Bifluranol in the treatment of benign prostatic hyperplasia (BPH)

Bifluranol, a fluorinated bibenzyl drug with antiandrogenic properties has been studied for its efficacy in the treatment of benign prostatic hyperplasia. Thirty five patients with bladder outflow obstruction received either Bifluranol 1.5 mg orally, t.d.s. or placebo in a double-blind trial. After twelve weeks there was improvement in symptoms of flow, urinary stream (p <0.01) and frequency (p <0.05) in the Bifluranol treated group. A significant reduction in residual urine volume was noted in the active treated group (p <0.05) but mean and peak urine flow rates, voided volume and prostate volume did not reach statistical significance. It is concluded that Bifluranol has a measurably beneficial effect in urinary outflow obstruction due to BPH and further investigative studies with this drug are in progress.     

Non-inferiority of silodosin to tamsulosin in treating patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH)

Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Silodosin administered by 4 mg twice daily is as effective as tamsulosin 0.2 mg daily in treating patients with LUTS associated with BPH. Relative to tamsulosin, silodosin has less cardiovascular side effects as judged by the minimal changes of blood pressure and pulse rats after treatment.

OBJECTIVE

? To test the hypothesis that the efficacy of silodosin would not be inferior to tamsulosin in treating patients with lower urinary tract symptoms associated with benign prostate hyperplasia (BPH).

PATIENTS AND METHODS

? At nine medical centres, 209 patients with an International Prostate Symptom Score (IPSS) of ≥13 were randomized to silodosin (4 mg twice daily) or tamsulosin (0.2 mg once daily) for 12 weeks. ? The primary efficacy measure was the mean change from baseline to endpoint in IPSS. ? The non‐inferiority margin of the IPSS change was set at 1.0. ? Secondary efficacy measures included change in maximal urinary flow rate (Q_max) and health‐related quality of life (HRQL) score.

RESULTS

? Of the 170 (81.3%) patients who completed the study, 86.2% in the silodosin group vs 81.9% in the tamsulosin group achieved a ≥25% decrease in IPSS (P= 0.53). ? The mean difference (silodosin minus tamsulosin) in IPSS change from baseline was ?0.60 (95% confidence interval ?2.15, 0.95), inferring the non‐inferiority of silodosin to tamsulosin. ? The mean changes in the Q_max and HRQL score from baseline were comparable between the groups (both, P > 0.05). Although patients receiving silodosin had a significantly higher incidence of abnormal ejaculation (9.7% vs tamsulosin 1.0%, P= 0.009), only 1.9% discontinued treatment. ? Tamsulosin treatment resulted in a significant reduction in mean systolic blood pressure (?4.2 mmHg, within‐group P= 0.004) relative to the negligible change of silodosin (?0.1 mmHg, within‐group P= 0.96)

CONCLUSION

? The trial shows the non‐inferiority of silodosin 4 mg twice daily to tamsulosin 0.2 mg once daily in patients with symptoms of BPH.     

Effects of Bowman-Birk inhibitor concentrate (BBIC) in patients with benign prostatic hyperplasia

BACKGROUND: The Bowman-Birk inhibitor is a soybean-derived protease inhibitor that has anti-inflammatory and anticarcinogenic activities. METHODS: A Phase I trial of Bowman-Birk inhibitor concentrate (BBIC) in 19 male subjects with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) has been performed. RESULTS: The results of the trial indicated that there was no dose-limiting toxicity of BBIC. There was a statistically significant decrease in serum PSA levels in all BBIC-treated patients. Some BBIC-treated patients exhibited a relatively large reduction in serum PSA levels, ranging up to a 43% reduction. There was also a statistically significant decrease in serum triglyceride levels and a decrease in prostate volume in the treated patients. The scores recorded in response to a urinary symptom questionnaire indicated improved urinary activities in the BBIC-treated patients; however, the control subjects exhibited similar improvements in urinary activities during the course of the trial. CONCLUSIONS: The data obtained in this trial, particularly the data suggesting that BBIC treatment may lead to reduced serum PSA levels and reduced prostate volumes, suggest that a Phase II clinical trial of BBIC for the therapy of BPH is warranted.     

Three-dimensional measurement and analysis of benign prostatic hyperplasia

BackgroundThe volume and thickness of intravesical prostatic protrusion and other characteristics of benign prostatic hyperplasia have not been investigated. We determine the effects of age and prostate volume on anatomical features of benign prostatic hyperplasia using three-dimensional measurement in this study.MethodsThis retrospective study included a total of 98 patients with benign prostatic hyperplasia. Three-dimensional models of prostate, central gland, peripheral zone, intravesical prostatic protrusion, prostatic urethra and bladder were reconstructed according to pelvic T2-weighted magnetic resonance imaging of these patients. The models were used to measure the intravesical prostatic protrusion volume, intravesical prostatic protrusion thickness, intravesical prostatic protrusion index, intravesical prostatic protrusion, prostate volume, peripheral zone volume, peripheral zone thickness, peripheral zone index, prostatic urethra thickness, the angle and distance of distal prostatic urethra with regard to coronal plane and sagittal plane and so on.ResultsIntravesical prostatic protrusion volume, intravesical prostatic protrusion thickness and peripheral zone volume of prostate volume >80 mL group were significantly higher than these in prostate volume <80 mL group (P<0.001, 0.01, 0.01, respectively). These parameters significantly increased with age (P<0.001, 0.01, 0.05, respectively). Peripheral zone index was significantly lower of prostate volume >80 mL group than these in prostate volume <80 mL group (P<0.05). Peripheral zone index significantly decreased with age (P<0.01). Intravesical prostatic protrusion index had no significant difference in all age groups. Peripheral zone thickness and prostatic urethra thickness had no significant difference in all groups. The distance and angle of distal prostatic urethra prostatic urethra with regard to coronal plane were significantly higher than these with regard to sagittal plane (both P<0.001).ConclusionsThe rearward slope of the prostatic urethra is greater than the left or right offset during the process of benign prostatic hyperplasia. Three-dimensional measurement provides good supports for further clinical and scientific research.     

Critical review of lasers in benign prostatic hyperplasia (BPH)

? Laser treatment of benign prostatic hyperplasia has challenged transurethral resection of the prostate (TURP) due to advances in laser technology, better understanding of tissue-laser interactions and growing clinical experience. ? Various lasers have been introduced including neodymium: yttrium aluminium garnet (YAG), holmium (Ho):YAG, potassium titanyl phosphate:YAG, thulium(Tm) and diode laser. Based on the different wave-length dependent laser-prostatic tissue interactions, the main techniques are coagulation, vaporization, resection and enucleation. ? The present review aims to help urologists to distinguish and to critically evaluate the role of different laser methods in the treatment by using an evidence-based approach. It also details further evidence for use in specific patient groups (in retention, on anticoagulation) and addresses the issues of cost and learning curve. ? Coagulation-based techniques have been abandoned; holmium ablation/resection of the prostate has been superseded by the enucleation technique Ho-laser enucleation of the prostate (HoLEP). The short-term efficacy of the emerging laser treatments such as diode and Tm prostatectomy has been suggested by low quality studies. HoLEP and photoselective vaporization of the prostate (PVP) represent valid clinical alternatives to TURP. HoLEP is the most rigorously analysed laser technique with durable efficacy for any prostate size and low early and late morbidity. PVP has grown in acceptance and popularity but long-term results from high quality studies are pending.     

Current role of lasers in the treatment of benign prostatic hyperplasia (BPH)

OBJECTIVE: Evaluate the current role of lasers in the treatment of benign prostatic hyperplasia (BPH). METHODS: The results of a MEDLINE search for randomised trials and case series of the last 5 yr and published review articles were analysed for the safety and efficacy of neodymium:yttrium aluminum garnet (Nd:YAG), potassium-titanyl-phosphate (KTP), and holmium (Ho):YAG laser prostatectomy. The analysis includes 12 reports on randomised clinical trials, 2 comparative studies, 10 review articles, and a total of >5000 patients. RESULTS: Laser treatment of BPH has evolved from coagulation to enucleation. Blood loss is significantly reduced compared with transurethral resection and open prostatectomy. Visual laser ablation of the prostate and interstitial laser coagulation cause coagulative necrosis with secondary ablation. Long postoperative catheterisation, unpredictable outcomes, and high reoperation rates have restricted the use of these techniques. Ablative/vaporising techniques have become popular again with the marketing of new high-powered 80-W KTP and 100-W Ho lasers. Vaporisation immediately removes obstructing tissue. Short-term results are promising, but large series, long-term results, and randomised trials are lacking. Holmium laser enucleation (HoLEP) allows whole lobes of the prostate to be removed, mimicking the action of the index finger in open prostatectomy. Prostates of all sizes can be operated on. It is at least as safe and effective as transurethral resection of the prostate and open prostatectomy, with significantly lower morbidity. It is the only laser procedure that provides a specimen for histologic evaluation. CONCLUSIONS: HoLEP appears to be a size-independent new "gold standard" in the surgical treatment of BPH.     

The efficacy and safety of dutasteride and finasteride in patients with benign prostatic hyperplasia: a systematic review and meta-analysis

BackgroundAlthough the efficacy and safety of monotherapy in the treatment of benign prostatic hyperplasia (BPH) have been established clinically, the efficacy and safety of dutasteride and finasteride have not been compared. The aim was to systematically evaluate the efficacy and safety of the two drugs in the treatment of BPH to provide medical evidence for clinical treatment.MethodsA search of relevant articles was conducted using the electronic databases PubMed, Embase, Medline, Cochrane Library, China Academic Journals Full-text Database (CJFD), Chinese Science and Technology Journal Database (VIP) and Wanfang Database. Randomized controlled trials (RCTs) comparing the efficacy of finasteride (control group) with that of dutasteride (experimental group) in the treatment of BPH with respect to the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), prostate volume (PV), quality of life (QOL), serum prostate-specific antigen (PSA) level and adverse drug reactions (ADRs) after medication were strictly evaluated and considered for inclusion. Rev Man 5.4 software was used for the meta-analysis.ResultsA total of 8 RCTs were included, with a total of 2,116, patients. The meta-analysis showed that compared with finasteride, dutasteride can effectively improve the Qmax of patients with BPH [mean difference (MD) =0.32; 95% confidence interval (CI): (0.01, 0.63); P=0.04]. There was no significant difference in reducing IPSS [MD =0.13; 95% CI: (−0.55, 0.82); P=0.70], improving PV [MD =−1.25; 95% CI: (−3.30, 0.79); P=0.23], reducing QOL [MD =−0.44; 95% CI: (−0.93, 0.05); P=0.08] and serum PSA level [MD =−0.04; 95% CI: (−0.15, 0.07); P=0.50], and the occurrence of ADRs [relative risk (RR) =−0.01; 95% CI: (−0.05, 0.04); P=0.72], there was no significant difference.DiscussionDutasteride is better than finasteride in improving the Qmax of patients with BPH. There was no statistically significant difference in symptoms, PV, PSA, QOL, or adverse reactions. Dutasteride is an effective and safe treatment for BPH. Due to the limitations of the methodological quality and sample size of the included studies, this conclusion needs to be verified by stratified RCTS with high volumes and long follow-up times.     

Association of TERT gene polymorphisms with clinical benign prostatic hyperplasia in a Chinese Han population of the Northwest region

BackgroundTo investigate the association between single nucleotide polymorphisms (rs10078761, rs12696304, rs2853669, rs16847897, rs2736100, rs10069690) of telomerase gene (TERT) and the risk clinical benign prostatic hyperplasia (BPH) in a Chinese Han population of the Northwest region.MethodsA total of 150 BPH patients and 150 healthy older males from the northwest Chinese Han population were included in this study. The sample size for this unmatched case-control study was estimated by the look-up table method. Meanwhile, the general information and disease data of patients were collected. Age was only collected in healthy control subjects for statistical correction. Genotypes were detected using a multiplex PCR + ligase detection reaction (LDR). Typing results and clinical data were statistically analyzed using multiple linear regression and logistic regression. Pearson correlation was used for Hardy-Weinberg equilibrium.ResultsThe included population is in Hardy-Weinberg equilibrium. There was no significant association between SNP and the risk of BPH by correlation analysis. However, 4 haplotypes (TCTGGT, TCTGTC, TGCCTC, and TGTGTC) were identified as risk factors of BPH by haplotype analysis. The SNP rs2853669 is an independent risk factor for smooth muscle type of hyperplasia. Besides, rs2736100, rs10078761, and rs10069690 which are in linkage disequilibrium are associated with the severity of BPH.ConclusionsPolymorphism of the TERT gene determines the different disease development and pathological manifestations of BPH in the Chinese Han population the Northwest region.     

The value of power Doppler imaging to predict the histologic components of benign prostatic hyperplasia

BACKGROUND: The response of symptoms caused by benign prostate hypertrophy (BPH) to alpha blockade is related to the area density of the smooth muscle of the prostate. If this density could be determined by ultrasound examination, ultrasound might be useful in predicting the efficacy of alpha-blocker therapy. In this study, various ultrasonographic parameters obtained by transrectal method (TRUS) were compared with histologically measured components. METHODS: Before surgery, ultrasonic power Doppler imaging (PDI) of the prostate was performed using a transrectal probe. The volume of total prostate, transition zone (TZ), and the presumed circle area ratio (PCAR) [1,2] were calculated. Pulsatile blood flow was recorded, and the resistive index (RI) was calculated. Based on the serum concentration of total prostate specific antigen (PSA), ratio of PSA to prostate volume (PSAD), and ratio of PSA to TZ (PSAT) were calculated. Prostate tissues were obtained from 26 patients undergoing transurethral resection, suprapubic prostatectomy, or radical cystectomy, and were analyzed by quantitative morphometry. Computer image analysis was used to determine the mean area densities of the smooth muscle (SM), connective tissue (CT), glandular epithelium (GE) and lumen (GL), and vascular lumen (V). Correlations between ultrasonographic parameters and morphometric data were studied. RESULTS: On microscopic examination, the specimens showed a wide variety, ranging from normal prostate to typical glandular hyperplasia. There was a correlation between RI and the ratios of the four components (SM: r = -0.42 P = 0.034; CT: r = -0.42 P = 0.030; GE: r = 0.42 P = 0.032; GL: r = 0.46 P = 0.018). However, correlations between the other five transrectal parameters and the composition of the prostate were not so clear. This may have been because the blood vessels are compressed within the surgical capsule together with the urethra. CONCLUSIONS: The present study demonstrates that when RI is calculated by PDI, it can be quite useful for predicting component ratios, thereby making it possible to predict the therapeutic efficacy of alpha-blockers in individual patients.     

Transurethral ethanol ablation of the prostate (TEAP): an effective minimally invasive treatment alternative to traditional surgery for symptomatic benign prostatic hyperplasia (BPH) in high-risk comorbidity patients

Objective  To evaluate the efficacy and safety of transurethral ethanol ablation of the prostate (TEAP) for patients with symptomatic benign prostatic hyperplasia (BPH) and high-risk comorbidities. Materials and methods  Thirty-six patients (mean age 77.3 years) with symptomatic BPH or persistent urinary retention were assessed at baseline and at 3, 6, and 12 months after treatment. All patients were affected by comorbidities (cardiovascular, respiratory, hematologic, neoplastic, dysmetabolic diseases, or coagulation disorders). Baseline evaluation was achieved by the International Prostate Symptom Score (IPSS) and quality of life (QoL) score, prostate-specific antigen (PSA), prostate transrectal ultrasound (TRUS), and the maximum peak flow rate with evaluation of post-voiding residual urine volume (PVR). Treatment was performed by injecting dehydrated ethanol at a rate correlated to prostate volume into the prostate. The primary end-point for response was ≥80% improvement of the maximum peak flow rate and significant reduction of the PVR; secondary end-points included symptom improvement (≥40% reduction in IPSS and QoL scores). Statistical analysis was carried out with Pearson’s Chi-square test and the non-parametric Wilcoxon test with an assigned statistical significance at P < 0.05. Results  During the active follow-up period, we observed a statistically significant decrease of the baseline at the end of the study in the total IPSS score and in the QoL score. The mean peak flow rate improved from 6.0 ± 2.40 ml/min to 15.2 ± 0.14 ml/min (P < 0.001), while the PVR decreased from a baseline value of 290.6 ± 14.14 ml to 4.2 ± 14.10 ml (P < 0.001). Conclusion  We found that TEAP is a safe minimally invasive treatment, which significantly improves voiding dysfunctions in patients with symptomatic BPH.     

Serenoa repens monotherapy for benign prostatic hyperplasia (BPH): an updated Cochrane systematic review

What's known on the subject? and What does the study add? For the past 30 years Serenoa repens has become a widely used phytotherapy in the USA and in Europe, mostly because of positive comparisons to α‐blockers and 5α‐reductase inhibitors. During the last 4 years we have seen two very high quality trials comparing Serenoa repens to placebo and up to 72 weeks' duration. These trials found Serenoa repens no better than placebo, even (in one trial) at escalating doses.

OBJECTIVE

• ? To estimate the effectiveness and harms of Serenoa repens monotherapy in the treatment of lower urinary tract symptoms (LUTS) consistent with benign prostatic hyperplasia (BPH).

MATERIALS AND METHODS

• ? We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and other sources through to January 2012 to identify randomised trials.
• ? Trials were eligible if they randomised men with symptomatic BPH to receive Serenoa repens extract monotherapy for at least 4 weeks in comparison with placebo, and assessed clinical outcomes and urodynamic measurements.
• ? Our primary outcome was improvement in LUTS, based on change in urological symptom‐scale scores.

RESULTS

• ? In all, 17 randomised controlled trials (N= 2008) assessing Serenoa repens monotherapy (typically 320 mg/day) vs placebo met inclusion criteria, although only five reported American Urological Association Symptom Index (AUASI) or International Prostate Symptom Scores (IPSS). Trial lengths ranged from 4 to 72 weeks. The mean age of all enrolees was 64.3 years and most participants were of White race. The mean baseline total score was 14 points, indicating moderately severe symptoms. In all, 16 trials were double blinded and adequate treatment allocation concealment was reported in six trials.
• ? In a meta‐analysis of three high quality long‐to‐moderate term trials (n= 661), Serenoa repens therapy was no better than placebo in reducing LUTS based on the AUASI/IPSS (weighted mean difference [WMD]?0.16 points, 95% confidence interval [CI]–1.45 to 1.14) or maximum urinary flow rate (Q_max; WMD 0.40 mL/s, 95% CI ?0.30 to 1.09). Based on mostly short‐term studies, Q_max measured at study endpoint were also not significantly different between treatment groups (WMD 1.15 mL/s, 95% CI ?0.23 to 2.53) with evidence of substantial heterogeneity (I² 58%).
• ? One long‐term dose escalation trial (72 weeks) found double and triple doses of Serenoa repens extract did not improve AUASI compared with placebo and the proportions of clinical responders (≥3 point decrease in the AUASI) were nearly identical (43% vs 44% for Serenoa repens and placebo, respectively) with a corresponding risk ratio of 0.96 (95% CI 0.76–1.22).
• ? Long‐term, Serenoa repens therapy was no better than placebo in improving nocturia in one high‐quality study (P= 0.19). Pooled analysis of nine short‐term Permixon® trials showed a reduction in the frequency of nocturia (WMD ?0.79 times/night, 95% CI–1.28 to ?0.29), although there was evidence of heterogeneity (I² 76%)
• ? Adverse events of Serenoa repens extracts were few and mild, and incidences were not statistically significantly different vs placebo. Study withdrawals occurred in ≈10% and did not differ between Serenoa repens and placebo.

CONCLUSIONS

• ? Serenoa repens therapy does not improve LUTS or Q_max compared with placebo in men with BPH, even at double and triple the usual dose.
• ? Adverse events were generally mild and comparable to placebo.

     

经尿道前列腺电切术治疗高龄高危前列腺增生症(附216例)

目的探讨经尿道前列腺电切术（TURP）治疗高龄高危前列腺增生症（BPH）的安全性和有效性。方法在积极进行个体化围手术期处理的基础上对216例高龄高危BPH患者行TURP术。结果本组216例安全实施TURP,手术平均时间46min,电切前列腺组织平均41g。随访6～12个月,所有患者排尿通畅,无一例水中毒、永久性尿失禁及继发性出血。国际前列腺症状评分（IPSS）由30.5分降到7.8分,剩余尿（PVR）由156ml降至20ml,最大尿流率（Qmax）由8ml/s增至20ml/s,生活质量评分（QOL）由4.9分降到1.5分,治疗前后IPSS、PVR、Qmax、QOL改变有统计学意义。结论只要加强个体化围手术期的处理,TURP仍是治疗高龄高危BPH安全有效的方法。     

Efficacy and safety of Chinese herbal medicine for benign prostatic hyperplasia: systematic review of randomized controlled trials

Chinese herbal medicine is commonly used as a treatment for benign prostatic hyperplasia (BPH), but its efficacy and safety remain to be examined. To compare the efficacy and adverse events of Chinese herbal medicine alone or used adjuvantly with Western medications for BPH. Two independent reviewers searched the major electronic databases for randomized controlled trials comparing Chinese herbal medicine, either in single or adjuvant use with Western medication, with placebo or Western medication. Relevant journals and grey literature were also hand-searched. The outcome measures included changes in urological symptoms, urodynamic measures, prostate volume and adverse events. The frequency of commonly used herbs was also identified. Out of 13 922 identified citations of publications, 31 studies were included. Eleven studies with a Jadad score ≥3 were selected for meta-analysis. Chinese herbal medicine was superior to Western medication in improving quality of life and reducing prostate volume. The frequency of adverse events in Chinese herbal medicine was similar to that of placebo and less than that of Western medication. The evidence is too weak to support the efficacy of Chinese herbal medicine for BPH due to the poor methodological quality and small number of trials included. The commonly used herbs identified here should provide insights for future clinical practice and research. Larger randomized controlled trials of better quality are needed to truly evaluate the efficacy of Chinese herbal medicine.     

Effect of age, castration, and testosterone replacement on the development and restoration of canine benign prostatic hyperplasia

An experiment was designed to test the effect of castration and testosterone replacement on the development of benign prostatic hyperplasia (BPH) in young and on the restoration of BPH in old beagles. Twenty beagles were divided by age into young (1.5-2.5-yr) and old (6.0-8.5-yr) groups. Each of these groups was further divided randomly into two additional groups of age-matched, intact, untreated control and castrate beagles. The latter were then treated with testosterone-filled Silastic implants designed to clamp serum testosterone at concentrations similar to those observed in adult beagles for 7 months beginning 5 months after castration. Histopathologic characterization of each prostate was completed on biopsy material obtained at the beginning and end of the experiment. Prostate weights were determined each month for 12 months via a noninvasive two-dimensional X-ray procedure. Testosterone treatment for 7 months allowed BPH to develop in young and restored BPH in old beagles. These results suggest that testosterone in the adult beagle acts permissively to allow BPH to develop in the prostate of the aging dog. Some other testicular product may be required for the continued growth of BPH in aged beagles.