Lower urinary tract symptoms, benign prostatic hyperplasia, erectile dysfunction, and phosphodiesterase-5 inhibitors

Many patients who present to their healthcare provider with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) will also have erectile dysfunction (ED), and vice versa. Although alpha-adrenergic receptor blockers and 5-alpha-reductase inhibitors are highly effective in treating BPH-associated LUTS, these agents have sexual adverse effects that cause many men to discontinue therapy. The discovery of nitric oxide as a major factor in the mechanism of erection has led to the development of new drugs for ED, including the phosphodiesterase (PDE) inhibitors. Preliminary data support the theory that inhibition of PDE isoenzymes in the prostate may improve LUTS due to BPH through relaxation of prostatic smooth muscle. Further studies of PDE inhibitors in men with ED and BPH-associated LUTS are indicated.     

Epidémiologie de la dysfonction érectile (2ème partie). Facteurs de risque

Epidemiological studies in the general population or target populations in several countries in the world have revealed a large number of risk factors for erectile dysfunction: diabetes mellitus, hypertension, smoking, dyslipidaemia, cardiovascular diseases, psychological disorders, certain medications, chronic renal failure, socioeconomic factors and lifestyle, obesity, lower urinary tract symptoms, poor health and bicycling. Cardiovascular risk factors are predictors of erectile dysfunction and erectile dysfunction is now considered to be a manifestation of vascular disease. Further studies are necessary to establish the pathophysiological mechanisms of certain risk factors and the possible value of preventive measures.     

Safety and efficacy of the potassium-titanyl-phosphate laser and photoselective vaporization of the prostate for benign prostatic hyperplasia

The currently commercially available 80-W potassium-titanyl-phosphate laser used for photoselective vaporization of the prostate in men with lower urinary tract symptoms and benign prostatic hyperplasia (BPH) is a safe and effective therapeutic alternative for a wide spectrum of prostate sizes and configurations. Efficacy data from multicenter prospective studies, comparative studies against other interventions, and single-center long-term outcomes suggest the efficacy to be at least equivalent to that of transurethral resection of the prostate, with a very good safety profile. New technological developments promise to further enhance the utility of this laser for application in BPH and urology.     

Is There a Role for alpha-Blockers for the Treatment of Voiding Dysfunction Unrelated to Benign Prostatic Hyperplasia?

alpha-Adrenoreceptor antagonists have become the primary medical treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). It was presumed that the primary mechanism by which alpha-blockers reduced lower urinary tract symptoms (LUTS) was by relaxation of smooth muscle in the prostate through a sympathetic response. Reduction of outlet resistance leads to changes in bladder function, thus improving both storage and voiding symptoms. However, it was observed that many patients with BPH-associated LUTS had significant improvement in storage symptoms without subjective or objective improvement in voiding. Storage symptoms associated with detrusor overactivity (frequency, urgency, and urge incontinence) are typically thought of as being parasympathetically mediated, and therefore anticholinergic medications have been the mainstay of pharmacological treatment, but recent work has suggested that several nonparasympathetic-mediated mechanisms may cause detrusor overactivity. Because alpha receptors appear to play a role in lower urinary tract function at multiple sites and levels, alpha-blockers could be used to treat voiding dysfunction not related to BPH. In addition, these nonprostate effects should be gender-independent, making the use of alpha-blockers plausible in women with specific types of voiding dysfunction.     

Medical treatment of benign prostatic hyperplasia

Medical therapy for the treatment of benign prostatic hyperplasia (BPH) became an accepted standard of care in the 1990s following the reports of randomized, double-blind, placebo-controlled studies showing that finasteride, a 5-α reductase inhibitor, and terazosin, an α-blocker, significantly improved lower urinary tract symptoms and increased peak urinary flow rates in men with BPH. This article reviews novel approaches to the pharmacological treatment of BPH.     

Validity of the "bother score" in the evaluation and treatment of symptomatic benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a condition that is common among older men. It causes a variety of clinically significant lower urinary tract signs and symptoms. BPH is rarely life-threatening; the decision to seek treatment is frequently based on the degree to which patients find the symptoms bothersome and disruptive of daily activities. Recently developed reliable and valid outcome measures to evaluate treatments for BPH are clinical tools that urologists can use to determine the extent of bother and make treatment decisions. A single question used to determine the "bother score" provides a widely used and statistically valid measure of the need for treatment of BPH. Validation data support the argument that the bother score is a statistically reliable measure of treatment outcome in patients with BPH who view their symptoms as bothersome.     

Advances in stem cell therapy for the lower urinary tract

Lower urinary tract diseases are emotionally and financially burdensome to the individual and society. Current treatments are ineffective or symptomatic. Conversely, stem cells (SCs) are regenerative and may offer long-term solutions. Among the different types of SCs, bone marrow SCs (BMSCs) and skeletal muscle-derived SCs (SkMSCs) have received the most attention in pre-clinical and clinical trial studies concerning the lower urinary tract. In particular, clinical trials with SkMSCs for stress urinary incontinence have demonstrated impressive efficacy. However, both SkMSCs and BMSCs are difficult to obtain in quantity and therefore neither is optimal for the eventual implementation of SC therapy. On the other hand, adipose tissue-derived SCs (ADSCs) can be easily and abundantly obtained from "discarded" adipose tissue. Moreover, in several head-on comparison studies, ADSCs have demonstrated equal or superior therapeutic potential compared to BMSCs. Therefore, across several different medical disciplines, including urology, ADSC research is gaining wide attention. For the regeneration of bladder tissues, possible differentiation of ADSCs into bladder smooth muscle and epithelial cells has been demonstrated. For the treatment of bladder diseases, specifically hyperlipidemia and associated overactive bladder, ADSCs have also demonstrated efficacy. For the treatment of urethral sphincter dysfunction associated with birth trauma and hormonal deficiency, ADSC therapy was also beneficial. Finally, ADSCs were able to restore erectile function in various types of erectile dysfunction (ED), including those associated with diabetes, hyperlipidemia, and nerve injuries. Thus, ADSCs have demonstrated remarkable therapeutic potentials for the lower urinary tract.     

Quality of life and sexual function in patients with benign prostatic hyperplasia

Incidence of benign prostatic hyperplasia (BPH), one of the most common conditions affecting adult men, increases dramatically after the age of 50. The various symptoms of BPH, which include lower urinary tract symptoms (LUTS), can adversely affect quality of life (QOL). Many men with BPH and LUTS wait until symptoms become significantly bothersome before seeking medical attention. Evaluating the exact severity and significance of symptoms has been difficult with previous methodology. Over the last decade, assessment tools have become available to quantify the symptoms of BPH and LUTS. This article addresses the impact of BPH, its management, and the overall effects it has on QOL.     

Preventing progression in men with mild symptoms of benign prostatic hyperplasia: a potential role for phytotherapy

Prevalence of benign prostate hyperplasia (BPH) is increasing with the aging population worldwide. Throughout the 20th century, men with minimally symptomatic BPH were generally advised to defer treatment. Treatment deferral or watchful waiting has always appeared reasonable because mild lower urinary tract symptoms suggestive of bladder outlet obstruction are not bothersome and are often regarded as part of the aging process, progression is usually slow, and symptoms often regress spontaneously. This review examines the evidence of the natural history of BPH, highlighting the group of patients with mild symptoms, the risk factors for progression, and the potential role of phytotherapy in this group of men.     

La dysfonction érectile associée à une hypertrophie bénigne de prostate (HBP) symptomatique: son lien avec le stade évolutif de l’HBP, et son évolution sous différentes thérapeutiques

Introduction

Although the relationship between the lower urinary tract symptoms (LUTS) and the erectile dysfunction (ED) is no more debated, its underlying mechanism remains obscure so far. Several studies emphasized the correlation between the severity of LUTS and the sexual function, and the impact of the different medications used. This study is the first to highlight the association between the stage of evolution of BPH (complicated and noncomplicated BPH) and the severity of the ED.

Objectives

To assess the correlation between ED and the stage of evolution of BPH, and to evaluate the impact of different medications on ED.

Patients and methods

This is a prospective trial relating of 100 patients admitted for urologic consultation, in the Universitary Hospital Center of Fez in Morocco, in a period of 12 months. To evaluate the severity of ED, we used International Index of Erectile Function (IIEF). In our patients, it was not possible to use the International Prostate Symptom Score (IPSS) to assess the severity of urinary symptoms, and it was not possible to date exactly the beginning of LUTS. Hence, we studied patients’ age, the stage of evolution of BPH (complicated or noncomplicated BPH) and the response of the ED to different treatments.

Results

The average man age was 64.3 years. Forty patients had complicated BPH and 60 patients had noncomplicated BPH. Thirty patients (75%) among 40 with complicated BPH had severe ED, whereas an ED rate of 33% (20 patients) was noticed in patients presenting with noncomplicated BPH. Alpha-blockers (tamsulosin) improved erectile function in 12 patients (20%) among those with noncomplicated BPH. Patients presenting with complicated BPH underwent surgical procedure (either transurethral resection of the prostate or open prostatectomy). Erectile function was not statistically improved in this group of patients.

Conclusion

ED showed a correlation with the stage of evolution of symptomatic BPH. Indeed, the risk of ED is higher in patients with complicated BPH. The alphablockers improved the erectile function in the group of noncomplicated BPH, contrary to the surgical approach.     

Les inhibiteurs de la phosphodiestérase de type 5 : une révolution dans le traitement des sympt?mes du bas appareil urinaire?

Context

The incidence of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) increases with age, affecting 50% of patients aged over 50 years and 90% of those aged over 80 years. The prevalence and severity of erectile dysfunction (ED) also increase with age. Its prevalence is estimated to be 31.6% in men over 40 years. LUTS as well as ED significantly affect the quality of life of patients and their partners. Several studies have shown that LUTS represent an independent risk factor for ED. The severity of LUTS is correlated with that of ED. The pathophysiological hypothesis linking LUTS to ED are an increase in sympathetic tone, alteration of NO/cGMP system, alteration of rho kinase system, and pelvic atherosclerosis.

Goal

Some treatments of LUTS have adverse effects on the erectile function. The phosphodiesterase type 5 inhibitors (IPDE 5) revolutionized the treatment of ED.

Material and methods

Several recent clinical studies evaluated the effect of daily treatment by IPDE 5 on LUTS secondary to BPH among patients with or without ED.

Results

This review shows that IPDE 5 administration improves LUTS significantly in 12 randomized clinical trials, as well as in both storage and voiding parts of the international prostate symptom score (IPSS) and in quality of life questionnaire. No adverse events were observed, and ED, which has a high prevalence among this population, was also improved.

Conclusion

The treatment of LUTS by IPDE 5 looks very promising, even though they are not yet approved for this indication in France.     

Landmark studies impacting the medical management of benign prostatic hyperplasia

The treatment of benign prostatic hyperplasia (BPH) has changed dramatically over the past 10 years. Phase 3 studies of the safety and effectiveness of alpha-blockers (eg, terazosin and doxazosin) and 5-alpha-reductase inhibitors (eg, finasteride) for the treatment of BPH began to appear in the literature in 1992. This article reviews the results of landmark studies of these agents, either separately as monotherapy or as combined therapy, for the treatment of BPH. The relationship between prostate size and lower urinary tract symptoms (LUTS) is discussed. Although prostate volume is not as strongly correlated with these symptoms as was once believed, it has been shown to be an important predictor of risk for developing acute urinary retention. alpha-Blockers represent an effective treatment for LUTS independent of prostate volume; the clinical benefit of finasteride for LUTS is limited primarily to men with large prostates. Finasteride decreases the risk of progression to acute urinary retention and the requirement for surgical intervention; this benefit is greatest in men with enlarged prostates.     

Evaluating men with benign prostatic hyperplasia

The clinical manifestations of benign prostatic hyperplasia (BPH) include lower urinary tract symptoms (LUTS), poor bladder emptying, urinary retention, detrusor instability, urinary tract infection, hematuria, and renal insufficiency. However, the majority of men with BPH present with LUTS only. Because LUTS can indicate a variety of conditions, evaluation of symptomatic men must first aim to identify or exclude BPH and, if present, assess its severity. It is important to assess symptom severity at baseline and during follow-up, using the American Urological Association Symptom Index or the International Prostate Symptom Score. Further testing can then be tailored to narrow the diagnosis and guide treatment decisions. Factors such as patient age and concomitant malignancy will also affect management, but the main goal of treatment remains the improvement of quality of life for the patient.     

Medical therapy for benign prostatic hyperplasia: new terminology, new concepts, better choices

This article discusses 3 areas of medical therapy for benign prostatic hyperplasia (BPH) that are undergoing extensive research and evaluation: 1) the use of muscarinic receptor antagonists to treat lower urinary tract symptoms (LUTS) in men with BPH; 2) the definition of an "enlarged prostate"; and 3) sexual function and LUTS. Fears of worsening obstructive symptoms or causing acute urinary retention often keep practitioners from prescribing muscarinic receptor antagonists to men who might have concomitant bladder outlet obstruction; a multicenter, multinational, double-blind study showed that tolterodine is safe for men with low postvoid residual volumes. Most urologists accept that a prostate volume of more than 40 mL is consistent with an enlarged prostate; there is more debate regarding prostate volumes of 30 to 40 mL. Recently presented data suggest that combination medical therapy might be effective for men having prostates with volumes of more than 25 mL. The association between voiding and sexual function has been increasingly recognized and investigated, and there seem to be common pathophysiologic mechanisms governing both conditions. Targeted treatment algorithms addressing both conditions seem warranted.     

Androgens and estrogens in benign prostatic hyperplasia: past, present and future

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5α-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17β. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs.     

The role of gonadotropin-releasing hormone antagonists for the treatment of benign prostatic hyperplasia

Medical therapy is the preferred first-line approach in the management of lower urinary tract symptoms in men with benign prostatic hyperplasia. The magnitude of the improvement in lower urinary tract symptoms observed in response to combination therapy (alpha-blocker plus 5-alpha reductase inhibitors) does not approach that achieved with prostatectomy. Various drugs have been under consideration, including BXL628, lonidamine, and phosphodiesterase inhibitors, all of which have had unacceptable side effects. The gonadotropin-releasing hormone antagonist cetrorelix is associated with dose-dependent symptom improvement and reduction of prostate volume. Elucidating the mechanism for cetrorelix-mediated improvement in lower urinary tract symptoms will likely contribute to unraveling the pathophysiology of lower urinary tract symptoms in men.     

Prevalence of spina bifida occulta in patients with functional disorders of the lower urinary tract and its relation to urodynamic and neurophysiological measurements.

OBJECTIVE--To determine the relation between neurophysiological abnormalities and the radiological detection of spina bifida occulta in patients with dysfunction of the lower urinary tract. DESIGN--Blind assessment and subsequent decoding of mixed batch of abdominal radiographs from patients with and without urological symptoms for evidence of spina bifida occulta and comparison of results with those of previous control series. SETTING--Review study among tertiary referrals to an incontinence clinic of a city hospital. PATIENTS--One hundred and thirty eight adults with proved urodynamic abnormalities in whom neurophysiological measurements were available. INTERVENTIONS--None. END POINT--Correlation of neurophysiological abnormalities in lower urinary tract dysfunction with presence and type of spina bifida occulta and level of opening of posterior sacral arcs. MEASUREMENTS AND MAIN RESULTS--On decoding radiographs those from patients without urological symptoms showed a similar prevalence of spina bifida occulta to that in the control series (631/2707 controls; 23%). By contrast, patients with urological symptoms had a significantly increased prevalence of spina bifida occulta at S1 and S2 and a higher level of opening of posterior sacral arcs. The increased prevalence of the bony defect was particularly striking in men with urgency and instability and in women with stress incontinence. No significant correlation was found between any particular neurophysiological abnormality and the presence of spina bifida. CONCLUSIONS--In patients with dysfunction of the lower urinary tract neurophysiological abnormalities may be associated with congenital dysraphic lesions in the lower lumbar spine and sacrum. There appears to be no direct causal relation between the radiological and neurophysiological abnormalities but the findings suggest a common aetiological factor.     

PPARγ: a molecular link between systemic metabolic disease and benign prostate hyperplasia

The emergent epidemic of metabolic syndrome and its complex list of sequelae mandate a more thorough understanding of benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) in the context of systemic metabolic disease. Here we discuss the nature and origins of BPH, examine its role as a component of LUTS and review retrospective clinical studies that have drawn associations between BPH/LUTS and type II diabetes, inflammation and dyslipidemia. PPARγ signaling, which sits at the nexus of systemic metabolic disease and BPH/LUTS through its regulation of inflammation and insulin resistance, is proposed as a candidate for molecular manipulation in regard to BPH/LUTS. Finally, we introduce new cell and animal models that are being used to study the consequences of obesity, diabetes and inflammation on benign prostatic growth.     

Clinical evaluation of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is the most common neoplastic condition afflicting men and constitutes a major factor impacting male health. Clinical evaluation to assess the presence and degree of voiding dysfunction and/or the role of BPH in its presence has an increasingly broad spectrum of treatment goals. The goals of the evaluation of such men are to identify the patient's voiding or, more appropriately, urinary tract problems, both symptomatic and physiologic; to establish the etiologic role of BPH in these problems; to evaluate the necessity for and probability of success and risks of various therapeutic approaches; and to present the results of these assessments to the patient so he can make an informed decision about management recommendations and available alternatives.     

老年男性脑卒中患者排尿功能障碍的尿动力学评估

目的:存在阻塞性尿路疾患的老年男性在发生脑血管意外后,是否可通过早期症状或排尿症状类型(梗阻性还是刺激性)来预判排尿功能障碍的病因。方法:选择57例脑卒中后主诉排尿障碍的老年男性患者,所有患者均有继发于良性前列腺增生(BPH)的膀胱出口梗阻(BOO)症状。采集病史并行体检,57位患者均实行尿动力学检查,检查结果行A-G图分析并分类为:有梗阻,无梗阻及可疑梗阻。结果:患者平均年龄70岁(54-87),按排尿障碍的主诉类型分组(纯刺激症状42%,纯梗阻症状34%,两者混合24%),其中51例(89%)在脑卒中发生后即出现排尿症状,47(82%)例患者出现逼尿肌反射亢进(DH),在三组患者中无显著统计学差异。压力流率分析显示,36(63%)位患者有出口梗阻,无梗阻14(24%)例,可疑梗阻7(13%)例。在3组患者中亦无显著统计学差异。结论:所有老年男性患者呈现的症状不能预测膀胱出口梗阻或逼尿肌反射亢进的尿动力学结果。中风发生后排尿功能障碍症状的发生率明显升高,表明由脑血管意外引起的排尿功能障碍合并前期具有膀胱出口梗阻疾病时,可能会使后者的症状恶化,反之亦然。