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Muacevic A, Adler JR, Nachiappa Ganesh R. Cleistanthins A and B Ameliorate Testosterone-Induced Benign Prostatic Hyperplasia in Castrated Rats by Regulating Apoptosis and Cell Differentiation. Cureus 2022; 14:e32141. [PMID: 36601166 PMCID: PMC9805890 DOI: 10.7759/cureus.32141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/01/2022] [Indexed: 12/04/2022] Open
Abstract
Background The aging male population is at higher risk for benign prostatic hyperplasia (BPH) wherein increased proliferation of stromal and epithelial cells of the prostate is observed. In this study, we investigated the effect of cleistanthins A and B on the inhibition of testosterone-induced BPH in castrated rats. Methodology Male Wistar rats were divided into eight groups (n = 6) and surgical castration was performed. BPH was induced by the administration of testosterone propionate in corn oil at 5 mg/kg for four weeks. The control group received corn oil, and the model group received testosterone propionate. The standard treatment group received finasteride orally along with testosterone. Cleistanthins A and B at 0.3, 1, and 3 mg/kg were administered by oral gavage along with testosterone. After four weeks, rats were sacrificed, and prostates were weighed and assessed for histomorphological, inflammatory, apoptotic, and proliferative markers. Results Cleistanthins A and B decreased prostatic enlargement and histopathological abnormalities. Elevated serum dihydrotestosterone levels were lowered significantly in both the cleistanthin A and cleistanthin B groups compared to the BPH model group. Cleistanthins A and B significantly lowered the serum interleukin (IL)-1β and tumor necrosis factor-alpha inflammatory markers in the test groups. Western blot analysis revealed cleistanthin A downregulated the IL-6, signal transducer and activator of transcription 3/cyclin D1 signaling pathway. Both cleistanthins A and B upregulated the apoptotic markers caspase-3 and cleaved caspase-3, whereas the cell proliferation markers cyclin D1 and proliferating cell nuclear antigen were found to be downregulated. Conclusions Both cleistanthins A and B inhibited BPH in a rat model by apoptotic induction and impeded cell proliferation.
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A Combination of Natural Products, BenPros (Green Tea Extract, Soybean Extract and Camellia Japonica Oil), Ameliorates Benign Prostatic Hyperplasia. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12126121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men and causes lower urinary tract symptoms due to excessive proliferation of prostate stromal and epithelial cells. The present study investigated the improving effect of BenPros, an edible natural product mixture (green tea extract, soybean extract and camellia japonica oil), against the development of BPH in vitro and in vivo. BenPros treatment showed inhibitory ability on testosterone-induced androgen receptor, prostate-specific antigen (PSA), and 5α-reductase protein expression in LNCap-LN3 cells and anti-inflammatory effects on LPS-induced increases in interleukin-6 and tumor necrosis factor-α in RAW264.7 cells. In a testosterone propionate (TP)-induced BPH rat model, BenPros decreased the up-regulated serum 5α-dihydrotestosterone and PSA levels. Moreover, BenPros also significantly reduced PSA protein expression in prostate tissue. Furthermore, TP-induced increased expression of cyclooxygenase 2 and B-cell lymphoma 2 (Bcl-2) were reduced by BenPros, resulting in an increase in the Bcl-2/BCL2-related X ratio. These regulatory abilities of BenPros on BPH inducing markers also reduced prostate size and epithelial thickness based on histological analysis. These results indicate that BenPros has a protective ability against BPH in vitro and in vivo, and it may be a promising candidate as a functional food in regulating BPH.
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Origanum majorana L. Extract Attenuated Benign Prostatic Hyperplasia in Rat Model: Effect on Oxidative Stress, Apoptosis, and Proliferation. Antioxidants (Basel) 2022; 11:antiox11061149. [PMID: 35740046 PMCID: PMC9219805 DOI: 10.3390/antiox11061149] [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: 04/03/2022] [Revised: 06/01/2022] [Accepted: 06/08/2022] [Indexed: 11/16/2022] Open
Abstract
Benign prostatic hyperplasia (BPH) is a widespread androgenic illness influencing elderly men. It is distinguished by prostatic epithelial and stromal muscle cell proliferation. Inflammation, oxidative stress, and apoptosis have all been interrelated to the development of BPH. Marjoram (Origanum majorana L.) is a herb with reported antiproliferative, proapoptotic, and antioxidative properties, which have not yet been studied in relation to BPH. Consequently, in this work, an ethanolic extract of O. majorana was prepared in two doses (250 and 500 mg/kg/day) to be injected into castrated rats after induction of a testosterone-BPH model. Testosterone propionate (TP) was subcutaneously injected (0.5 mg/kg/day) for one week after castration to induce BPH. Forty adult Wistar male rats were randomly allocated into five groups: control, BPH model, high and low O. majorana doses (250, 500 mg/kg/day), and finasteride (FN) (0.8 mg/kg/day) as a positive control. Treatment was continued with drugs/normal saline for 28 days. Rat’s body and prostate were weighed, prostate index (PI) and % of prostate growth inhibition were calculated, serum dihydrotestosterone (DHT), prostatic content of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA), DN damage, histopathological changes, immune expression of proliferating cell nuclear antigen (PCNA), caspase-3, α-SMA, and TGF-β1 were assessed. In addition, molecular quantitative PCR and ELISA analyses were performed to identify the expression of mRNAs and related proteins of both caspase-3 and TGF-β1 in prostate tissue from O. majorana-treated and untreated groups. Rats with BPH had significantly higher prostate weights and PI, higher DHT, DNA damage (8-hydroxyguanine, 8-OH-dG), and MDA levels with prominent PCNA, α-SMA, and TGF-β expression, but lower SOD, CAT, and TAC activity and caspase-3 expression. O. majorana (250 and 500 mg/kg/day)-treated groups revealed a decrease in prostate weights and PI, lower levels of DHT, suppressed oxidative stress, reduced tissue proliferation and fibrosis, and restored antioxidant and proapoptotic activity. Additionally, quantitative PCR and ELISA analysis showed that treatment with O. majorana significantly upregulated the expression of caspase-3 and downregulated the expression of TGF-β in prostate tissues of BPH rats. The data were confirmed by the immunohistological reactivity of these targeted markers in the prostate tissues. These effects were more significant with O. majorana 500 mg/mL/rat. In conclusion, the current study indicates the efficient use of O. majorana in the treatment of testosterone-induced BPH through its antiproliferative, proapoptotic, and antioxidative mechanisms.
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da Silva SB, Feitosa SGD, de L Alves SM, Santos RCA, Dos Anjos JV, Araújo AV. A Concise and Useful Guide to Understand How Alpha1 Adrenoceptor Antagonists Work. Mini Rev Med Chem 2022; 22:2383-2405. [PMID: 35507746 DOI: 10.2174/1389557522666220504141949] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/23/2022] [Accepted: 03/16/2022] [Indexed: 11/22/2022]
Abstract
Adrenoceptors are the receptors for the catecholamines, adrenaline and noradrenaline. They are divided in α (α1 and α2) and β (β1, β2 and β3). α1-Adrenoceptors are subdivided in α1A, α1B and α1D. Most tissues express mixtures of α1-adrenoceptors subtypes, which appear to coexist in different densities and ratios, and in most cases their responses are probably due to the activation of more than one type. The three subtypes of α1-adrenoceptors are G-protein-coupled receptors (GPCR), specifically coupled to Gq/11. Additionally, the activation of these receptors may activate other signaling pathways or different components of these pathways, which leads to a great variety of possible cellular effects. The first clinically used α1 antagonist was Prazosin, for Systemic Arterial Hypertension (SAH). It was followed by its congeners, Terazosin and Doxazosin. Nowadays, there are many classes of α-adrenergic antagonists with different selectivity profiles. In addition to SAH, the α1-adrenoceptors are used for the treatment of Benign Prostatic Hyperplasia (BPH) and urolithiasis. This antagonism may be part of the mechanism of action of tricyclic antidepressants. Moreover, the activation of these receptors may lead to adverse effects such as orthostatic hypotension, similar to what happens with the antidepressants and with some antipsychotic. Structure-activity relationships can explain, in part, how antagonists work and how selective they can be for each one of the subtypes. However, it is necessary to develop new molecules which antagonize the α1-adrenoceptors or make chemical modifications in these molecules to improve the selectivity, pharmacokinetic profile and/or reduce the adverse effects of known drugs.
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Affiliation(s)
- Sidiane B da Silva
- Laboratório de Nutrição, Atividade Física e Plasticidade Fenotípica - Centro Acadêmico de Vitória - Universidade Federal de Pernambuco. R. Alto do Reservatório, s/n Bela Vista - Vitória de Santo Antão, PE, 50608-680, Brazil
| | - Sidney G D Feitosa
- Departamento de Química Fundamental - Universidade Federal de Pernambuco. Av. Jornalista Aníbal Fernandes, s/n, Cidade Universitária - Recife, PE, 50740-560, Brazil
| | - Silvia M de L Alves
- Laboratório de Nutrição, Atividade Física e Plasticidade Fenotípica - Centro Acadêmico de Vitória - Universidade Federal de Pernambuco. R. Alto do Reservatório, s/n Bela Vista - Vitória de Santo Antão, PE, 50608-680, Brazil
| | - Ruth C A Santos
- Laboratório de Nutrição, Atividade Física e Plasticidade Fenotípica - Centro Acadêmico de Vitória - Universidade Federal de Pernambuco. R. Alto do Reservatório, s/n Bela Vista - Vitória de Santo Antão, PE, 50608-680, Brazil
| | - Janaína V Dos Anjos
- Departamento de Química Fundamental - Universidade Federal de Pernambuco. Av. Jornalista Aníbal Fernandes, s/n, Cidade Universitária - Recife, PE, 50740-560, Brazil
| | - Alice V Araújo
- Núcleo de Saúde Pública, Centro Acadêmico de Vitória - Universidade Federal de Pernambuco R. Alto do Reservatório, s/n Bela Vista - Vitória de Santo Antão, PE, 50608-680, Brazil
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Allahgholi M, Rahmani H, Javdani D, Sadeghi-Adl Z, Bender A, Módos D, Weiss G. DDREL: From drug-drug relationships to drug repurposing. INTELL DATA ANAL 2022. [DOI: 10.3233/ida-215745] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Analyzing the relationships among various drugs is an essential issue in the field of computational biology. Different kinds of informative knowledge, such as drug repurposing, can be extracted from drug-drug relationships. Scientific literature represents a rich source for the retrieval of knowledge about the relationships between biological concepts, mainly drug-drug, disease-disease, and drug-disease relationships. In this paper, we propose DDREL as a general-purpose method that applies deep learning on scientific literature to automatically extract the graph of syntactic and semantic relationships among drugs. DDREL remarkably outperforms the existing human drug network method and a random network respected to average similarities of drugs’ anatomical therapeutic chemical (ATC) codes. DDREL is able to shed light on the existing deficiency of the ATC codes in various drug groups. From the DDREL graph, the history of drug discovery became visible. In addition, drugs that had repurposing score 1 (diflunisal, pargyline, fenofibrate, guanfacine, chlorzoxazone, doxazosin, oxymetholone, azathioprine, drotaverine, demecarium, omifensine, yohimbine) were already used in additional indication. The proposed DDREL method justifies the predictive power of textual data in PubMed abstracts. DDREL shows that such data can be used to 1- Predict repurposing drugs with high accuracy, and 2- Reveal existing deficiencies of the ATC codes in various drug groups.
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Affiliation(s)
- Milad Allahgholi
- School of Computer Engineering, Iran University of Science and Technology, Tehran, Iran
| | - Hossein Rahmani
- School of Computer Engineering, Iran University of Science and Technology, Tehran, Iran
| | - Delaram Javdani
- School of Computer Engineering, Iran University of Science and Technology, Tehran, Iran
| | - Zahra Sadeghi-Adl
- School of Computer Engineering, Iran University of Science and Technology, Tehran, Iran
| | - Andreas Bender
- Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, UK
| | - Dezsö Módos
- Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, UK
- Earlham Institute, Norwich Research Park, Norwich, Norfolk, UK
| | - Gerhard Weiss
- Department of Data Science and Knowledge Engineering (DKE), Maastricht University, Maastricht, The Netherlands
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López-Ramos H, Latorre C, Patiño G, Arenas J. Guía de manejo Hiperplasia Prostática Benigna (SCU 2021). Rev Urol 2021. [DOI: 10.1055/s-0041-1731669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Hugo López-Ramos
- Profesor y Jefe del Programa de Urología. Pontificia Universidad Javeriana. Hospital Universitario San Ignacio. Bogotá, Colombia
| | | | - Germán Patiño
- Urólogo. Unidad de Urología Reconstructiva. Hospital Universitario San Ignacio. Bogotí, Colombia
| | - Juliana Arenas
- Departamento de Urologia. Pontificia Universidad Javeriana. Hospital Universitario San Ignacio. Bogotá, Colombia
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Akgül M, Yazıcı C, Şipal T, Arda E. The clinical significance of abnormal ejaculation by silodosin. Is it important? Andrologia 2021; 53:e14086. [PMID: 33951747 DOI: 10.1111/and.14086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 03/25/2021] [Accepted: 04/09/2021] [Indexed: 11/30/2022] Open
Abstract
We aimed to evaluate the effect of the abnormal ejaculation (AEj) on patients using silodosin in terms of drug cessation. We also analysed the possible factors that may affect the decisions of patients with AEj to proceed or change their medication. The patients (n = 118) treated with silodosin 8 mg daily were prospectively analysed. In order to evaluate the erectile function, ejaculatory function, depression and sexual satisfaction; IIEF, MSHQ-EjD, Beck's depression and Golombok-Rust questionnaires were given to patients respectively. Patients were re-evaluated at the 3rd month of their treatment. The rate of AEj was 52.5%. Nearly 42% of the patients with AEj desired to stop their medication whereas it was 7.1% at patients without AEj (p < .001). The pre-treatment International Prostate Symptom Score (IPSS) and the decrease in IPSS score were significantly lower in patients who demand to stop their treatment (p < .05). AEj was significantly higher in patients who wanted to stop their medication (p < .001). Even if they had an AEj, patients who were happy with the clinical efficacy of silodosin did not want to change their drug. In addition to this, pre-treatment ejaculatory status was an important indicator for patients to decide drug cessation due to AEj side effect of silodosin.
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Affiliation(s)
- Murat Akgül
- Department of Urology, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey
| | - Cenk Yazıcı
- Department of Urology, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey
| | - Timuçin Şipal
- Clinic of Urology, Tekirdağ Çerkezköy State Hospital, Tekirdağ, Turkey
| | - Ersan Arda
- Department of Urology, Faculty of Medicine, Trakya University, Edirne, Turkey
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An Actual Use Study of Tamsulosin in Men with Bothersome Urinary Symptoms in a Simulated Over-the-Counter Setting. UROLOGY PRACTICE 2020. [DOI: 10.1097/upj.0000000000000059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Over-the-Counter Tamsulosin for Men with Urinary Symptoms: A Simulated Self-Selection Study. UROLOGY PRACTICE 2020. [DOI: 10.1097/upj.0000000000000058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Post-operative urinary retention after lower extremity arthroplasty and the peri-operative role of selective alpha-1 adrenergic blocking agents in adult male patients: a propensity-matched retrospective cohort study. INTERNATIONAL ORTHOPAEDICS 2019; 44:39-44. [DOI: 10.1007/s00264-019-04420-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Accepted: 09/23/2019] [Indexed: 10/25/2022]
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Kava BR, Verbeek AE, Wruck JM, Gittelman M. Tamsulosin dispensation patterns in the United States: a real-world, longitudinal, population claims database analysis. Transl Androl Urol 2019; 8:329-338. [PMID: 31555556 DOI: 10.21037/tau.2019.07.02] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background Tamsulosin remains the single most popular uroselective alpha adrenoceptor antagonist approved for the treatment of lower urinary tract symptoms (LUTS) attributable to benign prostatic hyperplasia (BPH). Over the last 3 decades, the utilization of tamsulosin has extended to conditions beyond its original indication. To identify potential changes to prescribing patterns and the extent of tamsulosin use for conditions beyond its original indication, we evaluated tamsulosin dispensing patterns in the United States using a large, multi-payer claims database. Methods We conducted a retrospective analysis using IMS PharMetrics Plus™. Patients with a tamsulosin dispensation/BPH diagnosis code (index dates), identified during a 12-month selection period (October 2012-September 2013), were included if continuously enrolled in a health plan during the 18-month analysis period (12 months pre-index-6 months post-index). Patient and provider characteristics were evaluated using descriptive statistics and were contrasted with previously reported data from the literature. Results Of 133,977 patients dispensed tamsulosin during the analysis period, 72,583 (54.2%) were new users [59,197 (81.6%) men; 13,386 (18.4%) women]. Tamsulosin was newly initiated in men and women mostly by primary care physicians (PCPs; 31.6%) and emergency medicine physicians (21.6%). During the analysis period, 35,071 (59.2%) male new tamsulosin users did not receive a BPH diagnosis code during the analysis period. Of 199,468 men with a BPH diagnosis code, 143,444 (71.9%) were newly diagnosed, mostly [70,412 (49.1%)] by urologists. Few men received hypotension diagnosis: 252 (0.4%) new tamsulosin users within 1 month of starting tamsulosin and 640 (0.4%) within 1 month of a new BPH diagnosis. Conclusions Tamsulosin was prescribed in patients without a recorded diagnosis of BPH and in women. Physicians were comfortable prescribing tamsulosin in the presence of comorbidity and polypharmacy, and PCPs and emergency medicine physicians were the primary prescribers. These results have important implications for future retrospective research for tamsulosin.
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Affiliation(s)
- Bruce R Kava
- Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Anna E Verbeek
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA
| | - Jan M Wruck
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA
| | - Marc Gittelman
- South Florida Medical Research, Uromedix/Division of 21st Century Oncology, Aventura, FL, USA
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The AAHKS Clinical Research Award: Prophylactic Tamsulosin Does Not Reduce the Risk of Urinary Retention Following Lower Extremity Arthroplasty: A Double-Blinded Randomized Controlled Trial. J Arthroplasty 2019; 34:S17-S23. [PMID: 30982761 DOI: 10.1016/j.arth.2019.03.039] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 03/11/2019] [Accepted: 03/13/2019] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Postoperative urinary retention (POUR) is common. Selective alpha-1 adrenergic antagonists, such as tamsulosin, are effective for treating urinary retention. The purpose of this study is to determine whether perioperative prophylactic tamsulosin reduces the incidence of POUR following total hip and knee arthroplasty. METHODS Male patients 35 years of age and older undergoing primary total hip or knee arthroplasty at a single center from 2015 to 2018 were eligible for inclusion. Patients were randomized to receive tamsulosin 0.4 mg or placebo daily for 5 days preoperatively, the morning of surgery, and the first postoperative day. The incidence of POUR was determined during the postoperative hospitalization. RESULTS A total of 176 patients were enrolled in the study. Two patients were withdrawn prior to randomization. The remaining 174 were randomized to tamsulosin (n = 87) or placebo (n = 87). After an additional 43 patients were withdrawn prior to surgery, 131 patients completed the study (tamsulosin, n = 64; placebo, n = 67). A total of 42 patients (32.1%) developed POUR, with 18 cases (28.1%) in the tamsulosin group and 24 cases (35.8%) in the placebo group (P = .345), resulting in an odds ratio of 0.701 and a risk difference of 7.69%. CONCLUSION Prophylactic tamsulosin did not reduce the incidence of POUR after hip and knee arthroplasty compared to placebo. The odds ratio indicates an approximately 30% decreased odds of developing POUR in the tamsulosin group, albeit not statistically significant. Tamsulosin does not appear to be effective as a prophylactic measure for reducing POUR in male hip and knee arthroplasty patients.
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Roehrborn CG, Lowe FC, Gittelman M, Wruck JM, Verbeek AE. Management of Male Lower Urinary Tract Symptoms in a Simulated, Over-the-Counter Setting: An Exploratory Study of Tamsulosin. Drugs Aging 2019; 36:179-188. [PMID: 30607798 DOI: 10.1007/s40266-018-0621-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
BACKGROUND Lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH) are common in men, considerably affecting quality of life. AIMS The self-directed use of over-the-counter (OTC) tamsulosin (0.4 mg) and potential safety risks were evaluated in an open-label, uncontrolled, exploratory, 8-week OTC-simulated study. METHODS Men (≥ 18 years) were recruited via mass advertising about bothersome LUTS. In a working retail environment, respondents reviewed the product and decided whether it was appropriate for them to use (self-selection phase). After purchasing the product, participants' ability to use it as directed by the proposed drug facts label (DFL) was assessed (home-use phase). RESULTS Of 1446 eligible men, 679 completed the self-selection phase, and 73.9% (502/679) self-selected to use tamsulosin correctly according to the DFL. Of 369 participants who purchased tamsulosin and entered the home-use phase, 321 took one or more doses of tamsulosin and participated in at least one telephone interview. In total, 85.4% (274/321) of participants adhered to the 'Stop Use' and 'Directions' instructions in the DFL. Overall, 139 (39.6%) participants experienced one or more adverse events (AEs); 65 (18.5%) were deemed drug-related, including dizziness (11 [3.1%]), ejaculation disorder (6 [1.7%]), and semen volume decrease (6 [1.7%]). No unexpected AEs were reported. CONCLUSIONS Of the men interested in self-managing their LUTS, a majority had moderate-to-severe LUTS of long duration. Most men were able to appropriately self-select and use tamsulosin in concordance with DFL instructions and directions. No unexpected AEs were reported during self-directed use. With further label refinement, an over-the-counter tamsulosin option might be feasible. TRIAL REGISTRATION ClinicalTrials.gov NCT01726270.
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Affiliation(s)
| | - Franklin C Lowe
- Weiler Hospital, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Marc Gittelman
- South Florida Medical Research, Uromedix/Division of 21st Century Oncology, Aventura, FL, USA
| | - Jan M Wruck
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA
| | - Anna E Verbeek
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
- Sanofi, 55 Corporate Drive, Bridgewater, NJ, 08807, USA.
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Guevara-Cuellar CA, Parody-Rúa E, Garcia-Perdomo HA, Arenas-Duque A. Cost-Effectiveness of Combination Therapy Versus Monotherapy in Benign Prostatic Hyperplasia: A Colombian Experience. Value Health Reg Issues 2018; 17:174-182. [PMID: 30415110 DOI: 10.1016/j.vhri.2018.09.004] [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: 09/12/2017] [Revised: 08/23/2018] [Accepted: 09/05/2018] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To estimate the incremental cost-effectiveness ratio of pharmacological treatment for benign prostatic hyperplasia from the payer's perspective. METHODS The cost-effectiveness of 5 mg finasteride, 0.5 mg dutasteride, 10 mg alfuzosin, 10 mg terazosin, 0.4 mg tamsulosin, 4 mg doxazosin, and the combination therapy of 5 mg finasteride and 8 mg doxazosin was evaluated using a Markov model over a 30-year period. The costs were estimated using national tariffs and were reported in US dollars. Cost and effectiveness outcomes were discounted at a rate of 5% per year. Men (aged ≥40 years) with moderate to severe lower urinary tract symptoms and uncomplicated benign prostatic hyperplasia were included in the analysis. Outcomes included costs and quality-adjusted life-years. A probabilistic sensitivity analysis was performed on important parameters with Monte-Carlo simulation. RESULTS Finasteride alone or in combination with doxazosin dominated all α-blockers. After excluding dominated alternatives, the incremental cost-utility ratio for combination therapy was $377 per quality-adjusted life-year, being a cost-effective alternative using the threshold of $15 000. Model results were robust to changes in costs, utility weights, and probabilities. Acceptability curves consistently demonstrated that the combination therapy was most likely cost-effective. CONCLUSIONS The combination of finasteride and doxazosin is cost-effective compared with dutasteride, tamsulosin, terazosin, and alfuzosin in patients with benign prostatic hyperplasia with moderate or severe symptoms who are older than 40 years.
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Affiliation(s)
- César Augusto Guevara-Cuellar
- Facultad de Ciencias de la Salud, Centro de Estudios en Protección Social y Economía de la Salud (PROESA), Universidad Icesi, Cali, Colombia.
| | - Elizabeth Parody-Rúa
- Facultad de Ciencias Naturales, Centro de Estudios en Protección Social y Economía de la Salud (PROESA), Universidad Icesi, Cali, Colombia
| | | | - Andrea Arenas-Duque
- Centro de Estudios en Protección Social y Economía de la Salud (PROESA), Universidad Icesi, Cali, Colombia
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Safety of Tamsulosin: A Systematic Review of Randomized Trials with a Focus on Women and Children. Drug Saf 2018; 41:835-842. [PMID: 29737501 DOI: 10.1007/s40264-018-0674-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Although tamsulosin is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH), it has also been assessed in clinical studies for other conditions/symptoms and in other populations such as women and children. In this systematic review of randomized studies, the overall safety of tamsulosin was assessed, focusing on these understudied populations. METHODS Literature searches were conducted using Embase, Medline, and PubMed (inception-December 2015). A study was included if patients were randomized to receive treatment with any dose of tamsulosin capsules, tablets, or an oral controlled absorption system and numerical safety results were reported. RESULTS Overall, 160 articles involving 46,072 participants met the inclusion criteria. Of these, four studies included women only and three included children. The mean [standard deviation (SD)] age ranged from 7.3 (4.2) to 76.8 (7.1) years. The studies (n; %) evaluated healthy subjects (18; 11%) or patients with lower urinary tract symptoms/BPH (90; 56%), ureteral stones/renal colic (42; 26%), prostatitis (4; 3%), or other conditions (6; 4%). Patients discontinued tamsulosin primarily because of adverse events (AEs) or insufficient response. AEs in women and children were abdominal pain, asthenia, constipation, dizziness, dry mouth, drowsiness, dyspepsia, headache, incontinence, nasal congestion, nausea, orthostatic hypotension, and somnolence. Due to heterogeneity across studies, statistical analysis could not be conducted. DISCUSSION No unexpected AEs were observed in an all-comers population treated with tamsulosin for various conditions/symptoms. The overall safety profile in women and children seemed to be generally consistent with the profile in men, the indicated population.
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Roehrborn CG, Miner MM, Sadovsky R. Over-the-counter medication availability could augment self-management of male lower urinary tract symptoms. Postgrad Med 2018; 130:452-460. [PMID: 29932780 DOI: 10.1080/00325481.2018.1487238] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
In this review, we focus on current trends in the management of male lower urinary tract symptoms (LUTS), defined here as LUTS, namely, storage, voiding, and post-micturition symptoms presumed secondary to benign prostatic hyperplasia (BPH), and discuss possible novel approaches toward better care. According to results of a PubMed database search covering the last 10 years and using keywords pertaining to male LUTS, this condition continues to be globally undiagnosed or diagnosed late, partly because of men's hesitation to seek help for perceived embarrassing problems or problems considered a normal part of aging. In addition, the prevalence of male LUTS is continually increasing because of a constantly aging population. Male LUTS can be bothersome and affect the quality of life (QoL) and sexual function. Additional effective alternatives for managing this condition need to be identified and incorporated into the current care model. Considering that most male LUTS such as frequency, hesitancy, urgency, and intermittency are easy to self-identify, a self-management approach toward male LUTS is proposed. Limited evidence supports the efficacy of phytotherapies and herbals as self-management options for male LUTS. However, introducing over-the-counter (OTC) medication with proven efficacy, accompanied by lifestyle and behavioral modifications, may be a promising approach that will encourage more men to treat their symptoms in a timely manner. Formal guidelines, along with appropriate education programs for patients and support from the healthcare community, will be needed to ensure that the promise of this approach is fully materialized.
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Affiliation(s)
- Claus G Roehrborn
- a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA
| | - Martin M Miner
- b Men's Health Center , Miriam Hospital , Providence , Rhode I , USA.,c Family Medicine and Urology , Warren Alpert School of Medicine, Brown University , Providence , RI , USA
| | - Richard Sadovsky
- d Department of Family Medicine , SUNY-Downstate Medical Center , Brooklyn , NY , USA
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Add-on Therapy With the α-Blockers Tamsulosin and Naftopidil Improves Voiding Function by Enhancing Neuronal Activity in Prostatic Hyperplasia Rats. Int Neurourol J 2018; 22:20-29. [PMID: 29609419 PMCID: PMC5885138 DOI: 10.5213/inj.1836064.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 03/26/2018] [Indexed: 12/17/2022] Open
Abstract
Purpose Benign prostatic hyperplasia (BPH) impacts quality of life in men by causing lower urinary tract symptoms. α1-Adrenoceptor (α1-AR) blockers improve lower urinary tract symptoms. We investigated the efficacy of add-on therapy with α1-AR blockers on BPH rats. Methods Rats in the drug-treated groups were orally administered each drug once a day for 30 days after orchiectomy. To induce BPH, rats were castrated and testosterone (20 mg/kg) was injected subcutaneously once per day for 30 days. Cystometry was conducted to measure voiding contraction pressure and the interval contraction time, immunohistochemistry was performed to measure c-Fos and nerve growth factor (NGF) expression in the neuronal voiding centers, and nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry was used to measure nitric oxide synthase (NOS) expression. Results Orchiectomy and testosterone injection decreased voiding contraction pressure and the interval contraction time, suggesting BPH symptoms. Voiding contraction pressure and the interval contraction time were greater in the group that received the combination treatment (tamsulosin with naftopidil) than in the tamsulosin monotherapy or naftopidil monotherapy groups. c-Fos, NGF, and NOS expression in the neuronal voiding centers was enhanced by BPH induction. c-Fos, NGF, and NOS expression was suppressed by the combination treatment (tamsulosin with naftopidil) to a greater extent than was the case for tamsulosin monotherapy or naftopidil monotherapy. Conclusions Combination therapy of tamsulosin and naftopidil showed greater efficacy for the treatment of BPH than tamsulosin monotherapy or naftopidil monotherapy; therefore, combination therapy can be considered as a novel therapeutic method for BPH.
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Dogan M, Kutluksaman B, Keles I, Karalar M, Halat AO. The Effects of Systemic Alfuzosin and Tamsulosin Hydrochloride on Choroidal Thickness and Pupil Diameter Sizes in Cases with Benign Prostatic Hyperplasia. Curr Eye Res 2017; 42:1638-1643. [PMID: 28937828 DOI: 10.1080/02713683.2017.1359306] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
PURPOSE To compare the effects of alfuzosin hydrochloride and tamsulosin hydrochloride on choroidal thickness (CT) and pupil diameter (PD) sizes in patients with benign prostatic hyperplasia. SUBJECTS AND METHODS Sixty-three men patients with newly diagnosis of benign prostatic hyperplasia were randomly assigned to either alfuzosin hydrochloride or to tamsulosin hydrochloride groups in this prospective, randomized, parallel-group clinical trial. Enhanced depth imaging spectral-domain optical coherence tomography, pupillography were obtained at baseline, 1st and 3rd month, and choroidal thicknesses and pupil diameter sizes were compared between the two groups. RESULTS The mean subfoveal choroidal thickness (SCT), nasal choroidal thickness (NCT), and temporal choroidal thickness (TCT) in AH group were 275.70 ± 32.14 μm, 269.7 ± 33.54 μm and 270.71 ± 33.52 μm at baseline, respectively; and they were 275.46 ± 31.6 μm, 268.73 ± 33.08 μm and 270.73 ± 33.05 μm at baseline in TH group, respectively (P = 0.97, P = 0.84, P = 0.99, for SCT, NCT, and TCT, respectively). The mean SCT, NCT, and TCT after 3 months were 278.93 ± 34.58 μm, 272.62 ± 34.17 μm, and 273.6 ± 34.17 μm in AH group, respectively; and they were 274.36 ± 31.91 μm, 264.70 ± 33.59 μm, and 267.72 ± 33.6 μm in TH group, respectively (P = 0.6, P = 0.37, P = 0.43, for SCT, NCT, and TCT, respectively). The mean scotopic pupil diameter (SPD), mesopic pupil diameter (MPD), and photopic pupil diameter (PPD) sizes in AH group were 6.46 ± 0.84 mm, 5.07 ± 0.72 mm and 3.66 ± 0.46 mm at baseline, respectively; and they were 6.44 ± 1.14 mm, 5.01 ± 0.79 mm and 3.62 ± 0.53 mm at baseline in TH group, respectively (P = 0.89, P = 0.74, P = 0.68, for SPD, MPD, and PPD, respectively). The mean SPD, MPD, and PPD sizes after 3 months were 5.96 ± 0.76 mm, 4.67 ± 0.74 mm, and 3.15 ± 0.47 mm in AH group, respectively; and they were 6.42 ± 0.89 mm, 5.05 ± 0.75 mm, and 3.55 ± 0.53 mm in TH group respectively (P = < 0.001, P = < 0.001, P = < 0.001, for SPD, MPD, and PPD, respectively). CONCLUSION The repeated measure of ANOVA for the mean CT values within AH group showed statistically significant increases in baseline CTs, although these differences did not reach statistical significance between 2 groups at follow-ups. We found significant different outcomes for PD sizes during study in the groups. The mean outcome in this study is that using αAR antagonists have potential effects on CT and PD sizes. Abbreviations and Acronyms: AH: alfuzosin hyrdrochloride; ANOVA: analyses of variance; AR: adrenergic receptor; BCVA: best-corrected visual acuity; BPH: benign prostatic hyperplasia; CT: choroidal thickness; EDI-OCT: enhanced depth imaging spectral-domain optical coherence tomography; IFIS: intraoperative floppy iris syndrome; MPD: mesopic pupil diameter; NCT: nasal choroidal thickness; PD: pupil diameter; PPD: photopic pupil diameter; SCT: subfoveal choroidal thickness; SPD: scotopic pupil diameter; TCT: temporal choroidal thickness; TH: tamsulosin hydrochloride.
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Affiliation(s)
- Mustafa Dogan
- a Afyon Kocatepe University , Department of Ophthalmology , Afyonkarahisar , Turkey
| | | | - Ibrahim Keles
- c Afyon Kocatepe University , Department of Urology , Afyonkarahisar , Turkey
| | - Mustafa Karalar
- c Afyon Kocatepe University , Department of Urology , Afyonkarahisar , Turkey
| | - Ahmet Omer Halat
- d Konya Research and Training Hospital , Department of Urology , Konya , Turkey
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Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells. Oncotarget 2017; 8:87194-87208. [PMID: 29152074 PMCID: PMC5675626 DOI: 10.18632/oncotarget.19909] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 07/19/2017] [Indexed: 11/25/2022] Open
Abstract
Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.
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Castiñeiras J, Cózar JM, Miñana B, Brenes FJ, Brotons F, Fernández-Pro A, Martín JA, Martínez-Berganza ML, Molero JM. WITHDRAWN: Management and follow-up of the male with Lower Urinary Tract Symptoms secondary to Benign Prostate Hyperplasia. Actas Urol Esp 2016:S0210-4806(16)30166-8. [PMID: 28024923 DOI: 10.1016/j.acuro.2016.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2016] [Accepted: 10/10/2016] [Indexed: 10/20/2022]
Affiliation(s)
| | - J M Cózar
- Complejo Hospitalario Universitario de Granada, Granada, España
| | - B Miñana
- Hospital General Universitario Morales Meseguer, Murcia, España. Universidad católica San Antonio. UCAM. Murcia.
| | - F J Brenes
- Centro de Atención Primaria Llefià. Barcelona
| | - F Brotons
- Centro de Salud Vila-real II, Castellón España
| | | | - J A Martín
- Centro de Salud de Buenavista, Toledo, España
| | | | - J M Molero
- Centro de Salud San Andrés, Madrid, España
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21
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Brenes Bermúdez FJ, Brotons Muntó F, Castiñeiras Fernández J, Cozar Olmo JM, Fernández-Pro Ledesma A, Martín Jiménez JA, Martínez-Berganza Asensio ML, Miñana López B, Molero García JM. [Consensus document on the management and follow-up of the male with lower urinary tract symptoms secondary to benign prostate hyperplasia]. Semergen 2016; 42:547-556. [PMID: 28314432 DOI: 10.1016/j.semerg.2016.09.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 09/20/2016] [Indexed: 11/29/2022]
Abstract
Benign prostate hyperplasia (BPH) is a high-incidence condition. Its diagnosis and treatment is shared between urologists and Primary Care physicians. Its management uses up a significant amount of resources. The Spanish Society of Primary Care Physicians (SEMERGEN), the Spanish Society of General Practitioners and Family Doctors (SEMG), the Spanish Society of Family and Community Medicine (semFYC), and the Spanish Association of Urology (AEU) have prepared a document on the management and monitoring of BPH, in which the aim is to incorporate the latest evidence in order to update the previously published guidelines, and present them here in condensed form. The main objective of these new recommendations is to raise the awareness of Primary Care physicians and assist them in its diagnostic evaluation, treatment and monitoring, as well as providing unified consensus criteria for referral to the secondary care level.
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Affiliation(s)
| | | | | | - J M Cozar Olmo
- Complejo Hospitalario Universitario de Granada, Granada, España
| | | | | | | | - B Miñana López
- Hospital General Universitario Morales Meseguer, Murcia, España
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Rak A, Canale V, Marciniec K, Żmudzki P, Kotańska M, Knutelska J, Siwek A, Stachowicz G, Bednarski M, Nowiński L, Zygmunt M, Zajdel P, Sapa J. Arylsulfonamide derivatives of (aryloxy)ethyl pyrrolidines and piperidines as α 1-adrenergic receptor antagonist with uro-selective activity. Bioorg Med Chem 2016; 24:5582-5591. [PMID: 27658792 DOI: 10.1016/j.bmc.2016.09.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Revised: 09/06/2016] [Accepted: 09/08/2016] [Indexed: 02/01/2023]
Abstract
A series of arylsulfonamide derivatives of (aryloxy)ethyl pyrrolidines and piperidines was synthesized to develop new α1-adrenoceptor antagonists with uroselective profile. Biological evaluation for α1- and α2-adrenorecepor showed that tested compounds 13-37 displayed high-to-moderate affinity for the α1-adrenoceptor (Ki=34-348nM) and moderate selectivity over α2-receptor subtype. Compounds with highest affinity and selectivity for α1-adrenoceptor were evaluated in vitro for their intrinsic activity toward α1A- and α1B-adrenoceptor subtypes. All compounds behaved as antagonists at both α1-adrenoceptor subtypes, displaying 2- to 6-fold functional preference to α1A-subtype. Among them, N-{1-[2-(2-methoxyphenoxy)ethyl]piperidin-4-yl}isoquinoline-4-sulfonamide (25) and 3-chloro-2-fluoro-N-{[1-(2-(2-isopropoxyphenoxy)ethyl)piperidin-4-yl]methyl}benzene sulfonamide (34) displayed the highest preference to α1A-adrenoceptor. Finally, compounds 25 and 34 (2-5mg/kg, iv), in contrast to tamsulosin (1-2mg/kg, iv), did not significantly decrease systolic and diastolic blood pressure in normotensive anesthetized rats to determine their influence on blood pressure.
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Affiliation(s)
- Aleksandra Rak
- Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Vittorio Canale
- Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Krzysztof Marciniec
- Department of Organic Chemistry, Medical University of Silesia, 4 Jagiellonska Street, 41-200 Sosnowiec, Poland
| | - Paweł Żmudzki
- Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Magdalena Kotańska
- Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Joanna Knutelska
- Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Agata Siwek
- Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Gabriela Stachowicz
- Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Marek Bednarski
- Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland.
| | - Leszek Nowiński
- Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Małgorzata Zygmunt
- Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Paweł Zajdel
- Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
| | - Jacek Sapa
- Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland
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Asnis GM, Caneva E, Henderson MA. A review of antidepressant-induced urinary hesitancy: a focus on levomilnacipran ER including two case presentations(5633). Expert Opin Drug Saf 2016; 15:717-25. [PMID: 26967743 DOI: 10.1517/14740338.2016.1164138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Levomilnacipran ER was recently FDA approved as Fetzima® for the treatment of MDD. Urinary hesitancy can be an adverse event associated with levomilnacipran treatment. AREAS COVERED This manuscript details the longitudinal course of levomilnacipran-induced urinary hesitancy in 2 cases that were in a pivotal clinical trial, examining possible predisposing factors and treatment issues. This manuscript also reviews the literature comparing urinary hesitancy associated with levomilnacipran versus other antidepressants. Antidepressants that are potent norepinephrine reuptake inhibitors like levomilnacipran, may have increased rates of associated urinary hesitancy. The latter can cause significant discomfort and a compromised quality of life. Occasionally, it can progress to urinary retention necessitating an emergency medical intervention. EXPERT OPINION All patients being treated with antidepressants should be carefully monitored for this side effect. Discontinuation of treatment or reduction of the dose of antidepressant frequently relieves urinary hesitancy; alternatively, treatment with an alpha1A antagonist, e.g., tamsulosin may relieve antidepressant-induced urinary hesitancy within hours to days; such strategies allow for continued antidepressant treatment without urinary hesitancy recurring. Thus, with appropriate clinical care, the benefits using levomilnacipran outweigh its risks.
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Affiliation(s)
- Gregory M Asnis
- a Department of Psychiatry and Behavioral Sciences , Albert Einstein College of Medicine/Montefiore Medical Center , Bronx , NY , USA
| | | | - Margaret A Henderson
- a Department of Psychiatry and Behavioral Sciences , Albert Einstein College of Medicine/Montefiore Medical Center , Bronx , NY , USA
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Shim SR, Kim JH, Chang IH, Shin IS, Hwang SD, Kim KH, Yoon SJ, Song YS. Is Tamsulosin 0.2 mg Effective and Safe as a First-Line Treatment Compared with Other Alpha Blockers?: A Meta-Analysis and a Moderator Focused Study. Yonsei Med J 2016; 57:407-18. [PMID: 26847294 PMCID: PMC4740534 DOI: 10.3349/ymj.2016.57.2.407] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 05/27/2015] [Accepted: 06/16/2015] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg or other alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis and meta-regression. MATERIALS AND METHODS We conducted a meta-analysis of efficacy of tamsulosin 0.2 mg using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzed using adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980 to June 2013. RESULTS Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alpha-blockers (terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardized mean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control group was 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosin group versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (number of patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax. CONCLUSION This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alpha-blockers as an initial treatment strategy for men with lower urinary tract symptoms.
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Affiliation(s)
- Sung Ryul Shim
- Institute for Clinical Molecular Biology Research, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jae Heon Kim
- Department of Urology, Soonchunhyang University College of Medicine, Seoul, Korea.
| | - In Ho Chang
- Department of Urology, Chung-Ang University Hospital, Urological Science Institute, Chung-Ang University College of Medicine, Seoul, Korea
| | - In Soo Shin
- Department of Education, College of Education, Jeonju University, Jeonju, Korea
| | - Sung Dong Hwang
- Department of Social Welfare, Kyungpook National University College of Social Science, Daegu, Korea
| | - Khae Hwan Kim
- Department of Urology, Gil Hospital, Gachon University College of Medicine, Incheon, Korea
| | - Sang Jin Yoon
- Department of Urology, Gil Hospital, Gachon University College of Medicine, Incheon, Korea
| | - Yun Seob Song
- Department of Urology, Soonchunhyang University College of Medicine, Seoul, Korea
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25
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Feasibility of an Alternative Option for the Management of Male Lower Urinary Tract Symptoms. J Urol 2016; 195:125-30. [DOI: 10.1016/j.juro.2015.08.098] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2015] [Indexed: 11/19/2022]
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Welk B, McArthur E, Fraser LA, Hayward J, Dixon S, Hwang YJ, Ordon M. The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study. BMJ 2015; 351:h5398. [PMID: 26502947 PMCID: PMC4620650 DOI: 10.1136/bmj.h5398] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
STUDY QUESTION Do men starting treatment with prostate-specific α antagonists have increased risk of fall and fracture? METHODS Administrative datasets from the province of Ontario, Canada, that contain patient level data were used to generate a cohort of 147,084 men aged ≥ 66 years who filled their first outpatient prescription for prostate-specific α antagonists tamsulosin, alfuzosin, or silodosin between June 2003 and December 2013 (exposed men) plus an equal sized cohort matched 1:1 (using a propensity score model) who did not initiate α antagonist therapy. The primary outcome was a hospital emergency room visit or inpatient admission for a fall or fracture in the 90 days after exposure. STUDY ANSWER AND LIMITATIONS The men exposed to prostate-specific α antagonist had significantly increased risks of falling (odds ratio 1.14 (95% CI 1.07 to 1.21), absolute risk increase 0.17% (0.08 to 0.25%)) and of sustaining a fracture (odds ratio 1.16 (1.04 to 1.29), absolute risk increase 0.06% (0.02 to 0.11%)) compared with the unexposed cohort. This increased risk was not observed in the period before α antagonist use. Secondary outcomes of hypotension and head trauma were also significantly increased in the exposed cohort (odds ratios 1.80 (1.59 to 2.03) and 1.15 (1.04 to 1.27) respectively). The two cohorts were similar across 98 different covariates including demographics, comorbid conditions, medication use, healthcare use, and prior medical investigation. Potential unmeasured confounders, such as physical deconditioning, mobility impairment, and situational risk factors, may exist. The data used to identify the primary outcomes had limited sensitivity, so the absolute risks of the outcomes are probably underestimates. The study only included men ≥ 66 years old, and 84% of exposed men were prescribed tamsulosin, so results may not be generalizable to younger men, and there may not be statistical power to show small differences in outcomes between the drugs. WHAT THIS STUDY ADDS Prostate-specific α antagonists are associated with a small but significant increased risk of fall, fracture, and head trauma, probably as a result of induced hypotension. FUNDING, COMPETING INTERESTS, DATA SHARING This project was conducted at the Institute for Clinical Evaluative Sciences (ICES) Western Site through the Kidney, Dialysis, and Transplantation (KDT) research program. BW has received a research grant from Astellas, and L-AF does consultancy for Amgen.
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Affiliation(s)
- Blayne Welk
- Department of Surgery, Western University, London ON N6A 4V2, Ontario, Canada Institute for Clinical Evaluative Sciences, London, Ontario Department of Epidemiology and Biostatistics, Western University, London, Ontario
| | - Eric McArthur
- Institute for Clinical Evaluative Sciences, London, Ontario
| | | | - Jade Hayward
- Institute for Clinical Evaluative Sciences, London, Ontario
| | - Stephanie Dixon
- Institute for Clinical Evaluative Sciences, London, Ontario Department of Epidemiology and Biostatistics, Western University, London, Ontario
| | - Y Joseph Hwang
- Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Michael Ordon
- Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario
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Foster JL, Mohorn PL, Luis AJ. Constipation-Induced Acute Urinary Retention in the Intensive Care Unit. Am Surg 2015. [DOI: 10.1177/000313481508100809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Jenna L. Foster
- Department of Pharmaceutical Services and Clinical Nutrition Palmetto Health Richland Columbia, South Carolina
| | - Phillip L. Mohorn
- Department of Clinical Pharmacy and Outcomes Sciences South Carolina College of Pharmacy at the University of South Carolina Columbia, South Carolina; and the Department of Pharmaceutical Services and Clinical Nutrition Palmetto Health Richland Columbia, South Carolina
| | - Alejandro J. Luis
- Department of Surgical Services Palmetto Health Richland Columbia, South Carolina
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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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Yuan JQ, Mao C, Wong SYS, Yang ZY, Fu XH, Dai XY, Tang JL. Comparative Effectiveness and Safety of Monodrug Therapies for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: A Network Meta-analysis. Medicine (Baltimore) 2015; 94:e974. [PMID: 26166130 PMCID: PMC4504542 DOI: 10.1097/md.0000000000000974] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2015] [Revised: 05/13/2015] [Accepted: 05/17/2015] [Indexed: 11/25/2022] Open
Abstract
A wide array of drugs are available for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), but the evidence for the comparative effectiveness is controversial.The objective of this study is to evaluate the comparative effectiveness and safety of monodrug therapies for BPH.Data sources are MEDLINE, EMBASE, and the Cochrane Library.We included randomized controlled trials that compared α-blockers, 5-alpha reductase inhibitors (5ARIs), muscarinic receptor antagonists (MRAs), phosphodiesterase-5 inhibitor (PDE5-Is), or placebo for the treatment of BPH.Comparative effectiveness and safety were pooled by both traditional meta-analysis and network meta-analysis. Summary effect size was calculated as mean difference (MD) and relative risk (RR), together with the 95% confidence intervals (CIs).This study included 58,548 participants from 124 trials in total. When compared with placebo, α-blockers, 5ARIs, and PDE5-Is reduced International Prostate Symptom Score (IPSS) by -1.35 to -3.67 points and increased peak urinary flow rate (PUF) by -0.02 to 1.95 mL/s, with doxazosin (IPSS: MD, -3.67[-4.33 to -3.02]; PUF: MD, 1.95[1.61 to 2.30]) and terazosin (IPSS: MD, -3.37 [-4.24 to -2.50]; PUF: MD, 1.21[0.74 to 1.66]) showing the greatest improvement. The improvement in the IPSS was comparable among tamsulosin, alfuzosin, naftopidil, silodosin, dutasteride, sildenafil, vardenafil, and tadalafil. The incidence of total adverse events and withdraws due to adverse events were generally comparable among various agents.In conclusion, α-blockers, 5ARIs, and PDE5-Is are effective for BPH, with doxazosin and terazosin appearing to be the most effective agents. Drug therapies for BPH are generally safe and well-tolerated, with no major difference regarding the overall safety profile.
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Affiliation(s)
- Jin-Qiu Yuan
- From the Division of Epidemiology, School of Public Health and Primary Care (JY, CM, ZY, XF, JT); Department of Community and Family Medicine, The Chinese University of Hong Kong (SW); Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of the Chinese University of Hong Kong, Shenzhen, Guangdong Province (JY, CM, ZY, XF, JT); and Kidney Internal Medical Department, Mianyang Central Hospital, Mianyang, China (XD)
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30
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Gutiérrez A, Gámez R, Noa M, Mas R, Valle M, Mendoza N, Nodal C, Pérez Y, Oyarzábal Á, Bucarano I, Goicochea E, Jiménez S, García H. Long-Term (24 Months) Carcinogenicity Study of D-004, a Lipid Extract From Roystonea regia Fruits, in Sprague Dawley Rats. Int J Toxicol 2015; 34:138-50. [PMID: 25823441 DOI: 10.1177/1091581815576375] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Ariadne Gutiérrez
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Rafael Gámez
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Miriam Noa
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Rosa Mas
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Maikel Valle
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Nilda Mendoza
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Carlos Nodal
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Yohani Pérez
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Ámbar Oyarzábal
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Isury Bucarano
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Edy Goicochea
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Sonia Jiménez
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
| | - Haydee García
- Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba
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Shim SR, Kim JH, Choi H, Lee WJ, Kim HJ, Bae MY, Hwang SD, Kim KH, Bae JH, Yoon SJ. General effect of low-dose tamsulosin (0.2 mg) as a first-line treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia: a systematic review and meta-analysis. Curr Med Res Opin 2015; 31:353-65. [PMID: 25350225 DOI: 10.1185/03007995.2014.980887] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
PURPOSE In Asian countries, low-dose tamsulosin (0.2 mg) is used widely but this dose has been less popular than 0.4 mg tamsulosin or other types of alpha blockers. The aim of this study was to investigate the efficacy and safety of low-dose tamsulosin by systematic review and meta-analysis. METHODS We conducted a meta-analysis of improvements of lower urinary tract symptoms using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QOL). Relevant studies were found using MEDLINE, Embase, and the Cochrane library. Final inclusion was determined by randomized controlled trials (RCT) and performance of IPSS. RESULTS A total of fourteen studies were included, with a total sample size of 2147 subjects (1044 experimental and 1103 controls). Study durations ranged from 4 to 52 weeks. The mean change of IPSS improvement from baseline for tamsulosin was -7.18 (95% CI: -7.83, -6.54). The mean change of QOL improvement from baseline was -1.34 (95% CI: -1.46, -1.22). The overall Qmax improvement from baseline was 2.32 ml/sec (95% CI: 1.95, 2.70). The mean change of PVR improvement from baseline was -11.12 ml (95% CI: -17.61, -4.64). Regarding safety, four studies did not report any adverse events while others reported that adverse events were all tolerated. CONCLUSIONS Although this study did not consider placebo effect and has high IPSS baseline scores, this study clarifies that low-dose tamsulosin has generally positive effect and safety in treatment of LUTS and could be a suitable option as an initial treatment, especially for patients with low body mass index, as is typical of Asian people.
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Affiliation(s)
- Sung Ryul Shim
- Department of Epidemiology and Medical Informatics, Korea University , Seoul , Korea
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Haghsheno MA, Mellström D, Peeker R, Hammarsten J, Lorentzon M, Sundh V, Karlsson M, Ohlsson C, Damber JE. Lower urinary tract symptoms are associated with low levels of serum serotonin, high levels of adiponectin and fasting glucose, and benign prostatic enlargement. Scand J Urol 2014; 49:155-61. [PMID: 25253423 DOI: 10.3109/21681805.2014.936495] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE The aim of this study was to test whether lower urinary tract symptoms (LUTS) and urinary incontinence are associated with the metabolic syndrome (MetS). The association between LUTS and benign prostatic enlargement (BPE) was also investigated. MATERIAL AND METHODS A cross-sectional, representative risk factor analysis of LUTS, as measured by the International Prostate Symptom Score (IPSS), and urinary incontinence was conducted. Among 950 representative individuals, aged 69-81 years, the association between clinical, anthropometric, endocrine, metabolic and inflammatory factors on the one hand, as both major and minor aspects of MetS, and LUTS and urinary incontinence, on the other hand, was analysed. The prostate gland volume was measured in a subgroup of 155 randomly selected individuals and the association between LUTS and BPE was estimated. RESULTS No significant association was found between LUTS or urinary incontinence and the major aspects of the MetS. However, in a multivariate analysis, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. Furthermore, in a subgroup of 155 individuals, the prostate gland volume correlated positively with LUTS. CONCLUSIONS The study did not show an association between LUTS or urinary incontinence and the major components of the MetS. However, serum serotonin showed an independent negative correlation with LUTS and with urinary incontinence while fasting serum glucose and serum adiponectin showed a positive correlation with LUTS. The data confirm the general knowledge that BPE may be one of the causative factors of LUTS.
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Affiliation(s)
- Mohammad-Ali Haghsheno
- Department of Urology, Institute of Clinical Sciences, Sahlgrenska University Hospital , Gothenburg , Sweden
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Hale N, Choi K, Lohri J. Primary Care Evaluation and Treatment of Men With Lower Urinary Tract Symptoms. J Osteopath Med 2014; 114:566-71. [DOI: 10.7556/jaoa.2014.110] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Abstract
Lower urinary tract symptoms (LUTS) affect 50% to 90% of men aged 50 years or older. Primary care physicians should be knowledgeable about the diagnosis and management of this condition. The authors performed detailed PubMed searches using the terms lower urinary tract symptoms, benign prostatic hyperplasia, benign prostatic enlargement, and overactive bladder. The authors then reviewed the relevant literature on the evaluation and treatment of men with LUTS. According to the literature, accurate recognition of LUTS is predicated on a focused history and physical examination, as well as serum prostate-specific antigen measurement and urinalysis. For patients with mild symptoms, watchful waiting with ongoing monitoring and lifestyle modifications may be appropriate. For patients with moderate to severe symptoms, pharmacologic therapy is effective. When substantial LUTS persist despite appropriate pharmacologic therapy, specialty urologic evaluation and treatment is warranted.
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Dal Moro F. The dark knight of syncope: the urologist! J Intern Med 2013; 274:291-2. [PMID: 23586818 DOI: 10.1111/joim.12076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- F. Dal Moro
- Department of Surgical; Oncological and Gastroenterological Sciences - Urology; University of Padova; Padova Italy
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