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Kim HB, Han CH, Jeon JH, Kim E, Kwon O, Choi YE, Yang C, Park YC, Kim YI. Effectiveness and safety of electroacupuncture and its cotreatment with electronic moxibustion in the treatment of patients with moderate benign prostatic hyperplasia using alpha blocker: An assessor-blinded, randomized, controlled pilot study. Medicine (Baltimore) 2022; 101:e30386. [PMID: 36086755 PMCID: PMC10980475 DOI: 10.1097/md.0000000000030429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 07/27/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Benign prostatic hyperplasia (BPH) is a disease that affects the quality of life by causing lower urinary tract symptoms (LUTS) in men. Electroacupuncture (EA) and moxibustion therapy have been suggested as an adjunct therapy for improving LUTS in patients with BPH, but clinical studies evaluating the effectiveness of EA and its cotreatment with electronic moxibustion (EM) in patients who have been prescribed alpha blockers have yet to be reported. Therefore, this study aimed to evaluate the effectiveness and safety of EA and EM. METHODS Twenty-eight patients diagnosed with BPH were randomized to treatment group (TG, n = 14) or control group (CG, n = 14). The TG continued to use the previously prescribed alpha blocker and received the cotreatment of EA and EM 3 times a week for 6 weeks. The CG continued to use the previously prescribed alpha blocker alone for 6 weeks. The primary outcome was the mean change in the international prostate symptom score (IPSS) from baseline to week 6. The secondary outcomes were IPSS at week 3 and 12, clinical relevance, IPSS life satisfaction, EuroQol-Five dimensions, average urinary flow rate, maximum urinary flow rate, and prostate volume. RESULTS The IPSS decreased at all time points with a statistically significant difference between the 2 groups (3W: P = .0313; 6W: P = .0010; 12W: P = .0304). Based on the minimal clinically important difference (MCID, 3 points), there were significant differences between the TG and the CG at week 3, 6, and 12 (3W: P = .0461; 6W: P = .0123; 12W: P = .0216). Significant group × week interaction effects were found for the IPSS score (P = .0018), as determined from analyses using repeated measures analysis of variance. There were no significant differences between the 2 groups in IPSS life satisfaction, EuroQol-Five dimensions, average urinary flow rate, maximum urinary flow rate, and prostate volume. CONCLUSION EA and its cotreatment with EM might have a beneficial effect as an adjunct therapy in improving LUTS in patients with BPH. Large-scale randomized controlled trials are warranted to confirm the effectiveness and safety of EA and its cotreatment with EM.
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Affiliation(s)
- Hyo Bin Kim
- Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea
| | - Chang-Hyun Han
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
- Korean Convergence Medicine, University of Science and Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Ju Hyun Jeon
- Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea
| | - Eunseok Kim
- Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea
- Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea
| | - Ojin Kwon
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Young Eun Choi
- Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Changsop Yang
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Yang Chun Park
- Division of Respiratory Medicine, Department of Internal Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea
| | - Young Il Kim
- Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea
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Sakalis V, Gkotsi A, Charpidou D, Tsafrakidis P, Apostolidis A. The effect of pharmacotherapy on prostate volume, prostate perfusion and prostate-specific antigen (prostate morphometric parameters) in patients with lower urinary tract symptoms and benign prostatic obstruction. A systematic review and meta-analysis. Cent European J Urol 2021; 74:388-421. [PMID: 34729231 PMCID: PMC8552938 DOI: 10.5173/ceju.2021.132.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 06/15/2021] [Accepted: 06/30/2021] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION The clinical effect of pharmacotherapy on prostate morphometric parameters is largely unknown. The sole exception is 5α-reductase inhibitors (5-ARI) that reduce prostate volume and prostate-specific antigen (PSA). This review assesses the effect of pharmacotherapy on prostate parameters effect on prostate parameters, namely total prostate volume (TPV), transitional zone volume (TZV), PSA and prostate perfusion. MATERIAL AND METHODS We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting on morphometric parameters' changes after pharmacotherapy, as primary or secondary outcomes. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RCTs' quality was assessed by the Cochrane tool and the criteria of the Agency for Healthcare Research and Quality. The effect magnitude was expressed as standard mean difference (SMD). The study protocol was published on PROSPERO (CRD42020170172). RESULTS Sixty-seven RCTs were included in the review and 18 in the meta-analysis. The changes after alpha-blockers are comparable to placebo. Long-term studies reporting significant changes from baseline, result from physiologic growth. Finasteride and dutasteride demonstrated large effect sizes in TPV reduction ([SMD]: -1.15 (95% CI: -1.26 to -1.04, p <0.001, and [SMD]:-0.66 (95% CI: -0.83 to -0.49, p <0.001, respectively), and similar PSA reductions. Dutasteride's effect appears earlier (1st vs 3rd month), the changes reach a maximum at month 12 and are sustained thereafter. Phosphodiesterase-5 (PDE-5) inhibitors have no effect on morphometric parameters. Phytotherapy's effect on TPV is non-significant [SMD]: 0.12 (95% CI: -0.03 to 0.27, p = 0.13). Atorvastatin reduces TPV as compared to placebo (-11.7% vs +2.5%, p <0.01). Co-administration of testosterone with dutasteride spares the prostate from the androgenic stimulation as both TPV and PSA are reduced significantly. CONCLUSIONS The 5-ARIs show large effect size in reducing TPV and PSA. Tamsulosin improves perfusion but no other effect is evident. PDE-5 inhibitors and phytotherapy do not affect morphometric parameters. Atorvastatin reduces TPV and PSA as opposed to testosterone supplementation.
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Affiliation(s)
- Vasileios Sakalis
- Department of Urology, Agios Pavlos General Hospital of Thessaloniki, Thessaloniki, Greece
- 2 Department of Urology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Anastasia Gkotsi
- Department of Urology, Agios Pavlos General Hospital of Thessaloniki, Thessaloniki, Greece
| | - Dimitra Charpidou
- Department of Urology, Agios Pavlos General Hospital of Thessaloniki, Thessaloniki, Greece
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Traish AM. Post-finasteride syndrome: a surmountable challenge for clinicians. Fertil Steril 2020; 113:21-50. [PMID: 32033719 DOI: 10.1016/j.fertnstert.2019.11.030] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 11/04/2019] [Accepted: 11/25/2019] [Indexed: 12/28/2022]
Abstract
Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men with pattern hair loss (androgenetic alopecia) or benign prostatic hyperplasia. These serious adverse side effects include persistent or irreversible sexual, neurological, physical and mental side effects. To date, there are no evidence-based effective treatments for PFS. Although increasing number of men report persistent side effects, the medical community has yet to recognize this syndrome nor are there any specific measures to address this serious and debilitating symptoms. Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that use of these drugs is associated with development of sexual dysfunction, which may persist in a subset of men, irrespective of age, drug dose or duration of study. Also, increased depression, anxiety and suicidal ideation in a subset of men treated with these drugs were commonly reported in a number of studies. It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm. Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological and physical adverse side effects, in a subset of men. These constellations of symptoms constitute the basis for PFS in individuals predisposed to epigenetic susceptibility. Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities.
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Affiliation(s)
- Abdulmaged M Traish
- Department of Urology, Boston University School of Medicine, Boston, Massachusetts.
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Markić D, Kaštelan Ž, El-Saleh A, Španjol J. Benign prostatc hyperplasia – medicamentous treatment. MEDICINA FLUMINENSIS 2017; 53:273-284. [DOI: 10.21860/medflum2017_182960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2025]
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Topbaş E, Sökmen D, Sökmen BK, Eyyüpoğlu SE. The importance of medical and nursing care of the open prostatectomy-related vesico-cutaneous fistula. INTERNATIONAL JOURNAL OF UROLOGICAL NURSING 2017. [DOI: 10.1111/ijun.12136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Eylem Topbaş
- Amasya University, School of Health, Nursing Department; Amasya Turkey
| | - Doğukan Sökmen
- Private Derindere Hospital İstanbul, Urology Department; İstanbul Turkey
| | - Bedriye Koyuncu Sökmen
- Florence Nightingale Şişli Hospital İstanbul Bilim University Radiology Department; İstanbul Turkey
| | - Seyit Erkan Eyyüpoğlu
- Amasya University, Sabuncuoğlu Şerefeddin Training and Research Hospital, Urology Department; Amasya Turkey
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Das Post-Finasterid-Syndrom. GYNAKOLOGISCHE ENDOKRINOLOGIE 2017. [DOI: 10.1007/s10304-017-0126-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Gupta AK, Carviel J, MacLeod MA, Shear N. Assessing finasteride-associated sexual dysfunction using the FAERS database. J Eur Acad Dermatol Venereol 2017; 31:1069-1075. [PMID: 28300347 DOI: 10.1111/jdv.14223] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 02/23/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND Postmarketing reports suggest that finasteride causes sexual dysfunction despite a low incidence reported in clinical trials. Therefore, the extent of risk remains unknown. OBJECTIVE To determine whether the risk of sexual dysfunction is higher among individuals treated with finasteride compared to a baseline risk for all other drugs using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS A case by non-case disproportionality approach was used whereby a reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated. The National Ambulatory Medical Care Survey (NAMCS) was used to confirm results. RESULTS A significant disproportionality in reporting of sexual dysfunction with the use of finasteride was observed whether finasteride was indicated for hair loss (ROR = 138.17, 95% CI: 133.13, 143.4), prostatic hyperplasia (ROR = 93.88, 95% CI: 84.62, 104.16) or any indication (ROR = 173.18, 95% CI: 171.08, 175.31). When these results were stratified by age, disproportionality was strongest at 31-45 years. CONCLUSION Use of finasteride has led to an increase in reports of sexual dysfunction where it is believed to be the primary suspect.
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Affiliation(s)
- A K Gupta
- Department of Medicine, University of Toronto School of Medicine, Toronto, ON, Canada.,Mediprobe Research Inc., London, ON, Canada
| | - J Carviel
- Mediprobe Research Inc., London, ON, Canada
| | | | - N Shear
- Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
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Fertig R, Shapiro J, Bergfeld W, Tosti A. Investigation of the Plausibility of 5-Alpha-Reductase Inhibitor Syndrome. Skin Appendage Disord 2016; 2:120-129. [PMID: 28232919 DOI: 10.1159/000450617] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 09/05/2016] [Indexed: 11/19/2022] Open
Abstract
Postfinasteride syndrome (PFS) is a term recently coined to characterize a constellation of reported undesirable side effects described in postmarketing reports and small uncontrolled studies that developed during or after stopping finasteride treatment, and persisted after drug discontinuation. Symptoms included decreased libido, erectile dysfunction, sexual anhedonia, decreased sperm count, gynecomastia, skin changes, cognitive impairment, fatigue, anxiety, depression, and suicidal ideation. The aim of this study is to review the existing medical literature for evidence-based research of permanent sexual dysfunction and mood changes during treatment with 5-alpha-reductase inhibitors including finasteride and dutasteride.
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Affiliation(s)
- Raymond Fertig
- Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, Fla, USA
| | - Jerry Shapiro
- The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, N.Y., USA
| | - Wilma Bergfeld
- Departments of Dermatopathology Fellowship, Cleveland Clinic, Cleveland, Ohio, USA; Departments of Pathology, Dermatopathology Fellowship, Cleveland Clinic, Cleveland, Ohio, USA
| | - Antonella Tosti
- Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, Fla, USA
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Olesovsky C, Kapoor A. Evidence for the efficacy and safety of tadalafil and finasteride in combination for the treatment of lower urinary tract symptoms and erectile dysfunction in men with benign prostatic hyperplasia. Ther Adv Urol 2016; 8:257-271. [PMID: 27928428 PMCID: PMC5131741 DOI: 10.1177/1756287216650132] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Benign prostatic hyperplasia (BPH) is an age-related phenomenon associated with prostatic enlargement and bladder outlet obstruction that can cause significant lower urinary tract symptoms (LUTS). These LUTS have a negative impact on an individual's quality of life, which is why treatment of symptomatic BPH has become a major priority. Although surgical interventions exist for treating BPH, pharmacological therapies are often preferred due to their minimal invasiveness and high degree of effectiveness. The three classes of drugs approved for treating BPH include α-blockers, 5-α-reductase inhibitors (5-ARIs) and phosphodiesterase 5 (PDE-5) inhibitors. Individually, each class of drug has been studied and shown to improve symptom relief through a variety of different mechanisms. A more recent focus has been on the development of combinatorial therapies that combine classes of drugs in order to provide maximal benefit. The mTOPS and CombAT studies were the first of their kind to examine whether the combination of 5-ARIs and α-blockers was more effective than monotherapy alone. Both studies found similar results in that the combinatorial therapy was superior to monotherapy. Over the last decade other combinatorial therapies have been at the forefront of investigation. One in particular is the combination of tadalafil, a PDE-5 inhibitor, with finasteride, a 5-ARI. Studies have shown that the combination of tadalafil and finasteride is a safe, effective, and well tolerated treatment for BPH. Evidence suggests that this combination may be particularly effective in reducing treatment-related sexual adverse events associated with 5-ARI treatments. The following review will explore in detail the current evidence surrounding treatment of BPH LUTS using tadalafil and finasteride.
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Affiliation(s)
| | - Anil Kapoor
- McMaster Institute of Urology, 50 Charlton Avenue, G344 Mary Grace Wing, Hamilton, ON, Canada L8N 4A6
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Assessment and management of male lower urinary tract symptoms (LUTS). Int J Surg 2016; 25:164-71. [DOI: 10.1016/j.ijsu.2015.11.043] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 11/07/2015] [Accepted: 11/21/2015] [Indexed: 11/19/2022]
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Oelke M, Speakman MJ, Desgrandchamps F, Mamoulakis C. Acute Urinary Retention Rates in the General Male Population and in Adult Men With Lower Urinary Tract Symptoms Participating in Pharmacotherapy Trials: A Literature Review. Urology 2015; 86:654-65. [DOI: 10.1016/j.urology.2015.06.025] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 06/08/2015] [Accepted: 06/18/2015] [Indexed: 11/26/2022]
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Mangera A, Chapple C. Update summarising the conclusions of the international consultation on male lower urinary tract symptoms. World J Clin Urol 2015; 4:83-91. [DOI: 10.5410/wjcu.v4.i2.83] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Revised: 10/07/2014] [Accepted: 05/11/2015] [Indexed: 02/05/2023] Open
Abstract
The International Consultation on Urological Disease have recently published comprehensive conclusions, based on evidence reviewed by eight committees, on aspects of male lower urinary tract symptoms (LUTS). In this review, we summarise the conclusions from four of the committees, namely, the evidence regarding the epidemiology of male LUTS, patient assessment, nocturia and medical management. It is indisputable that with an expanding and ageing global population the prevalence of male LUTS is likely to increase. Therefore symptom prevention and preservation of quality of life (QoL) feature highly in the guidelines. There are now a number of different medical options, proven to lead to significant improvements in symptom scores, flow rate and QoL available to men with LUTS. Meta-analyses have shown the benefits for alpha blockers, antimuscarinics, 5-α reductase and phosphodiesterase-5 inhibitors. High level evidence also exists for combinations of all of the above with alpha blockers and so men with concomitant storage symptoms, prostate volume > 30 mL, PSA > 1.4 or erectile dysfunction may be considered for combination treatment of an alpha blocker with an antimuscarinic, 5-α reductase inhibitor or phosphodiesterase-5 inhibitor respectively. In an era of personalised medicine, appropriate patient selection is likely to provide the key to the most effective clinical management strategy.
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Descazeaud A, de La Taille A, Giuliano F, Desgrandchamps F, Doridot G. [Negative effects on sexual function of medications for the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia]. Prog Urol 2015; 25:115-27. [PMID: 25605342 DOI: 10.1016/j.purol.2014.12.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Revised: 11/21/2014] [Accepted: 12/18/2014] [Indexed: 10/24/2022]
Abstract
PURPOSE The aim of this review is to discuss the negative effects on sexual function of medications for lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS-BPH). METHODS An international non-systematic literature review was performed. It included randomized trials of seven drugs of interest and the summaries of the characteristics of these products. This work did not aim comparison between the drugs. RESULTS Only maximal reported frequencies are presented in this abstract. With prolonged-release alfuzosin, they were 2.8% vs. 1.3% for erectile dysfunction, compared to placebo and 1% vs. 0% for ejaculatory dysfunction. With doxazosin, the incidence was 5.8% vs. 3.3% for erectile dysfunction, 3.6% vs. 1.9% for reduced libido and 0.4% vs. 1.4% for ejaculatory disorders. The incidence of ejaculatory disorders with tamsulosin, was 11% vs. <1% with the placebo and with silodosin, it was 28.1% vs. 1.1%. With finasteride, at 12 months, the highest frequency was 9% vs. 5% for erectile dysfunction, 4.4% vs. 1.5% for ejaculatory disorders and 6.4% vs. 3.4% for reduced libido. At 24 months, for dutatsteride, frequencies were 7.3% vs. 4.0% for erectile dysfunction, 2.2% vs. 0.8% for ejaculatory disorders and 4.2% vs. 2.1% for reduced libido. For tadalafil, a phosphodiesterase-5 inhibitor, and tolerodine, an anticholinergic drug, no negative effect on ejaculation or libido has been reported. For plant extracts, no sexual adverse effects (AEs) were reported among the most common AEs. CONCLUSION The medications for LUTS-BPH may alter erection, ejaculation or libido. A greater knowledge of the adverse effects of each of these drugs could guide physicians in the clinical management of men with BPH-LUTS.
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Affiliation(s)
- A Descazeaud
- Service de chirurgie urologique, CHU de Limoges, 87042 Limoges cedex, France.
| | - A de La Taille
- Service d'urologie, faculté de médecine de Créteil, groupe hospitalier Henri-Mondor, 94000 Créteil, France
| | - F Giuliano
- Service de médecine physique et de réadaptation, faculté des sciences de la santé, université de Versailles Saint-Quentin en Yvelines, hôpital Raymond-Poincaré, 92380 Garches, France
| | - F Desgrandchamps
- Service d'urologie et de transplantation, hôpital Saint-Louis, université Paris 7, institut des maladies émergentes et des thérapies innovantes (iMETI), 75010 Paris, France
| | - G Doridot
- 24, boulevard Vital-Bouhot, 92521 Neuilly-Sur-Seine cedex, France
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Game X, Cornu JN, Robert G, Descazeaud A, Droupy S, Benard-Laribiere A, Bastide C, Guy L, Bruyére F, Karsenty G. [Drug therapy of urethral diseases]. Prog Urol 2013; 23:1287-98. [PMID: 24183087 DOI: 10.1016/j.purol.2013.09.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2013] [Accepted: 09/16/2013] [Indexed: 02/02/2023]
Abstract
AIM To describe drugs targeting urethra and prostate to treat dysfunctions such LUTS related to BPH, primary bladder neck obstruction (PBNO), detrusor sphincter dyssynergia (DSD) or sphincter deficiency (SD). METHOD Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies web sites (HAS and ANSM). RESULTS To treat LUTS related to BPH alpha-blockers (AB) and 5-alpha reductase inhibitors (5ARIs) have a clearer efficacy than plant extract. Daily Phosphodiesterase 5 inhibitors (PDE5Is) alone or in association with AB also demonstrate efficacy in this indication. AB are an option in PBNO and DSD related to multiple sclerosis. Although Botulinum toxin A derived molecules decrease urethral pressure in patient with DSD related to spinal cord injury or multiple sclerosis, efficiency remains to be demonstrated. Duloxetine a serotonin reuptake inhibitor increases urethral sphincter pressure and reduce stress urinary incontinence in women and men. Nevertheless, moderate efficacy combine with frequent side effects lead French regulation agency to reject its agreement. CONCLUSION Armamenterium to treat urethral dysfunctions has recently increases. Two new therapeutic classes emerge: PDE5Is to treat LUTS related to BPH and an SRIs (Duloxetine) to treat stress urinary incontinence. Efficacy and safety evaluation of all the possible associations between drugs targeting urethra and/or bladder is needed to a subtler and more efficient pharmacologic modulation of lower urinary tract dysfunction.
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Affiliation(s)
- X Game
- Département d'urologie, transplantation rénale et andrologie, CHU Rangueil, TSA 50032, 31059 Toulouse, France
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Bell JR, Laborde E. Update on the sexual impact of treatment for benign prostatic hyperplasia. Curr Urol Rep 2013; 13:433-40. [PMID: 23065462 DOI: 10.1007/s11934-012-0278-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
There is an established link between lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). The medical and surgical management of LUTS can affect erectile function (EF), cause ejaculatory dysfunction (EjD) or affect libido. This article will review the effects of these therapies on sexual function.
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Affiliation(s)
- John Roger Bell
- Department of Urology, Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
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Spatafora S, Casarico A, Fandella A, Galetti C, Hurle R, Mazzini E, Niro C, Perachino M, Sanseverino R, Pappagallo GL. Evidence-based guidelines for the treatment of lower urinary tract symptoms related to uncomplicated benign prostatic hyperplasia in Italy: updated summary from AURO.it. Ther Adv Urol 2013. [PMID: 23205056 DOI: 10.1177/1756287212463112] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The first Italian national guidelines were developed by the Italian Association of Urologists and published in 2007. Since then, a number of new drugs or classes of drugs have emerged for the treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH), new data have emerged on medical therapy (monotherapies and combination therapies), new surgical techniques have come into practice, and our understanding of disease pathogenesis has increased. Consequently, a new update of the guidelines has become necessary. METHODS A structured literature review was conducted to identify relevant papers published between 1 August 2006 and 12 December 2010. Publications before or after this timeframe were considered only if they were recognised as important milestones in the field or if the literature search did not identify publications within this timeframe. The quality of evidence and strength of recommendations were determined according to the Grading of Recommendations Assessment, Development and Evaluation framework. MAIN FINDINGS Decisions on therapeutic intervention should be based on the impact of symptoms on quality of life (QoL) rather than the severity of symptoms (International Prostate Symptom Score (IPSS) score). A threshold for intervention was therefore based on the IPSS Q8, with intervention recommended for patients with a score of at least 4. Several differences in clinical recommendations have emerged. For example, combination therapy with a 5α-reductase inhibitor plus α blocker is now the recommended option for the treatment of patients at risk of BPH progression. Other differences include the warning of potential worsening of cognitive disturbances with use of anticholinergics in older patients, the distinction between Serenoa repens preparations (according to the method of extraction), and the clearly defined threshold of prostate size for performing open surgery (>80 g). While the recommendations included in these guidelines are evidence based, clinical decisions should also be informed by patients' clinical and physical circumstances, as well as patients' preferences and actions. CONCLUSIONS These guidelines are intended to assist physicians and patients in the decision-making process regarding the management of LUTS/BPH, and support the process of continuous improvement of the quality of care and services to patients.
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Affiliation(s)
- Sebastiano Spatafora
- Department of Surgery, Azienda Ospedaliera S. Maria Nuova, viale Risorgimento 80, 42100 Reggio Emilia, Italy
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Uckert S, Oelke M. Phosphodiesterase (PDE) inhibitors in the treatment of lower urinary tract dysfunction. Br J Clin Pharmacol 2012; 72:197-204. [PMID: 21745238 DOI: 10.1111/j.1365-2125.2010.03828.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Several disorders of the human upper and lower urinary tract, such as urinary stone disease, lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and detrusor overactivity, can be therapeutically addressed by influencing the function of the smooth musculature of the ureter, prostate or urinary bladder, respectively. In order to ensure a drug effect without significant adverse events, a certain degree of tissue selectivity is mandatory. The treatment of said conditions aims to focus on orally available drugs acting via intracellular signalling pathways. Specifically, the cyclic nucleotide monophosphate cyclic GMP represents an important mediator in the control of the outflow region (bladder, urethra). The use of phosphodiesterase (PDE) inhibitors, such as sildenafil, tadalafil, vardenafil, avanafil or udenafil, known to restrain the degradation of the second messenger cyclic GMP, offers great opportunities in the treatment of lower urinary tract dysfunction. PDE inhibitors are regarded as efficacious, have a rapid onset of action and favourable effect-to-side-effect ratio. The role of PDE5 inhibitors in the treatment of BPH/LUTS and the overactive bladder has already been addressed in randomized, double-blind, placebo-controlled trials, as well as preliminary open-label studies enrolling either several hundreds or only 20 patients. The purpose of this review is to focus on the potential use and clinical significance of PDE inhibitors in the treatment of storage and voiding dysfunctions of the lower urinary tract. The strategy of modulating the activity of PDE isoenzymes might represent a novel approach in patients with lower urinary tract dysfunction (LUTD).
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Affiliation(s)
- Stefan Uckert
- Hannover Medical School, Division of Surgery, Department of Urology and Urological Oncology, Hannover, Germany.
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Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML. Adverse Side Effects of 5α‐Reductase Inhibitors Therapy: Persistent Diminished Libido and Erectile Dysfunction and Depression in a Subset of Patients. J Sex Med 2011; 8:872-84. [DOI: 10.1111/j.1743-6109.2010.02157.x] [Citation(s) in RCA: 183] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Uckert S, Kuczyk MA. Cyclic nucleotide metabolism including nitric oxide and phosphodiesterase-related targets in the lower urinary tract. Handb Exp Pharmacol 2011:527-42. [PMID: 21290241 DOI: 10.1007/978-3-642-16499-6_23] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
The clinical data on the use of the orally active phosphodiesterase (PDE) type 5 inhibitors sildenafil (VIAGRA™), vardenafil (LEVITRA™), and tadalafil (CIALIS™) for the treatment of male erectile dysfunction have boosted research activities on the physiology and pharmacology of the organs of the lower urinary tract (LUT). This includes both intracellular signal transduction in the prostate, urinary bladder (detrusor), and urethra, as well as central brain and spinal cord pathways controlling the function of the LUT. Such efforts provided the basis for the development of new therapeutic modalities into the management of dysfunctions/ syndromes of the LUT, some of which are already offered to the patients. The pharmacological treatment of the overactive bladder and the so-called benign prostatic syndrome, including LUT symptomatology and bladder outlet obstruction secondary to benign prostatic enlargement, has primarily focused on selective, orally available drugs acting by influencing intracellular regulatory mechanisms. These agents are regarded efficacious, have a fast onset of drug action in the target tissue and an improved effect-to-side-effect ratio. Better understanding of the functional significance of proteins related to cyclic nucleotide-dependent pathways, such as nitric oxide synthase, cytosolic and membrane-bound guanylyl cyclases, PDE isoenzymes and cyclic AMP- and cyclic GMP-binding protein kinases, the relative distribution in tissues of the LUT, and the consequences for urogenital function, seems to be of particular interest in order to identify new or more selective pharmacological approaches to manage disorders of the LUT. The present review focuses on cyclic nucleotide-related targets involved in the control of the function of the bladder, prostate, and urethra and the significance of those proteins in the process of evolving new pharmacological options for the treatment of LUT symptoms secondary to benign prostatic hyperplasia as well as dysfunctions of the storage and voiding capability of the urinary bladder.
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Affiliation(s)
- Stefan Uckert
- Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany.
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Uckert S, Stief CG. Treatment of erectile dysfunction and lower urinary tract symptoms by phosphodiesterase inhibitors. Handb Exp Pharmacol 2011:307-22. [PMID: 21695646 DOI: 10.1007/978-3-642-17969-3_13] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
To date, it is widely accepted that several disorders of the male and female urogenital tract, such as erectile dysfunction, bladder overactivity, urinary stone disease, the benign prostatic syndrome, as well as symptoms of female sexual arousal and orgasmic dysfunctions, can be therapeutically approached by influencing the function of the smooth musculature of the respective organs. To achieve a pronounced drug effect without significant adverse events, a certain degree of tissue selectivity is mandatory. Selective intervention in intracellular pathways regulating smooth muscle tone has become the most promising strategy to modulate tissue and organ function. Since the concept of taking a pill to relieve symptoms of lower urinary tract dysfunction is now widely accepted following the successes of phosphodiesterase 5 (PDE5) inhibitor treatment of erectile dysfunction, the treatment of urological diseases has focused on orally available drugs acting via influencing intracellular signaling pathways, thereby combining a high response rate with the advantage of an on-demand intake. Specifically, the use of isoenzyme-selective PDE inhibitors offers great opportunities in the medical treatment of various genitourinary diseases. These agents are regarded to be safe and to be efficacious, i.e., having a fast onset of drug action and an improved effect-to-side-effect ratio. As experience with this class of compounds and their use in urology is rapidly growing, basic and clinical research in this field will most likely expand the pharmacological armamentarium of innovative treatment options in the next few years. The purpose of this review is to summarize current, as well as potential, upcoming indications for the use of PDE inhibitors in the pharmacotherapy of male erectile dysfunction and lower urinary tract symptoms.
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Affiliation(s)
- Stefan Uckert
- Division of Surgery, Department of Urology and Urological Oncology, Hannover Medical School, 30625 Hannover, Germany.
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Tacklind J, Fink HA, MacDonald R, Rutks I, Wilt TJ, Cochrane Urology Group. Finasteride for benign prostatic hyperplasia. Cochrane Database Syst Rev 2010; 2010:CD006015. [PMID: 20927745 PMCID: PMC8908761 DOI: 10.1002/14651858.cd006015.pub3] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND Benign prostatic hyperplasia (BPH), a non-malignant enlargement of the prostate in aging men, can cause bothersome urinary symptoms (intermittency, weak stream, straining, urgency, frequency, incomplete emptying). Finasteride, a five-alpha reductase inhibitor (5ARI), blocks the conversion of testosterone to dihydrotestosterone, reduces prostate size, and is commonly used to treat symptoms associated with BPH. OBJECTIVES To compare the clinical effectiveness and harms of finasteride versus placebo and active controls in the treatment of lower urinary tract symptoms (LUTS). SEARCH STRATEGY We searched The Cochrane Library (which includes CDSR (Cochrane Database of Systematic Reviews), DARE (Database of Abstracts of Reviews of Effects), HTA (Heath Technology Assessments), and CENTRAL (Cochrane Central Register of Controlled Trials, and which includes EMBASE and MEDLINE), LILACS (Latin American and Caribbean Center on Health Sciences Information) and Google Scholar for randomized, controlled trials (RCTs). We also handsearched systematic reviews, references, and clinical-practice guidelines. SELECTION CRITERIA Randomized trials in the English language with placebo and/or active arms with a duration of at least 6 months. DATA COLLECTION AND ANALYSIS JT extracted the data, which included patient characteristics, outcomes, and harms. Our primary outcome was change in a validated, urinary symptom-scale score, such as the AUA/IPSS. A clinically meaningful change was defined as 4 points. We also categorized outcomes by trial lengths of ≤ 1 year (short term) and > 1 year (long term). MAIN RESULTS Finasteride consistently improved urinary symptom scores more than placebo in trials of > 1 year duration, and significantly lowered the risk of BPH progression (acute urinary retention, risk of surgical intervention, ≥ 4 point increase in the AUASI/IPSS). In comparison to alpha-blocker monotherapy, finasteride was less effective than either doxazosin or terazosin, but equally effective compared to tamsulosin. Both doxazosin and terazosin were significantly more likely than finasteride to improve peak urine flow and nocturia, versus finasteride. Versus tamsulosin, peak urine flow and QoL improved equally well versus finasteride. However, finasteride was associated with a lower risk of surgical intervention compared to doxazosin, but not to terazosin, while finasteride and doxazosin were no different for risk of acute urinary retention. Two small trials reported no difference in urinary symptom scores between finasteride and tamsulosin. Finasteride + doxazosin and doxazosin monotherapy improved urinary symptoms equally well (≥ 4 point improvement).For finasteride, there was an increased risk of ejaculation disorder, impotence, and lowered libido, versus placebo. Versus doxazosin, finasteride had a lower risk of asthenia, dizziness, and postural hypotension, and versus terazosin, finasteride had a significant, lower risk of asthenia, dizziness, and postural hypotension. AUTHORS' CONCLUSIONS Finasteride improves long-term urinary symptoms versus placebo, but is less effective than doxazosin. Long-term combination therapy with alpha blockers (doxazosin, terazosin) improves symptoms significantly better than finasteride monotherapy. Finasteride + doxazosin improves symptoms equally - and clinically - to doxazosin alone. In comparison to doxazosin, finasteride + doxazosin appears to improve urinary symptoms only in men with medium (25 to < 40 mL) or large prostates (≥ 40 mL), but not in men with small prostates (25 mL).Comparing short to long-term therapy, finasteride does not improve symptoms significantly better than placebo at the short term, but in the long term it does, although the magnitude of differences was very small (from < 1.0 point to 2.2 points). Doxazosin improves symptoms better than finasteride both short and long term, with the magnitude of differences ∼2.0 points and 1.0 point, respectively. Finasteride + doxazosin improves scores versus finasteride alone at both short and long term, with mean differences ∼2.0 points for both time points. Finasteride + doxazosin versus doxazosin improves scores equally for short and long term.Drug-related adverse effects for finasteride are rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo. Versus doxazosin, which has higher rates of dizziness, postural hypotension, and asthenia, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder. Finasteride significantly reduces asthenia, postural hypotension, and dizziness versus terazosin. Finasteride significantly lowers the risk of asthenia, dizziness, ejaculation disorder, and postural hypotension, versus finasteride + terazosin.
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Affiliation(s)
| | - Howard A Fink
- Minneapolis VA Medical CenterGeriatric Research Education and Clinical Center, Box 11GOne Veterans DriveMinneapolisMinnesotaUSA55417
| | - Roderick MacDonald
- Minneapolis VA Medical CenterGeneral Internal Medicine (111‐0)One Veterans DriveMinneapolisMinnesotaUSA55417
| | - Indy Rutks
- Minneapolis VA Medical CenterGeneral Internal Medicine (111‐0)One Veterans DriveMinneapolisMinnesotaUSA55417
| | - Timothy J Wilt
- Minneapolis VA Medical CenterGeneral Internal Medicine (111‐0)One Veterans DriveMinneapolisMinnesotaUSA55417
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Smith AB, Carson CC. Finasteride in the treatment of patients with benign prostatic hyperplasia: a review. Ther Clin Risk Manag 2009; 5:535-45. [PMID: 19707263 PMCID: PMC2710385 DOI: 10.2147/tcrm.s6195] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Benign prostatic hyperplasia (BPH) is a complex and progressive disease common in aging men. While associated with bothersome lower urinary tract symptoms, it may also result in additional serious complications such as refractory hematuria, acute urinary retention, and BPH-related surgery. Medical therapy has been offered as an approach to halt this progression and perhaps reverse the pathophysiology of BPH. While alpha-blockers provide rapid relief in the form of improved flow rate, their effects may not reduce the overall risk of BPH-related complications. 5α-reductase inhibitors were therefore introduced to affect the underlying disease process by inhibiting the enzyme which converts testosterone to dihydrotesterone, the primary androgen involved in normal and abnormal prostate growth. Through this inhibition, prostate size is decreased, thereby reducing the risk of acute urinary retention and BPH-related surgery while providing symptom control. These effects are most pronounced in men with enlarged prostates (>25 mL) who are at the greatest risk of disease progression. This article reviews the literature for finasteride used in the treatment of BPH and provides evidence for its efficacy, safety and tolerability, applicability for combination therapy, and considerations of its effects on prostate cancer risk.
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Affiliation(s)
- Angela B Smith
- University of North Carolina Division of Urologic Surgery, Chapel Hill, NC, USA
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De Nunzio C, Miano R, Trucchi A, Agrò EF, Tubaro A. Finasteride for prostatic disease: an updated and comprehensive review. Expert Opin Drug Metab Toxicol 2008; 4:1561-8. [DOI: 10.1517/17425250802587058] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Emberton M, Fitzpatrick JM, Garcia-Losa M, Qizilbash N, Djavan B. Progression of benign prostatic hyperplasia: systematic review of the placebo arms of clinical trials. BJU Int 2008; 102:981-6. [DOI: 10.1111/j.1464-410x.2008.07717.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Curr Urol Rep 2008; 9:295-301. [PMID: 18765129 DOI: 10.1007/s11934-008-0052-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Alpha-blockers, the current common treatment for lower urinary tract symptoms (LUTS), are also used to treat bladder outlet obstruction (BOO), but the effect is not as clinically significant as in LUTS. All currently marketed phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to significantly affect LUTS, although BOO-related efficacy has not been determined. Therefore, the extent of a causal relationship between LUTS and underlying benign prostatic enlargement (BPE) is questionable. LUTS may also be interpreted as symptoms related to detrusor overactivity, especially when no significant BOO is associated with BPE. Research is required to understand the efficacy of PDE5 inhibitors in LUTS but not in BOO. For vardenafil, nonclinical experiments and initial, preliminary clinical data suggest that the underlying effect may occur on the detrusor and not the prostate.
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Noguchi M, Kakuma T, Tomiyasu K, Kurita Y, Kukihara H, Konishi F, Kumamoto S, Shimizu K, Kondo R, Matsuoka K. Effect of an extract ofGanoderma lucidumin men with lower urinary tract symptoms: a double-blind, placebo-controlled randomized and dose-ranging study. Asian J Androl 2008; 10:651-8. [DOI: 10.1111/j.1745-7262.2008.00336.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Uckert S, Sormes M, Kedia G, Scheller F, Knapp WH, Jonas U, Stief CG. Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue. Urology 2008; 71:526-30. [PMID: 18342202 DOI: 10.1016/j.urology.2007.10.051] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2007] [Revised: 09/21/2007] [Accepted: 10/25/2007] [Indexed: 12/29/2022]
Abstract
OBJECTIVES To further evaluate the mechanism of action of phosphodiesterase (PDE) inhibitors on the human prostate, the effects of PDE4 and PDE5 inhibitors on the tension induced by norepinephrine (NE) and on the intracellular levels of cyclic nucleotides in isolated human prostatic tissue were investigated. METHODS Using the organ bath technique, the effects of increasing concentrations (1 nM to 10 microM) of the PDE5 inhibitors sildenafil, tadalafil, and vardenafil and the PDE4 inhibitors rolipram and RP 73401 on the tension induced by NE (40 microM) of prostate strip preparations were investigated. The accumulation of cyclic guanosine monophosphate and cyclic adenosine monophosphate in response to drug exposure was determined by radioimmunoassays. RESULTS The tension induced by NE was dose dependently reversed by the drugs with the following rank order of efficacy: tadalafil greater than RP 73401 greater than rolipram greater than or equal to vardenafil greater than sildenafil. The maximal reversion of tension values ranged from 52.3% (tadalafil) to 17% (sildenafil). Of the PDE inhibitors, only tadalafil induced a 50% reversion of the initial tension. The most prominent enhancement in tissue cyclic adenosine monophosphate was registered in response to RP 73401 (11-fold), and cyclic guanosine monophosphate levels were significantly elevated by tadalafil, vardenafil, and sildenafil (28-fold, 12-fold, and 3-fold, respectively). CONCLUSIONS Our results have demonstrated that drugs interfering with the cyclic nucleotide-mediated pathways can reverse the tension induced by NE in isolated prostatic tissue and elevate cyclic adenosine monophosphate and cyclic guanosine monophosphate. Our findings serve to explain how PDE inhibitors can affect symptoms of lower urinary tract symptoms and benign prostatic hyperplasia.
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Affiliation(s)
- Stefan Uckert
- Department of Urology, Hannover Medical School, Hannover, Germany.
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Madersbacher S, Marszalek M, Lackner J, Berger P, Schatzl G. The Long-Term Outcome of Medical Therapy for BPH. Eur Urol 2007; 51:1522-33. [PMID: 17416456 DOI: 10.1016/j.eururo.2007.03.034] [Citation(s) in RCA: 93] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2007] [Accepted: 03/17/2007] [Indexed: 10/23/2022]
Abstract
OBJECTIVES The lack of cure with medical therapy implies life-long treatment emphasising the need for a thorough understanding of the long-term outcome. We review the natural history, markers for progression, placebo effect, efficacy, pharmacoeconomic aspects, and preventive measures. METHODS Literature review with particular reference to long-term controlled studies using plant extracts, alpha1-blockers, 5alpha-reductase inhibitors (5-ARIs), and combination therapy. RESULTS There is a long-lasting (>or=12 mo) placebo response of symptoms (20% decrease) and maximum flow rate (10% rise). The five long-term controlled trials of plant extracts are inconclusive and therefore their role in contemporary medical management is still controversial. The alpha1-blockers provide fast amelioration of symptoms yet have no relevant impact on the risk of acute urinary retention or surgery. Combination therapy should be reserved for moderately or severely symptomatic patients with a high risk of progression; in the majority of patients the alpha1-blocker can be safely stopped after 6-12 mo. The preventive use of 5-ARIs in men with no or mild symptoms at risk of progression is scientifically sound yet not generally accepted mainly for economic reasons. CONCLUSIONS A sharp contrast exists between the duration of the longest controlled trial (4.5 yr) and the situation in real life with treatment periods up to one or two decades of life. Real-life and registry data will be the only source of this important information in the future.
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Affiliation(s)
- Stephan Madersbacher
- Department of Urology, Danube Hospital, and Medical University of Vienna, Austria.
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Ückert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG. Update on Phosphodiesterase (PDE) Isoenzymes as Pharmacologic Targets in Urology: Present and Future. Eur Urol 2006; 50:1194-207; discussion 1207. [DOI: 10.1016/j.eururo.2006.05.025] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2004] [Accepted: 05/08/2006] [Indexed: 01/23/2023]
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Chung BH, Hong SJ, Cho JS, Seong DH. Relationship between serum prostate-specific antigen and prostate volume in Korean men with benign prostatic hyperplasia: a multicentre study. BJU Int 2006; 97:742-6. [PMID: 16536765 DOI: 10.1111/j.1464-410x.2006.06016.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To evaluate the relationship between prostate specific antigen (PSA) and prostate volume (PV) in Korean men, as PV is a key predictor of both disease progression and response to medical therapy in patients with benign prostatic hyperplasia (BPH), and PSA has been suggested as a proxy marker to estimate the total PV, mainly in Caucasians. PATIENTS AND METHODS From 1999 to 2004, men aged 50-79 years with lower urinary tract symptoms (LUTS) and BPH were enrolled into this multicentre study. The analyses included 5716 patients presenting to 11 medical centres with LUTS (International Prostate Symptom Score >8, peak urinary flow rate <15 mL/s); they had a mean age of 64.3 years, mean baseline PV of 36.9 mL, and mean baseline PSA level of 2.2 ng/mL. Men with a baseline PSA of >10 ng/mL were excluded, to reduce the likelihood of including occult prostate cancer. A biopsy was taken in those with suspicious findings on a digital rectal examination or serum PSA level of >4 ng/mL, to exclude prostate cancer. Receiver operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to predict threshold PV in men with BPH. RESULTS The PV and serum PSA level had an age-dependent log-linear relationship, the strength of which increased with age. The ROC curve analysis showed that PSA had good predictive value for various prostate volume thresholds (30, 40 and 50 mL). CONCLUSIONS The PSA-PV relationship in Korean men is similar to that in Caucasians, but Korean men have a slightly lower PSA level and a smaller PV than Caucasians. The approximate age-specific criteria for detecting Korean men with a PV of >40 mL were a PSA level of >1.3 ng/mL, >1.7 ng/mL and >2.0 ng/mL for men with BPH in their sixth, seventh and eighth decade, respectively.
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Affiliation(s)
- Byung Ha Chung
- Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
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Uckert S, Oelke M, Stief CG, Andersson KE, Jonas U, Hedlund P. Immunohistochemical Distribution of cAMP- and cGMP-Phosphodiesterase (PDE) Isoenzymes in the Human Prostate. Eur Urol 2006; 49:740-5. [PMID: 16460876 DOI: 10.1016/j.eururo.2005.12.050] [Citation(s) in RCA: 109] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2005] [Accepted: 12/23/2005] [Indexed: 11/18/2022]
Abstract
OBJECTIVES With the introduction of sildenafil citrate (Viagra), the concept of phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to be involved in the control of the normal function of the prostate. The aim of the present study was to evaluate by means of immunohistochemistry the expression and distribution of some cAMP- and cGMP-PDE isoenzymes in the prostate. MATERIAL & METHODS Cryostat sections (10 microM) of formaldehyde-fixated tissue segments excised from the transition zone of human prostates were incubated with primary antibodies directed against the PDE isoenzymes 3, 4, 5, and 11. Then, sections were exposed to either fluorescein isothiocyanate- (FITC) or Texas Red- (TR) labeled secondary antibodies and visualization was commenced by means of laser fluorescence microscopy. RESULTS TR-immunofluorescence indicating the presence of PDE4 (cAMP-PDE) was abundantly observed in the fibromuscular stroma as well as in glandular structures of the transition zone. In contrast to the distribution of PDE4, immunoactivity indicating PDE5 (cGMP-PDE) and 11 (dual substrate PDE) was mainly observed in glandular and subglandular areas. No immunostaining for PDE3 (cGMP-inhibited PDE) was detected. CONCLUSION Our results confirm the presence of PDE isoenzymes 4, 5 and 11 in the transition zone of the human prostate and present evidence that these isoenzymes are not evenly distributed. These findings are in support of the hypothesis that there might be a rationale for the use of PDE inhibitors in the pharmacotherapy of BPH and LUTS.
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Affiliation(s)
- Stefan Uckert
- Hannover Medical School, Department of Urology, Hannover, Germany.
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Roberts RO, Lieber MM, Jacobson DJ, Girman CJ, Jacobsen SJ. Limitations of using outcomes in the placebo arm of a clinical trial of benign prostatic hyperplasia to quantify those in the community. Mayo Clin Proc 2005; 80:759-64. [PMID: 15948299 DOI: 10.1016/s0025-6196(11)61530-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
OBJECTIVES To quantify potential biases that may occur when placebo arms of clinical trials are used to characterize the natural history of disease and to compare incidence rates of benign prostatic hyperplasia (BPH) outcomes in community-dwelling men with outcomes in the placebo arm of a clinical trial of BPH. SUBJECTS AND METHODS White men aged 50 years or older at baseline were selected randomly from the Olmsted County, Minnesota, community in 1990 and were monitored biennially through 1996 for urologic outcomes. Symptom progression, acute urinary retention, and minimally Invasive or surgical treatment of BPH were assessed from a validated questionnaire and a review of community medical records. Findings from the Olmsted County Study (N=1193) and a selected subcohort (n=238) were compared with those from the placebo arm of the Medical Therapy of Prostatic Symptoms trial (N=737). RESULTS During more than 5088 person-years of follow-up (mean, 4.9 years) In the Olmsted County Study, Incidence rates per 1000 person-years were 8.5 (95% confidence Interval [CI], 6.4-11.2) for acute urinary retention, 97.1 (95% CI, 88.7-106.0) for symptom progression, 6.6 (95% CI, 4.8-9.0) for surgery or minimally invasive treatment, and 105.1 (95% CI, 96.4-114.4) for any outcomes for all men. For those meeting trial Inclusion criteria (selected subcohort, n=238), Incidence rates were 18.3, 86.5, 16.8, and 109.4, respectively. By comparison, Incidence rates per 1000 person-years for the placebo arm of the Medical Therapy of Prostatic Symptoms clinical trial for BPH (mean follow-up, 4.5 years) were 6 for acute urinary retention, 36 for symptom progression, and 45 for any outcome, but the estimate of 13 for surgery or minimally invasive treatment was higher than for men in the Olmsted County Study. CONCLUSIONS Compared with community-dwelling men, men in the placebo arm of this clinical trial of BPH treatments had a substantially lower risk of BPH-related outcomes. Extrapolation of findings from the placebo arm of clinical trials to describe the natural history of disease in community-dwelling men should be done with caution and appropriate recognition of limitations.
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Affiliation(s)
- Rosebud O Roberts
- Department of Health Sciences Research and Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
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Kim ED. The use of baseline clinical measures to predict those at risk for progression of benign prostatic hyperplasia. Curr Urol Rep 2004; 5:267-73. [PMID: 15260926 DOI: 10.1007/s11934-004-0049-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Although histologic changes of benign prostatic hyperplasia (BPH) begin in men when they are in their thirties, symptomatic BPH characterized by lower urinary tract symptoms (LUTS) typically do not develop for several decades. Progression of BPH may lead to significant voiding symptoms, acute urinary retention, and the need for prostate surgery. However, developing LUTS is not inevitable for men with histologic evidence of BPH. The ability to predict those men who are at risk for BPH progression is increasingly important because of recent evidence provided by the Medical Therapy of Prostate Symptoms study. This landmark study demonstrated that 5alpha-reductase inhibitors, alone or in combination with selective alpha-blockers, can delay or prevent the progression of BPH. In addition, the most important and consistent predictive factors for BPH progression are baseline prostate-specific antigen and prostate volume. Integration of these clinical parameters into clinical practice is influencing the decision regarding which men should observe or initiate treatment. This article highlights recent studies regarding the use of baseline clinical parameters on predicting BPH progression.
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Affiliation(s)
- Edward D Kim
- Department of Surgery, Division of Urology, University of Tennessee Medical Center, 1928 Alcoa Highway, Knoxville, TN 37920, USA.
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Abstract
Benign prostatic hyperplasia (BPH) is a common condition, which increases with increasing age. Although not a life-threatening condition, BPH can significantly affect quality of life. BPH manifests clinically with lower urinary tract symptoms (LUTS) and may be associated with sexual dysfunction. As many as 60% of men aged 60 years have some degree of clinical BPH. With the projected increases in the distribution of people over the age of 60, BPH isset to become an even greater problem in men's health.
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Affiliation(s)
- Majid Shabbir
- Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, London NW3 2QG, England
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36
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Chapple CR. Pharmacological therapy of benign prostatic hyperplasia/lower urinary tract symptoms: an overview for the practising clinician. BJU Int 2004; 94:738-44. [PMID: 15329091 DOI: 10.1111/j.1464-410x.2004.05022.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Less than 10 years ago surgery and watchful-waiting were the only widely accepted management options for lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and benign prostatic obstruction (BPO). There has been an enormous decline in the popularity of surgery and it is now apparent that medication is the most frequently used treatment for BPH/LUTS; this has arguably therefore been the most major change in urological clinical practice in the last decade. Currently alpha(1)-adrenoceptor antagonists are the commonest medical therapy, and are thought to act by relaxing prostatic smooth muscle, the neural or so-called 'dynamic' component of BPO. 5alpha-reductase inhibitors (finasteride, dutasteride) are another option for BPH/LUTS, which reduce prostatic mass and therefore the mechanical or 'static' component of BPO. In the last 10 years there have been four direct comparative studies between alpha(1)-adrenoceptor antagonists and finasteride, including their combination, the results of which, and their implications for therapy, are discussed. Another group of agents are the phytotherapeutic extracts, which act via various mechanisms, many as yet poorly defined. This review critically assesses existing publications relating to the medical management of BPH/LUTS.
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Affiliation(s)
- Christopher R Chapple
- Department of Urology, Sheffield Teaching Hospitals NHS Trust, Royal Hallamshire Hospital, Sheffield, UK.
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Roehrborn CG, Bruskewitz R, Nickel JC, McConnell JD, Saltzman B, Gittelman MC, Malek GH, Gottesman JE, Suryawanshi S, Drisko J, Meehan A, Waldstreicher J. Sustained Decrease in Incidence of Acute Urinary Retention and Surgery With Finasteride for 6 Years in Men With Benign Prostatic Hyperplasia. J Urol 2004; 171:1194-8. [PMID: 14767299 DOI: 10.1097/01.ju.0000112918.74410.94] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE We determined the effect of long-term treatment with finasteride on the incidence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH) related surgery in men with BPH. MATERIALS AND METHODS The Proscar (Merck and Co., Inc., Whitehouse Station, New Jersey) Long-Term Efficacy and Safety Study (PLESS) was comprised of 3040 men with enlarged prostates, moderate to severe symptomatic BPH and no clinical evidence of prostate cancer. Patients were randomized to placebo or 5 mg finasteride daily for 4 years. Of the 3016 randomized patients with available efficacy data 62% completed the original 4-year study (1006 on finasteride and 891 on placebo) and 89% of these (908 from the original finasteride arm and 785 from the placebo arm) continued in a 2-year open extension on finasteride. Followup was attempted in discontinued patients. Complete 6-year outcomes data, including 6-year followup in 770 men who had discontinued treatment during years 1 to 6, were available for 2463 (82%) of the 3016 originally randomized patients. RESULTS For patients on continuous finasteride treatment the decrease in incidence of AUR and/or BPH related surgery in the 4-year base study was sustained during the open extension. In patients who were switched from placebo to finasteride in the extension, the incidence of AUR and/or BPH related surgery was similar to that in the continuous finasteride arm. CONCLUSIONS The 6-year data from PLESS confirmed and further extended the findings from the original 4-year trial, demonstrating that finasteride treatment led to a sustained decrease in the incidence of AUR and/or BPH related surgery in men with BPH and enlarged prostates.
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Affiliation(s)
- Claus G Roehrborn
- The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9100, USA.
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Abstract
A 43-year-old man presented suffering from decreasing vision in both eyes for 3 months. The patient's visual acuity was 6/20 (non-corrected) in the right eye and 6/10 (-1.75/-1.00 x 91) in the left. Ocular examination of both eyes revealed anterior subcapsular opacities of both lenses with the right eye being more severe than the left. He had been taking finasteride (Propecia; Merck, Sharp and Dohme) at 1 mg/day for 3 years to treat early stage of androgenic alopecia. It was highly suspected that finasteride was associated with the anterior subcapsular opacity on the lens, and the patient therefore discontinued use of finasteride. He underwent uneventful cataract extraction surgery and intraocular lens implantation of the right eye. One month after cataract surgery in the right eye, the best-corrected visual acuity was right 6/6 (-1.25) and left 6/10 (-2.00/-0.50 x 100). To the best of the authors' knowledge, this is the first reported case of Propecia-associated cataract.
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Roehrborn CG, Lee M, Meehan A, Waldstreicher J. Effects of finasteride on serum testosterone and body mass index in men with benign prostatic hyperplasia. Urology 2003; 62:894-9. [PMID: 14624915 DOI: 10.1016/s0090-4295(03)00661-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To examine the effect of finasteride on serum testosterone in men with benign prostatic hyperplasia (BPH). METHODS The Proscar Long-Term Efficacy and Safety Study (PLESS) was a 4-year trial comparing the safety and efficacy of finasteride 5 mg with placebo in 3040 men with moderate to severe symptomatic BPH and enlarged prostates. PLESS included the prospective measurement of annual serum testosterone in a randomly selected subset of patients comprising approximately 10% of the randomized population (n = 301). RESULTS Finasteride treatment led to a modest, but significant (P <0.001), increase relative to placebo in serum testosterone, with this increase greatest in patients who had low baseline testosterone levels. The larger testosterone increases seen in finasteride-treated patients in the lower baseline testosterone tertiles were associated with significant mean reductions relative to placebo at year 4 in body mass index (BMI), ranging from 0.6 to 0.8 kg/m2. No statistically significant between-group difference was found in BMI in the upper testosterone tertile. The sexual adverse experience profiles for finasteride and placebo were similar across the baseline testosterone cohorts examined. CONCLUSIONS Finasteride treatment led to a generally modest increase relative to placebo in serum testosterone, with the greatest increases occurring in men with low baseline testosterone levels. The physiologic significance of these changes in men with low baseline testosterone levels is unclear, but the associated reduction in BMI is intriguing and may be related, because BMI is known to be negatively correlated with serum testosterone levels in men.
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Affiliation(s)
- Claus G Roehrborn
- University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110, USA
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40
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Eri LM, Thomassen H, Brennhovd B, Håheim LL. Accuracy and repeatability of prostate volume measurements by transrectal ultrasound. Prostate Cancer Prostatic Dis 2003; 5:273-8. [PMID: 12627211 DOI: 10.1038/sj.pcan.4500568] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2001] [Revised: 11/28/2001] [Accepted: 12/12/2001] [Indexed: 11/08/2022]
Abstract
We evaluated six alternative methods of prostate volume determination by transrectal ultrasound, three based on planimetry and three based on measurement of prostate diameters. Prostate volume measurements were made on an average of 6.5 occasions over a 3 y period on 41 patients with benign prostatic hyperplasia, using standard techniques. We defined the average of multiple planimetries as the prostate reference volume. Agreement with the reference volume and reproducibility at repeat testing was in the same range for single planimetry and volume determinations based on the formulas height (H) x width (W) x length (L) x pi/6 and W x W x H x pi/6, but was poorer using the formula W x W x W x pi/6. Using the average result of two successive planimetry measurements increased the reproducibility of planimetry, being statistically significantly better than for one single planimetry (P=0.024) or for the formula W x W x H x pi/6 (P=0.048). Our study suggests that the simple formula based methods of prostate volume determination provide results that are only marginally inferior to one single planimetry, but results are improved by performing two planimetry measurements.
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Affiliation(s)
- L M Eri
- Department of Urology, Aker University Hospital, Oslo, Norway
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Lowe FC, McConnell JD, Hudson PB, Romas NA, Boake R, Lieber M, Elhilali M, Geller J, Imperto-McGinely J, Andriole GL, Bruskewitz RC, Walsh PC, Bartsch G, Nacey JN, Shah S, Pappas F, Ko A, Cook T, Stoner E, Waldstreicher J. Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia. Urology 2003; 61:791-6. [PMID: 12670567 DOI: 10.1016/s0090-4295(02)02548-7] [Citation(s) in RCA: 84] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVES To summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important. METHODS The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate glands. The initial 1-year placebo-controlled study was followed by a 5-year open-label extension. In total, 6-year finasteride data were available in 487 patients originally randomized to finasteride, and 5-year data were available on 238 patients originally randomized to placebo. RESULTS After 6 years of treatment with finasteride 5 mg, the mean quasi-American Urological Association Symptom Score improved by 4.0 points, the median prostate volume decreased by 24%, and the mean maximal urinary flow rate increased by 2.9 mL/s (P <0.001 for all parameters). Long-term finasteride treatment was well tolerated, with a low incidence of drug-related sexual adverse events occurring during the first year and even fewer occurrences during the 5-year open extension. CONCLUSIONS Treatment with finasteride leads to durable improvement in urinary tract symptoms, flow rate, and prostate volume, with no increase in the prevalence of drug-related adverse events over time.
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Affiliation(s)
- Franklin C Lowe
- Department of Urology, Saint Luke's-Roosevelt Hospital Center, New York, NY 10019, USA
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Jiménez Cruz JF, Quecedo Gutiérrez L, Del Llano Señarís J. [Finasteride: 10 years of clinical use. Systematic review of the literature]. Actas Urol Esp 2003; 27:202-15. [PMID: 12812118 DOI: 10.1016/s0210-4806(03)72906-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
INTRODUCTION After ten years of clinical use of Finasteride in patients with BPH, we carried out a systematic review of the literature including the assessment of their quality and grading the level of evidence for clinical recommendations. METHODS Using Medline, Embase, Healthstar and Cochrane Library from 1990 until 2002, we select all the studies referring patients between 50 to 85 with symptoms of BPH, metrics of flow, prostatic volume, postmictional residue, detrusor pressure, adverse effects, cost-effectiveness and quality of life. RESULTS We found out 135 references, of which 36 accomplish the inclusion criteria. Of those, 3 have got level I of evidence, 12 level II, 6 level III and 10 level IV. Three are economic studies and two evaluate the quality of life. DISCUSSION With a high level of evidence and after ten years of clinical use, Finasteride shows its effectiveness in reducing the symptoms of patients with prostate bigger than 40 ml and/or PSA of more than 1.4 ngr/ml, with scarce adverse effects with a clear improvement of quality of life. Therefore, it is recommended (grade A) for clinical use. CONCLUSIONS Finasteride, through prostate volume reduction, modify natural evolution of BPH, decreasing the risk of acute urine retention and surgery.
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Wessells H, Roy J, Bannow J, Grayhack J, Matsumoto AM, Tenover L, Herlihy R, Fitch W, Labasky R, Auerbach S, Parra R, Rajfer J, Culbertson J, Lee M, Bach MA, Waldstreicher J. Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia. Urology 2003; 61:579-84. [PMID: 12639651 DOI: 10.1016/s0090-4295(02)02401-9] [Citation(s) in RCA: 112] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
OBJECTIVES To evaluate the incidence and resolution of sexual adverse experiences (AEs) in men with benign prostatic hyperplasia treated with finasteride 5 mg compared with placebo. METHODS The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men, aged 45 to 78 years, with symptomatic benign prostatic hyperplasia, enlarged prostates, and no evidence of prostate cancer. Patients completed a questionnaire at screening regarding their history of sexual dysfunction. During treatment, spontaneously self-reported sexual AEs were recorded. RESULTS At screening, 46% of patients in each treatment group reported some history of sexual dysfunction. During year 1 of the study, 15% of finasteride-treated patients and 7% of placebo-treated patients had sexual AEs that were considered drug related by the investigator (P <0.001). During years 2 to 4, no between-group difference was noted in the incidence of new sexual AEs (7% in each group). The drug-related sexual AE profile for finasteride was similar for men with or without a history of sexual dysfunction. Sexual AEs resolved while continuing therapy in 12% of finasteride patients and 19% of placebo patients. Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively. CONCLUSIONS Compared with placebo, men treated with finasteride experienced new drug-related sexual AEs with an increased incidence only during the first year of therapy.
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Lam JS, Romas NA, Lowe FC. Long-term treatment with finasteride in men with symptomatic benign prostatic hyperplasia: 10-year follow-up. Urology 2003; 61:354-8. [PMID: 12597947 DOI: 10.1016/s0090-4295(02)02149-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
OBJECTIVES To evaluate the safety and efficacy of finasteride 5 mg during a 10-year period in men with enlarged prostates from a single center who participated in the double-blind and extension phases of the multicenter, Phase III, North American benign prostatic hyperplasia (BPH) trial. It is important that the long-term safety and efficacy of drugs intended for chronic administration in men with BPH be well understood. METHODS The Phase III North American BPH trial involved a 1-year, placebo-controlled, double-blind study, followed by a 5-year open extension with finasteride 5 mg/day. The trial enrolled men with symptomatic BPH, an enlarged prostate on digital rectal examination, and no evidence of prostate cancer. Of the 46 patients originally enrolled from our institution, 43 were randomized to receive finasteride or placebo, of whom 41 (95%) completed the double-blind study and entered the 5-year extension. Thirty (73%) of these 41 patients completed the 5-year extension. Patients continued to be followed up by their physicians for an additional 5 years, for a total follow-up of at least 10 years. RESULTS Twenty-four (56%) of the original 43 patients randomized to finasteride or placebo were judged as successfully treated during the 10-year finasteride follow-up (17 patients taking finasteride alone at 10 years and 7 patients who were taking finasteride alone when they discontinued during the 10-year follow-up for reasons not related to finasteride treatment). Altogether, 22 (51%) of the original 43 randomized patients continued finasteride treatment at 10 years (17 taking finasteride alone, 4 taking finasteride plus an alpha-blocker, and 1 taking finasteride for treatment of hematuria). Finasteride was well tolerated, with no new adverse experiences occurring with increasing duration of exposure to the drug. CONCLUSIONS This long-term follow-up study has demonstrated that appropriately selected patients with symptomatic BPH and enlarged prostates are likely to have a long-term response to taking finasteride 5 mg daily.
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Affiliation(s)
- John S Lam
- Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York, USA
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Abstract
PURPOSE OF REVIEW Medical therapy is now the first-line treatment for most men with symptomatic benign prostatic hyperplasia. This review aims to highlight the recent contributions to our understanding of 5 alpha-reductase inhibitor usage. RECENT FINDINGS For the last decade, finasteride has been the only available 5 alpha-reductase inhibitor, acting upon the type 2 isoenzyme of 5-alpha reductase. Dutasteride is the first drug that can inhibit both isoenzymes and is soon to be available. Biochemically it achieves greater and more rapid dihydrotestosterone suppression compared with finasteride. Clinically, it appears to be at least as good in terms of improving symptoms and flow rates, and reducing the risk of acute urinary retention or the requirement for benign prostatic hyperplasia-related surgery. However, until these two drugs are formally compared, the true benefits of additional type 1 isoenzyme inhibition are unknown. The recently reported Medical Therapy of Prostatic Symptoms trial has convincingly demonstrated superior outcomes with combination therapy compared with monotherapy, unlike previous trials of shorter duration. The ability of 5 alpha-reductase inhibitors to prevent disease progression was also confirmed. Newer roles for 5 alpha-reductase inhibitors are also being defined. Finasteride has been shown to reduce and control benign prostatic hyperplasia-related haematuria, although its value in controlling perioperative bleeding is less clear. Their role as chemopreventive agents for prostate cancer is also under investigation. SUMMARY Recent studies have both clarified and extended the roles of 5 alpha-reductase inhibitors in benign prostatic hyperplasia, and these may expand further if chemopreventive abilities are proved. In addition, dual isoenzyme inhibition will soon be available.
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Affiliation(s)
- Charlotte L Foley
- Prostate Cancer Research Unit, Institute of Urology and Nephrology, University College London, 67 Riding House Street, London W1W 7EY, UK.
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Edwards JE, Moore RA. Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials. BMC Urol 2002; 2:14. [PMID: 12477383 PMCID: PMC140032 DOI: 10.1186/1471-2490-2-14] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2002] [Accepted: 12/12/2002] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Benign prostatic hyperplasia affects older men. This systematic review determined efficacy and adverse effects of finasteride. REVIEW METHODS PubMed, the Cochrane Library, reference lists of reports, and reviews were searched for randomised, double-blind trials of finasteride in benign prostatic hyperplasia. Outcomes included symptom score, urinary flow rate, prostate volume, discontinuation, and adverse effects. Relative risk and NNT or NNH were calculated for dichotomous data. Sensitivity analyses assessed influences of baseline symptom severity, initial prostate volume, a dominating trial, and previous interventions. RESULTS Three trials had active controls and 19 had placebo. In placebo-controlled trials, 8820 patients received finasteride 5 mg and 5909 placebo over 3-48 months. Over 48 months finasteride produced greater improvements in total symptom score, maximum urinary flow rate, and prostate volume. Significantly more sexual dysfunction, impotence, ejaculation disorder and decreased libido occurred with finasteride at 12 months; the NNH for any sexual dysfunction at 12 months was 14. Significantly fewer men treated with finasteride experienced acute retention or had surgery at 24 or 48 months than with placebo; at 12 months the NNT was 49 (31 to 112) to avoid one acute urinary retention and 31 (21 to 61) to avoid one surgery. Sensitivity analyses showed benefit with finasteride 5 mg to be constant irrespective of the initial prostate volume. CONCLUSIONS Information from many patients in studies of high quality showed beneficial effects of finasteride in terms of symptoms, flow rate and prostate volume. More utility would result if patient centred outcomes were reported in dichotomous form.
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Affiliation(s)
- Jayne E Edwards
- Pain Research and Nuffield Department of Anaesthetics, University of Oxford, Oxford Radcliffe Hospitals, The Churchill, Headington, Oxford, UK
| | - R Andrew Moore
- Pain Research and Nuffield Department of Anaesthetics, University of Oxford, Oxford Radcliffe Hospitals, The Churchill, Headington, Oxford, UK
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Vaughan D, Imperato-McGinley J, McConnell J, Matsumoto AM, Bracken B, Roy J, Sullivan M, Pappas F, Cook T, Daurio C, Meehan A, Stoner E, Waldstreicher J. Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia. Urology 2002; 60:1040-4. [PMID: 12475666 DOI: 10.1016/s0090-4295(02)01971-4] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
OBJECTIVES To evaluate the effects of finasteride, a specific type II 5-alpha-reductase inhibitor, on symptoms of benign prostatic hyperplasia, prostate volume, and urinary flow during a 7 to 8-year period. METHODS A total of 190 men with symptomatic benign prostatic hyperplasia and enlarged prostates entered one of two Phase II double-blind 3 to 6-month studies. Of these, 156 patients continued taking open-label finasteride, and more than 70 patients completed 7 to 8 years of treatment. The symptoms were scored using a patient self-administered modified Boyarsky symptom questionnaire. Prostate volume was measured by magnetic resonance imaging or ultrasonography, and the maximal urinary flow rate was assessed noninvasively. RESULTS Treatment with finasteride for 7 to 8 years led to sustained improvement in symptoms, reduction in prostate volume (28% from baseline), and increased urinary flow (median 2.5 mL/s from baseline). Decreases in dihydrotestosterone (86%) and prostate-specific antigen (54%) levels were also maintained. Long-term finasteride treatment was safe and generally well tolerated. CONCLUSIONS Long-term treatment with finasteride was well tolerated and resulted in durable symptom relief and improvement in prostate volume and urinary flow.
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Affiliation(s)
- D Vaughan
- Cornell University Medical Center, New York, New York, USA
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Fujita T, Matsumoto Y, Kimura T, Yokota S, Sawada M, Majima M, Ohtani Y, Kumagai Y. Pharmacokinetics and pharmacodynamics of TF-505, a novel nonsteroidal 5alpha-reductase inhibitor, in normal subjects treated with single or multiple doses. Br J Clin Pharmacol 2002; 54:283-94. [PMID: 12236849 PMCID: PMC1874425 DOI: 10.1046/j.1365-2125.2002.01656.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
AIMS To assess the tolerability, pharmacokinetics and pharmacodynamics of a novel nonsteroidal and noncompetitive inhibitor of type I and type II 5alpha-reductases, (-)-(S)-4-[1-[4-[1-(4-isobutylphenyl) butoxy]benzoyl]indolizin-3-yl]butyric acid (TF-505), after single and multiple oral doses in healthy volunteers. METHODS In the single-dose study, six young adult males in each dose group received 25 mg or 50 mg of TF-505, and six older males (>or= 40 years) in each dose group received 75 mg or 100 mg of TF-505. The subjects were given the drug in ascending dose and in the fasting state. Six subjects also received 50 mg of TF-505 after breakfast in a two-period crossover manner. In the multiple-dose study, six older males in each dose group received 12.5 mg or 25 mg TF-505 after breakfast daily for 7 days. Plasma concentrations of TF-505, dihydrotestosterone (DHT) and testosterone were measured. The pharmacokinetics of TF-505 were analysed by a compartment model with first-order absorption, first-order elimination and a lag time. Pharmacokinetic and pharmacodynamic relationships were evaluated by indirect response modelling with inhibition of input. RESULTS Maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) increased proportionately after the single dose up to 50 mg and with the multiple doses. Linearity was not detected between 75 and 100 mg of TF-505. Dose dependency was also noted for the effect of TF-505 on DHT concentrations following single doses up to 50 mg and multiple doses. Plasma DHT concentrations decreased maximally to 58.2, 49.5, 54.2 and 49.8% of basal values at 8-12 h after single administration of 25, 50, 75 and 100 mg TF-505, respectively, and to 60.5 and 49.4% at the 7th and 5th dose following multiple doses of 12.5 and 25 mg TF-505, respectively. The predicted effect curves matched the observed data when the indirect response model was applied to the time course of the suppressant effect of TF-505 on plasma DHT concentrations after both the single and multiple studies. Fifty percent inhibitory concentrations (IC50) of 0.82, 1.48, 1.31 and 0.88 micro g ml(-1), zero-order rate constants for the onset of plasma DHT concentration changes (kin) of 17.8, 17.4, 17.0 and 10.7% h(-1) and first-order rate constants for increase in plasma DHT concentrations to basal values (kout) of 0.17, 0.16, 0.17 and 0.10 h(-1) for the single study at doses of 25, 50, 75 and 100 mg, respectively, were attained. In the multiple-dose study, IC50s were 1.74 and 1.49 micro g ml(-1) for the 12.5 and 25 mg doses, respectively. No serious adverse events related to TF-505 were observed. CONCLUSIONS TF-505 was well tolerated in healthy male volunteers. Accumulation of TF-505 in plasma was not observed during multiple dosing. The indirect response model described the relationships between pharmacokinetics and pharmacodynamics of TF-505. Such modelling is expected to yield an appropriate dosage regimen in subsequent clinical trials.
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Affiliation(s)
- Tomoe Fujita
- Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Japan.
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Affiliation(s)
- C Kouriefs
- Department of Urology, St Helier Hospital, Carshalton, Surrey, UK.
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Vicente Rodríguez J. [Treatment of benign prostatic hypertrophy: present situation and future prospects]. Actas Urol Esp 2002; 26:481-90. [PMID: 12224431 DOI: 10.1016/s0210-4806(02)72816-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Review article offering an up-to-date view and a forecast for the future evolution of a disease which over the last few years has been the subject of increasingly scientific thoroughness. It deals with the natural history of the disease and the application of basic knowledge from other fields. It establishes the importance of a therapeutic evaluation of the results obtained with alternative medical and surgical approaches in the management of this entity. This review of benign prostate hyperplasia analyses the present realities and the future perspectives of the disease. It includes the most important contributions from international consensus and recommendations, and evaluation of the impact of drug treatment, the discredit of alternative options, the contribution of basic sciences to the understanding of the development of prostate cancer and the future of surgical management (TUR) and its alternatives.
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