Short‐term effects of crossover treatment with silodosin and tamsulosin hydrochloride for lower urinary tract symptoms associated with benign prostatic hyperplasia

Objectives: To compare the efficacy and safety of silodosin and tamsulosin in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) by a randomized crossover method. Methods: BPH patients with the complaint of LUTS were included in this study, and were randomly divided into two groups: a silodosin‐preceding group (4 weeks of twice‐daily administration of silodosin at 4 mg, followed by 4 weeks of once‐daily administration of tamsulosin at 0.2 mg) or a tamsulosin‐preceding group (4 weeks' administration of tamsulosin, followed by 4 weeks' administration of silodosin). No drug withdrawal period was provided when switching the drug. Results: In the first treatment period, both drugs significantly improved the International Prostate Symptom Score total score, but the improvement by silodosin was significantly superior to that by tamsulosin. After crossover treatment, significant improvement was observed only with silodosin treatment. Moreover, intergroup comparison of changes revealed that silodosin showed significant improvement of straining and nocturia with first and crossover treatments, respectively, compared with tamsulosin. Silodosin also significantly improved quality of life (QOL) score in both treatment periods, while tamsulosin significantly improved QOL score only in the first treatment period. The most frequent adverse drug reaction was ejaculatory disorder with silodosin; however, the incidence of dizziness with silodosin was similar to that with tamsulosin. Conclusions: In BPH/LUTS patients, silodosin exhibits excellent efficacy in improving subjective symptoms in both initial and crossover treatment, and it appears to improve the QOL of patients.     

Outcomes and complications of naftopidil versus tamsulosin for elderly men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to assess the outcomes and complications of naftopidil in treating elderly men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and compared them with those administered with tamsulosin. A literature review was performed to identify the available randomised controlled trials concerning the comparison between naftopidil and tamsulosin for men with LUTS/BPH. We searched the following databases: the Cochrane Library Database, PubMed, Embase and Web of Science. Eleven publications involving 1,114 men (557 in the naf group and 557 in the tam group) were pooled in our analysis. We found no significant differences in the total IPSS, IPSS storage score, IPSS voiding score, quality of life index, peak urinary flow rate, average flow rate and post-void residual volumes. We assessed cardiovascular and sexual adverse events, acute urinary retention, surgical intervention, withdrawals due to any reason and withdrawals due to adverse events. The incidence of adverse events was similar among patients in naf and tam groups. In conclusion, naftopidil shared comparable efficacy and similar incidence of adverse events with tamsulosin and appears to be a promising agent for and alternative to tam. However, more prospective trials with high quality and long-term treatment duration are needed to verify this observation.     

锯叶棕果实提取物治疗BPH引起的下尿路症状疗效观察

目的:探讨锯叶棕果实提取物治疗BPH引起的下尿路症状的疗效。方法:采用锯叶棕果实提取物单药治疗30例前列腺增生伴下尿路症状患者8周,分别比较患者治疗前后的最大尿流率、前列腺体积、剩余尿量、IPSS评分及QOL评分的变化情况。结果:治疗8周后,患者的最大尿流率、剩余尿量、IPSS评分及QOL评分均有明显改善,前列腺体积则无明显变化。所有患者均无明显不良反应。结论:锯叶棕果实提取物能有效改善BPH患者的下尿路症状。     

他汀类药物的使用与良性前列腺增生和下尿路症状相关性的临床研究

目的:探讨服用他汀类药物是否可延缓良性前列腺增生(BPH)和下尿路症状的临床进展。方法:选择2003年1月至2008年12月于我院体检中心体检的50~69岁男性作为研究对象,制定纳入标准,随访5年,通过比较IPSS评分、最大尿流率(Qmax)和前列腺体积(PV)探讨他汀类药物的使用与前列腺增生和下尿路症状临床进展的相关性。结果:总共有653例男性纳入本研究,其中他汀类药物使用组(1组)283例,他汀类药物未使用组(2组)370例,两组入选时的年龄、IPSS评分、Qmax和PV差异均无显著性(P0.05),随访过程中因出现明显的排尿困难各剔除24例(1组)和35例(2组)。5年随访过程中1组和2组的IPSS评分都逐渐升高,但1组升高程度明显低于2组(P0.01),1组和2组的Qmax都逐渐下降,但1组下降程度明显低于2组(P0.01);1组[PV5年分别为(22.60±4.99)、(25.80±5.20)、(27.92±5.05)、(29.11±5.24)、(29.97±5.26)ml]和2组[5年分别为(24.30±4.98)、(28.50±5.14)、(32.84±4.77)、(36.99±4.78)、(40.90±4.78)ml]的PV都逐渐增大,但1组增大程度明显小于2组(P0.01)。结论:使用他汀类药物可明显延缓BPH和下尿路症状的临床进展,且长时间服用疗效更显著。     

他达拉非治疗继发于良性前列腺增生下尿路症状的研究进展

他达拉非作为新一代的选择性磷酸二酯酶-5抑制剂(PDE5Is)为男性勃起功能障碍(ED)的治疗带来了全新的理念。继发于男性良性前列腺增生症(BPH)的下尿路症状(LUTS)由于其病因的复杂性,治疗效果受到多因素的影响,使得传统的临床治疗方法不可避免地存在各种难以预测的并发症。目前日益受到关注的他达拉非每日一次口服方案(OAD)治疗ED的新方案在临床研究中表现出了对继发于BPH的LUTS的显著的疗效,在治疗的早期,国际前列腺症状评分(IPSS)就得以显著改善。还有研究表明在同时存在ED和LUTS症状的BPH患者中,他达拉非也显著有效。本文旨在回顾PDE5Is对BPH相关症状治疗的相关研究进展,综述他达拉非治疗继发于BPH的LUTS的有效性和安全性证据。     

Comparative efficacy of two alpha-adrenoreceptor antagonists, doxazosin and alfuzosin, in patients with lower urinary tract symptoms from benign prostatic enlargement

OBJECTIVES: To compare doxazosin and alfuzosin in patients with moderate to severe lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction. PATIENTS AND METHODS: In all, 210 men with LUTS were randomized to receive doxazosin 1-8 mg once daily or alfuzosin 5-10 mg divided in two or three daily doses in a 14-week, multicentre, double-blind, baseline-controlled, dose-titration study. The International Prostate Symptom Score (IPSS) and maximum urinary flow rate were used to assess the efficacy of the treatment. RESULTS: At study completion, the mean dose of doxazosin was 6.1 mg/day and alfuzosin 8.8 mg/day. The least squares mean (se) change from baseline in total IPSS was -9.23 (0.6) for doxazosin and -7.45 (0.6) (both P < 0.001) for alfuzosin. The respective mean change from baseline in irritative symptoms was -3.5 (0.2) and -2.8 (0.3) (both P < 0.001). The differences between the treatment groups were statistically significant in favour of doxazosin (total IPSS, P = 0.036; irritative symptoms, P = 0.049). The improvement between groups was also significantly different for postvoid residual urine volume, at -29.19 (8.6) and + 9.59 (8.9) mL for doxazosin and alfuzosin, respectively (P = 0.002). Improvements in mean and maximum urinary flow rates were similar for both treatments, at + 1.5 and + 1.2, and + 2.8 and + 2.5 mL/s, respectively. Doxazosin and alfuzosin were both well tolerated, with most all-cause adverse events reported as mild or moderate. CONCLUSIONS: The mean doses of doxazosin and alfuzosin used in this study were not equipotent. Doxazosin 6.1 mg/day produced significantly greater improvements than alfuzosin 8.8 mg/day in total and irritative urinary symptom scores and postvoid residual urine volume in men with moderate to severe LUTS. Changes in maximum and mean flow rates were comparable. Doxazosin and alfuzosin were both well tolerated.     

Clinical guidelines for male lower urinary tract symptoms and benign prostatic hyperplasia

The present article is the abbreviated English translation of the Japanese guidelines for male lower urinary tract symptoms and benign prostatic hyperplasia updated as of the end of 2016. The target patients are men aged >50 years complaining of lower urinary tract symptoms, with or without benign prostatic hyperplasia, and the target readers are non‐urological general physicians and urologists. Mandatory assessment for general physicians is medical history, physical examination, urinalysis and measurement of serum prostate‐specific antigen. Additional mandatory assessment for urologists is symptoms and quality of life assessment by questionnaires, uroflowmetry, residual urine measurement, and prostate ultrasonography. Nocturia requires special attention, as it can result from nocturnal polyuria and/or sleep disturbance rather than lower urinary tract disorders. Functional lower urinary tract disorders with or without benign prostatic hyperplasia are primarily managed by conservative therapy and medications, such as α₁‐blockers and phosphodiesterase‐type 5 inhibitors. Use of other medications or combination pharmacotherapy is to be reserved for urologists. 5α‐Reductase inhibitors and anticholinergics or β3 agonists are indicated for men with enlarged prostates and overactive bladder symptoms, respectively. Surgical intervention for bladder outlet obstruction is considered for persistent symptoms or benign prostatic hyperplasia‐related comorbidities. Surgical modalities should be optimized by the patient's characteristics, performance of equipment and the surgeon's experience.     

Relationship between lower urinary tract symptoms and serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia

Study Type – Aetiology (case series)
Level of Evidence 4

OBJECTIVES

To investigate a possible association between the severity of lower urinary tract symptoms (LUTS) and the serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia (BPH) that underwent surgery for severe benign prostatic obstruction.

PATIENTS AND METHODS

In all, 127 selected men with symptomatic BPH attending our urology clinic were recruited. The clinical conditions of BPH were assessed by digital rectal examination, serum prostate‐specific antigen (PSA) determination, International Prostate Symptom Score (IPSS), transrectal ultrasonography and maximum urinary flow rate (Q_max) value at uroflussimetry. Before surgery, we measured the serum concentrations of total testosterone (TT) and free testosterone (FT), oestradiol, prolactin, luteinizing hormone and follicle‐stimulating hormone. We excluded men with endocrine diseases, those with prostate disease who were receiving antiandrogen therapy and those with psychological diseases. The relationships between the IPSS score and serum sex hormone levels were determined.

RESULTS

The final study population consisted of 122 men (mean age of 70.66 years), as five were excluded (three due to incomplete evaluation and two who were diagnosed with prostate cancer). On statistical analysis, the total IPSS was significantly associated with age (r= 0.405, P < 0.001) and TT (r= 0.298, P= 0.020) but not with FT or the serum levels of the other sex hormones. The serum levels of testosterone and IPSS did not correlate with prostate volume and Q_max. PSA level and age correlated with prostate volume (r= 0.394, P < 0.001; r = 0.374, P < 0.001, respectively). We distinguished two subgroups of patients: the first group of 40 men with an IPSS of <19 and the second group of 82 with an IPSS of >19, and we evaluated the median levels of TT in each group. There was an increased risk of LUTS in men with a greater serum concentration of TT (P= 0.042), although the mean TT level was in the normal range.

CONCLUSIONS

In the present study, the severity of LUTS was associated with age and serum levels of TT but only age correlated with the measures of BPH, especially prostate volume. The potential effects of testosterone on LUTS may well be indirect. Additional large studies are needed to confirm these preliminary results.     

Influence of hypertension on lower urinary tract symptoms in benign prostatic hyperplasia

AIM: To clarify the influence of hypertension on lower urinary tract symptoms (LUTS) we examined the relationship between blood pressure, LUTS, and the effect of terazosin on LUTS in patients with benign prostatic hyperplasia (BPH). METHODS: The subjects were patients who had LUTS and BPH. They were treated with terazosin (1 mg, twice-a-day) for 12 weeks. Calculation of the International Prostate Symptom Score (IPSS), measurement of blood pressure, and uroflowmetry were performed before and after 12 weeks of therapy. Patients were divided into a normotensive (NT) group and a hypertensive (HT) group at the time of first examination. RESULTS: The IPSS for urinary frequency and nocturia in BPH-HT patients (n = 21; mean age, 71 years) were significantly higher than those in the BPH-NT patients (n = 21; mean age, 69 years) before the administration of terazosin. The total IPSS the BPH-HT patients was also significantly higher than that of the BPH-NT patients. There were no differences of uroflowmetric parameters between the two groups. After 12 weeks of therapy, systolic and diastolic blood pressure decreased in the BPH-HT patients, but not in the BPH-NT patients. However, the systolic pressure of the BPH-HT patients was still significantly higher than that of the BPH-NT patients. The score for each IPSS parameter decreased in both groups, but the difference of the score between the two groups increased. CONCLUSION: Hypertension may worsen LUTS and may decrease the improvement of symptoms by terazosin.     

Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 ml or greater

PURPOSE: We examined data from the Medical Therapy of Prostatic Symptoms trial to determine the relationship between baseline TPV and the effect of medical therapy in men with LUTS secondary to BPH. MATERIALS AND METHODS: A total of 3,047 patients with LUTS were randomized to placebo, 4 to 8 mg doxazosin, 5 mg finasteride or the combination of doxazosin and finasteride. Average treatment duration was 4.5 years The primary outcome was time to overall clinical progression of BPH, defined as a confirmed 4 point or greater increase in AUA SS, acute urinary retention, incontinence, renal insufficiency or recurrent urinary tract infection. Secondary outcomes were the need for invasive therapy for BPH, and changes in AUA SS and the maximum urinary flow rate with time. TPV was measured by transrectal ultrasound at baseline and study end. RESULTS: In patients with a small prostate (baseline TPV less than 25 ml) combination therapy was no better than doxazosin alone for decreasing the risk of clinical progression of BPH and need for invasive therapy as well as improving AUA SS and the maximum urinary flow rate. However, in patients with moderate size (25 to less than 40 ml) or enlarged (40 ml or greater) glands combination therapy led to a clinical benefit in these outcomes that was superior to that of doxazosin or finasteride. CONCLUSIONS: Combination therapy with doxazosin and finasteride led to a greater decrease in the risk of clinical progression of BPH than either drug alone in patients with LUTS with a baseline TPV of 25 ml or greater.     

联合应用坦索罗辛和托特罗定治疗男性顽固性下尿路症状的临床研究

目的:探讨及对比联合应用高选择性α受体阻滞剂(坦索罗辛)和M受体阻滞剂(托特罗定)及单用高选择性α受体阻滞剂治疗男性顽固性下尿路症状的临床疗效及安全性。方法:2009年4月至2009年12月期间收集我院184例顽固性下尿路症状(LUTS)的男性前列腺增生患者,病程4周至2年。所有患者均为应用高选择性α受体阻滞剂(坦索罗辛)0.2 mg,1次/d,治疗1周后LUTS症状无改善。入选病例随机分成2组,其中坦索罗辛组89例继续应用坦索罗辛0.2 mg,1次/d,治疗4周;联合治疗组95例联合应用高选择性α受体阻滞剂(坦索罗辛)和M受体阻滞剂(托特罗定),给予坦索罗辛0.2 mg 1次/d+托特罗定2 mg 2次/d,治疗4周。分组治疗前后分别进行国际前列腺症状储尿期症状评分(储尿期IPSS)、生活质量评分(QOL)和最大尿流率(Qmax)检测,评估治疗后LUTS症状的改善情况。结果:坦索罗辛组储尿期IPSS、QOL总体评分分别由治疗前的(13.23±4.39)、(4.23±1.27)分下降到治疗后的(12.21±4.07)、(3.53±0.9)分,Qmax由治疗前的(12.31±8.39)ml/s上升到治疗后的(14.12±8.62)ml/s,与治疗前相比差异均无显著性(P>0.05)。联合治疗组储尿期IPSS、QOL总体评分分别由治疗前的(14.45±5.31)、(4.45±0.79)分降到治疗后的(6.56±2.03)、(2.34±0.73)分,Qmax由治疗前的(11.41±9.21)ml/s上升到治疗后的(15.52±8.35)ml/s,与联合治疗前相比差异均有显著性(P<0.01)。184例患者均无严重并发症出现。结论:联合应用坦索罗辛和托特罗定能明显缓解男性顽固性下尿路症状,改善患者的生活质量。未见严重不良反应和急性尿潴留发生。     

Efficacy of alfuzosin and sildenafil combination in male patients with lower urinary tract symptoms

Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are frequently encountered in ageing males. We compared the efficacy of alfuzosin 10 mg alone or in combination with sildenafil 50 mg in the treatment of LUTS due to benign prostatic hyperplasia. One hundred male patients older than 45 years were randomized to two groups containing 50 patients each; one group receiving alfuzosin 10 mg and the other group alfuzosin 10 mg combined with sildenafil 50 mg. International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Q(max)), prostate volume and post-void residual urine were evaluated. The mean age was 60.2 ± 17.8. Mean data of evaluated parameters in both groups at the end of 3rd month compared with baseline values are given respective order as; 5.1 (26.8%) and 5.8 (28.2%) points decreases in IPSS; 1.6 (41.1%) and 1.8 (45%) points decreases in QoL; and 3.4 (29.6%) and 3.4 (33%) points increases in Q(max) . The outcomes of our study cannot be interpreted in such a way to report that alpha blocker-PDE5 inhibitor combination has a better efficacy than alpha blocker treatment alone in patients with LUTS.     

Phosphodiesterase 5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a systematic review

Study Type – Therapy (systematic review)
Level of Evidence 1a What’s known on the subject? and What does the study add? Phosphodiesterase 5 inhibitors improve lower urinary tract symptoms (LUTS), however the maximum urinary flow rate is not significantly affected. Also, the underlying mechanism of action of these drugs on LUTS is not well understood. This systematic review confirms the findings of the individual studies included; however the high heterogeneity between them precluded meta‐analysis and further recommendations.

OBJECTIVE

? To review the evidence in support of the effectiveness of phosphodiesterase 5 inhibitors in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH).

METHODS

? Relevant studies were identified by performing a literature search using MEDLINE® and The Cochrane Library®. The criteria used during the search included randomized, placebo‐controlled trials of treatment for LUTS secondary to BPH using the International Prostate Symptom Score as an outcome measure.

RESULTS

? Four trials that included a total of 1928 patients met the inclusion criteria. All four studies showed a statistically significant difference in the International Prostate Symptom Score, quality of life and erectile function in favour of phosphodiesterase 5 inhibitors. ? No study showed a statistically significant improvement of the maximum urinary flow. ? Meta‐analysis of the results was not possible because of heterogeneity across the studies.

CONCLUSIONS

? Phosphodiesterase 5 inhibitors used in the clinical setting can significantly improve LUTS secondary to BPH, erectile function and quality of life. Maximum urinary flow improvement is not statistically significant. ? Future research should focus on pathophysiological principles and cost analysis.