9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Pharmacology of the lower urinary tract: update on LUTS treatment

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The number of compounds used in the pharmacological treatment of lower urinary tract symptoms (LUTS) of patients who do not respond to conservative measures has been relatively stable during the last decade, with the exception of the introduction of the new class of β3 adrenoceptor agonists. However, different combinations have been investigated, and the long-term use of these compounds has raised new concerns about adherence and safety. This review summarizes the current state of pharmacology for LUTS, and presents a thorough discussion of the possible challenges concerning their future use. In this narrative review, we analyze the most recent articles related to LUTS pharmacotherapy, after an initial review of mechanisms of bladder function relevant in present clinical practice. The main problems with pharmacotherapy in LUTS are associated with its moderate efficacy, low persistence on treatment, and the incidence of short- and long-term adverse events (AE) associated with some compounds. The long-term AE, such as cognitive impairment in the elderly vulnerable patients associated with antimuscarinic drugs or persistent erectile dysfunction in sexually active men after treatment with 5-α-reductase inhibitors (5-ARI), are some of the problems addressed in this review. Combination therapy taking advantage of the synergistic mechanisms of action between some classes of compounds may overcome AE associated with dose escalation. LUTS pharmacotherapy offers moderate results to most patients but not a full cure. The use of combination drugs to achieve better clinical results, reduce AE and improve both efficacy and adherence, will be used more frequently in the future. The recently raised concern on potential long-term irreversible AE associated with some of these drugs, like antimuscarinics and 5-ARI, are critically important and require further investigation.

          Related collections

          Most cited references95

          • Record: found
          • Abstract: found
          • Article: not found

          The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.

          Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy. Copyright 2003 Massachusetts Medical Society
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study.

            To estimate and compare the prevalence and associated bother of lower urinary tract symptoms (LUTS) in the general populations of the USA, UK and Sweden using current International Continence Society (ICS) definitions, as no previous population-based studies evaluating the prevalence of LUTS in the USA, using the 2002 ICS definitions, have been conducted. This cross-sectional, population-representative survey was conducted via the Internet in the USA, the UK and Sweden. Members of Internet-based panels were randomly selected to receive an e-mailed invitation to participate. If interested, respondents selected a link to an informed consent page, followed by the survey. Participants were asked to rate how often they experienced individual LUTS during the previous 4 weeks, on a five-point Likert scale, and, if experienced, how much the symptom bothered them. Descriptive statistics were used to summarize and present the data. Responses rates for the USA, the UK and Sweden were 59.6%, 60.6% and 52.3%, respectively, with a final sample of 30,000 (USA 20,000; UK 7500; Sweden 2500). The mean age (range) of the participants was 56.6 (40-99) years; the mean percentages for race were 82.9% white, 6.7% black, 6.0% Hispanic and 4.4% Asian/other. The prevalence of LUTS was defined by two symptom frequency thresholds, i.e. at least 'sometimes' and at least 'often' for all LUTS except incontinence, where frequency thresholds were at least 'a few times per month' and at least 'a few times per week'. The prevalence of at least one LUTS at least 'sometimes' was 72.3% for men and 76.3% for women, and 47.9% and 52.5% for at least 'often' for men and women, respectively. For most LUTS, at least half of the participants were bothered 'somewhat' or more using a frequency threshold of at least 'sometimes'. For a threshold of at least 'often', 'somewhat' or more bother was reported by > or =70% of participants except for terminal dribble in men and split stream in women. In this large population study of three countries, LUTS are highly prevalent among men and women aged >40 years. In general, LUTS experienced 'often' or more are bothersome to most people.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study.

              Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and prostatic enlargement. To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention (AUR), BPH-related surgery, and BPH clinical progression over 4 yr in men at increased risk of progression. The Combination of Avodart and Tamsulosin (CombAT) study was a 4-yr, multicenter, randomised, double-blind, parallel-group study in 4844 men > or =50 yr of age with a clinical diagnosis of BPH, International Prostate Symptom Score > or =12, prostate volume > or =30 cm(3), prostate-specific antigen 1.5-10 ng/ml, and maximum urinary flow rate (Q(max)) >5 and or =125 ml. Oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. The 4-yr primary end point was time to first AUR or BPH-related surgery. Secondary end points included BPH clinical progression, symptoms, Q(max), prostate volume, safety, and tolerability. Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery. Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression. Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr. Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies, with the exception of an imbalance in the composite term of cardiac failure among the three study arms. The lack of placebo control is a study limitation. The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement. CLINICALTRIALS.GOV IDENTIFIER: NCT00090103 (http://www.clinicaltrials.gov/ct2/show/NCT00090103).
                Bookmark

                Author and article information

                Contributors
                Journal
                Ther Adv Urol
                Ther Adv Urol
                TAU
                sptau
                Therapeutic Advances in Urology
                SAGE Publications (Sage UK: London, England )
                1756-2872
                1756-2880
                13 May 2020
                Jan-Dec 2020
                : 12
                : 1756287220922425
                Affiliations
                [1-1756287220922425]Department of Urology in Hospital de São João, Alameda Professor Hernâni Monteiro, Porto, 4200-319, Portugal
                [2-1756287220922425]Faculty of Medicine of Porto, Porto, Portugal
                [3-1756287220922425]Department of Urology, Hospital São João, Porto, Portugal
                [4-1756287220922425]Faculty of Medicine of Porto, Porto, Portugal
                [5-1756287220922425]i3S Institute Investigation and Innovation in Health
                [6-1756287220922425]Department of Urology, Hospital São João, Porto, Portugal
                [7-1756287220922425]Faculty of Medicine of Porto, Porto, Portugal
                [8-1756287220922425]i3S Institute Investigation and Innovation in Health
                Author notes
                Author information
                https://orcid.org/0000-0002-4304-7023
                Article
                10.1177_1756287220922425
                10.1177/1756287220922425
                7238773
                e2dc70c3-562a-4e53-8ba7-9c2ebf0935db
                © The Author(s), 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 1 October 2019
                : 30 March 2020
                Categories
                Review
                Custom metadata
                January-December 2020
                ts1

                bph,combination therapies,luts,oab,oral pharmacotherapy,update
                bph, combination therapies, luts, oab, oral pharmacotherapy, update

                Comments

                Comment on this article