Managing patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

Many men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia can be managed safely and effectively by primary care providers. After a basic evaluation to exclude other diseases that may cause lower urinary tract symptoms, quantifying the degree of symptoms and bother, and perhaps making an assessment of prostate size, the primary care provider can determine which men require immediate evaluation by a urologist and which men may choose among various treatment options, including watchful waiting and various single agent or combination medication strategies. Recent information about risk factors for disease progression has also helped to inform patient decisions on which treatment option is best for the individual patient. The purpose of this review is to provide primary care providers with an approach to the management of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.     

Natural History of Lower Urinary Tract Symptoms Secondary to BPH

In the past, “clinical benign prostatic hyperplasia” was used as a term indicating urinary symptoms accompanied by benign prostatic hyperplasia. However, there were no definitive criteria for this condition. Although we empirically knew that prostate size was associated with lower urinary tract symptoms, urinary flow rate, acute urinary retention, and prostatectomy, there was no definitive evidence about these experiences. To understand this condition with a lack of diagnostic criteria, it is necessary to understand its natural history based on reliable epidemiological data. Community-based and population-based studies are suitable methodologies to investigate this natural history because these studies are more representative of men in general with limited bias. However, there have been only a few community-based studies about lower urinary tract symptoms suggestive of benign prostatic hyperplasia including the prostate volume. The most famous ones were conducted in Olmsted County in the U.S., Shimamaki-mura in Japan and Krimpen in Netherlands. In this article, we mainly review the results from these three cross-sectional and longitudinal community-based studies on BPH and LUTS.     

Saw palmetto and lower urinary tract symptoms: what is the latest evidence?

The use of dietary supplements for treating a wide range of health conditions has grown rapidly in the United States. In the field of men’s health, the most common dietary supplement used is an extract of the berry of the saw palmetto plant, with which men commonly self-medicate in order to treat lower urinary tract symptoms. Throughout the past two decades, substantial literature has emerged examining the biologic and clinical effects of saw palmetto extracts. Several lines of evidence suggest that saw palmetto may exert physiologic effects consistent with a beneficial clinical effect on the mechanisms of benign prostatic hyperplasia. Although most clinical studies tend to suggest a modest efficacy benefit of saw palmetto, more recent studies are less consistent and the precise clinical value of saw palmetto for treating lower urinary tract symptoms remains undefined. Overall, there appear to be few safety concerns with short-term use of this herbal medicine, although large-scale and longer-term safety studies have not been performed. Higher-quality studies are currently underway to better define the potential benefits and risks of plant-based extracts for treating symptoms related to benign prostatic hyperplasia.     

Benign prostatic hyperplasia

In both ageing men and women, there is an increasing incidence of lower urinary tract symptoms (LUTS) which are increasing. These infections have many possible causes, including smooth muscle dysfunction, neurological factors and benign prostatic hyperplasia. Up to 15% to 25% of men aged 50-65 years have LUTS of sufficient severity to interfere with their quality of life. Although benign prostatic hyperplasia is an important cause of these symptoms, and can have serious consequences, clinicians should be aware of these other causes so that the appropriate diagnosis is made before invasive treatments are started. New medical treatments, including alpha-adrenergic blocking agents and 5 alpha-reductase inhibitors mean that many men without complications such as infection, bleeding, or chronic retention, and with mild to moderate symptoms, should be managed in primary care. Combined local protocols between primary and secondary care will help to establish which men with persistent symptoms or complications need referral for a urological opinion to determine the need for further investigation and more invasive forms of management. We review the pathophysiology of the disease, and current approaches to investigation and management of this common problem.     

High Rates of Prostate-specific Antigen Testing in Men with Evidence of Benign Prostatic Hyperplasia

Purpose: Benign prostatic hyperplasia is common among men who may be candidates for prostate cancer screening using prostate-specific antigen (PSA) testing. Patterns of PSA testing among men with evidence of benign prostatic hyperplasia have not been studied.Methods: We examined the prevalence and correlates of a self-reported history of PSA testing. In 1994, 33,028 US health professionals without prostate cancer aged 47 to 85 years provided information on prior PSA testing, lower urinary tract symptoms characteristic of benign prostatic hyperplasia, history of prostatectomy, and prostate cancer risk factors. In 1995, a subset of 7,070 men provided additional information on diagnosis and treatment of benign prostatic hyperplasia.Results: From 39% of men in their 50s to 53% of men in their 80s reported PSA testing in the prior year (P <0.0001 for trend with age). Men were more likely to report PSA testing if they had lower urinary tract symptoms characteristic of benign prostatic hyperplasia (age-adjusted odds ratio for severe symptoms 2.2, 95% confidence interval 1.8 to 2.6), a prior history of prostatectomy (age-adjusted odds ratio 1.1, 95% confidence interval 1.02 to 1.2), or a physician diagnosis of benign prostatic hyperplasia (odds ratio 1.9, 95% confidence interval 1.7 to 2.2; adjusted for age, signs or symptoms of benign prostatic hyperplasia, and prostate cancer risk factors).Conclusions: These US health professionals reported preferential use of PSA testing among men least likely to benefit from early cancer detection (older men) and among men most likely to have a false-positive PSA result (men with benign prostatic hyperplasia). Physician and patient education are needed to promote more rational and selective use of this screening test.     

Mode of action of α-adrenoceptor antagonists in the treatment of lower urinary tract symptoms

It generally is thought that the beneficial effect of α₁-adrenoceptor (AR) antagonists on lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia is caused mainly by relaxation of prostatic/urethral smooth muscle. However, the frail correlation between LUTS and prostatic enlargement or outflow obstruction have focused interest on the role of extraprostatic a-ARs in the pathogenesis of LUTS. However, the exact mode and sites of action of the α₁-AR antagonists used for the treatment of LUTS have not been established.     

Fact or fiction: What do the benign prostatic hyperplasia data tell us?

Benign prostatic hyperplasia (BPH) is the most common benign neoplasm in men. Our understanding of this condition has improved greatly over the years and recent advances have changed our approach to management. At the end of the 19th century, prostatic enlargement was treated effectively by bilateral orchiectomy. Unsurprisingly, this treatment option never gained widespread popularity. Less than 10 years ago, surgery and watchful waiting were the only considered treatment options for BPH. We now have a number of medical therapies and minimally invasive treatment options available that can effectively manage lower urinary tract symptoms secondary to benign prostatic obstruction. However, with increased choice comes the increased need for clarity in selection and application of these various treatment options. In the current environment of evidence-based clinical practice, awareness and interpretation of data from the numerous studies is paramount. The lessons learned from these trials should be reflected clearly in our practice, with clinical management based on fact, not fiction. In this review, we critically assess the available data and understanding of the management of BPH.     

Symptoms Predictive for Efficacy of Naftopidil in Patients with Benign Prostate Hyperplasia

Objectives: To evaluate the lower urinary tract symptoms predicting the efficacy of the α1‐adrenoreceptor (AR) antagonist naftopidil in patients with benign prostate hyperplasia. Methods: The efficacy of naftopidil was examined on the basis of changes in the international prostate symptom score (IPSS). All patients received naftopidil (50 mg/day) for 12 weeks. We defined a “responder” as a patient whose total IPSS improved by five or more points and assessed the lower urinary tract symptoms predicting the efficacy of treatment by performing multivariate and probit analyses. Results: Among 132 patients whose data could be analyzed, the efficacy rate was 50.8%. All IPSS items except the urgency score were significantly higher in the responders than the non‐responders before treatment, and all IPSS items were lower in the responders after treatment. In the responder group, significant improvements were observed in the total IPSS score, quality of life (QOL) index, maximum flow rate (Q_max), residual urine volume, and all IPSS items after treatment. In contrast, in the non‐responder group, no parameter except the QOL index improved significantly. The probit analysis demonstrated that the score for weak stream (≥3) or nocturia (≥4) in the IPSS were factors predicting an effective response to naftopidil treatment. Conclusions: Weak stream and/or nocturia are the key symptoms that predict the efficacy of naftopidil treatment in patients with benign prostatic hyperplasia. Those with a score of ≥3 for weak stream or of ≥4 for nocturia are expected to achieve a good response in the subjective symptoms with administration of naftopidil.     

Permixon: A review

Phytotherapy for benign prostatic hyperplasia and lower urinary tract symptoms has been popular in Europe and is becoming increasingly popular in the United States. The most popular agent has been an extract of Serenoa repens (saw palmetto berry). Numerous clinical trials have been performed and have indicated its efficacy and potential adverse side effects, which have been few. One of the limitations of phytotherapy in general is the lack of a standard formulation. This paper focuses on the Permixon brand of saw palmetto berry.     

Evaluation and Management of Urgency and Urge Urinary Incontinence in Men

The overactive bladder (OAB) syndrome is increasingly being recognized as a major contributor to the lower urinary tract symptoms in men previously thought to be only due to bladder outlet obstruction from benign prostatic hyperplasia. Medical and surgical treatments that have historically been used to treat women with OAB are being applied to men with great efficacy and a good safety profile. Additionally, treatments such as the β-3 agonist mirabegron, phosphodiesterase-5 inhibitors, sacral and peripheral neuromodulation, and intravesical botulinum toxin injection are promising emerging therapies for the OAB syndrome. This review discusses the evaluation of the male patient with OAB symptoms such as urgency and urge incontinence, and explores the different therapeutic options available for management of men with OAB.     

Metabolic syndrome and lower urinary tract symptoms secondary to benign prostatic hyperplasia

Increasing evidence recently has pointed toward a relationship between lower urinary tract symptoms (LUTS) and the presence of metabolic syndrome. This relationship has been supported by recent epidemiologic findings. Possible pathophysiologic links also have been proposed to explain the relationship between these two syndromes. The increasing prevalence of obesity in the United States makes this an increasingly relevant problem. Animal studies support a link between autonomic nervous system (ANS) overactivity and the development of urinary symptoms, low bladder compliance, compensatory prostatic hyperplasia, and blockage of the same using α-blockade. There appears to be a significant link between ANS overactivity as part of the metabolic syndrome and LUTS secondary to benign prostatic hyperplasia (BPH). However, it is unlikely that ANS overactivity could be responsible for the development of LUTS. Rather, ANS overactivity plays a key role in increasing the severity of LUTS above an intrinsic basal intensity that is determined by the genitourinary anatomic/pathophysiologic characteristics of each BPH patient. This paper defines metabolic syndrome as a collection of abnormalities, including being overweight (visceral abdominal fat distribution), dyslipidemia, hypertension, impaired glucose metabolism, elevated C-reactive protein (chronic inflammation), and autonomic-sympathetic overactivity, with insulin resistance as the hypothesized underlying pathogenic mechanisms.     

Comparison of Naftopidil 75 mg with Tamsulosin Hydrochloride 0.2 mg in the Treatment of Lower Urinary Tract Symptoms with Benign Prostatic Hyperplasia

Objective: To compare the efficacy of two α₁‐adrenoceptor antagonists, α_1D‐adrenoceptor‐selective naftopidil (Naf) 75 mg and α_1A‐adrenoceptor‐selective tamsulosin hydrochloride (Tam) 0.2 mg, for the treatment of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Methods: Seventy‐seven patients with LUTS secondary to BPH were enrolled. Data were gathered from patients retrospectively: 41 patients who were prescribed Naf 75 mg for 4 weeks and 36 patients who were prescribed Tam 0.2 mg for 4 weeks, respectively. The efficacy criteria were improvement in LUTS International Prostate Symptom Score (IPSS) and quality of life (QOL) scores after dosing. Results: Naf 75 mg significantly improved symptoms in all 11 categories (overall IPSS, incomplete emptying, voiding symptoms [Intermittency, poor flow and straining], storage symptoms [daytime frequency, urgency and nocturia frequency], QOL index, intermittency, poor flow, straining, daytime frequency, urgency, and nocturia frequency) (P < 0.05). Tam 0.2 mg significantly suppressed 10 of the 11 tested symptom categories except straining (P < 0.05). Comparison data of the two drugs tended to show Naf 75 mg had better efficacy on nocturia frequency than Tam 0.2 mg (P < 0.05). Conclusion: Naf 75 mg might show a better efficacy for LUTS with BPH in nocturia frequency than Tam 0.2 mg.     

Aquablation™: Early Clinical Results

The treatment of lower urinary tract symptoms due to bladder outlet obstruction secondary to benign prostatic enlargement is continually evolving. Aquablation is a new ablation modality which uses a high-velocity saline stream to ablate prostatic tissue via a transurethral approach. Using robot assistance and real-time transrectal ultrasound guidance, ablation is highly targeted, and hydrodissection negates the need for thermal energy apart from electrocautery for hemostasis. Early phase I and phase II clinical trials show aquablation has a promising safety profile and clinical efficacy. There have been no significant complications in human clinical trials, including urinary incontinence and sexual function-related adverse events. A larger multi-center randomized controlled trial is currently underway to validate these early findings.     

Update in the Use of Botulinum Toxin for the Treatment of Benign Prostatic Hyperplasia/ Lower Urinary Tract Symptoms

Over the past decade there are a number of encouraging reports of clinical success of intraprostatic injection of botulinum toxin A (BoNT/A) as a method of management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). The rational is a unique dual mechanism of action on the smooth muscle and glandular components of the prostate. BoNT is able to block the presynaptic release of acetylcholine from the parasympathetic efferent nerve. The efficacy may also result from an inhibitory on the ganglionic and post-ganglionic fibers of autonomic nervous system inducing diffuse atrophy and apoptosis of prostate glands. The injection of BoNT/A into the prostate is a minimally invasive outpatient alternative treatment of BPH/LUTS. To date, several studies have demonstrated the efficacy of intraprostatic injection of BoNT/A against symptomatic BPH and this article discusses the efficacy and safety of BoNT therapy for treatment of BPH /LUTS.     

Molecular Basis of α1-AR and its Clinical Application in Male LUTS Medical Therapy

Alpha1-adrenoceptor (??₁-AR) antagonists are now considered to be the first-line agents for the management for men with lower urinary tract symptoms associated with benign prostate hyperplasia (LUTS/BPH). A number of ??₁-AR antagonists are currently approved in the United States, Europe and Asia, all of which are generally well tolerated; however, there are differences in the efficacy and adverse effect profiles among the various ??₁-AR antagonists and patients. Recent molecular approaches have provided not only new knowledge about ??₁-AR subtypes (??_1a-, ??_1b- and ??_1d-AR) but also new strategies to improve the efficacy and reduce the adverse effects of LUTS medical therapy. Precious understanding of the subtype-specific roles of ??₁-AR provides a better strategy for LUTS medical treatment. Additionally, in the future, molecular approaches may enable personalized medicine for LUTS based on individual differences in the genetic background.     

Contemporary Combination Therapy in the Treatment of LUTS/BPH

The primary treatment of lower urinary tract symptoms thought to be associated with histological benign prostatic hyperplasia causing bladder outflow obstruction (LUTS/BPH) has evolved from an emphasis on surgical through to medical therapies. More recently there has been an increasing trend toward developing combination pharmacotherapy utilizing agents with differing mechanism of action aimed at the various pathophysiolgies potentially underpinning voiding and storage symptoms. The focus has been on clinical benefit such as reducing disease progression, acute urinary retention and need for BPH surgery in the case of alpha-blockers (AB) and 5-alpha-reductase inhibitor combination. This effect appears to be appropriate in the subset of men with larger prostates. Anti-muscarinics with AB is safe and effective treatment in those with bothersome storage symptoms and LUTS/BPH, although only confirmed as not associated with retention based on the existing literature for men with low PVR’s </=200 ml. Further studies with longer follow up are needed to establish long-term efficacy and safety of this combination. Phosphodiesterase inhibitors with AB is an emerging combination that has demonstrated considerable improvement in IPSS and in some cases flow rates in the small number of randomized studies conducted, confirmed by a recent meta-analysis. The major challenge in the future will be determining which specific groups of men are most likely to benefit from which combination therapies whilst considering cost implications and the potential for increased side effects consequent upon using two therapeutic classes in combination.     

Evaluation and Management of Lower Urinary Tract Symptoms After Outlet Surgery for Benign Prostatic Hyperplasia

There are many options available in the surgical treatment of outlet obstruction secondary to benign prostatic hyperplasia (BPH). While most patients exhibit improvement in their lower urinary tract symptoms (LUTS) following intervention, up to 35 % of patients may exhibit persistent or recurrent LUTS. In the present review, we discuss the pathophysiology of LUTS after bladder outlet surgery and discuss considerations in evaluating and managing such patients. We highlight the crucial role of thorough evaluation with complete urodynamics testing, as pure obstruction only accounts for a minority of post-operative LUTS. Hence, detrusor contractility, detrusor overactivity, urethral sphincter function, and urinary incontinence must be assessed to appropriately guide subsequent therapy and improve patients’ quality of life.     

Update on the Use of Phytotherapy for Voiding Symptoms

Phytotherapy—the use of plant extracts as medicine or health-promoting agents—is increasing in popularity. The most recent available survey, conducted in 2007 by the Centers for Disease Control and Prevention’s National Center for Health Statistics, showed that adults in the United States spent 33.9 billion dollars out of pocket annually on complementary and alternative medical therapies. Of that total, 14.8 billion dollars (44%) was spent on herbal or phytotherapy products. These remedies are commonly used to treat urologic disorders such as benign prostatic hyperplasia, lower urinary tract symptoms, chronic prostatitis/chronic pelvic pain syndrome, overactive bladder, and interstitial cystitis/painful bladder syndrome. Although these agents show some promise for symptom relief, their use remains controversial due to the lack of established mechanisms of action, efficacy, and safety. Clinical trials are often flawed, as most studies of small scale and short duration are; they are not blinded or controlled, and most have no placebo group.     

An Outcomes Review of Minimally Invasive Transurethral Convective Water Vapor Energy (WAVE) Therapy for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

The Rezūm® System utilizing convective water vapor energy (WAVE?) has been proven to safely and effectively ablate obstructive tissue of the prostate, including the median lobe. Clinical trials have demonstrated rapid and significant relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) while improving quality of life scores. Moreover, durability of these beneficial results has been demonstrated through 12 months of follow-up. The most common side effects include dysuria, urgency, and hematuria, which are typically of short duration. Importantly, erectile and ejaculatory functions are preserved. This thermal therapy can be performed in an outpatient or office setting under oral sedation, prostate block, or conscious IV sedation.     

Combination therapy for benign prostatic hyperplasia: Does size matter?

Lower urinary tract symptoms (LUTS) in men are often associated with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH). The current standard of care for men with LUTS is treatment with α-adrenergic receptor antagonists to reduce outlet tone or 5-α-reductase inhibitors to reduce prostatic volume. Up to 60% of men with BOO secondary to BPH have storage symptoms attributable to detrusor overactivity (DO), which makes treatment with anticholinergics, either alone or in combination, an attractive proposition. We present a review of the literature concerning the use of anticholinergic drugs in men with LUTS and focus on the studies that relate to enlarged prostate volumes. There have been a number of uncontrolled studies and one large, randomized controlled trial (RCT) evaluating anticholinergic drugs in men with LUTS, overactive bladder, and BPH. The results of these studies were not stratified by prostate size. A recent post-hoc analysis of the RCT, however, now provides data stratified by prostate size.