greece
| | - Nikolaos Pyrgidis
- Department of Urology, Faculty of Medicine, Aristotle University of Thessaloniki School of Health Sciences, Thessaloniki, Greece
- Department of Urology, Martha-Maria Hospital Nuremberg, Nuremberg, Germany
| | - Ioannis Sokolakis
- Department of Urology, Martha-Maria Hospital Nuremberg, Nuremberg, Germany
| | - Andreas Ouranidis
- Department of Pharmaceutical Technology, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Petros Sountoulides
- Department of Urology, Faculty of Medicine, Aristotle University of Thessaloniki School of Health Sciences, Thessaloniki, Greece
| | - Anna-Bettina Haidich
- Department of Hygiene, Social-Preventive Medicine & Medical Statistics, Aristotle University of Thessaloniki Medical School, University Campus, Thessaloniki, Greece
| | - Koenraad van Renterghem
- Department of Urology, Jessa Hospital, Hasselt University, Hasselt, Belgium
- Department of Urology, University Hospitals Leuven, Leuven, Belgium
| | | | - Dimitrios Hatzichristou
- Department of Urology, Faculty of Medicine, Aristotle University of Thessaloniki School of Health Sciences, Thessaloniki, Greece
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Mari A, Antonelli A, Cindolo L, Fusco F, Minervini A, De Nunzio C. Alfuzosin for the medical treatment of benign prostatic hyperplasia and lower urinary tract symptoms: a systematic review of the literature and narrative synthesis. Ther Adv Urol 2021; 13:1756287221993283. [PMID: 33912246 PMCID: PMC8047826 DOI: 10.1177/1756287221993283] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 01/05/2021] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) are a bothersome frequent symptom in adult males. This systematic review analyzed the available evidence on the pharmacokinetic and pharmacodynamic features of alfuzosin, and its clinical efficacy both as monotherapy and in combination with other drugs for the treatment of male LUTS/BPH. METHODS A systematic review of the last 10 years was performed using the MEDLINE, EMBASE and Cochrane libraries in March 2020. The protocol for this systematic review was registered on PROSPERO (Central Registration Depository: CRD42020136120) and is available in full on the University of York website. RESULTS Alfuzosin is a quinazoline derivative and, although a nonspecific α1-blocker, exhibits a selective concentration in the prostate compared with plasma in patients with BPH. Three registration trials assessed the safety and efficacy of alfuzosin. The 10 mg daily formulation has a three-layered matrix containing the active substance between two inactive coats allowing a drug release over 20 h. Alfuzosin showed high tolerability, few vasodilatory effects and a low rate of ejaculation disorders over older alpha-blocking compounds thanks to the high uroselectivity of alfuzosin and its preferential concentration at urinary level. Six randomized clinical trials (RCTs) assessed efficacy and safety of alfuzosin versus other alpha-blockers ± placebo: three studies comparing with tamsulosin, one with doxazosin, and two with silodosin or tamsulosin. One RCT investigated the clinical outcomes of alfuzosin with finasteride, two with propiverine and two with phosphodiesterase-5 inhibitors. CONCLUSIONS Alfuzosin is an effective drug for the treatment of LUTS/BPH, with a lower rate of sexual disorders compared with other alpha-blockers. Alfuzosin is also safe with low adverse events in case of concomitant antihypertensive therapy and in patients with cardiovascular morbidity. Safety and efficacy of alfuzosin has been reported also in case of combination therapy with antimuscarinic agents and PDE5i.
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Affiliation(s)
- Andrea Mari
- Department of Urology, University of Florence, Careggi Hospital, San Luca Nuovo, Florence, Italy
- Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi University Hospital, Florence, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Alessandro Antonelli
- Department of Urology, Azienda Ospedaliera Universitaria Integrata Verona, University of Verona, Italy
| | - Luca Cindolo
- Department of Urology, Villa Stuart Private Hospital, Rome, Italy
- “Cure Group”, Hesperia Hospital, Modena, Italy
| | - Ferdinando Fusco
- Department of Woman, Child and General and Specialized Surgery University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Andrea Minervini
- Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi University Hospital, Florence, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Cosimo De Nunzio
- Division of Urology, Ospedale Sant’Andrea, Sapienza University of Rome, Rome, Italy
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Qiangzhao L, Xiaofeng Z, Fenghai Z, Qiong L, Fa Z, Bohong G, Xinsheng X. Efficacy and tolerability of combination therapy with alpha-blockers and phosphodiesterase-5 inhibitors compared with monotherapy for lower urinary tract symptoms: Protocol for a systematic review and network meta-analysis. Medicine (Baltimore) 2020; 99:e22834. [PMID: 33120811 PMCID: PMC7581165 DOI: 10.1097/md.0000000000022834] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 08/26/2020] [Accepted: 09/21/2020] [Indexed: 11/26/2022] Open
Abstract
PURPOSE This study aimed to compare the efficacy and safety of combination therapy consisting of α-blockers and different phosphodiesterase type 5 inhibitors for lower urinary tract symptoms (LUTS) by performing a network meta-analysis. METHOD Relevant articles were retrieved from the Cochrane Library, PubMed, and EMBASE databases. Bayesian network meta-analyses were performed with a random-effect model to compare the efficacy and safety of combination therapy with α-blockers and phosphodiesterase-5 inhibitors for LUTS. The odds ratio (OR), mean difference (MD) and surface under the cumulative ranking curve (SUCRA) were calculated with the GeMTC R package. RESULTS Twenty randomized trials with 4131 patients were included in this network meta-analysis. Based on the SUCRA values, vardenafil (10 mg) combined with α-blockers ranked first, first and sixth; sildenafil (25 mg) combined with α-blockers ranked second, third and first; and tadalafil (20 mg) combined with α-blockers ranked third, second and fourth in IPSS, post void residual, and maximum flow rate, respectively. CONCLUSIONS Combination therapy with α-blockers and phosphodiesterase-5 inhibitors was effective and well tolerated for LUTS. For men who prioritize high efficacy, vardenafil (10 mg) combined with α-blockers seems to be the treatment of choice. For men wishing to optimize minimally invasive treatment, sildenafil (25 mg) and tadalafil (20 mg) combined with α-blockers appears to have a possible advantage in terms of avoiding adverse effects.
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Affiliation(s)
| | | | - Zhou Fenghai
- Department of Urology, Gansu Provincial Hospital
| | - Lian Qiong
- Department of Radiology, Lanzhou University Second Hospital, Lanzhou, Gansu, P.R. China
| | - Zhang Fa
- Department of Urology, Gansu Provincial Hospital
| | - Guo Bohong
- Department of Urology, Gansu Provincial Hospital
| | - Xi Xinsheng
- Department of Urology, Gansu Provincial Hospital
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The hemodynamic interactions of combination therapy with α-blockers and phosphodiesterase-5 inhibitors compared to monotherapy with α-blockers: a systematic review and meta-analysis. Int Urol Nephrol 2020; 52:1407-1420. [DOI: 10.1007/s11255-020-02454-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 03/25/2020] [Indexed: 12/22/2022]
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Leukes V, Walzl G, du Plessis N. Myeloid-Derived Suppressor Cells as Target of Phosphodiesterase-5 Inhibitors in Host-Directed Therapeutics for Tuberculosis. Front Immunol 2020; 11:451. [PMID: 32269568 PMCID: PMC7109258 DOI: 10.3389/fimmu.2020.00451] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 02/27/2020] [Indexed: 01/11/2023] Open
Abstract
Resistance toward current and new classes of anti-tuberculosis (anti-TB) antibiotics are rapidly emerging; thus, innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for shortening therapy regimens without inducing drug resistance. Development of new TB drugs is lengthy and expensive, and success is not guaranteed; thus, alternatives are needed. Repurposed drugs have already passed Food and Drug Administration (FDA) as well as European Medicines Agency (EMA) safety requirements and may only need to prove efficacy against Mycobacterium tuberculosis (M.tb). Phosphodiesterases (PDEs) hydrolyze the catalytic breakdown of both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) to their inactive mononucleotides. Advances in molecular pharmacology have identified 11 PDE families; and the success of sildenafil, a PDE-5 selective inhibitor (PDE-5i), in treating pulmonary hypertension and erectile dysfunction has invigorated research into the therapeutic potential of selective PDE inhibitors in other conditions. Myeloid-derived suppressor cells (MDSCs) suppress anti-TB T-cell responses, likely contributing to TB disease progression. PDE-5i increases cGMP within MDSC resulting in the downregulation of arginase-1 (ARG1) and nitric oxide synthase 2 (NOS2), reducing MDSC's suppressive potential. The effect of this reduction decreases MDSC-induced T-cell-suppressive mechanisms. This review highlights the possibility of HDT targeting of MDSC, using a PDE-5i in combination with the current TB regimen, resulting in improved TB treatment efficacy.
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Affiliation(s)
- Vinzeigh Leukes
- Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
| | - Gerhard Walzl
- Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
| | - Nelita du Plessis
- Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa
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Ückert S, Kedia GT, Tsikas D, Simon A, Bannowsky A, Kuczyk MA. Emerging drugs to target lower urinary tract symptomatology (LUTS)/benign prostatic hyperplasia (BPH): focus on the prostate. World J Urol 2019; 38:1423-1435. [PMID: 31506747 DOI: 10.1007/s00345-019-02933-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 08/28/2019] [Indexed: 01/07/2023] Open
Abstract
OBJECTIVES The benign prostatic syndrome, comprising lower urinary tract symptomatology secondary to benign prostatic hyperplasia/enlargement, represents a major health care issue in westernized countries. The pharmacological management involves alpha-adrenoceptor antagonists, intervention into the hormonal control of prostate growth using inhibitors of the enzyme 5-alpha-reductase, and stimulation of the nitric oxide/cyclic GMP pathway by tadalafil, an inhibitor of the phosphodiesterase type 5. METHODS This review summarizes the achievements which have been made in the development of drug candidates assumed to offer opportunities as beneficial treatment options in the management of the benign prostatic syndrome. RESULTS A review of the literature has revealed that the line of development is focusing on drugs interfering with peripheral neuromuscular/neuronal mechanisms (nitric oxide donor drugs, agonists/antagonists of endogenous peptides, botulinum toxin, NX-1207), the steroidal axis (cetrorelix) or the metabolic turn-over (lonidamine), as well as the combination of drugs already established in the treatment of lower urinary tract symptomatology/benign prostatic hyperplasia (phosphodiesterase 5 inhibitor plus alpha-adrenoceptor antagonist). CONCLUSION Many research efforts have provided the basis for the development of new therapeutic modalities for the management of lower urinary tract dysfunctions, some of which might be offered to the patients in the near future.
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Affiliation(s)
- Stefan Ückert
- Division of Surgery, Department of Urology and Urological Oncology, Hannover Medical School, 30623, Hannover, Germany.
| | - George T Kedia
- Division of Surgery, Department of Urology and Urological Oncology, Hannover Medical School, 30623, Hannover, Germany
| | - Dimitrios Tsikas
- Core Unit Proteomics, Center of Pharmacology and Toxicology, Hannover Medical School, Hannover, Germany
| | - Annika Simon
- Department of Internal Medicine, Hannover Medical School, Hannover, Germany
| | | | - Markus A Kuczyk
- Division of Surgery, Department of Urology and Urological Oncology, Hannover Medical School, 30623, Hannover, Germany
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Tadalafil 5 mg Alone or in Combination with Tamsulosin 0.4 mg for the Management of Men with Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Prospective Observational Trial. J Clin Med 2019; 8:jcm8081126. [PMID: 31362410 PMCID: PMC6723816 DOI: 10.3390/jcm8081126] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 07/17/2019] [Accepted: 07/25/2019] [Indexed: 01/27/2023] Open
Abstract
Tadalafil 5 mg represents the standard for men with Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS)/benign prostatic enlargement (BPE). We carried out an observational trial aiming to assess the efficacy and safety of Tadalafil compared with Tadalafil plus Tamsulosin. Seventy-five patients complaining of ED and LUTS were treated for 12-weeks with Tadalafil plus placebo (TAD+PLA-group) or with combination therapy tadalafil plus tamsulosin (TAD+TAM-group). Efficacy variables were: International Index of Erectile Function (IIEF), International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax) and safety assessments. Data were evaluated using paired samples T-test (baseline vs. 12-weeks) and analysis of variance (Δgroup-TAD+PLA vs. Δgroup-TAD+TAM). At baseline, both groups presented similar characteristics and symptoms scores (all: p > 0.05). From baseline to 12-weeks, all the subjects showed a significant improvement of IIEF, total-IPSS, storage-IPSS, Qmax (all: p < 0.001). Conversely, a significant improvement of voiding-IPSS was observed in TAD+TAM-group (−3.5 points, p < 0.001). Indeed, TAD+PLA-group showed a not significant improvement of voiding-IPSS (−2.0 points, p = 0.074). When we compared between-groups differences at 12-weeks, IIEF (p = 0.255), total-IPSS (p = 0.084) and storage-IPSS (p = 0.08) did not show any statistically significant differences, whereas, voiding-IPSS and Qmax were significantly better in TAD+TAM-group (p = 0.006 and p = 0.027, respectively). No severe treatment adverse events (TAEs) were reported in both groups. Tadalafil achieved the same improvements of IIEF, total-IPSS, storage-IPSS when compared to combination therapy. Instead, Qmax and voiding-IPSS were better managed with combination therapy, without change of TAEs.
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Sun Y, Peng B, Lei GL, Wei Q, Yang L. Study of phosphodiesterase 5 inhibitors and α-adrenoceptor antagonists used alone or in combination for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. MINERVA UROL NEFROL 2019; 72:13-21. [PMID: 31241273 DOI: 10.23736/s0393-2249.19.03408-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION This study sought to compare the improvement in lower urinary tract symptoms (LUTS) and complications of phosphodiesterase type 5 inhibitors (PDE5i) and alpha-blockers (Abs) in combination or alone among males with benign prostatic hyperplasia (BPH). EVIDENCE ACQUISITION We searched the PubMed, Embase, and Cochrane Library databases to identify all studied variables, including lower urinary tract symptoms (LUTS), BPH, Abs, and PDE5i and performed comparisons between combination treatment and single treatments as primary endpoints. Efficacy analysis including the International Prostate Symptom Score (IPSS), quality of life (QOL), maximum urinary flow rate (Qmax), postvoiding residual volume (PVR), and International Index of Erectile Function erectile function domain (IIEF-EF) score. Complications were also recorded. In addition, the secondary endpoint was a comparison of the efficacy and complications between the two single treatments. EVIDENCE SYNTHESIS Nineteen studies involving 2,426 patients met the inclusion criteria. The data synthesized from these studies indicated that the combination treatment is better in efficiency than PDE5i or Abs alone in including IPSS (P<0.00001 in PDE5i; P=0.01 in Abs), QOL (P<0.00001 in PDE5i; P<0.00001 in Abs), Qmax (P<0.00001 in PDE5i; P<0.00001 in Abs), PVR (P=0.04 in PDE5i; P<0.00001 in Abs), and IIEF-EF (P<0.00001 in PDE5i; P<0.00001 in Abs). Regarding complications, only headache (P<0.00001), dyspepsia (P=0.01), and flushing (P=0.04) were more frequent in individuals undergoing the combination treatment. CONCLUSIONS Combination treatment is more effective than PDE5i or Abs alone, though the side effects are not significantly different.
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Affiliation(s)
- Yi Sun
- Department of Urology, West China Hospital, Sichuan University, Xiang, China
| | - Bo Peng
- Department of Urology, Jianyang People Hospital, Jianyang, China
| | - Guo-Lin Lei
- Department of Urology, Jianyang People Hospital, Jianyang, China
| | - Qiang Wei
- Department of Urology, West China Hospital, Sichuan University, Xiang, China -
| | - Lu Yang
- Department of Urology, West China Hospital, Sichuan University, Xiang, China
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Kallidonis P, Adamou C, Kotsiris D, Ntasiotis P, Verze P, Athanasopoulos A. Combination Therapy with Alpha-blocker and Phosphodiesterase-5 Inhibitor for Improving Lower Urinary Tract Symptoms and Erectile Dysfunction in Comparison with Monotherapy: A Systematic Review and Meta-analysis. Eur Urol Focus 2019; 6:537-558. [PMID: 31133414 DOI: 10.1016/j.euf.2019.05.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Revised: 04/27/2019] [Accepted: 05/09/2019] [Indexed: 11/15/2022]
Abstract
CONTEXT The effects of combination therapy consisted of an α-blocker and a phosphodiesterase-5 inhibitor (PDE5I) for the treatment of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). OBJECTIVE To systematically investigate the efficacy and safety of combination therapy in comparison with monotherapy. EVIDENCE ACQUISITION The study complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement and the recommendations of the European Association of Urology Guidelines office. The study was registered in the PROSPERO database with ID CRD42018086619. Only comparative prospective studies, randomized or quasirandomized, with at least one control group with monotherapy were selected for the meta-analysis. The primary endpoint was the quality of life related to LUTS and ED, measured with the International Prostate System Score (IPSS), maximum flow rate (Qmax), postvoid residual (PVR), and International Index of Erectile Function (IIEF). Secondary endpoints included the adverse events rate. In the subgroup analysis of the influence of adding a PDE5I to the treatment of LUTS, the use of different PDE5Is was considered. EVIDENCE SYNTHESIS After the screening of 6687 publications, 25 randomized controlled trials were considered eligible to be included in the meta-analysis. In the combination group, IPSS was lower and Qmax was higher than in the α-blocker group, with mean differences (MDs) of 1.41 (95% confidence interval [CI]: 0.42, 2.41; I2 = 71%, p = 0.005) and -1.01 ml/s (95% CI: -1.58, -0.43; I2 = 58%, p = 0.0006), respectively. The mean change of the IPSS was bigger in the combination group, with an MD of -1.72 (95% CI: -2.55, -0.89; I2 = 37%, p < 0.0001). The mean change of Qmax was insignificant, with an MD of -0.61 (95% CI: -1.57, 0.34; I2 = 63%, p = 0.21), as well as PVR and the mean change of PVR, with MDs of 0.65 (95% CI: -5.37, 6.66; I2 = 76%, p = 0.83) and -20.79 (95% CI: -48.94, 7.37; I2 = 75%, p = 0.15), respectively. The IIEF and the mean change of the IIEF had no difference between the combination group and the PDE5I-monotherapy group, with MDs of 1.82 (95% CI: -0.91, 4.54; I2 = 40%, p = 0.19) and 0.25 (95% CI: -1.11, 1.62; I2 = 47%, p = 0.72), respectively. Regarding the adverse events, the meta-analysis was in favor of monotherapy. None of the studies reported any serious or severe adverse event. CONCLUSIONS Treatment with combination therapy is more effective for the improvement of the IPSS. Less significant improvement was shown in Qmax. The beneficial effect of combination therapy regarding ED remains equivocal. The combination therapy seemed to be safe and well tolerated. PATIENT SUMMARY In this study, we review the effects of the combination therapy consisting of an α-blocker and a phosphodiesterase-5 inhibitor for the treatment of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). We found strong evidence to suggest the combination therapy for the improvement of LUTS. Benefits regarding the treatment of ED are less clear.
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Affiliation(s)
| | | | | | | | - Paolo Verze
- Department of Neurosciences, Reproductive Sciences and Odontostomatology-Urology Unit, Naples, Italy
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Calogero AE, Burgio G, Condorelli RA, Cannarella R, La Vignera S. Treatment of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction. Aging Male 2018; 21:272-280. [PMID: 29378485 DOI: 10.1080/13685538.2018.1432586] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
This article summarizes years of challenging research on erectile dysfunction (ED), a condition that has an important social and cultural relevance. Preclinical and clinical research progress has led to new therapeutic approaches to ED in patients with different comorbidities and particularly in those with low urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). These goals were possible only by combined work of specialists and researchers of different and intertwined medical disciplines. Currently, tadalafil (5 mg/d) is the best choice; other phosphodiesterase-5 inhibitors (PDE5i) are not included among options, despite the growing evidence of therapeutic effects. Different regimens of tadalafil may be prescribed based on patient needs, severity of LUTS/BPH - ED profile, and clinical experience. An integrated approach is necessary to choose for a combined therapy with PDE5i and α-blockers following urological and cardiac counseling in terms of outcomes and adverse effects.
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Affiliation(s)
- Aldo E Calogero
- a Department of Clinical and Experimental Medicine , University of Catania , Catania , Italy
| | - Giovanni Burgio
- a Department of Clinical and Experimental Medicine , University of Catania , Catania , Italy
| | - Rosita A Condorelli
- a Department of Clinical and Experimental Medicine , University of Catania , Catania , Italy
| | - Rossella Cannarella
- a Department of Clinical and Experimental Medicine , University of Catania , Catania , Italy
| | - Sandro La Vignera
- a Department of Clinical and Experimental Medicine , University of Catania , Catania , Italy
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Pattanaik S, Mavuduru RS, Panda A, Mathew JL, Agarwal MM, Hwang EC, Lyon JA, Singh SK, Mandal AK, Cochrane Urology Group. Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia. Cochrane Database Syst Rev 2018; 11:CD010060. [PMID: 30480763 PMCID: PMC6517182 DOI: 10.1002/14651858.cd010060.pub2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Benign prostatic hyperplasia (BPH) refers to non-malignant enlargement of the prostate gland that may cause bothersome lower urinary tract symptoms (LUTS). Alpha-blockers (ABs) and 5-alpha reductase inhibitors (5-ARIs) are the mainstay of medical treatment. Recently, phosphodiesterase inhibitors (PDEIs) that so far have been used mainly to treat erectile dysfunction were introduced to treat male LUTS. OBJECTIVES To assess the effects of PDEIs compared to placebo and other standard of care drugs (ABs and 5-ARIs) in men with LUTS consistent with BPH. SEARCH METHODS We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, and clinical trials registries of the World Health Organization (WHO) and the National Institutes of Health (NIH) (updated 2 August 2018). We performed citation tracking and handsearching of abstracts and conference proceedings. We also contacted study authors to ask for additional information. SELECTION CRITERIA We considered for inclusion in this systematic review randomised controlled trials (RCTs) comparing PDEIs versus placebo, ABs, or 5-ARIs for at least four weeks in men with BPH-LUTS. DATA COLLECTION AND ANALYSIS Three review authors independently screened the literature and extracted data. Primary outcomes were effects on urinary symptoms as assessed by the International Prostate Symptom Score (IPSS-total; score ranging from 0 to 35, with higher values reflecting more symptoms), urinary bother as assessed by the Benign Prostatic Hyperplasia Impact Index (BPHII; score ranging from 0 to 13, with higher values reflecting more bother), and adverse events (AEs). We used GRADE to rate the quality of evidence. We considered short-term (up to 12 weeks) and long-term (12 weeks or longer) results separately. MAIN RESULTS We included a total of 16 randomised trials in this review. The results for primary outcomes are as follows.PDEI versus placebo: PDEIs may result in a small improvement in IPSS-total score (mean difference (MD) 1.89 lower, 95% confidence interval (CI) 2.27 lower to 1.50 lower; n = 4293; low-quality evidence) compared to placebo, and may reduce the BPHII score slightly (MD 0.52 lower, 95% CI 0.71 lower to 0.33 lower; n = 3646; low-quality evidence). Rates of AEs may be increased (risk ratio (RR) 1.42, 95% CI 1.21 to 1.67; n = 4386; low-quality evidence). This corresponds to 95 more AEs per 1000 participants (95% CI 47 more to 151 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.PDEI versus AB: PDEIs and ABs probably provide similar improvement in IPSS-total score (MD 0.22 higher, 95% CI 0.49 lower to 0.93 higher; n = 933; moderate-quality evidence) and may have a similar effect on BPHII score (MD 0.03 higher, 95% CI 1.10 lower to 1.16 higher; n = 550; low-quality evidence) and AEs (RR 1.35, 95% CI 0.80 to 2.30; n = 936; low-quality evidence). This corresponds to 71 more AEs per 1000 participants (95% CI 41 fewer to 264 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.PDEI and AB versus AB alone: the combination of PDEI and AB may provide a small improvement in IPSS-total score (MD 2.56 lower, 95% CI 3.92 lower to 1.19 lower; n = 193; low-quality evidence) compared to AB alone. We found no evidence for BPHII scores. AEs may be increased (RR 2.81, 95% CI 1.53 to 5.17; n = 194; moderate-quality evidence). This corresponds to 235 more AEs per 1000 participants (95% CI 69 more to 542 more per 1000). Study results were limited to treatment duration of four to 12 weeks.PDEI and AB versus PDEI alone: the combination of PDEI and AB may provide a small improvement in IPSS-total (MD 2.4 lower, 95% CI 6.47 lower to 1.67 higher; n = 40; low-quality evidence) compared to PDEI alone. We found no data on BPHII or AEs. Study results were limited to a treatment duration of four weeks.PDEI and 5-ARI versus 5-ARI alone: in the short term (up to 12 weeks), the combination of PDEI and 5-ARI probably results in a small improvement in IPSS-total score (MD 1.40 lower, 95% CI 2.24 lower to 0.56 lower; n = 695; moderate-quality evidence) compared to 5-ARI alone. We found no evidence on BPHII scores or AEs. In the long term (13 to 26 weeks), the combination of PDEI and 5-ARI likely results in a small reduction in IPSS-total score (MD 1.00 less, 95% CI 1.83 lower to 0.17 lower; n = 695; moderate-quality evidence). We found no evidence about effects on BPHII scores. There may be no difference in rates of AEs (RR 1.07, 95% CI 0.84 to 1.36; n = 695; low-quality evidence). This corresponds to 19 more AEs per 1000 participants (95% CI 43 fewer to 98 more per 1000).We found no trials comparing other combinations of treatments or comparing different PDEI agents. AUTHORS' CONCLUSIONS Compared to placebo, PDEI likely leads to a small reduction in IPSS-total and BPHII sores, with a possible increase in AEs. There may be no differences between PDEI and AB with regards to improvement in IPSS-total, BPHII, and incidence of AEs. There appears to be no added benefit of PDEI combined with AB compared to PDEI or AB alone or PDEI combined with 5-ARI compared to ARI alone with regards to urinary symptoms. Most evidence was limited to short-term treatment up to 12 weeks and of moderate or low certainty.
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Affiliation(s)
- Smita Pattanaik
- Post Graduate Institute of Medical Education and ResearchDepartment of PharmacologyChandigarhIndia160012
| | - Ravimohan S Mavuduru
- Post Graduate Institute of Medical Education and ResearchDepartment of UrologyChandigarhIndia
| | - Arabind Panda
- Christian Medical CollegeDepartment of UrologyVelloreIndia
| | - Joseph L Mathew
- Post Graduate Institute of Medical Education and ResearchDepartment of PediatricsChandigarhIndia160012
| | - Mayank M Agarwal
- Post Graduate Institute of Medical Education and ResearchDepartment of UrologyChandigarhIndia
| | - Eu Chang Hwang
- Chonnam National University Medical School, Chonnam National University Hwasun HospitalDepartment of UrologyHwasunKorea, South
| | - Jennifer A Lyon
- Children's Mercy HospitalLibrary Services2401 Gillham RoadKansas CityMissouriUSA64118
| | - Shrawan K Singh
- Post Graduate Institute of Medical Education and ResearchDepartment of UrologyChandigarhIndia
| | - Arup K Mandal
- Post Graduate Institute of Medical Education and ResearchDepartment of UrologyChandigarhIndia
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Zhang J, Li X, Yang B, Wu C, Fan Y, Li H. Alpha-blockers with or without phosphodiesterase type 5 inhibitor for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review and meta-analysis. World J Urol 2018; 37:143-153. [PMID: 29948047 DOI: 10.1007/s00345-018-2370-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 06/07/2018] [Indexed: 01/05/2023] Open
Abstract
PURPOSE Recently, several randomized controlled trials (RCTs) explored the effects of α-blockers with or without phosphodiesterase type 5 inhibitors (PDE5-Is) for lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). However, the results were inconsistent. We performed this meta-analysis to evaluate the role of combination therapy (α-blockers and PDE5-Is) in patients with LUTS/BPH. MATERIALS AND METHODS Databases including PubMed, Cochrane library, Web of Science, and Embase were searched for qualified RCTs. Pooled mean differences (MDs) and odds ratios (ORs) were calculated to measure the effects and adverse events in combination therapy. Moreover, subgroup analyses of ethnicity, dosage of PDE5-Is, treatment duration, and severity of LUTS/BPH were performed. In addition, trial sequential analyses (TSAs) were used to assess whether the evidence for the results was sufficient. RESULTS Overall, this study identified 11 eligible RCTs, including 855 LUTS/BPH patients. Patients receiving combination therapy had better improvement in international prostate symptom score (IPSS: MD: 1.66, 95% CI - 3.03 to - 0.29), maximum urinary flow rate (Qmax: MD: 0.94, 95% CI 0.24-1.64), and international index of erectile function (IIEF: MD: 4.73, 95% CI 2.95-6.51), comparing those without PDE5-Is. Besides, subgroup analyses indicated that the effects of combination treatment were associated with ethnicity, treatment duration, and severity of LUTS/BPH. By TSA, the findings in the current study were based on sufficient evidence. CONCLUSIONS Our results indicated that combination therapy can significantly improve IPSS, Qmax, and IIEF in patients with LUTS/BPH. Combination therapy might be more suitable for these patients.
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Affiliation(s)
- Jianzhong Zhang
- Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xiao Li
- Department of Urology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 210009, China
| | - Bin Yang
- Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Cheng Wu
- Department of Urology, Dongtai People's Hospital, Jiangsu, 224200, China
| | - Yanghua Fan
- Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Hongjun Li
- Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.
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Sun X, Guan W, Liu H, Tang K, Yan L, Zhang Y, Zeng J, Chen Z, Xu H, Ye Z. Efficacy and safety of PDE5-Is and α-1 blockers for treating lower ureteric stones or LUTS: a meta-analysis of RCTs. BMC Urol 2018; 18:30. [PMID: 29724204 PMCID: PMC5934901 DOI: 10.1186/s12894-018-0345-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 04/23/2018] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Lower ureteric stones and lower urinary tract symptoms are common in urology.Drug treatment is one of standard therapy,but the efficacy was controversial.Thus we aimed to investigate the efficacy and safety of monotherapy or combination therapy of adrenoceptor1 blockers and phosphodiesterase5 inhibitors for treatment. METHODS Randomized controlled trials up to November 2016 were retrieved from PubMed, the Cochrane Library, Web of Science and Embase. A total of 17 studies were included. We analyzed data through random or fixed effect models. The heterogeneity between studies was assessed by the I2 test statistic. RESULTS As for lower ureter stones, our analysis demonstrated tadalafil had a significantly lower incidence of abnormal ejaculation than adrenoceptor1 blockers (2.31 95%CI 0.22to0.84, P = 0.01),while combination therapy had a higher expulsion rate (2.49 95%CI 1.44to4.29, P = 0.001) and shorter expulsion time (- 1.98 95%CI -3.08to0.88, P = 0.0004) than tamsulosin. As for lower urinary tract symptoms, our analysis indicated adrenoceptor1 blockers was more effective than phosphodiesterase5 inhibitors on decreasing International Prostate Symptom Score (1.96 95%CI 0.03to3.89, P = 0.05) and Post-Void Residual (9.41 95%CI 1.40to14.41, P = 0.02) and phosphodiesterase5 inhibitors showed a greater effect than adrenoceptor1 blockers on improving Erectile Dysfunction (2.23 95%CI 1.24to3.22, P<0.0001).Combination therapy had a significantly better effect on International Prostate Symptom Score (1.47 95%CI 1.25to1.69, P<0.0001), Maximum flow rate (0.87 95%CI 0.71to1.04, P<0.0001), Post-Void Residual (10.74 95%CI 3.53to17.96,P = 0.004) and Quality of life (0.59 95%CI 0.22to0.97, P = 0.002) but was associated with higher incidences of adverse events (3.40 95%CI 1.82to6.36, P = 0.0001) than adrenoceptor1 blockers. Combination therapy had a significantly better effect on International Prostate Symptom Score (4.19 95%CI 3.34to5.04, P<0.0001), Maximum flow rate (1.86 95%CI 1.32to2.39, P<0.0001), Post-Void Residual (22.58 95%CI 9.13to36.04, P = 0.001) and Quality of life (0.68 95%CI 0.37to1.00, P<0.0001) without higher incidences of adverse events than PDE5-Is. CONCLUSIONS In conclusion, this meta-analysis suggested combination therapy had a best efficacy of therapy for lower ureteric stones or lower urinary tract symptoms correlated with benign prostatic hyperplasia than monotherapy. Adrenoceptor1 blockers was more effective than phosphodiesterase5 inhibitors on International Prostate Symptom Score and Post-Void Residual. Both monotherapy and combination therapy were safe.
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Affiliation(s)
- Xifeng Sun
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.,Institute of Urology of Hubei Province, Wuhan, 430030, China
| | - Wei Guan
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Haoran Liu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.,Institute of Urology of Hubei Province, Wuhan, 430030, China
| | - Kun Tang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.,Institute of Urology of Hubei Province, Wuhan, 430030, China
| | - Libin Yan
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.,Institute of Urology of Hubei Province, Wuhan, 430030, China
| | - Yangjun Zhang
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.,Institute of Urology of Hubei Province, Wuhan, 430030, China
| | - Jin Zeng
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.,Institute of Urology of Hubei Province, Wuhan, 430030, China
| | - Zhiqiang Chen
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.,Institute of Urology of Hubei Province, Wuhan, 430030, China
| | - Hua Xu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. .,Institute of Urology of Hubei Province, Wuhan, 430030, China.
| | - Zhangqun Ye
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.,Institute of Urology of Hubei Province, Wuhan, 430030, China
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Use of 5-Phosphodiesterase Inhibitors in Patients with Luts Secondary to Bph: Our Experience and Review of the Literature. Urologia 2018. [DOI: 10.5301/urologia.5000021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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26
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Xybilun ® , actualité 2018 de la dysfonction érectile. SEXOLOGIES 2018. [DOI: 10.1016/j.sexol.2018.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Barone I, Giordano C, Bonofiglio D, Andò S, Catalano S. Phosphodiesterase type 5 and cancers: progress and challenges. Oncotarget 2017; 8:99179-99202. [PMID: 29228762 PMCID: PMC5716802 DOI: 10.18632/oncotarget.21837] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 09/23/2017] [Indexed: 01/05/2023] Open
Abstract
Cancers are an extraordinarily heterogeneous collection of diseases with distinct genetic profiles and biological features that directly influence response patterns to various treatment strategies as well as clinical outcomes. Nevertheless, our growing understanding of cancer cell biology and tumor progression is gradually leading towards rational, tailored medical treatments designed to destroy cancer cells by exploiting the unique cellular pathways that distinguish them from normal healthy counterparts. Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain cancer cells. In this review, we present an overview of the experimental and clinical evidences highlighting the role of PDE5 in the pathogenesis and prevention of various malignancies. Current data are still not sufficient to draw conclusive statements for cancer patient management, but could provide further rational for testing PDE5-targeting drugs as anticancer agents in clinical settings.
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Affiliation(s)
- Ines Barone
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, Italy
| | - Cinzia Giordano
- Centro Sanitario, University of Calabria, Arcavacata di Rende, CS, Italy
| | - Daniela Bonofiglio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, Italy
| | - Sebastiano Andò
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, Italy
| | - Stefania Catalano
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, Italy
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Thomas D, Chughtai B, Kini M, Te A. Emerging drugs for the treatment of benign prostatic hyperplasia. Expert Opin Emerg Drugs 2017; 22:201-212. [PMID: 28829208 DOI: 10.1080/14728214.2017.1369953] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
INTRODUCTION Benign prostatic hyperplasia (BPH) is a common condition affecting over 50% of men as they reach their 5th decade of life. This leads to a number of sequelae such as lower urinary tract symptoms, urinary retention and a decrease in quality of life. Currently, the available treatments for BPH are alpha blockers and 5-alpha reductase inhibitors. Clinical studies have demonstrated these medical options are effective in alleviating a patient's symptoms, however there are a number of side effects. There is a paucity of information regarding long-term use of these medications. The purpose of this review is to identify potential and emerging medications for the treatment of BPH. Areas covered: Articles used in this review were retrieved from Pubmed, Google and through searching the PharmaProjects database over the last 10 years, giving the reader an in-depth knowledge about the current pharmacological agents available and other potential treatments for BPH. Expert opinion: The new paradigm of BPH treatment depends on addressing a patient's specific constellation of symptoms. This allows to tailor therapy of increasing efficacy and reduce adverse events that our patients have by increasing dosage.
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Affiliation(s)
- Dominique Thomas
- a Department of Urology , Weill Cornell Medicine-New York Presbyterian , New York , NY , USA
| | - Bilal Chughtai
- a Department of Urology , Weill Cornell Medicine-New York Presbyterian , New York , NY , USA
| | - Mitali Kini
- a Department of Urology , Weill Cornell Medicine-New York Presbyterian , New York , NY , USA
| | - Alexis Te
- a Department of Urology , Weill Cornell Medicine-New York Presbyterian , New York , NY , USA
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EFFECT OF TADALAFIL THAT WAS ADDITIONALLY ADMINISTERED TO PATIENTS RECEIVING AN ALPHA1-BLOCKER IN JAPANESE MEN WITH LOWER URINARY TRACT SYMPTOMS SUGGESTIVE OF BENIGN PROSTATIC HYPERPLASIA. Nihon Hinyokika Gakkai Zasshi 2017; 107:28-33. [PMID: 28132988 DOI: 10.5980/jpnjurol.107.28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
(Objectives) Alpha1-blockers have been widely used for the treatment of lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). As improvement of symptoms occur relatively early after the administration of alpha-1 blockers, the blockers are considered to be extremely beneficial. However, some patients respond poorly to the blockers, providing additional treatment is difficult. Here we examined the efficacy of tadalafil that was additionally administered to patients receiving an oral alpha-1 blocker. (Subjects and methods) The subjects were patients who had been diagnosed with BPH/LUTS, had received an oral alpha1-blocker for at least 1 month, and had responded poorly to the alpha-1 blocker treatment (International Prostate Symptom Score IPSS ≥8 and/or QOL index ≥3). Tadalafil 5 mg was administered on consecutive days to patients orally receiving an alpha-1 blocker. The following were measured before and at 4 and 8 weeks after the administration of tadalafil to evaluate the add-on effect of Tadalafil: IPSS, QOL index, Overactive Bladder Symptom Score (OABSS), maximal urinary flow rate, residual urine volume, and International Index of Erectile Function-5 (IIEF-5). (Results) We studied 41 patients until 8 weeks after the drug administration. Tadalafil produced significant improvement in IPSS, QOL index, OABSS, and IIEF-5 at 4 weeks after the administration, as compared with before administration (P < 0.05). The improvement was even more significant at 8 weeks. However, the maximal urinary flow rate or residual urine volume did not differ significantly at any time point. (Conclusions) The results of this study revealed that additional administration of tadalafil improves not only urinary conditions but also sexual function in patients with BPH/LUTS.
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Fawzi A, Kamel M, Salem E, Desoky E, Omran M, Elgalaly H, Sakr A, Maarouf A, Khalil S. Sildenafil citrate in combination with tamsulosin versus tamsulosin monotherapy for management of male lower urinary tract symptoms due to benign prostatic hyperplasia: A randomised, double-blind, placebo-controlled trial. Arab J Urol 2016; 15:53-59. [PMID: 28275519 PMCID: PMC5329701 DOI: 10.1016/j.aju.2016.11.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 11/20/2016] [Accepted: 11/22/2016] [Indexed: 12/02/2022] Open
Abstract
Objective To assess the additive effect of sildenafil citrate to tamsulosin in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) in men with or without erectile dysfunction (ED). Patients and methods In all, 150 men with untreated LUTS/BPH with or without ED were randomised to receive sildenafil 25 mg once daily (OD) or placebo OD (night time) combined with tamsulosin 0.4 mg OD (day time) for 6 months. Changes from pre-treatment scores in International Prostate Symptom Score (IPSS), IPSS-quality of life (QoL) score, maximum urinary flow rate (Qmax), and the five-item version of the International Index of Erectile Function questionnaire (IIEF-5) were assessed at 3 and 6 months. Safety profiles were assessed by physical examination and monitoring clinical adverse events. Results Group A comprised of men who received tamsulosin and sildenafil (75 men), whilst those in Group B received tamsulosin and placebo (75). The IPSS was significantly improved in Group A compared to Group B, at −29.3% vs −13.7% (P = 0.039) at 3 months and −37% vs −19.6% (P = 0.043) at 6 months after treatment. Qmax significantly improved in both groups compared with before treatment (P < 0.001). The IIEF-5 scores improved more in Group A than in Group B, at 58.7% vs 11.7% at 3 months and 62.4% vs 12.4% at 6 months after treatment (both P < 0.001). Conclusion Sildenafil citrate combined with tamsulosin improved LUTS, erectile function, and patient QoL more than tamsulosin monotherapy with the merit of a comparable safety profile in patients with LUTS/BPH.
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Key Words
- BMI, body mass index
- Benign prostatic hyperplasia (BPH)
- CONSORT, Consolidated Standards of Reporting Trials
- ED, erectile dysfunction
- IIEF-5, five-item version of the International Index of Erectile Function questionnaire
- Lower urinary tract symptoms (LUTS)
- NO, nitric oxide
- OD, once daily
- PDE5-I, phosphodiesterase type 5 inhibitor
- Qmax, maximum urinary flow rate
- QoL, quality of life
- RCT, randomised controlled trial
- SMD, standardised mean difference
- Sildenafil
- Tamsulosin
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Affiliation(s)
- Amr Fawzi
- Department of Urology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Mostafa Kamel
- Department of Urology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Emad Salem
- Department of Urology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Esam Desoky
- Department of Urology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Mohamed Omran
- Department of Urology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Hazem Elgalaly
- Department of Urology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ahmed Sakr
- Department of Urology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Aref Maarouf
- Department of Urology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Salem Khalil
- Department of Urology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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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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Kolontarev K, Govorov A, Kasyan G, Priymak D, Pushkar D. Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors. Cent European J Urol 2016; 69:398-403. [PMID: 28127458 PMCID: PMC5260456 DOI: 10.5173/ceju.2016.879] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/04/2016] [Accepted: 10/16/2016] [Indexed: 12/26/2022] Open
Abstract
INTRODUCTION Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptom (LUTS) development in men [1]. The intensity of the symptoms may vary from mild to severe, significantly affecting the quality of life. Erectile dysfunction (ED) is one of the most challenging issues in modern urology that significantly influences the quality of life in men worldwide. The objective of this literature review was to analyze the current drug therapies of patients with BPH-LUTS, with the special emphasis on PDE5 inhibitors. MATERIAL AND METHODS The authors searched the literature for the period from 2000 until 2015 in MEDLINE and PubMed. RESULTS Twenty-three articles were selected based on their reliability. A detailed analysis of the selected papers was performed. Primary attention was given to articles describing the use of PDE5. Works describing the use of different groups of drugs in patients with BPH-LUTS were also selected. CONCLUSIONS The current literature analysis suggests that the introduction of PDE5 inhibitors in clinical practice for the treatment of patients with BPH-LUTS will allow for significant expansion of the therapeutic options for the treatment of this disease.
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Affiliation(s)
| | | | - George Kasyan
- Moscow State University of Medicine and Dentistry, Moscow, Russia
| | | | - Dmitry Pushkar
- Moscow State University of Medicine and Dentistry, Moscow, Russia
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Gumrah A, Tanidir Y, Tinay I, Ozyurek M, Tarcan T. The effect of doxazosin and sildenafil citrate combination on bladder tissue contractility, alpha adrenergic receptor, and iNOS subtype expression in a male rat model of partially bladder outlet obstruction. Neurourol Urodyn 2016; 36:1479-1487. [DOI: 10.1002/nau.23155] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 09/12/2016] [Indexed: 01/06/2023]
Affiliation(s)
- Abdulkadir Gumrah
- Department of Urology; Marmara University School of Medicine; Istanbul Turkey
| | - Yiloren Tanidir
- Department of Urology; Marmara University School of Medicine; Istanbul Turkey
| | - Ilker Tinay
- Department of Urology; Marmara University School of Medicine; Istanbul Turkey
| | - Mustafa Ozyurek
- Ergun Özalp Basic Research Laboratory; Marmara University School of Medicine; Istanbul Turkey
| | - Tufan Tarcan
- Department of Urology; Marmara University School of Medicine; Istanbul Turkey
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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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Mostafa T. Useful Implications of Low-dose Long-term Use of PDE-5 Inhibitors. Sex Med Rev 2016; 4:270-284. [PMID: 27871960 DOI: 10.1016/j.sxmr.2015.12.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2015] [Revised: 12/24/2015] [Accepted: 12/24/2015] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Phosphodiesterase type 5 (PDE-5) hydrolyzes cyclic guanylate monophosphate (cGMP) specifically to 5' GMP, promoting successful corporeal vascular relaxation and penile erection during sexual stimulation. Oral PDE-5 inhibitors such as sildenafil, vardenafil, tadalafil, and avanafil have provided noninvasive, effective, well-tolerated treatment for erectile dysfunction (ED) patients and, at the same time, stimulated both academic and clinical interests. Lately, some oral PDE-5 inhibitors were released as low-dose preparations with the concept of potential daily administration and long-term use. AIM To highlight the possible potential implications of low-dose long-term use of PDE-5 inhibitors. METHOD A systematic review was carried out until December 2015 based on a search of all concerned articles in MEDLINE, medical subjects heading (MeSH) databases, Scopus, The Cochrane Library, EMBASE, and CINAHL databases without language restriction. Key words used to assess the outcome and estimates for concerned associations were: PDE-5 inhibitors; erectile dysfunction; low-dose; long-term; sildenafil; tadalafil; vardenafil; avanafil. MAIN OUTCOME MEASURES Demonstrating different implications for low-dose long-term use of PDE-5 inhibitors. RESULTS Low-dose and/or long-term use of PDE-5 inhibitors was shown to put forth beneficial sound effects in different medical implications with potentials that could be extended for different utilities. These implications included sexual, urogenital, cardiovascular, pulmonary, cutaneous, gastrointestinal, and reproductive, as well as neurological disorders. However, it is evident that most potential appliances were carried out experimentally on preclinical studies with off-label indications. CONCLUSION Making use of and exploring low-dose and/or long-term use of several PDE-5 inhibitors for their possible implications seem to be valuable in different medical disorders. Increased knowledge of the drug characteristics, comparative treatment regimens, optimal prescribing patterns, and well-designed clinical trials are needed before these agents can be recommended for use.
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Affiliation(s)
- Taymour Mostafa
- Department of Andrology, Sexology & STDs, Faculty of Medicine, Cairo University, Cairo, Egypt.
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Lee YC, Juan YS, Liu CC, Bao BY, Wang CJ, Wu WJ, Huang CN, Huang SP. The association of endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with responsiveness to a selective α1-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms. BJU Int 2016; 118:313-9. [DOI: 10.1111/bju.13468] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
- Yung-Chin Lee
- Department of Urology; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
- Department of Urology; Faculty of Medicine; Kaohsiung Medical University; Kaohsiung Taiwan
| | - Yung-Shun Juan
- Department of Urology; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
- Department of Urology; Faculty of Medicine; Kaohsiung Medical University; Kaohsiung Taiwan
- Department of Urology; Kaohsiung Municipal Hsiao-Kang Hospital; Kaohsiung Taiwan
| | - Chia-Chu Liu
- Department of Urology; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
- Department of Urology; Faculty of Medicine; Kaohsiung Medical University; Kaohsiung Taiwan
- Department of Health; Executive Yuan; Pingtung Hospital; Pingtung Taiwan
| | - Bo-Ying Bao
- Department of Pharmacy; China Medical University; Taichung Taiwan
- Sex Hormone Research Center; China Medical University Hospital; Taichung Taiwan
- Department of Nursing; Asia University; Taichung Taiwan
| | - Chii-Jye Wang
- Department of Urology; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
- Department of Urology; Faculty of Medicine; Kaohsiung Medical University; Kaohsiung Taiwan
| | - Wen-Jeng Wu
- Department of Urology; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
- Department of Urology; Faculty of Medicine; Kaohsiung Medical University; Kaohsiung Taiwan
| | - Chun-Nung Huang
- Department of Urology; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
- Department of Urology; Faculty of Medicine; Kaohsiung Medical University; Kaohsiung Taiwan
| | - Shu-Pin Huang
- Department of Urology; Kaohsiung Medical University Hospital; Kaohsiung Taiwan
- Department of Urology; Faculty of Medicine; Kaohsiung Medical University; Kaohsiung Taiwan
- Graduate Institute of Medicine; College of Medicine; Kaohsiung Medical University; Kaohsiung Taiwan
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Clinical efficacy of combination therapy with an alpha blocker and low-dose sildenafil on post-therapy lower urinary tract symptoms after low-dose-rate brachytherapy for prostate cancer. World J Urol 2016; 34:1269-74. [DOI: 10.1007/s00345-016-1777-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 01/28/2016] [Indexed: 10/22/2022] Open
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Zhao C, Kwan Park J. Phosphodiesterase Type 5 Inhibitor and Erectile Dysfunction in Lower Urinary Tract Symptoms. Low Urin Tract Symptoms 2015; 4 Suppl 1:75-80. [PMID: 26676704 DOI: 10.1111/j.1757-5672.2011.00121.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Benign prostatic hyperplasia (BPH) is one of the most common diseases in older men and mostly induces lower urinary tract symptoms (LUTS). Multiple studies have shown that BPH inducing LUTS are intensely correlated with erectile dysfunction (ED) and that severity of LUTS was proportional to ED severity. Although a direct causal relationship has not been clarified, a tentative pathophysiology has been suggested to interpret the relationship between two disorders. Androgen plays an important role in the maintenance of the functional and structural integrity of the lower urinary tract and penis. Low testosterone, especially free testosterone, worsened detrusor overactivity and replacement of testosterone improved LUTS in the hypogonadal BPH patients. Nitric oxide synthase and nitric oxide are decreased in the transition zone of the hyperplastic prostate but phosphodiesterase types 4, 5, 11 are prominent in transition zone of hyperplastic prostate. Phosphodiesterase type 5 (PDE5) inhibitor with a long half-life could obtain the desired effect; therefore, tadalafil and undenafil frequently have been used to evaluate the effects in the two disorders. In clinical trials, tadalafil showed improvement of BPH-induced LUTS, but few of the studies showed a significant improvement on uroflowmetry. PDE5 inhibitors increase the concentration of cyclic guanosine monophosphate (cGMP) in plasma and smooth muscle, promoting erection of the penis, as well as relaxation of the bladder neck and prostate, leading to natural voiding. Sexual function and LUTS should be assessed and discussed with the patient when choosing the appropriate strategy and the patient's response to treatment should also be evaluated at the same time.
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Affiliation(s)
- Chen Zhao
- Department of Urology, Medical School, and Institute for Medical Sciences, and Research Institute of Chonbuk National University, Chonbuk National University Hospital, Jeonbuk, Korea
| | - Jong Kwan Park
- Department of Urology, Medical School, and Institute for Medical Sciences, and Research Institute of Chonbuk National University, Chonbuk National University Hospital, Jeonbuk, Korea
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Choi H, Kim HJ, Bae JH, Kim JH, Moon DG, Cheon J, Yeo JK. A Meta-Analysis of Long- Versus Short-Acting Phosphodiesterase 5 Inhibitors: Comparing Combination Use With α-Blockers and α-Blocker Monotherapy for Lower Urinary Tract Symptoms and Erectile Dysfunction. Int Neurourol J 2015; 19:237-45. [PMID: 26739178 PMCID: PMC4703931 DOI: 10.5213/inj.2015.19.4.237] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/14/2015] [Indexed: 11/21/2022] Open
Abstract
PURPOSE Combination therapy with an α-1-adrenergic blocker and phosphodiesterase type 5 inhibitors (PDE5Is) has shown improvements in lower urinary tract symptoms (LUTS) with negligible side effects. Nonetheless, decisive advantages in symptom improvement were insufficient, and there were no clinical differences between long- or short-acting PDE5Is in combination with combination medication. METHODS To review the studies on α-1-adrenergic blocker monotherapy and combination therapy with long vs. short-acting PDE5Is in their use in LUTS and erectile dysfunction (ED). A search of the MEDLINE, Embase, Cochrane Library, and KoreaMed databases was conducted from 2000 to 2014 using combinations of the relevant terms. Among the 323 relevant references discovered, 10 were selected for meta-analysis. The data showed that 616 men received combination therapy (PDE5Is with α-1-adrenergic blockers) or α-1-adrenergic blocker monotherapy. RESULTS Meta-analysis of the combination therapy showed it was more effective than α-blockers in improving symptoms, with a mean International Prostrate Symptom Score change difference of -1.93 while those of the long- vs. short-acting PDE5I were -2.12 vs. -1.70. Compared to maximum flow rate (Qmax) value with monotherapy, the Qmax increased more with the combination therapy (mean difference of 0.71) while change values were 0.14 and 1.13 for the long- and short-acting PDE5Is, respectively. Residual urine decreased more with the combination therapy than it did with α-1-adrenergic blocker monotherapy with a mean difference of -7.09 while the mean residual urine change values for long- vs. short-acting PDE5Is were -18.83 vs. -5.93. The International Index of Erectile Function value increased by 3.99, 2.85, and 4.85 following combination therapy, and therapy with long- and short-acting PDE5Is. CONCLUSIONS Our meta-analysis suggests that PDE5Is can significantly improve LUTS in men with benign prostatic hyperplasia/ED. Furthermore, combination PDE5I and α-1-adrenergic blocker could be a more effective treatment than α-1-adrenergic blocker monotherapy, and the differences between long and short-acting agents were minimal.
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Affiliation(s)
- Hoon Choi
- Department of Urology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Hyun Jung Kim
- Institute for Evidence-Based Medicine, The Korean Branch of Australasian Cochrane Center, Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jae Hyun Bae
- Department of Urology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Jae Heon Kim
- Department of Urology, Soonchunhyang University Seoul Hospital, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Du Geon Moon
- Department of Urology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Jun Cheon
- Department of Urology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Jeong-Kyun Yeo
- Department of Urology, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
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Wang XH, Wang X, Shi MJ, Li S, Liu T, Zhang XH. Systematic review and meta-analysis on phosphodiesterase 5 inhibitors and α-adrenoceptor antagonists used alone or combined for treatment of LUTS due to BPH. Asian J Androl 2015; 17:1022-1032. [PMID: 25994648 PMCID: PMC4814957 DOI: 10.4103/1008-682x.154990] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 11/26/2014] [Accepted: 03/04/2015] [Indexed: 12/24/2022] Open
Abstract
The aim of this systematic review is to determine the comparative effectiveness and safety of phosphodiesterase 5 inhibitors (PDE5-Is) and α-blockers used alone or combined for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). An electronic search of PubMed, Cochrane Library and Embase up to January 2014 was performed to identify randomized controlled trials comparing the efficacy and safety of PDE5-Is and α-blockers for treatment of lower urinary tract symptoms due to benign prostatic hyperplasia, which assessed IPSS score, maximum flow rate, postvoided residual urine, quality of life and Erectile Function (IIEF) score as outcomes. Data were analyzed by fixed or random effect models using Cochrane Collaboration review manager software. A total of 12 studies were included. Our novel data demonstrated that there was a trend that α-blockers were more efficacious than PDE5-Is on decreasing IPSS score and increasing maximum flow rate. α-blockers were significantly more effective than PDE5-Is on reduction of postvoided residual urine with a mean difference of 3.67 (95% CI 1.56 to 5.77, P = 0.0006) and PDE5-Is showed greater effect than α-blockers on increasing IIEF score with a mean difference of 9.82 (95% CI 3.80 to 15.85, P = 0.001). In conclusion, our novel data demonstrated that PDE5-Is plus ABs ranked the highest on the improvement of LUTS/BPH. PDE5-Is monotherapy was also effective in this kind of disorder except less reduction of PVR than ABs. In addition, both combined- or mono-therapy were safe.
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Affiliation(s)
- Xing-Huan Wang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Xiao Wang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Ming-Jun Shi
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Sheng Li
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Tao Liu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Xin-Hua Zhang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
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Peixoto CA, Gomes FODS. The role of phosphodiesterase-5 inhibitors in prostatic inflammation: a review. JOURNAL OF INFLAMMATION-LONDON 2015; 12:54. [PMID: 26379476 PMCID: PMC4570643 DOI: 10.1186/s12950-015-0099-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Accepted: 08/31/2015] [Indexed: 12/18/2022]
Abstract
Clinical and basic experimental evidence indicates that chronic inflammation is the greatest factor in benign prostatic hyperplasia (BPH) progression, which is the most common cause of Lower Urinary Tract Symptoms (LUTS). The use of anti-inflammatory agents such as steroids, cyclooxygenase-2 (COX-2) and phytotherapics have been investigated as forms of treatment for various prostate diseases. Recent evidence has demonstrated that PDE5 inhibitors (PDE5Is) improve symptoms of BPH/LUTS, possibly as a result of the relaxing of the smooth muscle fibers of the bladder and prostate by NO/cGMPc signaling, or by improving RhoA/Rho-kinase (ROCK), and reduction of the hyperactivity of the autonomic nervous system. However, some results have suggested that besides vasodilatation and their anti-proliferative effect, PDE5Is exert a direct anti-inflammatory effect, by raising cGMP. Given that inflammation is major factor in benign prostatic hyperplasia (BPH) progression, PDE5Is could act also restore prostatic function as they act as potent anti-inflammatory drugs. This review aims to provide a comprehensive summary of the use of phosphodiesterase-5 inhibitors to treat prostatic inflammation.
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Affiliation(s)
- Christina Alves Peixoto
- Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM-FIOCRUZ), Fundação Oswaldo Cruz, Av. Moraes Rego s/n, CEP: 50670-420, Cidade Universitária, Recife, PE Brazil
| | - Fabiana Oliveira Dos Santos Gomes
- Laboratório de Ultraestrutura, Centro de Pesquisas Aggeu Magalhães (CPqAM-FIOCRUZ), Fundação Oswaldo Cruz, Av. Moraes Rego s/n, CEP: 50670-420, Cidade Universitária, Recife, PE Brazil
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Yazici CM, Kurt O. Combination therapies for the management of nocturia and its comorbidities. Res Rep Urol 2015; 7:57-63. [PMID: 25945323 PMCID: PMC4408945 DOI: 10.2147/rru.s51140] [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] [Indexed: 01/20/2023] Open
Abstract
Nocturia is the most bothersome lower urinary tract symptom. It has a multifactorial etiology. It had been thought nocturia was a nonspecific symptom of lower urinary system dysfunction, but it has been determined that many diseases, related to different organ systems, might be reasons for this nonspecific symptom. Along with the importance of systemic diseases that cause nocturia, the symptom itself has adverse effects on patients’ health and quality of life. There are several studies reporting a direct relationship between nocturia and depression, cognitive dysfunction, mood disturbances, falls, and fractures. For this reason, it is important to treat nocturia both to increase quality of life and to decrease related complications. Treatment opportunities have been under investigation for 20 years. Most of the studies in the literature have reported the results of single-drug medication on nocturia, which may be insufficient for a situation that has such a multifactorial etiology. In this review, we evaluated the success of different treatment combinations on nocturia.
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Affiliation(s)
- Cenk Murat Yazici
- Department of Urology, Namik Kemal University School of Medicine, Tekirdag, Turkey
| | - Omer Kurt
- Department of Urology, Namik Kemal University School of Medicine, Tekirdag, Turkey
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Nocturia: Current Levels of Evidence and Recommendations From the International Consultation on Male Lower Urinary Tract Symptoms. Urology 2015; 85:1291-9. [PMID: 25881866 DOI: 10.1016/j.urology.2015.02.043] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Revised: 02/09/2015] [Accepted: 02/17/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To evaluate published evidence on nocturia in men and derive expert recommendations. METHODS The International Consultations on Urological Diseases-Société Internationale d'Urologie convened a Consultation of experts on male lower urinary tract symptoms. The Consultation assigned standardized levels of evidence and grades of recommendation to various studies of nocturia epidemiology, pathophysiology, assessment, and treatment. RESULTS Evidence review and consensus recommendations were made in the areas of epidemiology, pathophysiology, assessment, and treatment. CONCLUSION The review presents a condensed summary of the International Consultations on Urological Diseases-Société Internationale d'Urologie evaluation of nocturia, which offers contemporaneous expert consensus on this topic, with an assessment algorithm emphasizing the potential contribution of systemic conditions to the symptom.
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Zhang LT, Park JK. Are phosphodiesterase type 5 inhibitors effective for the management of lower urinary symptoms suggestive of benign prostatic hyperplasia? World J Nephrol 2015; 4:138-147. [PMID: 25664256 PMCID: PMC4317624 DOI: 10.5527/wjn.v4.i1.138] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Revised: 07/22/2014] [Accepted: 10/10/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To review the efficacy of phosphodiesterase type 5 inhibitors (PDE5-Is) in lower urinary tract symptoms (LUTS) suggestive of benign prostate hyperplasia (LUTS/BPH).
METHODS: A comprehensive research was conducted to identify all publications relating to benign prostate hyperplasia and treatment with sildenafil, vardenafil and tadalafil. To assess the efficacy, the changes in total international prostate symptom score (IPSS), IPSS subscore including voiding, storage and quality of life (QoL), Benign prostatic hyperplasia Impact Index (BII), maximum urinary flow rate (Qmax) and the International Index of Erectile Function (IIEF) were extracted. A meta-analytical technique was used for the analysis of integrated data from the included studies to evaluate the mean difference in the results.
RESULTS: Total IPSS score, IIEF and BII showed a significant improvement in trials in which LUTS/BPH with or without erectile dysfunction (ED) were compared with the placebo. For LUTS/BPH, the mean differences of total IPSS score, IIEF and BII are -2.17, 4.88 and -0.43, P < 0.00001, respectively. For LUTS/BPH with comorbid ED, the mean difference are -1.97, 4.54 and -0.52, P < 0.00001, respectively. PDE5-Is appear to improve IPSS storage, voiding and QoL subscore (mean difference = -0.71, -1.23 and -0.33, P < 0.00001, respectively). Although four doses of tadalafil (2.5, 5, 10 and 20 mg) failed to reach significance in Qmax (mean difference = 0.22, P = 0.10), the 5 mg dose of tadalafil significantly improved the Qmax (mean difference = 0.33, P = 0.03).
CONCLUSION: PED5-Is demonstrated efficacy for improving LUTS in BPH patients with or without ED and could be considered to be the first line treatment for LUTS/BPH.
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Gacci M, Carini M, Salvi M, Sebastianelli A, Vignozzi L, Corona G, Maggi M, McVary KT, Kaplan SA, Oelke M, Serni S. Management of benign prostatic hyperplasia: role of phosphodiesterase-5 inhibitors. Drugs Aging 2015; 31:425-39. [PMID: 24811735 DOI: 10.1007/s40266-014-0177-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Several studies have highlighted a strong association between benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) and erectile dysfunction (ED), particularly in elderly men. Many epidemiological trials, such as in vitro and in vivo studies, have reported the emerging role of metabolic syndrome, including abdominal obesity, impaired glucose metabolism, hypertriglyceridemia, low high-density lipoprotein cholesterol, and hypertension, in the development and progression of urinary and sexual symptoms. Moreover, many authors have focused their studies on the identification of all the shared pathogenetic mechanisms of LUTS/BPH and ED, including alteration of cyclic guanosine monophosphate and RhoA-ROCK pathways or vascular and neurogenic dysfunction. All these are potential targets for proposed phosphodiesterase type 5 inhibitors (PDE5-Is). Therefore, several trials have recently been designed to evaluate the role of PDE5-Is alone or in combination with conventional treatment for BPH, such as α-adrenergic blockers, in men affected by LUTS/BPH, with or without ED. Different PDE5-Is are in clinical use worldwide and currently six of them are licensed for the oral treatment of ED. All these compounds differ in pharmacokinetic factors, with influence on drug action, and subsequently in the overall safety and efficacy profile.
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Affiliation(s)
- M Gacci
- Department of Urology, University of Florence, Careggi Hospital, Viale Pieraccini 18, 50139, Florence, Italy,
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Reges R, Regadas RP, Cerqueira JBG, Gonzaga-Silva LF. Phosphodiesterase inhibitors for treatment of voiding dysfunction: An overview of experimental and clinical evidence. World J Clin Urol 2014; 3:249-257. [DOI: 10.5410/wjcu.v3.i3.249] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 06/14/2014] [Accepted: 07/17/2014] [Indexed: 02/06/2023] Open
Abstract
Recently, the focus of the origin of lower urinary tract symptoms (LUTS) has change from the prostate to the bladder. Regardless of the underlying mechanism associated with the origin of LUTS, alpha-blockers continue to be the most common medicine prescribed to treat LUTS due to benign prostatic obstruction (BPO). The newest class of drug introduced to treat LUTS/BPO is phosphodiesterase inhibitors (PDEi) and the aim of this study was to review the role of PDEi in the treatment of LUTS/BPO. In this review, the first evidence was evaluated based on epidemiological studies followed by randomized clinical trials which provide evidence on the administration of PDEi in patients with LUTS/BPO. Experimental studies were also assessed to tentatively elucidate the association between LUTS and erectile dysfunction, and to elucidate the underlying mechanism. There is still controversy regarding the administration of PDEi due to the fear of detrusor impairment, response to acute administration, and the effects of PDEi combined with alpha-blockers. Following this review, we conclude that treatment of BPO/LUTS with PDEi is beneficial, based on experimental studies, strong evidence and the large number of randomized clinical trials confirming their efficiency.
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Kaplan SA. Re: Efficacy and Safety of the Simultaneous Administration Of Mirodenafil and an α-Blocker in Men with BPH-LUTS: A Multicenter Open-Label Prospective Study. J Urol 2014. [DOI: 10.1016/j.juro.2014.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Asimakopoulos AD, De Nunzio C, Kocjancic E, Tubaro A, Rosier PF, Finazzi-Agrò E. Measurement of post-void residual urine. Neurourol Urodyn 2014; 35:55-7. [DOI: 10.1002/nau.22671] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Accepted: 08/01/2014] [Indexed: 11/08/2022]
Affiliation(s)
| | - Cosimo De Nunzio
- Department of Urology; Sant'Andrea Hospital; Faculty of Health Sciences “La Sapienza” University of Rome; Rome Italy
| | - Ervin Kocjancic
- Director division of Pelvic Health and Reconstructive Urology; Department of Urology; University of Illinois at Chicago; Chicago Illinois
| | - Andrea Tubaro
- Department of Urology; Sant'Andrea Hospital; Faculty of Health Sciences “La Sapienza” University of Rome; Rome Italy
| | - Peter F. Rosier
- University Medical Centre Utrecht; Department of Urology; Utrecht The Netherlands
| | - Enrico Finazzi-Agrò
- Unit for Functional Urology; Policlinico Tor Vergata; Department of Experimental Medicine and Surgery; Tor Vergata University of Rome; Rome Italy
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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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