Phytotherapie bei BPS

For decades, plant extracts have been amongst to the most popular drugs for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH)/benign prostatic enlargement (BPE). Only a few of the many published studies meet the criteria of the WHO-BPH consensus conference. The few placebo-controlled, long-term (>/=6 months) studies suggest a positive effect of some extracts (saw palmetto, beta-sitosterol, urtica, rye-grass, saw palmetto/urtica combination) on LUTS; an effect on uroflow, post-void residual volume, prostate volume and PSA was not consistently demonstrable. Randomised trials against an active comparator (alpha1-blocker, 5alpha-reductase inhibitors) are difficult to interpret. Due to the lack of prospective studies, several meta-analyses have been published that can not, however, replace prospective studies. None of the BPH-guidelines currently recommend plant extracts, yet universally conclude that this is an interesting approach. Further prospective studies using WHO standards are required to reliably determine the role of such extracts in the management of elderly men with LUTS due to BPH/BPE.     

Is Botulinum Neurotoxin Type A (BoNT-A) a Novel Therapy for Lower Urinary Tract Symptoms Due to Benign Prostatic Enlargement? A Review of the Literature

CONTEXT: The intraprostatic injection of botulinum neurotoxin type A (BoNT-A) is a minimally invasive but still-experimental treatment of lower urinary tract symptoms (LUTS) due to benign prostatic enlargment (BPE) based on an off-label use of the drug. OBJECTIVE: Report the mechanisms of action of BoNT-A on the prostate as well as the efficacy and safety of intraprostatic BoNT-A injection according to various injection protocols. EVIDENCE ACQUISITION: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) database and the abstract volumes of the 2005, 2006, and 2007 European Association of Urology (EAU), American Urological Association (AUA) and International Continence Society (ICS) meetings for studies on intraprostatic BoNT-A injection. EVIDENCE SYNTHESIS: Five experimental studies and 10 clinical studies were found. The level of evidence is 1b for one study and 3 for the other studies, with grades of recommendation of A and C, respectively. The experimental studies report induced relaxation of the prostate, atrophy, and reduction of its size through inhibition of the trophic effect of the autonomic system on the prostate gland. In the clinical studies, all patients had LUTS due to BPE and prostate volume varied from <20ml to >80ml. The dose varied from 100U to 300U of Botox((R)). The injection was performed transperineally, transrectally, or transurethrally under general, local, or without anesthesia. The follow-up period ranged from 3 mo to 19.8 mo. All studies reported an improvement of maximum urinary flow rate, quality-of-life index and reduction of International Prostate Symptoms Score, prostate-specific antigen (PSA) level, post-void residual volume, and prostate volume. Local or systemic side effects were rare. Only patients with retention needed a urethral drainage catheter. CONCLUSIONS: BoNT-A intraprostatic injection provides improvement in patients with LUTS due to BPE refractory to medical treatment. However, there is a need for large placebo controlled-studies and long-term results. So far the therapy is still experimental.     

Urodynamic Effects of Once-Daily Tadalafil in Men with LUTS Secondary to Clinical BPH

Lower urinary tract symptoms (LUTS) are common and increase with age in men with benign prostatic hypertrophy (BPH). Erectile dysfunction (ED) also increases with age and is often a comorbid condition with BPH. Treatment with phosphodiesterase type 5 (PDE5) inhibitors aimed at decreasing breakdown of nitric oxide (NO) is a mainstay of treatment for ED. Because NO has been found to mediate male prostatic and urinary function in multiple ways, there is increasing interest in PDE5 inhibitors addressing concomitant LUTS. Several studies have shown significant improvement in LUTS after treatment with PDE5 inhibitors; however, concern exists that PDE5 inhibitors exert their beneficial effects through impairment of bladder function. Because limited invasive urodynamic data exist to address these queries, tadalafil’s impact on bladder function was recently evaluated. Results indicate that tadalafil treatment had no negative impact on bladder function, as measured by detrusor pressure at maximum flow or any other urodynamic parameter assessed.     

Benign prostatic hyperplasia

Male lower urinary tract symptoms (LUTS) have a multifactorial aetiology and are not simply solely due to bladder outflow obstruction (BOO) from benign prostatic hyperplasia (BPH). Other causes of LUTS include bladder dysfunction, malignant prostatic disease, urethral disease and medical conditions such as polyuria. Complications from BPH include acute urinary retention, urinary tract infection and haematuria. Following investigation, men are treated with medical therapy for BPH using α-blockers and 5α-reductase inhibitors. Some men undergo surgery for their symptoms and this can be in the form of open prostatectomy, transurethral resection of the prostate (TURP) and a variety of laser ablating and enucleating techniques.     

Bladder wall thickness in normal adults and men with mild lower urinary tract symptoms and benign prostatic enlargement

There is evidence that increased bladder wall thickness can be a useful parameter in the evaluation of men with clinical benign prostatic hyperplasia (BPH). However, normal values for bladder wall thickness (BWT) in adults have not been established. BWT was measured by suprapubic ultrasonography. Bladder volume was calculated as the product of the ultrasonographic measurements of bladder height, width and depth, and a correction factor (0.6). Three groups were assessed: men with normal lower urinary tracts (n = 172; mean age, 39.9), women with normal lower urinary tracts (n = 166; mean age, 37.8), and men with mild lower urinary tract symptoms (LUTS) and clinical benign prostatic enlargement (BPE) (n = 150; mean age, 66.4). For the whole group of men and women with normal bladders, mean BWT was 3.35 mm, and BWT appeared normally distributed. There were a weak negative correlation with bladder volume (r = -0.12, P < 0.003) and a weak positive correlation for BWT and age for both men (r = 0.12, P < 0.014) and women (r = 0.17, P < 0.013). Mean BWT was 3.04 mm in healthy women, 3.33 mm in healthy men, and 3.67 mm in men with LUTS and BPE. Sub-dividing normal men into different age groups showed an increasing mean BWT of 3.08 mm (<20 years, n = 27), 3.25 mm (21-40 years, n = 75), 3.42 mm (41-60 years, n = 39), and 3.57 mm (>60 years, n = 31) for those sub-groups. BWT in normal adult women is 3.0 +/- 1 mm and 3.3 +/- 1. 1 mm in normal adult men. A small increase in BWT with age is seen for both genders, and BWT tends to be greater in men than in women. Men with LUTS and BPE show a moderate increase in BWT. Adjustments for bladder volume are for practical purposes negligible, although there is a small decrease in BWT with increasing volume.     

Update on the relationship between sexual dysfunction and lower urinary tract symptoms/benign prostatic hyperplasia

PURPOSE OF REVIEW: Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) is a condition that commonly affects older men and is often associated with sexual dysfunction. Recent evidence of an association between LUTS/BPH and sexual dysfunction will be reviewed, as well as the effects of pharmacological treatment options for symptomatic LUTS/BPH on sexual function. RECENT FINDINGS: Large-scale epidemiological studies conducted worldwide have provided strong evidence for an association between LUTS, erectile dysfunction and ejaculatory dysfunction. In multivariate analyses controlling for age, comorbidities, and lifestyle factors, LUTS have been clearly demonstrated to be an independent risk factor for erectile and ejaculatory dysfunction. Various pathophysiological mechanisms have been proposed for the association between LUTS and male sexual dysfunction. These include autonomic hyperactivity, alterations in Rho/Rho kinase pathway, endothelial (nitric oxide synthase/nitric oxide) dysfunction, pelvic ischemia, and age-related hormone imbalances. Owing to the link between LUTS/BPH and male sexual dysfunction, patients presenting with one of these conditions should be routinely screened for the other condition. In addition, because medical and surgical treatments for LUTS/BPH are commonly associated with sexual side effects, patients with LUTS/BPH should be monitored for treatment-related sexual outcomes. SUMMARY: LUTS/BPH is an independent risk factor for sexual dysfunction in aging men. Further studies are needed to define the mechanism(s) underlying the link between LUTS/BPH and male sexual dysfunction. Additional studies of combination therapy for LUTS/BPH, sexual dysfunction, and other age-associated comorbidities are needed to establish new approaches to the optimal management of these conditions in aging men.     

Sustained beneficial effects of intraprostatic botulinum toxin type A on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia

OBJECTIVE: To present a comprehensive experience with intraprostatic botulinum toxin-type A (BoNT-A) injection in men with symptomatic benign prostatic hyperplasia (BPH) and to assess the efficacy on lower urinary tract symptoms (LUTS) and quality of life (QoL). PATIENTS AND METHODS: In all, 41 men (mean age 69.1 years, sd 7.1 ) with an International Prostate Symptom Score of > or = 8, peak flow rate of < 12 mL/s, and who were refractory to medical treatment were injected with BoNT-A (Botox, Allergan, Inc., CA, USA) at 100 U (21 men, for prostate volume < 30 mL) or 200 U (20, for prostate volume > 30 mL) into the prostate transperineally under transrectal ultrasonography guidance. Study exclusion criteria were confirmed or suspected malignancy, previous pelvic surgery or trauma and previous invasive treatment for BPH. The clinical effects were evaluated at baseline and at 1, 3 and 6 months after treatment. RESULTS: There were no significant local or systemic side-effects in any men. LUTS and QoL indices improved by > 30% in 31 of the 41 men (76%), and four of five men with urinary retention for > 1 month could void spontaneously at 1 week to 1 month after the BoNT-A injection. In 12 of 41 men (29%) there was no change in prostate volume, yet seven of these men still had a > 30% improvement in maximum flow rate, LUTS and QoL. The efficacy was sustained at 12 months. CONCLUSION: BoNT-A injected into the prostate is safe and effective for men with symptomatic BPH. The mechanisms of relief of symptoms might not depend totally on the volume shrinkage; the inhibitory effect on the smooth muscle tone and aberrant sensory function might also be important.     

Correlation between lower urinary tract symptoms and urethral function in benign prostatic hyperplasia

AIM: To examine the potential correlation between urethral function and lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). METHODS: Thirty-one patients with clinical BPH, who were confirmed to have benign prostatic enlargement (BPE) of 20 ml or more, were enrolled into the study. A mark-sheet questionnaire was used for obtaining the LUTS history. Multichannel pressure-flow urodynamic studies were performed and external urethral sphincter pressure (PEUS), intravesical pressure (PVES), and bladder neck pressure (PBN) were recorded both at maximum cystometric capacity and during voiding with 5-microtip transducers, for the purpose of detecting BPE-specific urodynamic findings at different levels within the urethra. RESULTS: There was a positive correlation between hesitancy and detrusor bladder neck dyssynergia (DBND) (P = 0.0011) and between incomplete emptying and low PBN at maximum cystometric capacity (P = 0.0425). The hesitancy proved to have no correlation with bladder neck opening time (TBNO). CONCLUSION: Urodynamic evaluation of urethral function was beneficial for attributing LUTS to clinical BPH. Among various parameters, DBND was the most specific to clinical BPH, suggesting it to be a situation where a steep rise in PBN or prostatic urethral pressure remains greater than the increasing PVES, resulting in sustained difficulty in opening the bladder neck and subsequently the subjective sensation of hesitancy.     

Clinical guidelines for male lower urinary tract symptoms associated with non-neurogenic overactive bladder

The purpose of this guideline is to direct urologists and patients regarding how to identify overactive bladder (OAB) in male patients with lower urinary tract symptoms (LUTS) and to make an accurate diagnosis and establish treatment goals to improve the patients' quality of life (QoL). LUTS are commonly divided into storage, voiding, and postmicturition symptoms, and are highly prevalent in elderly men. LUTS can result from a complex interplay of pathophysiologic features that can include bladder dysfunction and bladder outlet dysfunction such as benign prostatic obstruction (BPO) or poor relaxation of the urethral sphincter. Diagnosis of OAB in male LUTS leads to accurate diagnosis of pure OAB and bladder outlet-related OAB, and appropriate treatment in men with residual storage symptoms after treatment for LUTS.     

Clinical relevance of transurethral resection of the prostate in "asymptomatic" patients with an elevated prostate-specific antigen level

OBJECTIVES: To determine the clinical relevance of transurethral resection of the prostate (TURP) in patients with minor lower urinary tract symptoms (LUTS) but elevated prostate-specific antigen (PSA) levels. METHODS: We retrospectively included 82 patients, aged 50.2-78.2 yr, with minor LUTS, elevated PSA (> or =4 ng/ml), and no signs of prostate cancer (PCa) after (multiple) negative multisite biopsies who underwent TURP after they were diagnosed by urodynamics with bladder outlet obstruction (BOO). We evaluated the clinical benefit of TURP by assessing its effect on International Prostate Symptom Score (IPSS) and PSA and the diagnostic value of histologic examination of the resected tissue for the presence of PCa. RESULTS: After TURP, histologic analysis of the resected specimen revealed that eight patients (9.8%) had PCa; seven of these patients had a tumour that needed further treatment. The remaining 74 patients (90.2%) were diagnosed with BOO due to benign prostatic hyperplasia/benign prostatic enlargement (BPH/BPE). In this group, the mean PSA level decreased from 8.8 ng/ml before TURP to 1.1 ng/ml in the first year and 1.3 ng/ml in the second year after TURP; the mean IPSS decreased from 8.8 to 1.5 in the first year after TURP. CONCLUSIONS: The current data suggest that patients with minor LUTS and elevated PSA without evidence of PCa are very likely to have BOO due to BPH/BPE and may benefit from TURP if obstruction is proved. However, a prospective trial is warranted to assess the impact of these results on clinical practice.     

Role of UPP in evaluating bladder outlet obstruction due to benign prostatic enlargement

AIMS: To study the role of UPP in assessing bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE). MATERIALS AND METHODS: Urodynamic results from 1281 elderly men with Lower urinary tract symptoms (LUTS) obtained from September 1999 through July 2005 were retrospectively analyzed. Independent sample t-test or Wilcoxon signed-rank test was used to compare the parameters of different groups according to PFS. Chi-square test was used to compare the percentage of urethral pressure profile (UPP) types between different groups. ROC curve was used to study the practical value of UPP parameters in diagnosing BOO. RESULTS: According to PFS, patients were divided into three groups: Obstructed, equivocal obstructed and unobstructed. There was significant difference between the unobstructed and obstructed group in the age of patients, bladder capacity, residual volume, voided volume, voided time, prostatic plateau area (PPA), prostatic length, functional profile length, pressure of bladder neck, and pressure of seminal colliculus, but not in maximum urethral closure pressure. All UPP parameters correlated significantly to the diagnosis of bladder outlet obstruction due to BPE. The largest area under the ROC curve was that of PPA. CONCLUSIONS: Our results indicate that PPA on UPP is useful in assessing the grade of obstruction due to BPE when PFS fails, a finding still to be evaluated by prospective studies.     

The Impact of Central Obesity on Storage Luts and Urinary Incontinence After Prostatic Surgery

In the developed and developing countries, the overall prevalence of central obesity in the elderly men is growing. In addition, the progressive aging of male population increased the possibilities of coexisting morbidities associated with obesity such as lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) or to prostate cancer (PCa) needing primary treatment, including radical prostatectomy (RP), which can further adversely affect the quality of life. Simple and radical prostatectomy are the most common surgical procedures in urologic unit all over the world for BPE and PCa, respectively. After both interventions, patients can present bothering storage LUTS that can worsen all the other clinical outcomes. Preset study will review the role of central obesity as a risk factor for storage LUTS or urinary incontinence, after prostatic surgery for BPE or PCa.     

The pathophysiology underlying overactive bladder syndrome possibly due to benign prostatic hyperplasia

The pathophysiology in the development of overactive bladder syndrome (OAB) possibly due to benign prostatic hyperplasia (BPH) has not fully been understood. The clinical study in male outpatients aged over 50 years with lower urinary tract symptoms showed that the frequency of urgency was significantly associated with aging, bladder outlet obstruction (BOO) and benign prostatic enlargement (BPE). From the results of the experiments we did using rats, the mechanisms underlying the development of OAB were suggested as follows. The functional impairment of acetylcholine neuron in the central nervous system is induced by aging and decreases the bladder capacity. Non-voiding contractions of the bladder may have some bearing on OAB associated with BOO. The C-fiber in the urethra may be involved in the generation of the detrusor overactivity associated with BPE. These results showed that the pathophysiology of OAB related to BPH is quite complex, suggesting that a multidisciplinary approach is necessary for the treatment.     

Overactive Bladder and Outlet Obstruction in Men

Lower urinary tract symptoms (LUTS), overactive bladder, (OAB), and benign prostatic hyperplasia (BPH) are very commonly experienced in men. The mainstay of pharmacotherapy for OAB is the antimuscarinic class of drugs. There has been reluctance to prescribe these agents to men with BPH due to the risk of precipitating urinary retention. Several trials have supported the efficacy and safety of antimuscarinics in treating men with LUTS, alone, or in combination with α-blocker therapy. The combination of 5-α-reductase inhibitors with antimuscarinic agents or surgery are other effective treatments for men with BPH and OAB.     

Medikamentöse Therapie der benignen Prostatahyperplasie

The majority of men with benign prostatic hyperplasia (BPH) seek medical help because of lower urinary tract symptoms (LUTS). Pharmacological treatment of BPH is indicated if the patient has no absolute indications for prostate surgery or benign prostatic obstruction (BPO), but LUTS with a decrease of quality of life. Plant extracts can be prescribed in men with mild to moderate symptoms. α-Blockers can quickly and effectively decrease LUTS and symptomatic disease progression. If patients have predominantly bladder filling symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of an α-blocker plus a muscarinic receptor antagonist is more effective than single drugs used alone. Especially in men with larger prostates, 5α-reductase inhibitors can decrease LUTS and the probability of acute urinary retention as well as need for prostate surgery. The combination of α-blocker plus 5α-reductase inhibitor can reduce LUTS and disease progression more effectively than single drugs.     

The medical management of lower urinary tract symptoms and benign prostatic hyperplasia

Prostatism is a widely used term assigned to the symptom complex of older men with voiding dysfunction. The cause of the syndrome has routinely been ascribed to an enlarged prostate. More recent thinking recognizes that many men with such symptoms do not, in fact, have prostate enlargement or benign prostatic hyperplasia (BPH) and that such symptoms are not a surrogate for BPH. Such recognition is essential if cost effective medical management of lower urinary tract symptoms (LUTS) is to be achieved. Prostate volume has emerged as a key factor in the selection of medical therapy of LUTS and BPH not only regarding symptom relief but also to the newer concept of the prevention of disease progression and the avoidance of future adverse events in those men with true BPH. In the United States, medical management is now first line therapy for LUTS. The proper selection of therapy based on the patient's individual pathophysiologic characteristics is now made possible by many new recent studies within the medical literature.     

Potential Role of α1-Adrenoceptors in the Aetiology of LUTS

It has been assumed that α₁-adrenoceptors contribute to the aetiology of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) mainly by increasing bladder outlet resistance due to an increase in the tone of prostatic smooth muscle. This paper reviews recent evidence that α₁-adrenoceptors can also contribute to BPH by affecting prostatic growth and additionally can contribute to LUTS by effects on the bladder and the spinal cord. While direct effects on prostatic smooth muscle and hence on voiding symptoms occur via α_1A-adrenoceptors, α_1D-adrenoceptors appear to contribute to effects on bladder and spinal cord and hence storage symptoms. In contrast α_1B-adrenoceptors do not appear to be involved in lower urinary tract function but may contribute to side effects of drugs used in LUTS treatment.     

Vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia

α-Blockers, the current common treatment for lower urinary tract symptoms (LUTS), are also used to treat bladder outlet obstruction (BOO), but the effect is not as clinically significant as in LUTS. All currently marketed phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to significantly affect LUTS, although BOO-related efficacy has not been determined. Therefore, the extent of a causal relationship between LUTS and underlying benign prostatic enlargement (BPE) is questionable. LUTS may also be interpreted as symptoms related to detrusor overactivity, especially when no significant BOO is associated with BPE. Research is required to understand the efficacy of PDE5 inhibitors in LUTS but not in BOO. For vardenafil, nonclinical experiments and initial, preliminary clinical data suggest that the underlying effect may occur on the detrusor and not the prostate.     

Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: sexual function

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), and sexual dysfunction, are common, highly bothersome conditions in older men, and the prevalence of both disorders increases with age. Sexual dysfunction manifests mainly as erectile dysfunction (ED), ejaculatory disorders, or decreased libido/hypoactive sexual desire (HSD). Whereas both reduced rigidity and reduced ejaculate volume are highly prevalent in ageing men, reduced rigidity and pain on ejaculation are considered to be most bothersome. Sexual dysfunction is much more prevalent in patients with LUTS/BPH than in men with no LUTS/BPH, even after controlling for confounding variables such as age or comorbidities. Hence LUTS/BPH is considered an independent risk factor for sexual dysfunction. Whether this is because of a common underlying pathology, or whether the considerable bother associated with LUTS/BPH leads to reduced sexual functioning, remains to be elucidated. Despite a decline in the frequency of sexual intercourse, as well as in overall sexual functioning, most ageing men report regular sexual activity and consider their sex life as an important dimension of their quality of life (QoL). However, most patients with LUTS/BPH experience a negative effect of their LUTS on their sex life. Hence, treatment of LUTS/BPH should aim to at least maintain or, if possible, improve sexual function. Current medical treatment of LUTS/BPH consists of monotherapy with alpha1-adrenoceptor (AR) antagonists, 5alpha-reductase inhibitors (RIs) or a combination of these. Whereas 5alpha-RIs increase the risk of ED, ejaculatory disorders and HSD, alpha1-AR antagonists can induce ejaculatory disorders, but do not provoke HSD or ED. Combined therapy carries the cumulative risk for sexual dysfunction associated with either type of drug. As already indicated, ED is generally perceived as more bothersome than ejaculatory disorders. In addition, alpha1-AR antagonists slightly improve overall sexual function, possibly by increasing blood flow in the penis through alpha1-AR blockade and/or to an increased overall QoL from the relief of LUTS. It can be concluded that alpha1-AR antagonists constitute a first-line therapy for LUTS/BPH because they combine good treatment efficacy with very few adverse effects on sexual function.     

Medikamentöse Therapie des benignen Prostatasyndroms

The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (>?30–40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment.