Benign prostatic hyperplasia is one of the most common diseases in men, with a prevalence rate of 50% in their 50s to 80% in their 80s, and is mostly treated with chronic drug therapy. The aim of this study was to analyze adverse drug reactions (ADR) to drugs used in benign prostate hyperplasia (BPH) treatment reported to HALMED from 2008 to 2021. Data on ADR reports in Croatia were obtained from the VigiFlow national database and on the use of drugs for BPH in Croatia from Drug Utilization Reports from HALMED. In the observed period, the number of reports on each BPH drug, total number of reports, seriousness of reported ADR, patient age and sex, type of reporter, and most reported ADRs were analyzed. Results showed that 438 ADR reports were received, of which 45.95% on tamsulosin as the most frequently used drug for BPH. Of all reports, 84% were non-serious, 96% were reported in men and 82% in patients older than 45 years. The most frequently reported ADRs were consistent with the known safety profile of BPH drugs. Pharmacists were the most common (47%) reporters of ADRs for BPH drugs, while 33% were reported by physicians. Analysis of the reported ADRs showed that most frequently reported ones were in line with the known safety profile of BPH drugs. However, given the prevalence of the disease and the extent of the use of BPH drugs, it could be argued that the number of reports could be higher (i.e., 34 reports/year). Reporting on ADRs is necessary to better understand the safety profile of drugs in the post-authorization period, and more information on the safe use of medicines could be collected by raising awareness of healthcare professionals.

UNASSIGNED: Recent studies have tried to establish an association between the use of alpha-1-adrenergic receptor antagonists (A1ARAs) used in benign prostatic hyperplasia (BPH) and the risk of PD. The objective of the study is to compare the risk of Parkinson\'s disease (PD) between terazosin/alfuzosin/doxazosin (TZ/AZ/DZ) users and tamsulosin users.
UNASSIGNED: PubMed, Google Scholar, and Embase were systematically searched from inception to April 2023. Observational studies comparing the risk of PD among patients using different types of A1ARAs were included in the meta-analysis. The primary outcome was the hazard ratio (HR) with a 95% CI for the risk of occurrence of PD among A1ARAs users of two different classes.
UNASSIGNED: This study was based on a total of 678 433 BPH patients, out of which 287 080 patients belonged to the TZ/AZ/DZ cohort and 391 353 patients belonged to the tamsulosin cohort. The pooled incidence of PD was higher in tamsulosin users (1.28%, 95% CI: 1.04-1.55%) than in TZ/AZ/DZ drug users (1.11%, 95% CI: 0.83-1.42%). The risk of occurrence of PD was significantly lower in patients taking TZ/AZ/DZ than tamsulosin (n= 610,363, HR = 0.82, 95% CI = 0.71-0.94, P = 0.01; I2 = 87.4%).
UNASSIGNED: This meta-analysis demonstrated that patients with BPH who take TZ/AZ/DZ have a lower risk for developing PD than those who take tamsulosin.

Adrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and in the management of therapy-resistant arterial hypertension, two conditions frequently found in older adults. This systematic review aims at presenting a complete overview of evidence over the benefits and risks of alpha-1 antagonist treatment in people ≥ 65 years, and at deriving recommendations for a safe application of alpha-1 antagonists in older adults from the evidence found.
A comprehensive literature search was performed (last update March 25th 2022) including multiple databases (Medline/Pubmed, Embase, the Cochrane Library) and using the PICOS framework to define search terms. The selection of the studies was done by two independent reviewers in a two-step approach, followed by a systematic data extraction. Quality appraisal was performed for each study included using standardised appraisal tools. The studies retrieved and additional literature were used for the development of recommendations, which were rated for strength and quality according to the GRADE methodology.
Eighteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 9 observational trials. Doxazosin in the management of arterial hypertension was associated with a higher risk of cardiovascular disease, particularly heart failure, than chlorthalidone. Regarding treatment of LUTS suggestive of BPH, alpha-1 antagonists appeared to be effective in the relief of urinary symptoms and improvement of quality of life. They seemed to be less effective in preventing disease progression. Analyses of the risk profile indicated an increase in vasodilation related adverse events and sexual adverse events for some agents. The risk of falls and fractures as well as the effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 7 out of 9 observational studies were of good quality.
It cannot be recommended to use doxazosin as first-line antihypertensive agent neither in older adults nor in younger patients. In the management of BPH alpha-1 antagonists promise to effectively relieve urinary symptoms with uncertainty regarding their efficacy in preventing long-term progression events.

BACKGROUND: Alpha1-adrenoceptor antagonists (α1-blockers) are first-line drugs for the treatment of lower urinary tract symptoms associated with benign prostate hyperplasia (BPH). Doxazosin gastrointestinal therapeutic system (GITS) and tamsulosin belong to the 2 most frequently prescribed α1-blockers. This systematic review and meta-analysis was performed to compare the efficacy and tolerability of these 2 α1-blockers.
METHODS: A systematic review of published randomized controlled trials in English or Chinese language was performed using the PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and Vip databases. After data extraction and quality assessment, the meta-analysis was performed to compare clinical parameters (International Prostate Symptom Score [IPSS] total [IPSS-T], storage [IPSS-S], voiding [IPSS-V], maximum urine flow [Qmax], and postvoid residual) and adverse events (AEs) that changed after first drug intake.
RESULTS: After the screening, 8 eligible randomized controlled trials with 1316 patients were identified. Doxazosin-GITS showed a significantly higher efficacy compared with tamsulosin (IPSS-T P < .001, IPSS-S P < .001, and IPSS-V P < .001). There were no significant differences between the 2 drugs for changes in Qmax (P = .477) or postvoid residual (P = .739). The overall AEs were significantly lower in the doxazosin-GITS group (risk ratio: 0.77; 95% CI: 0.54-1.08; P = .036). However, dizziness (P = .387), headache (P = .745), asthenia (P = .693), postural hypotension (P = .114), and retrograde ejaculation (P = .187) were similar between the 2 groups.
CONCLUSIONS: This meta-analysis indicates that doxazosin-GITS has significantly higher efficacy and lower AEs than tamsulosin in patients with lower urinary tract symptoms/benign prostate hyperplasia.

Alpha-blockers have been proven as an effective method for increasing the stone expulsion rate of distal ureteral stones. Limited studies have focused on doxazosin; its efficacy remained unclear. We performed this meta-analysis to investigate the efficacy and safety of doxazosin for patients diagnosed with distal ureteral stones less than 10mm.
We systematically searched Ovid MEDLINE®, Cochrane Library, EMBASE, and PubMed for articles comparing doxazosin and conventional care or tamsulosin for distal ureteral stones through October 2019. The outcome measures were stone expulsive rate (SER), stone expulsive time (SET), pain episodes, analgesics consumption, and adverse events.
We included 12 studies involving 836 participants with distal ureteral stones less than 10mm in our review. The present meta-analysis showed doxazosin could significantly increase SER [RR=1.64,95%CI (1.32, 2.04), P  < 0.00001], shorten SET [WMD=-3.97,95% CI (-5.68, -2.27), P  < 0.00001] compared with conventional care. In the subgroup analyses, doxazosin showed no benefit in the children subgroup (<16 years old) [RR=1.63,95% CI (0.73,3.64), P  =0.23]. No statistically significant difference was observed regarding the effectiveness of doxazosin and tamsulosin in SER, SET, and safety. 9 in 286 participants reported doxazosin-related adverse events; most were mild to moderate.
This meta-analysis may suggest that doxazosin is a safe and effective MET for distal ureteral stones less than 10mm. It is not demonstrated to have any significant difference with tamsulosin in SER, SET, and safety. However, it showed no benefits for patients<16 years old.

OBJECTIVE: To identify trends in the evidence base regarding the effectiveness of using α-blockers in children versus adults and compare outcomes.
METHODS: A literature search up using the key words including urolithiasis/renal/ureteric stone in children/paediatric population, medical expulsive treatment (MET), α-blocker/alfuzosin/tamsulosin/doxazosin. Included were randomized or controlled clinical trials in paediatric stone formers (aged ≤18 years). Outcome measures for assessment included the overall stone expulsion rate, expulsion time, the number of pain episodes and adverse drug effects and/or reactions. Further comparison of efficacy levels using respective studies from the adult population was performed in order to identify trends, similarities and differences.
RESULTS: A total of 8,259 articles were identified. Full text evaluation was possible for 28 articles. Although the picture is clearer in the paediatric group, the lack of reproducible results in adults certainly poses serious questions about data collection, analysis and interpretation in each individual study. The apparent paradox is due to the methodological differences between studies.
CONCLUSIONS: The effectiveness of α-blockers and other medication as MET needs to be studied in multi-institutional, double-blind, placebo-controlled studies that would aim to prove superiority to placebo in contemporary clinical situations, with realistic end points and standardized outcome measure determination.

Pathway-2 is the first randomised, double-blind and crossover trial that compares spironolactone as a fourth drug with alfa-blocker, beta-blocker and placebo. This study shows that spironolactone is the drug with more possibilities of success for the management of patients with difficult-to-treat hypertension in patients with a combination of three drugs and poor control. The results validate the widespread treatment with mineralocorticoid receptor antagonists in resistant hypertension.

The urodynamic outcomes for α1-blockers (ABs) treatment in patients with lower urinary tract symptoms related to benign prostatic enlargement (LUTS/BPE) is a matter of debate.
To perform a systematic review and meta-analysis of studies evaluating the ABs urodynamic outcomes in patients with LUTS/BPE. The primary endpoint was variation in bladder outlet obstruction index (BOOI). Secondary endpoints were the maximum urinary flow rate (Qmax) and detrusor pressure at Qmax (PdetQmax). A meta-analysis of placebo-controlled randomized clinical trials (RCTs) was performed to compare ABs with placebo.
A systematic review of PubMed/Medline, ISI Web of Knowledge, and Scopus databases was performed in May 2015. Seventeen studies were selected for inclusion.
The overall pooled data showed a mean BOOI change of -14.19 (p<0.0001), a mean PdetQmax change of -11. 39cm H2O (p<0.0001), and a mean Qmax improvement of 2.27ml/s (p<0.0001). Subgroup analysis showed a mean BOOI change of -14.88 (p=0.01) for alfuzosin, -19.41 (p=0.01) for doxazosin, -16.47 (p<0.0001) for naftopidil, -30.45 (p<0.0001) for silodosin, -14.27 (p=0.002) for tamsulosin, and -6.69 (p=0.005) for terazosin. Subanalysis of RCTs containing a placebo arm showed a significant improvement in BOOI in patients undergoing ABs treatment. Meta-regression revealed a significant positive association between the percentage of patients with obstruction at baseline and the improvement in BOOI after treatment with ABs.
ABs improve BOOI in patients with LUTS/BPE mainly by reducing PdetQmax, and this effect is higher in patients presenting with urodynamic obstruction at baseline. The free Qmax variation underestimates the real effect of ABs on benign prostatic obstruction.
Results of this meta-analysis suggest that α1-blockers objectively improve urinary voiding function in patients with benign prostatic obstruction.

BACKGROUND: During surgical treatment of pheochromocytoma,`haemodynamic instability may occur. To prevent this, patients receive preoperative treatment with an alpha-blocker. Nowadays, some centres use phenoxybenzamine, while others use doxazosin. The purpose of this review is to analyse the current evidence of the benefits and risks of phenoxybenzamine and doxazosin in the preoperative treatment of pheochromocytoma.
METHODS: The literature was reviewed by searching PubMed using the following search terms: pheochromocytoma, phenoxybenzamine, doxazosin and alpha-blockade. The filter was set on English language.
RESULTS: No randomised controlled trials were found. Five follow-up studies comparing phenoxybenzamine and doxazosin in the treatment of pheochromocytoma were retrieved and analysed. There was a trend that systolic arterial pressure is slightly better controlled by phenoxybenzamine. However, this resulted in more pronounced postoperative hypotension as well. The use of an alpha-blocker was often accompanied by other vasoactive agents. phenoxybenzamine was often accompanied by a beta-blocker to control reflex tachycardia, while patients on doxazosin received significantly more additional antihypertensive medicines. Most of the studies showed that the use of vasoactive drugs and fluid infusion does not differ significantly between the two drugs. Phenoxybenzamine caused significantly more orthostatic hypotension, oedema and complaints of a stuffy nose.
CONCLUSIONS: On the basis of the current evidence, there is no evidently superior alpha-blocker for the pretreatment of patients with pheochromocytoma. Perioperative haemodynamics seem to be slightly better controlled with phenoxybenzamine, at the cost of more pronounced postoperative hypotension. Side effects occurred less often in the doxazosin group.

BACKGROUND: Several drugs, currently used to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), can be associated with bothersome sexual side effects, including ejaculatory dysfunction (EjD).
OBJECTIVE: To provide a systematic review and meta-analysis of the available randomized clinical trials (RCTs) reporting the impact of medical treatments for LUTS due to BPH on ejaculatory function.
METHODS: EjD related to medical treatments for LUTS.
METHODS: A systematic literature search was performed using PubMed, Scopus and Cochrane databases. EjD was identified using both free text (\"ejaculat*,\" \"retrograde ejaculation,\" \"anejaculation,\" \"ejaculatory dysfunction\") and Mesh (\"Ejaculation\") searches.
RESULTS: Of 101 retrieved articles, 23 were included in the present meta-analysis. EjD was significantly more common with alpha-blockers (ABs) than with placebo (OR:5.88; P < 0.0001), in particular, considering Tamsulosin (OR:8.58; P = 0.006) or Silodosin (OR:32.5; P < 0.0001), with Tamsulosin associated with significantly lower risk of EjD than Silodosin (OR:0.09; P < 0.00001). Conversely, Doxazosin and Terazosin were associated with a risk similar to placebo. Meta-regression showed that EjD was associated with IPSS and with Qmax both before and after treatment with ABs, while multivariate analysis demonstrated that EjD was independently associated with the improvement of IPSS (adj.r:0.2012; P < 0.0001) and Qmax (adj.r:0.522; P < 0.0001). EjD was significantly more common with 5ARIs as compared with placebo (OR:2.73; P < 0.0001). Both Finasteride (OR 2.70; P < 0.0001) and Dutasteride (OR 2.81; P = 0.0002) were associated with significantly higher risk of EjD than placebo. EjD was significantly more common with combination therapy as compared with ABs alone (OR:3.75; P < 0.0001),or with 5ARIs alone (OR:2.76; P = 0.02).
CONCLUSIONS: ABs and 5ARI were both associated with significantly higher risk of EjD than placebo. More the AB is effective over time, greater is the incidence of EjD. Finasteride has the same risk of Dutasteride to cause EjD. Combination therapy with ABs and 5ARIs resulted in a 3-fold increased risk of EjD as compared with ABs or 5ARIs alone. These data can be relevant both for drug selection and patients counseling.