Efficacy and safety of tamsulosin hydrochloride compared to doxazosin in the treatment of Indonesian patients with lower urinary tract symptoms due to benign prostatic hyperplasia

AIM: The objective of the study was to compare the efficacy and safety of tamsulosin hydrochloride and doxazosin in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). METHODS: The safety and efficacy of tamsulosin (0.2 mg) and doxazosin (2 mg) was determined after once daily administration for 6 weeks in an open-label, randomized, multicenter study of 101 men with BPH. The International Prostatic Symptom Score (IPSS), maximal urinary flow rates (Qmax), average urinary flow rates (Qave) and residual urine were determined at baseline and again at 6 weeks as efficacy parameters. The primary parameters used for safety evaluation were vital signs (blood pressure and heart rate) and adverse events. The number of patients with a clinically significant response to treatment with tamsulosin or doxazosin was determined and defined as those with >20% improvement from the baseline Qmax or >20% decrease in total IPSS. RESULTS: The total IPSS decreased significantly in both the tamsulosin and doxazosin groups compared to baseline. There was a significant difference in the decrease in total IPSS between two groups. Qmax, Qave and residual urine significantly improved only in the tamsulosin group. There were no significant differences in systolic blood pressure, diastolic blood pressure or heart rate profile in the tamsulosin group; however, doxazosin resulted in a significant difference in systolic and diastolic blood pressure. Tamsulosin was well tolerated; only three patients (6%) in the tamsulosin group reported an adverse event (dizziness) while 11 patients (22%) in the doxazosin group reported an adverse event (dizziness), one of whom withdrew from the study. CONCLUSIONS: Tamsulosin was shown to be more effective than doxazosin in the treatment of LUTS due to BPH.     

Stromal/epithelial interactions of murine prostatic cell lines in vivo: a model for benign prostatic hyperplasia and the effect of doxazosin on tissue size

BACKGROUND: One of the major constraints in elucidating the mechanisms involved in the etiology of benign prostatic hyperplasia (BPH) is the lack of suitable model systems that are readily manipulable in vitro and in vivo. To address this issue, we have used murine prostatic cell lines to establish a novel in vivo model for studying prostatic cell interactions. METHODS: Luminal, basal, and smooth muscle (SM) cell lines were inoculated alone or in combinations under the renal capsule of intact or castrated male mice, and the growth and composition of prostatic tissue in the absence or presence of doxazosin was determined. RESULTS: Both the luminal and basal cell lines reconstituted prostatic tissue if co-inoculated under the renal capsule with normal SM cells, whereas none of the lines formed significant tissue when inoculated alone. Luminal cells produced and secreted prostatic secretory products. The growth of prostatic tissue formed from co-inoculation of basal and SM cells was androgen responsive. In addition, a significant reduction in prostatic tissue was noted in animals treated with doxazosin. CONCLUSION: We have established an in vivo model that uses prostatic epithelial and SM cell lines for investigating cellular interactions between epithelial and SM cells that regulate prostatic growth and function. This model will be useful for delineating the mechanisms by which prostatic cells interact and in determining the efficacy of new approaches aimed at interfering with prostatic stromal/epithelial interactions that result in abnormal cellular proliferation.     

Long-term (4 year) efficacy and tolerability of doxazosin for the treatment of concurrent benign prostatic hyperplasia and hypertension

BACKGROUND: The alpha1-adrenoceptor antagonist doxazosin has proved successful in treating patients with concurrent benign prostatic hyperplasia (BPH) and hypertension in short-term studies. However, both conditions are chronic and may worsen over time. The aim of this study was, therefore, to examine the tolerability and efficacy of doxazosin in the long-term treatment of concurrent BPH and hypertension. METHODS: This study was a longitudinal extension of earlier double-blind trials. Patients were enrolled into the study on a rolling basis. From a total of 178 BPH patients with hypertension enrolled into the study, 28 had reached 48 months of open-label treatment with doxazosin at the time of the final data cutoff. RESULTS: Treatment with doxazosin resulted in sustained benefits for BPH patients over the whole study period, with significant improvements in the severity (12.2%, P < 0.001) and bothersomeness (13.2%, P < 0.001) of BPH symptoms, and in the maximum urinary flow rate (26.6%, P < 0.05) from baseline to the end of the 4-year period. There was also a significant and sustained reduction in diastolic blood pressure. The efficacy of doxazosin treatment for both BPH and hypertension was maintained over the 4-year period, despite the tendency of these conditions to worsen with time. Comparison of adverse events in patients with long- and short-term hypertension and BPH demonstrates that the safety of doxazosin is not altered during long-term therapy. CONCLUSIONS: This study demonstrates that doxazosin appears to be well tolerated and efficacious in the long-term management of concurrent BPH and hypertension.     

The clinical efficacy and tolerability of doxazosin standard and gastrointestinal therapeutic system for benign prostatic hyperplasia

The therapeutic goal of treating benign prostatic hyperplasia (BPH) through early detection and effective therapy is to relieve the symptoms, improve patients' quality of life, decrease postvoid residual urine volume, and prevent the associated morbidity when the condition remains untreated. Alpha1-adrenoreceptor antagonists, e.g. doxazosin, terazosin, tamsulosin and alfuzosin, relax the bladder outlet to improve urinary flow, by reducing prostatic smooth muscle tone through the blockade of sympathetic adrenergic receptors. Doxazosin gastrointestinal therapeutic system (GITS) is a controlled-release formulation developed to enhance the pharmacokinetic profile of the drug while simultaneously minimizing possible adverse effects and reducing the need for dose titration. While both doxazosin standard and GITS are indicated for hypertension, they are also useful in the pharmacologically or naturally normotensive patient with BPH. In a cross-over trial comparing doxazosin GITS and tamsulosin, doxazosin gave a significantly greater improvement from baseline in symptoms. Results from recent trials (e.g. Medical Therapy of Prostatic Symptoms, MTOPS) showed that doxazosin was significantly more effective than the 5alpha-reductase inhibitor finasteride in relieving lower urinary tract symptoms, irrespective of prostate volume. The MTOPS trial showed clearly that over the long term, the combination of doxazosin and finasteride was more effective than either agent alone in significantly improving symptoms and reducing the clinical progression of BPH. Both doxazosin standard and GITS are well-tolerated, long-term therapies that are equally effective in younger and older men, and not associated with causing sexual dysfunction.     

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.     

前列腺增生症手术前后雄性激素变化的研究

目的　为了研究、探讨前列腺增生症手术前后雄性激素的变化和对全身的影响。方法　 2 3例前列腺增生症病例分别在手术前 1周和手术后 2周 ,采集血清样本 ,以测定血清中T、FT、DHT浓度 :采用经膀胱耻骨上前列腺内腺体摘除术 ,观察手术前后病人雄激素的改变和性激素改变发生的一系列主诉症状。结果　在前列腺内腺体摘除手术前后 ,血清中T、FT、DHT存在着明显的差异 ,分别下降 34.4 5 % ,33.5 3% ,5 0 .4 1% ,以DHT下降尤为明显 (P <0 .0 0 1)。前列腺摘除术后由于体循环中主要的雄激素明显下降 ,病人有雄激素下降的临床症状。结论　前列腺内腺体摘除术以后血清中雄激素将发生明显的变化 ,对于这个变化临床上应引起重视     

Evaluation for Madigan's prostatectomy in patients with benign prostatic hyperplasia

Aim: To comparatively evaluate the efficacy and post-operative complications of the Madigan's prostatectomy(MPC) and suprapubic prostatectomy (SPPC). Methods: A total of 43 patients with benign prostatic hyperplasiawere divided into two groups: 21 underwent MPC and 22, SPPC. In all the patients, the international prostate symp-tom score (IPSS) and urinary pressure-flow studies were assessed before and 6 months after operation. The InternationalContinence Society (ICS) nomogram, Abrams-Griffiths (AG) number and linear passive urethral resistance relationanalysis (L-PURR) were used to diagnose and grade bladder outlet obstruction (BOO). The IPSS and the urodynamicparameters before and after operation, as well as the advantages and post-operative complications were recorded andcompared. Results: Patients of both the MPC and SPPC groups had a significant improvement in IPSS and urody-namic parameters. Obstruction was relieved in 81.0% of MPC and 86.4% of SPPC patients. MPC has the advantagesof the absence o     

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。     

Madigan前列腺增生切除术

为了提高前列腺增生症的手术治疗效果，采用Ｍａｄｉｇａｎ手术治疗前列腺增生症患者２５例。１５例尿道完整，１０例损伤尿道缝合修复；术后出血少、恢复快；随访４～２５个月，无尿道狭窄、尿失禁等并发症。对手术优点、术中注意事项及适应证的选择进行了讨论。     

前列腺结石与良性前列腺增生患者前列腺体积的相关性研究

目的探讨前列腺结石与前列腺增生症患者前列腺体积的相关性。方法回顾性分析本院2012年1月至2013年12月出院诊断为良性前列腺增生的患者392例,根据经直肠前列腺彩超结果将患者分为前列腺结石阴性组与阳性组,比较两组的年龄、前列腺特异性抗原(PSA)、前列腺总体积、内腺体积以及各经线之间有无差别。结果结石阴性组与结石阳性组前列腺总体积(TPV)、总体积宽径(TPV-b)、内腺体积宽径(TZV-b)差别有统计学意义(P0.05);结石阴性组与结石阳性组的年龄、内腺体积(TZV)、血清总PSA(TPSA)密度以及其他各经线差别无统计学意义(P0.05)。结论前列腺结石与前列腺增生程度存在一定的内在关系,结石有可能促进前列腺组织的增生。     

尿液前列腺素E2与良性前列腺增生伴有膀胱过度活动症相关性研究

目的:分析伴有或不伴有膀胱过度活动症(OAB)的良性前列腺增生(BPH)患者尿液前列腺素E2(PGE2)的浓度,确定PGE2是否与BPH继发的OAB相关。方法:86例因下尿路症状(LUTS)就诊的BPH患者根据OAB症状评分(OABSS)分为OAB组和非OAB组。同时选取34例无LUTS的50岁以上男性为对照组。检测这些研究对象的尿液PGE2浓度,并检测BPH患者的残余尿、最大尿流率、前列腺体积和前列腺特异性抗原,记录国际前列腺症状评分(IPSS)和OABSS评分。OAB组给予口服坦索罗辛(0.2mg,1次/d)和酒石酸托特罗定(2mg,2次/d),非OAB组只给予坦索罗辛(0.2mg,1次/d)治疗。PGE2浓度除以尿肌酐浓度为标准化的尿PGE2值。结果:对照组PGE2浓度均明显小于OAB组和非OAB组(P均0.05);OAB组PGE2浓度高于非OAB组(P0.05)。经过12周治疗后,OAB组PGE2浓度随着OAB症状的改善明显下降(P0.05),而非OAB组PGE2浓度无明显变化(P0.05)。相关性分析显示OAB组的IPSS储尿期评分、OABSS评分都和PGE2浓度无关(P均0.05)。结论:伴有OAB症的BPH患者尿液PGE2的浓度明显高于正常者和不伴有OAB的BPH患者,并随着OAB的改善而下降。尿PGE2可作为BPH患者OAB存在与否的生物标志。     

Health care-seeking behavior in benign prostatic hyperplasia patients

ObjectiveLower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) are highly prevalent in aging men and have a significant impact on the quality of life of patients. Moreover, BPH is progressive and can cause worsening symptoms and the risk of serious long-term morbidity. An efficient diagnostic approach is an essential beginning in the management of BPH; thus, we conducted this study to assess health care-seeking behaviour in BPH patients.Materials and MethodsWe recruited 101 patients with BPH which was defined as enlarged prostate with the exclusion of the possibility of prostate cancer between September 2007 and April 2008. All patients were proved to have an enlarged prostate as measured by ultrasonography. All patients completed two questionnaires: one is International Prostate Symptom Score (IPSS)/quality-of-life questionnaire, and the other one consists of principal reasons for patients to seek medical advice, the expectation for BPH treatments and the unwanted side effect of medical treatments.ResultsThe majority of patients (71.3%) reported that bothersome urinary symptoms were the principal reason they sought medical advice. Other reasons included fear of prostate cancer (8.9%), attendance through physical check-up (14.9%), and a request by family or friends (1.0%). Patients seeking advice due to bothersome urinary symptoms had an average IPSS of 6.2 higher than those attending for any other reasons. As for ranking attributes of therapies, about half of the patients (48.6%) were very concerned about the risks of long-term complications, namely acute urinary retention and surgery. Other preferences for treatments comprised prostate size decrease (24.8%) and avoidance of prostate cancer (24.8%).ConclusionBothersome urinary symptoms drive most BPH patients to consult a physician. When considering medical treatments for BPH, about half of the patients wish to reduce the risk of long-term complication, such as acute urinary retention and BPH-related surgery.     

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.     

镍钛记忆合金支架治疗前列腺增生症216例

目的 总结镍钛记忆合金网状支架治疗高龄、高危前列腺增生症的经验。方法 前列腺增生患者216例,年龄67-89(平均76.5)岁。置管前国际前列腺症状评分(IPSS)为(21.7±5.6)分、最大尿流(Qmax)(8.7±3.1)ml/s,剩余尿量(RU)(158±114)ml。在低位腰麻或硬膜外麻醉下置管,随访1年进行尿常规检查、IPSS、Qmax、RU测定、记录不适反应。结果 置管一次成功194例,2次成功18例,成功率为98％;平均置管时间:15～45min,平均住院时间:12d。多数患者术后有尿频、尿急、血尿等症状。置管后3年IPSS、Qmax、RU分别为:(13.7±4.1)、(14.8±4.5)ml/s和(38.0±21.0)ml。结论 镍钛合金网状支架可作为治疗高龄、高危前列腺增生症患者的首选方法。     

Early efficacy of silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

Objectives: To evaluate the early efficacy of the α_1A‐adrenoceptor selective drug, silodosin, for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Methods: A total of 68 patients with an International Prostate Symptom Score (IPSS) of ≧8 and a Quality of Life (QOL) index of ≧2 were included. Changes in the IPSS and QOL index were evaluated before and after 1, 2, 3, 4, 5, 6, 7, 14, and 28 days of twice daily oral administration of 4 mg silodosin. Next, changes in IPSS subscores as well as voiding, storage, and post micturition symptoms were assessed. Changes in total IPSS based on symptom severity were also determined. Results: Total IPSS and QOL index improved significantly from 19.38 ± 7.46, 4.68 ± 1.07 at baseline to 15.81 ± 7.40, 4.22 ± 1.30 at day 1. The subscores of voiding, storage, and post micturition symptoms were significantly decreased from 8.93 ± 3.95, 7.97 ± 3.88, and 2.49 ± 1.70 at baseline to 7.28 ± 4.09, 6.52 ± 3.47, and 2.02 ± 1.56 at day 1, respectively. This trend continued throughout the study. Regardless of severity, total IPSS were significantly decreased at day 1 and maintained throughout the study. Conclusions: Silodosin may be considered a promising treatment for benign prostatic hyperplasia/lower urinary tract symptom patients.     

腹腔镜下耻骨后腹膜外保留尿道的前列腺切除术

目的探讨腹腔镜下经耻骨后腹膜外保留尿道的前列腺切除术治疗大腺体前列腺增生症的可行性。方法自2006年1月至2007年1月对9例前列腺增生症的病人采用腹腔镜行耻骨后腹膜外前列腺切除术,病人年龄为(77.8±6.8)岁,范围为(62～83)岁。经直肠前列腺B超显示前列腺大小为(101.3±36.2)g,范围为(62～172)g,均无明显中叶增生。腹腔镜手术包括耻骨后腹膜外腔的建立、排列成倒U字形5个穿刺套管的放置、前列腺被膜的切开、增生腺瘤的切除、前列腺部尿道的保护及前列腺被膜的缝合等主要步骤。结果9例病人手术顺利,术中出血(190±160.6)ml,范围为(60～600)ml,手术时间为(174±59.8)min,范围为(90～240)min。术后恢复顺利,尿管拔除时间为(8.4±3.8)d。术后3月复查病人尿流率、国际前列腺症状评分(IPSS)评分、生活质量评分(QOL)等较术前明显好转。术前有性功能的4例病人术后性功能无损。结论对腺体大的前列腺增生症行腹腔镜下经耻骨后腹膜外行前列腺切除术是可行的,病人创伤小、恢复快、效果满意。     

Predictors of outcome in patients with benign prostatic hyperplasia maintained on alpha-blockers

Aim: To determine factors that could predict failure of medical treatment or the need for surgical intervention in patients with benign prostatic hyperplasia (BPH) who were maintained on alpha-blockers. Methods: 124 eligible patients aged 51–82 years (mean 66.8) with lower urinary tract symptoms attributable to BPH treated with alpha-blockers were included in the study. Initial assessments included a complete medical history, physical examination, blood biochemistry, serum prostate-specific antigen and urinalysis. Baseline symptoms were assessed by International Prostate Symptoms Score (IPSS) questionnaire, peak urine flow rate (Qmax) and post-void residual urine volume (PVR). Transrectal ultrasound (TRUS), prostate biopsy, cystoscopy and urodynamic study were carried out when indicated. Mean follow-up was 47.7 months. Baseline parameters were compared between the cohort of patients requiring surgical intervention and the remaining cohort who were still maintained on alpha-blockers. Results: Forty-four patients (35.5%) demanded surgical intervention despite treatment with alpha-blockers. Patients requiring surgical intervention had significantly worse baseline IPSS, quality-of-life score, Qmax and PVR when compared with those not requiring surgery. Risk analysis using binary logistic regression model showed that IPSS (odds ratio: 1.096; P = 0.001) and PVR (odds ratio: 1.006; P = 0.008) were independent predictors for surgical intervention. Receiver–operating characteristics curves further demonstrated that IPSS was slightly better than PVR as a single predictor. Kaplan–Meier cumulative risk analyses showed that patients with baseline IPSS ≥ 14 or PVR ≥ 100 mL were more likely to require subsequent surgical intervention than their counterparts. Conclusions: In patients with BPH who were maintained on alpha-blockers, baseline IPSS and PVR were two useful independent predictors for failure of medical treatment and the need for surgical intervention.     

Changes in serum prostate-specific antigen following prostatectomy in patients with benign prostate hyperplasia

PURPOSE: To investigate how prostatectomy for patients with benign prostate hyperplasia (BPH) affected the serum prostate-specific antigen (PSA) levels. METHODS: In 193 patients who underwent prostatectomy for BPH, serum PSA levels were measured before and three months after the operation. The total prostate weight measured by transrectal ultrasonography (TRUS) and the weight of the surgical specimen were examined in relation to the pretreatment PSA value and the changes in PSA levels after the operation. RESULTS: The transition zone volume measured by TRUS could well estimate the weight of the surgical specimen in patients who underwent subcapsular prostatectomy and transurethral resection of the prostate. The concentration of preoperative serum PSA showed a significant correlation with the prostatic volume and with the transition zone volume. Removal of 1 g of BPH tissue reduced serum PSA levels by an average of 0.18 ng/mL. The change in serum PSA levels after the prostatectomy correlated with the total prostatic gland volume and with the transition zone volume. CONCLUSIONS: The elevated PSA levels in patients with BPH were caused by the enlargement of the transition zone. After the resection of the adenoma, PSA levels should be expected to decrease to the normal range.     

良性前列腺增生细胞因子变化的研究

目的　探讨与细胞增生有关的细胞因子与BPH发生的相关性。方法　人前列腺分对照组 (正常前列腺 )和实验组 (良性前列腺增生 )。常规组织学染色观察组织形态的变化 ,免疫组织化学方法观察bFGF ,VEGF和EGFR在BPH中的改变。结果　BPH的病理变化呈多类型化。BPH的组织中bFGF和VEGF在间质中明显增加 ;EGFR在腺上皮和间质细胞中都增加明显。结论　在BPH的组织异常增殖中 ,间质的增殖可能与bFGF和VEGF的分泌增多关系密切 ,而EGFR与间质和腺上皮的异常增殖均有关。