Time-dependent progress of lower urinary tract dysfunction in streptozotocin-induced diabetic rats with or without low-dose insulin treatment.

Objectives: To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Methods: Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra in vivo were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra in vitro were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Results: Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. In-vivo urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. Conclusions: DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.

Safety and efficacy of beta-3 adrenergic agonists in treating neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.

PURPOSE: To evaluate efficacy and safety of beta-3 adrenergic agonists in adults with neurogenic lower urinary tract dysfunction. MATERIALS AND METHODS: According to a protocol (CRD42022350079), we searched multiple data sources for published and unpublished randomized controlled trials (RCTs) up to 2nd August 2022. Two review authors independently screened studies and abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence (CoE). RESULTS: We found data to inform two comparisons: beta-3 adrenergic agonists versus placebo (4 RCTs) and anticholinergics (2 RCTs). Only mirabegron was used for intervention in all included studies. Compared to placebo, beta-3 adrenergic agonists may have a clinically unimportant effect on urinary symptoms score (mean difference [MD] -2.50, 95% confidence interval [CI] -4.78 to -0.22; I²=92%; 2 RCTs; 192 participants; low CoE) based on minimal clinically important difference of 3. We are very uncertain of the effects of beta-3 adrenergic agonists on quality of life (MD 10.86, 95% CI 1.21 to 20.50; I²=41%; 2 RCTs; 98 participants; very low CoE). Beta-3 adrenergic agonists may result in little to no difference in major adverse events (cardiovascular adverse events) (risk ratio 0.57, 95% CI 0.14 to 2.37; I²=0%; 4 RCTs; 310 participants; low CoE). Compared to anticholinergics, no study reported urinary symptom scores and quality of life. There were no major adverse events (cardiovascular adverse events) in either study group (1 study; 60 participants; very low CoE). CONCLUSIONS: Compared to placebo, beta-3 adrenergic agonists may have similar effects on urinary symptom scores and major adverse events. There were uncertainties about their effects on quality of life. Compared to anticholinergics, we are either very uncertain or have no evidence about urinary symptom scores, quality of life, and major adverse events.

[Practical use of Adenoprosin in combination therapy in men with lower urinary tract symptoms].

AIM: The aim of the observational cohort study is to study and evaluate the efficiency of the drug Adenoprosin in combination with other drugs in comparison with monotherapy. MATERIALS AND METHODS: Data from 6,442 patients at 221 medical institutions in 39 cities from November 2020 to December 2022 were analyzed. The drug Adenoprosin in the form of rectal suppositories was prescribed as monotherapy in group I, while patients in group II received Adenoprosin in a combination with other drugs. The efficacy of treatment was assessed using uroflowmetry data, prostate volume, postvoid residual volume and validated scales (NIH-CPSI, IIEF-5, IPSS, QoL). RESULTS: The diagnosis was validated in 6375 cases, including BPH (n=1498), chronic prostatitis (CP; n=3060), and in combination of both disorders (n=1817). A total of 3580 patients received Adenoprosin as monotherapy, while 2761 received combination therapy. In most cases, a combination therapy was prescribed in case of more severe disease. In patients with BPH, positive changes after treatment were noted in favor of group I according to change in postvoid residual volume (p<0.001) and prostate volume (p<0.001). Combination therapy demonstrated significant positive changes compared with monotherapy when assessing NIH-CPSI scores (p=0.005), IPSS scores (p<0.001) and the mean maximum urine flow rate (Qmax; p<0.001). Qmax increased significantly in both groups (from 14 ml/s to 17 ml/s in group I and from 12 ml/s to 14 ml/s in group II). CONCLUSION: Treatment of BPH, CP and their combination is a complex clinical task. The multiple nature of complaints often dictates the need for simultaneous administration of two or more drugs. Combination therapy involves the use of multiple therapeutic strategies to treat different aspects of BPH and CP. In patients with BPH, a combination therapy has been shown to be more effective than monotherapy with either class of drugs, as it reduces the risk of disease progression, acute urinary retention, and the need for surgery. However, combination therapy should be considered on an individual basis, taking into account symptoms, prostate size and overall health. There is no universal treatment method for BPH suitable for any patient. The treatment strategy should be chosen individually, considering all medical and social factors. All of the above applies to a large extent to the treatment of CP and CP + BPH. According to our results, Adenoprosin demonstrated efficacy both as monotherapy and in combination with other traditional drugs in the treatment of men with lower urinary tract symptoms.

Impact of Polypharmacy and Risk Factors for Exacerbation of Lower Urinary Tract Symptoms in Patients with Urological Conditions: A Retrospective Study in a Japanese Municipal Hospital.

Polypharmacy exacerbates lower urinary tract symptoms (LUTS). Japan exhibits a higher prevalence of concomitant medication use in drug therapy than other countries. Previous age- and sex-specific reports exist; however, none include patients of all ages. Therefore, this retrospective study determined the impact of polypharmacy and its associated risk factors on LUTS exacerbation in outpatients with urological conditions. We included patients receiving medication who visited the Department of Urology at the Gifu Municipal Hospital (Gifu, Japan) between January, 2018 and December, 2018. The association between LUTS and polypharmacy and the risk factors for LUTS exacerbation were investigated. Patients were categorized into two groups according to their polypharmacy status. We performed propensity score matching and compared the International Prostate Symptom Score (IPSS) between the groups using the unpaired t-test. Multiple logistic regression analysis was performed to examine the risk factors, including "polypharmacy" and "taking multiple anticholinergic medications" for LUTS exacerbation. When comparing the IPSS between the groups, the polypharmacy group was found to have significantly higher scores than the non-polypharmacy group in six items, including "total score" and "storage score." Multiple logistic regression analysis results showed high significance in three items, including "polypharmacy" (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.03-2.71) and "taking multiple anticholinergic medications" (OR = 8.68, 95% CI: 1.05-71.7). In conclusion, this study revealed that "polypharmacy" and "taking multiple anticholinergic medications" were risk factors for LUTS. Particularly, "polypharmacy" is associated with storage symptom exacerbation. Therefore, eliminating "polypharmacy" and "taking multiple anticholinergic medications" is expected to improve LUTS.

Single-dose Tadalafil Reduces Opening Urethral Pressure: A Randomized, Double-blind, Placebo-controlled, Crossover Trial in Healthy Women.

INTRODUCTION AND HYPOTHESIS: Phosphodiesterase enzymes are widely distributed in female urogenital tissues. Yet, the understanding of their physiological roles and the impact of phosphodiesterase inhibitors on lower urinary tract symptoms in women remains limited. Current hypotheses are conflicting: one suggests that vasodilation might expand the periurethral vascular plexus, leading to increased urethral pressure, whereas the other proposes a relaxation of urethral musculature, resulting in decreased pressure. To further clarify this, we investigated the effect of tadalafil on the opening urethral pressure and voiding function in healthy women. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover trial involving 24 healthy women. Participants were randomly assigned to receive a single dose of tadalafil (40 mg) or placebo during their initial visit and then switched to the alternative treatment during their second visit. Opening urethral pressure was measured with urethral pressure reflectometry during both resting and squeezing conditions of the pelvic floor. Subsequently, voiding parameters were recorded. RESULTS: Compared with placebo, a single dose of tadalafil significantly reduced opening urethral pressure during both resting (-6.8 cmH20; 95% confidence interval [CI], -11.8 to -1.9; p = 0.009) and squeezing conditions (-8.8 cmH20; 95% CI, -14.6 to -3.1; p = 0.005). Voiding parameters did not show significant differences (average flow rate: -0.8 ml/s [95% CI, -2.0 to 0.4; p = 0.2]; maximum flow rate: -1.7 ml/s [95% CI, -4.8 to 1.5; p = 0.3]). CONCLUSIONS: A single dose of 40 mg tadalafil moderately reduced urethral pressure in healthy women, without affecting voiding parameters. The clinical implications of this are yet to be determined.

The efficacy and safety of prostatic urethral lift as a minimally invasive therapeutic modality to treat lower urinary tract symptoms while maintaining sexual function in patients with benign prostatic hyperplasia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Benign prostatic hyperplasia (BPH) is prevalent among elderly men, necessitating focused attention. The Prostatic Urethral Lift (PUL) procedure, a minimally invasive intervention, has emerged as a promising option for BPH management. It has shown remarkable results in ameliorating lower urinary tract symptoms (LUTS), enhancing quality of life, and preserving sexual function. This study aims to evaluate the effectiveness and safety of PUL in BPH patients. METHODS: Key databases (MEDLINE, Cochrane CENTRAL, ScienceDirect, EBSCO, Google Scholar) were systematically searched using pertinent terms related to PUL and BPH. Following the PRISMA checklist, we considered only randomized controlled trials (RCTs) from 2013 to 2023. The assessment focused on LUTS, quality of life, sexual function, and adverse events within three months. Follow-up post-treatment mean values compared with controls (Sham) and the improvement from baseline to post-treatment follow-up duration were considered. Statistical analysis and risk of bias evaluation were conducted using Review Manager 5.4.1, presenting results as difference of mean values (MD) and risk ratios (RR). RESULTS: A meta-analysis with a Random Effects Model of 7 RCTs involving 378 confirmed BPH patients demonstrated significant improvements in the PUL arm including International Prostate Symptom Score (IPSS) (MD 5.51, p<0.0001), maximum urinary flow rate (Qmax) (MD 2.13, p=0.0001), BPH Impact Index (BPHII) (MD 2.14, p=0.0001), and IPSS-QoL (MD 1.50, p<0.0001), without significant increase of adverse events (RR 1.51; p=0.50). Positive outcomes were observed in sexual function variables and post-void residual measurements when post-treatment values were compared to baseline. CONCLUSIONS: PUL holds advantages over control interventions, providing encouraging prospects for BPH management. This study underscores the need for further exploration of PUL's efficacy and safety in BPH patients.

Proposing the "Continuum of UTI" for a Nuanced Approach to Diagnosis and Management of Urinary Tract Infections.

PURPOSE: Patients with suspected UTIs are categorized into 3 clinical phenotypes based on current guidelines: no UTI, asymptomatic bacteriuria (ASB), or UTI. However, all patients may not fit neatly into these groups. Our objective was to characterize clinical presentations of patients who receive urine tests using the "continuum of UTI" approach. MATERIALS AND METHODS: This was a retrospective cohort study of a random sample of adult noncatheterized inpatient and emergency department encounters with paired urinalysis and urine cultures from 5 hospitals in 3 states between January 01, 2017, and December 31, 2019. Trained abstractors collected clinical (eg, symptom) and demographic data. A focus group discussion with multidisciplinary experts was conducted to define the continuum of UTI, a 5-level classification scheme that includes 2 new categories: lower urinary tract symptoms/other urologic symptoms and bacteriuria of unclear significance. The newly defined continuum of UTI categories were compared to the current UTI classification scheme. RESULTS: Of 220,531 encounters, 3392 randomly selected encounters were reviewed. Based on the current classification scheme, 32.1% (n = 704) had ASB and 53% (n = 1614) did not have a UTI. When applying the continuum of UTI categories, 68% of patients (n = 478) with ASB were reclassified as bacteriuria of unclear significance and 29% of patients (n = 467) with "no UTI" were reclassified to lower urinary tract symptoms/other urologic symptoms. CONCLUSIONS: Our data suggest the need to reframe our conceptual model of UTI vs ASB to reflect the full spectrum of clinical presentations, acknowledge the diagnostic uncertainty faced by frontline clinicians, and promote a nuanced approach to diagnosis and management of UTIs.

Early investigational agents for the treatment of benign prostatic hyperplasia'.

INTRODUCTION: Benign prostatic hyperplasia (BPH), as a clinical entity that affects many people, has always been in the forefront of interest among researchers, pharmaceutical companies, and physicians. Patients with BPH exhibit a diverse range of symptoms, while current treatment options can occasionally cause adverse events. All the aforementioned have led to an increased demand for more effective treatment options. AREAS COVERED: This review summarizes the outcomes of new medications used in a pre-clinical and clinical setting for the management of male lower urinary tract symptoms (LUTS)/BPH and provides information about ongoing trials and future directions in the management of this condition. More specifically, sheds light upon drug categories, such as reductase­adrenoceptor antagonists, drugs interfering with the nitric oxide (NO)/cyclic guanosine monophosphate (GMP) signaling pathway, onabotulinumtoxinA, vitamin D3 (calcitriol) analogues, selective cannabinoid (CB) receptor agonists, talaporfin sodium, inhibitor of transforming growth factor beta 1 (TGF-ß1), drugs targeting the hormonal control of the prostate, phytotherapy, and many more. EXPERT OPINION: Clinical trials are being conducted on a number of new medications that may emerge as effective therapeutic alternatives in the coming years.

Testosterone replacement in men with sexual dysfunction.

BACKGROUND: Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction. OBJECTIVES: To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction. SEARCH METHODS: We performed a comprehensive search of CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and the trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform, with no restrictions on language of publication or publication status, up to 29 August 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, assessed the risk of bias, extracted data, and rated the certainty of evidence (CoE) according to GRADE using a minimally contextualized approach. We performed statistical analyses using a random-effects model and interpreted them according to standard Cochrane methodology. Predefined primary outcomes were self-reported erectile dysfunction assessed by a validated instrument, sexual quality of life assessed by a validated instrument, and cardiovascular mortality. Secondary outcomes were treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms (LUTS). We distinguished between short-term (up to 12 months) and long-term (> 12 months) outcomes. MAIN RESULTS: We identified 43 studies with 11,419 randomized participants across three comparisons: testosterone versus placebo, testosterone versus PDE5I, and testosterone with PDE5I versus PDE5I alone. This abstract focuses on the most relevant comparison of testosterone versus placebo. Testosterone versus placebo (up to 12 months) Based on a predefined sensitivity analysis of studies at low risk of bias, and an analysis combing data from the similar International Index of Erectile Function (IIEF-EF) and IIEF-5 instruments, TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference (MD) 2.37, 95% confidence interval (CI) 1.67 to 3.08; I² = 0%; 6 RCTs, 2016 participants; moderate CoE) on a scale from 6 to 30 with larger values reflecting better erectile function. We assumed a minimal clinically important difference (MCID) of greater than or equal to 4. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD -2.31, 95% CI -3.63 to -1.00; I² = 0%; 5 RCTs, 1030 participants; moderate CoE) on a scale from 17 to 85 with larger values reflecting worse sexual quality of life. We assumed a MCID of greater than or equal to 10. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio (RR) 0.83, 95% CI 0.21 to 3.26; I² = 0%; 10 RCTs, 3525 participants; moderate CoE). Based on two cardiovascular deaths in the placebo group and an assumed MCID of 3%, this would correspond to no additional deaths per 1000 men (95% CI 1 fewer to 4 more). TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or LUTS. Testosterone versus placebo (later than 12 months) We are very uncertain about the longer-term effects of TRT on erectile dysfunction assessed with the IIEF-EF (MD 4.20, 95% CI -2.03 to 10.43; 1 study, 42 participants; very low CoE). We did not find studies reporting on sexual quality of life or cardiovascular mortality. We are very uncertain about the effect of testosterone on treatment withdrawal due to adverse events. We found no studies reporting on prostate-related events or LUTS. AUTHORS' CONCLUSIONS: In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care.

Safety and efficacy of an α1 -blocker plus mirabegron compared with an α1 -blocker plus antimuscarinic in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and overactive bladder: A systematic review and network meta-analysis.

AIM: Antimuscarinics and the ß3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α1 -adrenoreceptor antagonists (α1 -blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an α1 -blocker plus mirabegron with an α1 -blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations. METHODS: Included records had to be from a parallel-group, randomized clinical trial that was ≥8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an α1 -blocker plus OAB agent with an α1 -blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Qmax ). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis. RESULTS: Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the α1 -blocker plus mirabegron and α1 -blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the α1 -blocker plus mirabegron group compared with the α1 -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Qmax . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α1 -blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation. CONCLUSION: This systematic review and meta-analysis showed that an α1 -blocker plus mirabegron and an α1 -blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting.

Evaluation of Tamsulosin 0.4 mg versus 0.8 mg in management of lower urinary tract symptoms due to benign prostatic enlargement.

PURPOSE: To compare the efficacy and the safety of Tamsulosin 0.4 mg/day and 0.8 mg/day in patients suffering from lower urinary tract symptoms due to benign prostatic obstruction. PATIENTS AND METHODS: A prospective interventional, double-blinded, controlled study was carried out on 93 patients who met the criteria and divided randomly into two groups: group A for Tamsulosin 0.4 mg/day and group B for Tamsulosin 0.8 mg/day. International prostate symptom score, post void residual urine volume, and maximum flow rate of urine were assessed before and after 4 weeks of treatment. RESULTS: Both study groups showed a significant reduction in storage sub-score but only frequency was significantly reduced in group B (P < 0.001). On the other hand, Tamsulosin 0.8 mg was superior to Tamsulosin 0.4 mg regarding voiding sub-score except for straining (P = 0.325). Accordingly, the total international prostate symptom score was significantly improved in group B versus group A (P < 0.001). Furthermore, maximum flow rate and post-void residual urine volume were notably improved in Group B as compared to Group A (P < 0.001). Of all adverse events only dizziness was noted to be statistically significant in Group B versus Group A (P < 0.001). CONCLUSION: Tamsulosin 0.8 mg has shown better outcomes in treating patients who suffer from lower urinary tract symptoms due to benign prostatic enlargement than Tamsulosin 0.4 mg, and besides that, it is well tolerated. TRIAL REGISTRATION NUMBER: M S 292/2020, SID: 373, date: 22/4/2020.

Efficacy of High-Dose Dexamethasone in Reducing the Symptoms of Postembolization Syndrome Following Prostatic Artery Embolization: Results of a Double-Blind Randomized Controlled Trial.

PURPOSE: To evaluate the efficacy of a single perioperative dose of dexamethasone in reducing postembolization syndrome following prostatic artery embolization. MATERIALS AND METHODS: We conducted a single-center double-blind randomized controlled trial from March 2021 to May 2022 (NCT04588857). Participants were randomized to receive either i.v. 24 mg dexamethasone or saline. The primary outcome measures were temperature, pain, and quality of life in the first 5 days following prostatic artery embolization. Sample size of 60 patients was needed for the assessment of primary outcomes. Participants were followed for 6 months and assessed for a variety of secondary outcome measures including inflammatory markers and lower urinary tract symptoms severity. RESULTS: Due to lack of clinical effect and mild symptoms in the control group, the trial was terminated early. 31 participants (16 dexamethasone vs. 15 control) were enrolled and analyzed. A difference in mean temperature was observed on day 1 (37.23 ± 0.64 °C control vs 36.74 ± 0.41 °C dexamethasone, p = 0.02, 95% CI 0.09-0.89). Difference in pain (score out of 10) was seen only on day 5 (1.48 ± 1.2 control vs. 2.9 ± 2.24 dexamethasone, p = 0.04, 95% CI - 2.78-- 0.04). A difference in C-reactive protein values was observed on day 2 (108 [54-161] mg/l control vs 10 [5-33] mg/l dexamethasone, p < 0.01). No significant differences in other outcomes were observed. No side effects were recorded. CONCLUSIONS: Twenty-four milligrams of dexamethasone bolus is safe but does not reduce postembolization syndrome following prostatic artery embolization.

Immediate effect of alpha-blockers in predicting LUTS improvement in BPH patients.

INTRODUCTION: Indications for treating Benign Prostatic Hyperplasia include reversing signs and symptoms or preventing the progression of the disease. Alpha-blockers are the most effective, least costly, and best tolerated of the drugs for relieving LUTS. The aim of the study is to investigate the immediate impact of alpha-blocker medications on lower urinary tract symptoms (LUTS). MATERIALS AND METHODOLOGY: About 100 patients were included in the study-50 patients in each of the groups A (tamsulosin) and B (silodosin). The first visit was the baseline examination before starting alpha-blockers and included history, DRE, UFM, USG KUBP with PVR, IPSS, serum PSA, serum creatinine, urine analysis, urine culture, and sensitivity. All above parameters were also at 1 week, 1 month, and 3 months following starting of alpha-blockers respectively, and compared with baseline. RESULT: As of the first, second, third, and fourth visits, the mean Qmax in group A was 10.3 ± 3.3 s, 15.08 ± 2.80 s, 15.66 ± 3.18 s, and 15.12 ± 3.24 s, respectively, while in group B it was 10.1 ± 3.1 s, 14.88 ± 2.80 s, 15.18 ± 3.18 s, and 15.08 ± 3.24 s, respectively (p < 0.001). The mean voiding time was 40.87 ± 23.91 s, 36.41 ± 20.73 s, 34.85 ± 21.37 s, and 32.07 ± 21.81 s, respectively in group A, and 41.27 ± 15.49 s, 37.23 ± 21.34 s, 38.59 ± 20.83 s, and 33.10 ±22.08. In group A, the mean PVR and IPSS scores were improved and also improved in group B. CONCLUSION: The first dose of tamsulosin and silodosin improves UFM and predicts the mid-term change in UFM as well as IPSS indices in the treatment of BPH-related LUTS.

Comparison of Monotherapies and Combination Therapy of Tamsulosin and Tadalafil for Treating Lower Urinary Tract Symptoms Caused by Benign Prostatic Hyperplasia with or without Erectile Dysfunction: A Meta-Analysis.

BACKGROUND: There is limited research into the efficacy and safety of tadalafil combined with tamsulosin for the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH), with or without erectile dysfunction (ED). Therefore, we aimed to investigate the efficacy and safety of combination therapy compared to that of monotherapy. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang Data Service Platform, and ClinicalTrials.gov to identify eligible studies. A total of 639 articles were retrieved, of which 12 were randomized controlled trials (RCTs) published as of February 2023 and included in this meta-analysis. RESULTS: After screening 639 articles, 12 RCTs including 1,531 subjects were considered eligible for the meta-analysis. The results showed that the total International Prostate System Score (total IPSS), maximum flow rate (Qmax), and quality of life (QoL) in tadalafil combined with tamsulosin were significantly better than those in monotherapy. Compared with tadalafil monotherapy, combination therapy mainly improved IPSS voiding. As for postvoid residual urine (PVR), the combination therapy did not improve PVR compared to the tadalafil group, but significantly improved PVR compared to the tamsulosin group. For the International Index of Erectile Function (IIEF), the curative effect of the combined group was better than that of the tamsulosin group but not better than that of the tadalafil group. In terms of safety, the adverse reactions (AEs) in the combined treatment group were significantly higher than those in the monotherapy group. None of the 12 RCTs reported serious adverse events. CONCLUSIONS: Tadalafil combined with tamsulosin was more effective in the treatment of male LUTS/BPH, with or without ED, on the improvement of total IPSS, QoL, and Qmax. However, the benefits of combination therapy for ED remain unclear. However, combination therapy seemed to have a higher incidence of adverse reactions.

Effects of L-Carnitine and Coenzyme Q10 Supplementation on Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia: A Randomized, Controlled, Clinical Trial.

The prevalence of benign prostatic hyperplasia (BPH) and its associated lower urinary tract symptoms (LUTS) increases with age. Considering that BPH drug treatment is associated with complications, this study aimed to investigate the effects of L-carnitine (LC) and Coenzyme Q10 (CoQ10) supplementation as an adjunct therapy to finasteride in the management of LUTS in older men affected with BPH. Fifty eligible volunteers (25 per group) were randomly assigned to either intervention (finasteride + LC and CoQ10 supplements) or control (finasteride + placebo) groups. International prostate symptom score (IPSS), international index of erectile function (IIEF), quality of life index (QoL), as well as serum levels of Prostate-specific antigen (PSA), were assessed. Prostate ultrasound evaluation was also performed, before and after 8 wk of intervention. Supplementation with LC and CoQ10 led to a significant decrease in prostate volume (p < 0.001) as well as a significant increase in IIEF (p < 0.001), compared to the control group. However, there were no significant between-group differences in IPSS (p = 0.503), QoL scores (p = 0.339), and PSA levels (p = 0.482). CoQ10 and LC supplements might be beneficial in combination with standard therapies in the management of BPH and its related complications.

Potential side effects of currently available pharmacotherapies in male lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

INTRODUCTION: The drug classes of α1-adrenoceptor antagonists, 5α-reductase inhibitors, and phosphodiesterase type 5 inhibitors are guideline-recommended treatments of lower urinary tract symptoms suggestive of benign prostatic hyperplasia; muscarinic receptor antagonists and ß3-adrenoceptor agonists are also recommended if storage symptoms are insufficiently addressed with one of the other three drug classes. AREAS COVERED: We provide a narrative review (no formalized literature searches performed) of the tolerability of these drug classes with emphasis on the more recently introduced medications, on combination treatment, and on more lately emerging risks. EXPERT OPINION/COMMENTARY: The tolerability profiles are distinct between drug classes but, with few exceptions, similar within a drug class. Within a drug, formulations with longer duration of action tend to have better tolerability. Efficacy gains using combination treatment at least partly come at a cost of lesser tolerability. Greater susceptibility to experience adverse events based on age, comorbidities, and comedications appears conceptually important but remains under-investigated in this therapeutic area.

Several classes of medicines are available to treat male lower urinary tract symptoms that are believed to result from an enlarged prostate. These include α₁-adrenoceptor antagonists (α-blockers), 5α-reductase inhibitors (ARI), and phosphodiesterase type 5 inhibitors (PDEI); muscarinic receptor antagonists and ß₃-adrenoceptor agonists are additionally used in men that have persisting storage symptoms upon treatment with the former three drug classes. Each drug class has a distinct tolerability profile. Within a drug class, medicines with a longer duration of action, either intrinsically or due to specific drug formulations, tend to have better tolerability. Men with greater age, comorbidities, and comedications may be at greater risk of experiencing side effects when medically treating their lower urinary tract symptoms. While combination of members of multiple drug classes may increase efficacy, this often comes at the price of experiencing more side effects. The relative benefit/risk ratio needs to be individually analyzed in each patient.

[Study of allelic variants of the CYP2D6 and CYP3A genes on the effectiveness and safety of tamsulosin therapy in patients with BPH: results of a pilot study].

INTRODUCTION: Tamsulosin is a member of the group of selective 1-adrenoblockers. Tamsulosin monotherapy is the most common first-line option in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and can be used regardless on severity of LUTS. The CYP2D6, CYP3A4, and CYP3A5 enzymes are involved in the metabolism of tamsulosin. Carriage of different allelic variants of CYP2D6, CYP3A4 and CYP3A5, involved in its metabolism, may potentially affect the variability of efficacy and safety of the drug. AIM: To evaluate the effect of carriage of allelic variants of cytochrome P450 superfamily enzyme genes (CYP2D6*3, CYP2D6*4, CYP2D6*9, CYP2D6*10, CYP2D6*41, CYP3A4*3, CYP3A4*22 and CYP3A5*3) on the efficiency and safety of tamsulosin in patients with LUTS associated with BPH. MATERIALS AND METHODS: All phases of the study were completed by 106 patients with LUTS/BPH (N40 according to ICD 10). All patients received monotherapy with tamsulosin 0.4 mg/day for a minimum of 8 weeks. Based on the severity of symptoms, they were divided into two groups using the International Prostate Symptom Score (IPSS). In Group 1, there were patients with moderate symptoms (IPSS score of 8-19) (n=57), while Group 2 consisted of those with severe symptoms (IPSS score >20) (n=49). Treatment outcomes were assessed using the IPSS score with determination of quality of life (QoL), transrectal ultrasound with evaluation of prostate volume and residual urine, and uroflowmetry. Follow-up visits were at 2, 4, and 8 weeks after the start of therapy. Genotyping of all patients was performed using polymerase chain reaction to determine the CYP2D6 (*3, *4, *9, *10, and *41), CYP3A4 (*3, *22), and CYP3A5*3 markers. RESULTS: In the group of patients with moderate symptoms, carriers of the CYP2D6*10 and CYP2D6*41 polymorphisms showed a significantly greater reduction in symptoms according to the overall IPSS score at 8 weeks (p=0.046) and in the micturition symptom subscale starting from 4 weeks of treatment (p<0.05). Carriers of the CYP2D6*10 polymorphism in both groups were associated with a decrease in residual urine volume at 8 weeks (p<0.05). The presence of the CYP3A5*3 variant in those with severe symptoms significantly improved quality of life during therapy. Allelic variants of the CYP2D6 and CYP3A genes did not affect the frequency of adverse events. CONCLUSION: The results obtained by calculating the prognostic significance of individual polymorphic markers pointed to the contribution of CYP2D6*10 and CYP2D6*41. Tamsulosin therapy is more effective in patients with LUTS who are carriers of these allele variants. The safety parameters of tamsulosin were not influenced by the studied polymorphic variants. It was found that CYP3A5*3 was associated with an increase in the subjective assessment of the patient's quality of life, but it is too early to draw final conclusions. The issue of the contribution of genetic factors to the efficiency and safety of treatment of LUTS in BPH requires further study with a larger sample size and analyzed parameters.

[Evaluation of the effect of Alfuprost MR on detrusor thickness and bladder mass in patients with detrusor hypertrophy caused by benign prostatic hyperplasia].

INTRODUCTION: Benign prostatic hyperplasia (BPH) can lead to the detrusor hypertrophy and deterioration of the bladder function with a decrease in its contractile activity. A number of publications are presented in the literature, the results of which indicate the possibility of reducing bladder hypertrophy with alpha-blockers. AIM: To carry out the retrospective analysis to study the effect of Alfuprost MR on urodynamic parameters, as well as the influence of the therapy on detrusor thickness and bladder mass in patients with detrusor hypertrophy and bladder outlet obstruction caused by BPH. MATERIALS AND METHODS: Outpatient records of 30 patients with lower urinary tract symptoms (LUTS) caused by BPH who received Alfuprost MR as monotherapy for 24 weeks were reviewed. Based on the diaries, the following parameters were assessed: total IPSS score, IPSS voiding (questions No. 1, 3, 5 and 6) and storage subscale scores (questions No. 2, 4 and 7), maximum flow rate (Qmax) according to uroflowmetry, the volume of the prostate and the postvoid residual (assessed by ultrasound), satisfaction with treatment on the quality-of-life score (QoL), as well as the changes in detrusor thickness and bladder mass index. RESULTS: An improvement in LUTS severity, starting from the 4th week of treatment, followed by a positive trend that persists until the 24th week of therapy with Alfuprost MR, was found. The overall average IPSS score improved by 39.0% by the 24th week of therapy. At the same time, voiding symptoms improved by 46.8%, and storage symptoms improved by 30.9% by 24 weeks of therapy. The average Qmax increased significantly (p<0.05) by 22.1% after 24 weeks of therapy. The average detrusor thickness decreased by 40,2%. Bladder mass index decreased significantly by an average of 34,3% (p<0.05). QoL score improved significantly (p<0.05) by 2.2 points after 24 weeks of therapy. CONCLUSION: During the 24-week treatment of patients with BPH, Alfuprost MR demonstrated clinical efficacy not only in reducing voiding symptoms and in improving the QoL, but also a positive effect on detrusor hypertrophy, as evidenced by changes in detrusor thickness and bladder mass index. The absence of any adverse events, including decrease in blood pressure and heart rate, allows us to recommend Alfuprost MR as an effective treatment for LUTS associated with BPH, which reduces detrusor hypertrophy and has a high safety profile and minimal vasodilating effects.