Toward a Scientific Nutritional Supplement Combination for Prostatism and Erectile Dysfunction I: From Known Pharmacology to Clinical Testing.

Prostatism and erectile dysfunction (ED) are highly prevalent and closely comorbid. Prescription treatments are limitingly expensive but robust in mechanisms of action (MoA). Nutritional supplements (NS) are low-cost but inadequately supported by evidence. Do any NS use robust MoA? Could their efficacy be amplified via dosing, concentration of active principles, and/or use in combination? The goal is to develop an effective NS for prostatism and ED using the MoA of prescription treatments. Literature reviews were conducted on dietary supplements for prostatism or ED and MoA of relevant drugs. The most promising NS employing these MoA were chosen. A pilot study of a prototype combination was conducted. A protocol was created for an adequate dose-response trial to test the NS combination in men with ED and prostatism. The main measures were response rates, International Prostate Symptom Score, and International Index of Erectile Function. For drugs, the MoAs best proven for prostatism and ED were nitric oxide augmentation, mild androgen inhibition, and anti-inflammatory effects. The following NS best simulate these MoA and are best supported for efficacy; for prostatism: beta sitosterol; for ED: panax ginseng, arginine, and citrulline. Pilot clinical data provided support. A plan for a formal dose-response clinical trial was approved by a central institutional review board. NS using effective MoA might suffice for prostatism and ED. Pilot testing of a combination NS with the best-supported MoA supported further development. A dose-response trial should be conducted using adequate doses of L-citrulline, beta-sitosterol, ginseng, and vitamin D3.

Naftopidil for the treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition in ageing men that may cause lower urinary tract symptoms (LUTS). Treatment aims are to relieve symptoms and prevent disease-related complications. Naftopidil is an alpha-blocker (AB) that has a high affinity for the A1d receptor that may have advantages in treating LUTS in this setting. This is an update of a Cochrane Review first published in 2009. Since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant. OBJECTIVES: To evaluate the effects of naftopidil for the treatment of LUTS associated with BPH. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, LILAC, and Web of Science), trials registries, other sources of grey literature, and conference proceedings with no restrictions on the language of publication or publication status up to 31 May 2018 SELECTION CRITERIA: We included all parallel RCTs. We also included cross-over design trials. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. Primary outcomes were urological symptom scores, quality of life (QoL) and treatment withdrawals for any reason; secondary outcomes were treatment withdrawals due to adverse events, acute urinary retention, surgical intervention for BPH, and cardiovascular and sexual adverse events. We considered outcomes measured up to 12 months after randomisation as short term, and later than 12 months as long term. We rated the certainty of the evidence according to the GRADE approach. MAIN RESULTS: We included 22 RCTs with 2223 randomised participants across four comparisons for short-term follow-up. This abstract focuses on only two of four comparisons for which we found data since two comparators (i.e. propiverine and Eviprostat (phytotherapy)) are rarely used. One study comparing naftopidil to placebo did not report any relevant outcomes and was therefore excluded. There were no trials that compared to combination therapy with naftopidil or any 5-alpha reductase inhibitors (5-ARIs) to combination therapy with other ABs and any 5-ARIs.All included studies were conducted in Asian countries. Study duration ranged from four to 12 weeks. Mean age was 67.8 years, prostate volume was 35.4 mL, and International Prostate Symptom Score was 18.3. We were unable to perform any of the preplanned subgroup analyses based on age and baseline symptom score.Naftopidil versus tamsulosinBased on 12 studies with 965 randomised participants, naftopidil may have resulted in little or no difference in urological symptom score (mean difference (MD) 0.47, 95% confidence interval (CI) -0.09 to 1.04 measured on a scale from 0 to 35 with higher score representing increased symptoms), QoL (MD 0.11, 95% CI -0.09 to 0.30; measured on a scale from 0 to 6 with higher scores representing worse QoL), and treatment withdrawals for any reason (risk ratio (RR) 0.92, 95% CI 0.64 to 1.34; corresponding to 7 fewer per 1000 participants, 95% CI 32 fewer to 31 more). Naftopidil may have resulted in little to no difference in sexual adverse events (RR 0.54, 95% CI 0.24 to 1.22); this would result in 26 fewer sexual adverse events per 1000 participants (95% CI 43 fewer to 13 more). We rated the certainty of evidence as moderate for urological symptom score and low for the other outcomes.Naftopidil versus silodosinBased on five studies with 652 randomised participants, naftopidil may have resulted in little or no difference in the urological symptom scores (MD 1.04, 95% CI -0.78 to 2.85), QoL (MD 0.21, 95% CI -0.23 to 0.66), and treatment withdrawals for any reason (RR 0.80, 95% CI 0.52 to 1.23; corresponding to 26 fewer per 1000 participants, 95% CI 62 fewer to 32 more). We rated the certainty of evidence as low for all these outcomes. Naftopidil likely reduced sexual adverse events (RR 0.15, 95% CI 0.06 to 0.42; corresponding to 126 fewer sexual adverse events per 1000 participants, 95% CI 139 fewer to 86 fewer). We rated the certainty of evidence as moderate for sexual adverse events. AUTHORS' CONCLUSIONS: Naftopidil appears to have similar effects in the urological symptom scores and QoL compared to tamsulosin and silodosin. Naftopidil has similar sexual adverse events compared to tamsulosin but has fewer compared to silodosin.

Does the addition of Serenoa repens to tamsulosin improve its therapeutical efficacy in benign prostatic hyperplasia?

BACKGROUND/AIM: It has been observed that a large number of patients with low urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH)) has been treated with a combination of tamsulosin (TAM) + Serenoa repens (SR) (TAM + SR). The aim of this study was to compare a combination TAM + SR with TAM and SR alone, to see if there was any difference in efficacy and tolerance of each in patients with LUTS/BPH. METHODS: In this prospective study patients had to have prostate volume (PV) < 50 mL, International Prostate Symptom Score (IPSS) of 7-18, Quality of Life score (QoLs) > 3, a maximal flow rate (Qmax) of 5-15 mL/s, with post voiding residual volume (PVR) < 150 mL and serum prostatic antigen (PSA) < 4 ng/mL. TAM (0.4 mg) was administered once a day, SR (320 mg) daily or SR (320 mg) + TAM (0.4 mg) daily for a median period of 6 months. RESULTS: A total of 297 patients were recruited, whereas 265 patients were fully available: 87 into the group TAM, 97 into the group SR and 81 into the group TAM + SR. There was no statistically significant difference between the treatment groups in the sense of demographic and other baseline parameters. No difference was found among the 3 treatment groups, neither in the major endpoint of the study in the sense of a change between baseline and final evaluation in total IPSS, obstructive and irritative subscores, improvement of QoLs, increase in Qmax, nor for the second endpoint including diminution of PV, PSA and PVR. During the treatment period 20 (23%) of the patients managed with TAM and 17 (21%) with TAM + SR had drug- treated with related adverse reactions. No adverse effect was detected in the group SR. CONCLUSION: Treatment of BPH by both SR and TAM seems to be efficacious alone. None of them had superiority over another and, additionally, a combined therapy (TAM + SR) does not provide extra benefits. Furthermore, SR is a well-tolerated agent that can be used alternatively in the treatment of LUTS/BPH.

Impact of medical therapy on transurethral resection of the prostate: two decades of change.

OBJECTIVE: • To examine how the introduction of medical therapy for symptomatic benign prostatic hyperplasia (BPH) might have changed the indications, patient characteristics and outcomes in men undergoing transurethral resection of the prostate (TURP) over two decades (1988-2008). PATIENTS AND METHODS: • All patients who underwent TURP for symptomatic BPH in a geographically defined area at our institution in 1988 (before the introduction of medical therapy for BPH), 1998 (when medical therapy was becoming an important therapy for BPH), and 2008 (when medical therapy was the primary first line therapy for BPH) were reviewed. • We assessed the total number of TURPs, indications for surgery, patient age, health status, weight of resected tissue, and pre- and postoperative events/complications. RESULTS: • There was a 60% decrease in TURPs from 1988 to 1998 with a moderate increase in number in 2008. • Failure of medical therapy was not an indication for TURP in 1988, but was at least one of the indications in 36% and 87% of patients in 1998 and 2008, respectively. • There was a substantial rise in the percentage of patients (but not total number or percentage of men at risk for BPH) presenting with acute or chronic urinary retention (AUR or CUR) at the time of their TURP (from 22.9% in 1988 to 42.9% in 2008, and from 14.6% in 1988 to 39.3% in 2008 for AUR and CUR, respectively). There was also a rise in the percentage of patients presenting with preoperative hydronephrosis (1.3% in 1988, 12.5% in 1998, 7.1% in 2008). • Inpatient stays decreased (from 4.1 day in 1988 to 2.7 days in 1998, and to 2.1 day in 2008), but the number of patients discharged with a catheter increased over the two decades (from 3.2% in 1988 to 12.5% in 1998, and to 28.6% in 2008). CONCLUSIONS: • The increasing use of medical therapy as a first line treatment for BPH has resulted in a dramatic decrease in TURPs which, in turn, has been associated with an apparent increase in risk of poor pre- and postoperative outcomes. However, the actual number (either the total number or as a percentage of men at risk for BPH) who have experienced these progression events has not changed and the postoperative outcomes are probably related to earlier catheter removal and hospital discharge. • It appears that we are performing TURP on the right patients.

[Associating Serenoa repens, Urtica dioica and Pinus pinaster. Safety and efficacy in the treatment of lower urinary tract symptoms. Prospective study on 320 patients]. / Associazione di Serenoa repens, Urtica dioica e Pinus pinaster. Sicurezza ed efficacia nel trattamento dei sintomi del basso tratto urinario. Studio prospettico su 320 pazienti.

INTRODUCTION: Serenoa repens (saw palmetto) has been employed for the treatment of lower urinary tract symptoms (LUTS) for several years. Its mechanism of action is believed to be due to antiandrogenic, antiproliferative and antinflammatory properties. An association of Serenoa with the nettle "Urtica dioica" showing antiproliferative activity and the pine "Pinus pinaster" derivative, showing antinflammatory action, has been proposed in recent years. Such an action is hoped to act not only by reducing LUTS but also by preventing the development of prostate cancer. MATERIAL AND METHODS: During the years 2007 and 2008, 320 patients suffering from LUTS were treated with an association of Serenoa repens 320 mg, Urtica dioica 120 mg and Pinus pinaster 5 mg, named IPBTRE. This treatment was administered to all patients for a minimal duration of 30 days to a maximum of a year, either alone or in association with antibiotics or alpha-blockers, if needed. Outcome analysis was based on evaluation of symptoms, prostate volume and maximum flow rate (Qmax). RESULTS: From a careful analysis of the data collected in our database, the following observations can be made: ages varied between 19 and 78 years. The patients were affected by BPH in 46% of cases, chronic prostatitis syndrome in 43%, chronic genital-pelvic pain in 7% and other conditions in 4%, the absolute numbers being 147, 138, 22 and 7 patients, respectively. No untoward side effect was reported in any case. Variations in symptom score could be fully evaluated only in 80 of 320 patients (25%), of whom 68 (85%) reported a significant benefit, with special reference to an improvement of pain, urgency, strangury and nocturia. Data on variations in prostate volume, as measured by digital rectal examination, were available in 84 (26.5%) patients. No significant change was observed. Qmax after treatment was measured in 83 (26%) patients. It did not show significant changes from the initial values. DISCUSSION: The association tested in our study appeared to be safe and well tolerated. No changes in flow rate and prostate volume were observed, but a marked reduction of LUTS was observed in 85% of evaluable cases, especially with regard to pain and irritative symptoms. Whether or not such an association may display a prevention of prostate cancer, may be investigated in additional studies.

A widespread population study of actual medical management of lower urinary tract symptoms related to benign prostatic hyperplasia across Europe and beyond official clinical guidelines.

BACKGROUND: The estimated prevalence of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) in men >50 yr of age is around 30%, similar in all industrialized countries. alpha(1)-Blockers and 5 alpha-reductase inhibitors (5-ARIs) are the two classes of drugs recommended by the European Association of Urology guidelines for the medical management of LUTS/BPH. OBJECTIVE: To compare actual clinical practice across Europe with guidelines, we assessed the use of all BPH-related drugs (alpha(1)-blockers, 5-ARIs, and plants) among European countries with a large-scale quantitative and descriptive study. DESIGN, SETTING, AND PARTICIPANTS: The amounts of BPH-related drugs prescribed in 19 European countries were obtained from the IMS Health database retrospectively from 2004 to 2008. Data were adjusted for each country by the number of people >50 yr of age. MEASUREMENTS: We determined the "prescription index" related to BPH, defined for each drug per country by days of treatment sold per year divided by the number of men at risk divided by 365 d. RESULTS AND LIMITATIONS: From 2004 to 2008, the yearly number of prescriptions was 11.6 million for 74 million people at risk. The global prescription index increased in all countries and was three-fold more important in southern countries than in northern ones. alpha(1)-Blockers are the most widely prescribed drugs, but the share of 5-ARIs is increasing. Phytotherapy prescription is country specific, varying from 0% to 40% of prescriptions and is not recommended by the guidelines. CONCLUSIONS: Major variations were seen among European countries concerning the prescriptions related to BPH, although the prevalence of the disease and the guidelines are similar. These results underline the importance of feedback from actual clinical practice. Analysis of actual prescription levels would complement evidence-based medicine as critical material for public health analysis, recommendations, and health insurance policies.

Established medical therapy for benign prostatic hyperplasia.

Benign prostatic hyperplasia is characterized by smooth muscle and epithelial proliferation primarily within the prostatic transition zone that can cause a variety of problems for a patient, the most frequent being bothersome lower urinary tract symptoms. In most cases, medical therapy has become the first-line treatment modality of choice, with a variety of pharmacologic mechanisms proving to be beneficial. Several large trials have shown the efficacy of alpha-receptor blocking and 5-alpha reductase inhibiting medications when used alone and in combination. Newer data has shown the benefit of anti-muscarinic medications in specific populations who suffer from bladder outlet obstruction causing storage urinary symptoms. Phytotherapeutic supplements are numerous and used frequently; however, data supporting safety and efficacy is limited, making treatment recommendations difficult. The available clinical trial data for all of these types of therapy is discussed in this article.

Naftopidil for the treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition in aging men causing lower urinary tract symptoms (LUTS). Treatment aims are to relieve symptoms and prevent disease progression. Of the different alpha-1 adrenergic receptors (ARs) in the prostate, alpha-1a receptors are known to be central to prostatic smooth-muscle contraction. Recent studies have shown that patients with BPH may also have a predominance of alpha-1d receptors. OBJECTIVES: To evaluate the efficacy and adverse effects of naftopidil, a selective alpha-1d oral alpha-blocking agent for the treatment of LUTS associated with BPH. SEARCH STRATEGY: Systematic review of trials published January 1950 to January 2009. Sources included MEDLINE and bibliographies of retrieved articles and review articles. SELECTION CRITERIA: Eligible trials included: men diagnosed with symptomatic BPH; compared Naftopidil to placebo, control, or combination therapy; evaluated clinically relevant outcomes between randomized groups; had at least 4-weeks follow up; and were published in English language. DATA COLLECTION AND ANALYSIS: Participant demographics and comorbidities, enrollment criteria, outcomes, adverse events, numbers and reasons for dropouts were extracted onto standardized extraction forms by one reviewer. The mean change and per cent improvement from baseline in AUA (American Urological Association Symptom Score) and IPSS (International Prostate Symptom Score) scores and other efficacy outcomes for treatment and control groups were calculated. If feasible, the efficacy outcomes and adverse events data were pooled. MAIN RESULTS: Eight trials were eligible (N = 744 participants). All trials were conducted in Japan. Study duration ranged from 4 to 17 weeks. The mean age of participants was 68 years; pretreatment mean IPSS = 17.8 and mean peak urine flow (Qmax) = 9.5 mL/s (milliliters/second). No trials compared naftopidil to placebo. In 5 trials (N = 419), naftopidil in doses of 25 to 75 mg/d (milligrams/day) showed a mean IPSS improvement similar to low-dose tamsulosin (0.2 mg/d) (8.4 versus 8.9 points). Compared to a phytotherapy preparation (eviprostat), naftopidil significantly improved total IPSS (-5.9 versus 0.4; P < 0.0002). In one trial, the addition of anticholinergic drugs (oxybutynin or propiverine hydrochloride) to naftopidil did not offer any significant improvement for IPSS or Qmax in comparison to treatment with naftopidil alone. Although IPSS did not significantly differ between high- (75 mg/d) and low-dose (25mg/d) naftopidil, high dose significantly improved Qmax compared to low dose (1.2 mL/s versus 0.2 mL/s). Adverse events reported were few, mild and similar to those seen with 0.2 mg/d tamsulosin. AUTHORS' CONCLUSIONS: There are no data from placebo controlled trials regarding the efficacy of naftopidil in men with symptomatic BPH. Limited information suggests that treatment with naftopidil provides short-term improvement in urinary symptom-scale scores (total IPSS/AUA), QoL (quality of life) score, and urinary symptoms from baseline comparable to low-dose tamsulosin. Adverse effects due to naftopidil were few and usually mild.

Phytotherapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia.

PURPOSE: We examined the available data from clinical trials for certain botanicals used for lower urinary tract symptoms secondary to benign prostatic hyperplasia, including Serenoa repens (saw palmetto), Pygeum africanum (African plum), Secale cereale (rye pollen) and Hypoxis rooperi (South African star grass). MATERIALS AND METHODS: MEDLINE and The Cochrane Library searches were done in June 2007 using the terms benign prostatic hyperplasia, lower urinary tract symptoms, phytotherapy, saw palmetto, Serenoa, Permixon, Pygeum africanum, Tadenan, Cernilton, Cernitin and Hypoxis. Search results were assessed for relevance and the inclusion of placebo controlled trials. RESULTS: Two systematic reviews and 3 clinical trials were examined in the evaluation of Serenoa repens. Data from the systematic reviews showed an improvement in flow rates and symptoms. The results of 1 clinical trial were equivocal and the remaining 2 trials clearly showed equivalence to placebo. Systematic reviews were used in the evaluation of P. africanum, Secale cereale and Hypoxis rooperi. P. africanum and H. rooperi showed an improvement in flow rates and symptoms compared to placebo, while S. cereale showed an improvement in symptoms but not flow rates compared to placebo. CONCLUSIONS: Most clinical trials of investigating the efficacy of botanicals suffer from well documented methodological flaws. Saw palmetto has been clearly shown as comparable to placebo in a trial of sound methodology. While preliminary results appear promising, to our knowledge the remaining botanicals have yet to be evaluated in a trial of similar quality.

Impact of phytotherapy on utility scores for 5 benign prostatic hyperplasia/lower urinary tract symptoms health states.

PURPOSE: Given the wide variety of lower urinary tract symptoms caused by benign prostatic hyperplasia, we ascertained the impact on quality of life for 5 domains of benign prostatic hyperplasia/lower urinary tract symptoms progression. In addition, with the increasing number of patients using alternative therapies to alleviate bother from benign prostatic hyperplasia/lower urinary tract symptoms, we investigated whether utility scores differed between phytotherapy users and nonusers. MATERIALS AND METHODS: Using an office based population 40 consecutive patients were identified as surgically naïve with benign prostatic hyperplasia/lower urinary tract symptoms based on the American Urological Association Symptom Index. A trained interviewer administered 2 surveys to the patients, that is a time trade-off questionnaire assessing the health states of urinary retention, urinary tract infection, incontinence, erectile dysfunction and ejaculatory dysfunction, as well as an alternative therapy questionnaire. Patient chart reviews were conducted to collect clinical parameters (age, American Urological Association Symptom Index, erectile dysfunction complaints, prostate specific antigen, quality of life, etc). Two-tailed student t tests were then performed to compare groups. Patients were stratified as phytotherapy users and phytotherapy nonusers. RESULTS: The time trade-off scores of the participants for urinary retention, urinary tract infection, incontinence, erectile dysfunction and ejaculatory dysfunction were 0.61 +/- 0.33, 0.57 +/- 0.34, 0.66 +/- 0.32, 0.73 +/- 0.31 and 0.71 +/- 0.32, respectively. Of the 17 patients having used phytotherapy for lower urinary tract symptoms, 9 were actively using alpha-blockers, 1 was on 5alpha-reductase inhibitor alone, and 2 were using alpha-blockers and 5alpha-reductase inhibitors. Of the 23 patients not having used phytotherapy, 5 were using alpha-blockers alone, and 6 were using alpha-blockers and 5alpha-reductase inhibitors. Patients who reported having used phytotherapy for lower urinary tract symptoms had lower scores in all 5 health states, statistically significant for urinary retention (0.49 +/- 0.37 vs 0.71 +/- 0.26, p <0.05), erectile dysfunction (0.60 +/- 0.39 vs 0.82 +/- 0.20, p <0.05) and ejaculatory dysfunction (0.55 +/- 0.39 vs 0.82 +/- 0.19, p <0.05). These 2 patient populations did not differ significantly with respect to the clinical parameters of age, American Urological Association Symptom Index, erectile dysfunction, prostate specific antigen or quality of life. CONCLUSIONS: This study is the first to demonstrate time trade-off utilities in a benign prostatic hyperplasia/lower urinary tract symptoms group by the 5 domains of disease progression. We have shown that benign prostatic hyperplasia/lower urinary tract symptoms patients who have used phytotherapy have markedly lower utility scores than those patients not having used phytotherapy despite comparable clinical parameters. These results have important implications for clinical trial design and health economics.

Double-blind randomized placebo-controlled study of Bixa orellana in patients with lower urinary tract symptoms associated to benign prostatic hyperplasia.

OBJECTIVE: To determine the efficacy of Bixa Orellana (BO) in patients with benign prostatic hyperplasia (BPH) presenting moderate lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: It is a prospective double-blind randomized placebo-controlled study. One thousand four hundred and seventy eight patients presenting moderate LUTS associated to BPH were interviewed, from whom we selected 136 to fulfill the criteria of inclusion and exclusion. Assignation was performed at random in blocks of four to receive B0 at a dose of 250 mg 3 times a day or placebo (Pbo) for 12 months, 68 patients were assigned to each group. From the patients in the study we obtained data of demographic, epidemiologic, symptom score, uroflowmetry and post void residual urine variables. RESULTS: Basically both groups were compared clinically, demographically and biochemically. Throughout the study variations of symptom score, mean delta symptom score during each visit and the final average delta were similar for both groups (BO - 0.79 +/- 1.87 and Pbo - 1.07 +/- 1.49) (p = 0.33). Similarly variations of Qmax mean, Qmax average delta and final average delta were similar (BO 0.44 +/- 1.07 and Pbo 0.47 +/- 1.32) (p = 0.88). Variations of post void residual urine mean, post void residual urine average delta in each visit and the final average delta were similar for both groups (BO 4.24 +/- 11.69 and Pbo 9.01 +/- 18.66) (p = 0.07). No differences were found in the answers of clinically significant improvement assessed with relative risk and risk differences, even though the proportion of adverse effects was similar for both groups. CONCLUSION: Patients with BPH that present moderate LUTS did not show any benefit receiving BO when compared to placebo.

Double-blind randomized placebo-controlled study of bixa orellana in patients with lower urinary tract symptoms associated to benign prostatic hyperplasia

OBJECTIVE: To determine the efficacy of Bixa Orellana (BO) in patients with benign prostatic hyperplasia (BPH) presenting moderate lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: It is a prospective double-blind randomized placebo-controlled study. One thousand four hundred and seventy eight patients presenting moderate LUTS associated to BPH were interviewed, from whom we selected 136 to fulfill the criteria of inclusion and exclusion. Assignation was performed at random in blocks of four to receive B0 at a dose of 250 mg 3 times a day or placebo (Pbo) for 12 months, 68 patients were assigned to each group. From the patients in the study we obtained data of demographic, epidemiologic, symptom score, uroflowmetry and post void residual urine variables. RESULTS: Basically both groups were compared clinically, demographically and biochemically. Throughout the study variations of symptom score, mean delta symptom score during each visit and the final average delta were similar for both groups (BO - 0.79 ± 1.87 and Pbo - 1.07 ± 1.49) (p = 0.33). Similarly variations of Qmax mean, Qmax average delta and final average delta were similar (BO 0.44 ± 1.07 and Pbo 0.47 ± 1.32) (p = 0.88). Variations of post void residual urine mean, post void residual urine average delta in each visit and the final average delta were similar for both groups (BO 4.24 ± 11.69 and Pbo 9.01 ± 18.66) (p = 0.07). No differences were found in the answers of clinically significant improvement assessed with relative risk and risk differences, even though the proportion of adverse effects was similar for both groups. CONCLUSION: Patients with BPH that present moderate LUTS did not show any benefit receiving BO when compared to placebo.

Pygeum africanum extract inhibits proliferation of human cultured prostatic fibroblasts and myofibroblasts.

OBJECTIVE: To investigate the effect of Pygeum africanum (PA) extract on the proliferation of cultured human prostatic myofibroblasts and fibroblasts; this extract is used for treating urinary disorders associated with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Primary cultures of prostatic stromal cells were obtained from histologically confirmed human BPH by enzymatic digestion. Cell proliferation was measured by 5-bromo2'-deoxy-uridine (BrdU) incorporation assays, and cytotoxicity by luminescent quantification of adenylate kinase activity. RESULTS: Cultured cells were labelled by an anti-vimentin antibody, and most of them by an alpha-smooth-muscle-actin antibody, revealing the presence of fibroblasts and myofibroblasts. BrdU incorporation tests showed that proliferation of cultured human stromal cells, stimulated by fetal calf serum, by basic fibroblast growth factor and by epidermal growth factor, was dose-dependently inhibited by PA extract (5-100 microg/mL). Except at 100 microg/mL, no acute cytotoxicity of the extract was detected after 24 h of culture. Similarly, the extract dose-dependently inhibited the proliferation of Madin-Darby canine kidney epithelial cells, but to a lesser extent; whatever the dose of extract, no acute toxicity was evident on this cell line. CONCLUSION: PA extract inhibits the proliferation of cultured human prostatic myofibroblasts and fibroblasts. We propose that cultured human prostatic cells offer a reliable model for preclinical screening of therapeutic agents, and to study the mechanisms underlying the inhibition of proliferation.