Management of benign prostatic hyperplasia by the primary care physician in the 21st century: the new paradigm

Benign prostatic hyperplasia (BPH) is one of the commonest causes of lower urinary tract symptoms (LUTS) in men over age 50. Fifty percent of men over age 50 will require some type of management for BPH/LUTS symptoms. Until about 15 years ago, the most common management for BPH was a transurethral resection of the prostate (TURP) operation. Initially, once a diagnosis of BPH has been made, most men are treated medically. One must first rule out other serious causes of these symptoms, such as prostate cancer, bladder cancer, and other obstructions. For men with an enlarged prostate, there is a good chance that therapy with a 5-alpha-reductase inhibitor (5-ARI) can prevent disease progression and the need for surgery. There has been a lot of recent work on different combination therapies for the treatment of BPH/LUTS. If a patient's serum prostate-specific antigen (PSA) level is greater than 1.5 ng/ml and his prostate volume is greater than 30 cc and he has significant LUTS, then combination medical therapy of an alpha blocker with a 5-ARI is the most effective therapy. After a careful workup, it is quite reasonable and appropriate for the primary care physician to initiate this therapy for a patient with BPH/LUTS.     

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.     

Doxazosin in the treatment of benign prostatic hypertrophy: an update

We evaluated the efficacy and safety of a1 - blocker doxazosin for treatment of lower urinary tract symptoms (LUTS) compatible with benign prostatic hypertrophy (BPH). Fourteen randomized controlled trials enrolled 6261 men, average age 64 years, who had moderately severe LUTS and flow impairment. Compared with baseline measures and placebo effect, doxazosin resulted in a statistically significant improvement in both LUTS and flow. However, when compared with placebo, the average magnitude of symptom improvement (International Prostate Symptom Score [IPSS] improvement <3 points) typically did not achieve a level detectable by patients. Combined doxazosin and finasteride therapy improved LUTS and reduced the risk of overall clinical progression of BPH compared to each drug separately in men followed over 4 years. Reported mean changes from baseline in the IPSS were −7.4, −6.6, −5.6, and −4.9 points for combination therapy, doxazosin, finasteride, and placebo, respectively. Combination therapy reduced the need for invasive treatment for BPH and the risk of long-term urinary retention. The absolute reductions compared with placebo were less than 4% and primarily seen in men with prostate gland volume >40 mL or PSA levels >4 ng/mL. Efficacy was comparable with other a1–blockers. Withdrawals from treatment for any cause were comparable to placebo. Dizziness and fatigue occurred more frequently with doxazosin compared to placebo.     

Current Understanding of the Interplay between Oab & Bph

Lower urinary tract symptoms (LUTS) are very common and bothersome to men. For many years all male LUTS, even the storage ones, were attributed to the prostate, which was the target of therapeutic approaches. Increasing knowledge of the contribution of bladder dysfunction to LUTS pathophysiology has brought into focus detrusor overactivity (DO) and its treatments. Available data indicate that in many cases DO and overactive bladder (OAB) symptoms are secondary to bladder outlet obstruction (BOO), due to prostatic disease. Accumulating evidence also suggests that the two pathologies may coexist because they share etiologic factors. Despite the prevalence of storage symptoms in men with benign prostatic hyperplasia (BPH), antimuscarinics, the main treatment for OAB, were infrequently used because of fear of urinary retention. Available clinical trials indicate that the addition of an antimuscarinic to prostate-targeted treatments, or treatment initiation with a combination regimen, is safe in terms of urinary retention and offers improvements in storage symptoms. Nevertheless, the improvement in overall quality of life is modest. Criteria for the selection of patients likely to benefit most from the addition of antimuscarinics to common BPH treatments are lacking.     

Medical management of benign prostatic hypertrophy

Benign prostatic hyperplasia (BPH) is a common condition of the aging male. The bladder outlet obstruction caused by this condition occurs despite variations in prostate size. Symptoms of BPH include the irritative and obstructive voiding symptoms termed lower urinary tract symptoms (LUTS). While transurethral surgery has long been the gold standard for treatment of LUTS, medical treatment has emerged as the first line of treatment for those men who fail expectant or watchful waiting treatment. Medical options include: alpha blockers, 5alpha-reductase inhibitors and newly identified PDE 5 inhibitors, drugs for erectile dysfunction that have a relieving effect on the symptoms of LUTS. Newer prostate selective alpha blockers have replaced older nonselective agents as first choice in treatment of most men, especially those with smaller prostates and in whom preservation of sexual function is important. While tamsulosin has the effect of an ejaculation, alfuzosin preserves ejaculatory function. 5alpha-reductase inhibitors may decrease ejaculate volume, libido and sexual function. While this effect is frequently a self limited, it can be a compliance issue for many men. PDE 5 inhibitors, while effective in relieving LUTS symptoms, have not shown effectiveness in reducing post void residual volumes or increasing urinary flow rates.     

Update on the use of dutasteride in the management of benign prostatic hypertrophy

Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary symptoms, with a prevalence of 50% by the sixth decade of life. Hyperplasia of stromal and epithelial prostatic elements that surround the urethra cause lower urinary tract symptoms (LUTS), urinary tract infection, and acute urinary retention. Medical treatments of symptomatic BPH include; 1) the 5α-reductase inhibitors, 2) the α1-adrenergic antagonists, and 3) the combination of a 5α-reductase inhibitor and a α1-adrenergic antagonist. Selective α1-adrenergic antagonists relax the smooth muscle of the prostate and bladder neck without affecting the detrussor muscle of the bladder wall, thus decreasing the resistance to urine flow without compromising bladder contractility. Clinical trials have shown that α1-adrenergic antagonists decrease LUTS and increase urinary flow rates in men with symptomatic BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. Inhibitors of 5α-reductase decrease production of dihydrotestosterone within the prostate resulting in decreased prostate volumes, increased peak urinary flow rates, improvement of symptoms, and decreased risk of acute urinary retention and need for surgical intervention. The combination of a 5α-reductase inhibitor and a α1-adrenergic antagonist reduces the clinical progression of BPH over either class of drug alone.     

Effects of warm needling therapy on symptoms of benign prostatic hyperplasia: A protocol for a systematic review and meta-analysis

Background:Benign prostatic hyperplasia (BPH) is the term for a type of non-malignant prostate enlargement that is most often diagnosed in men of middle age and older. Lower urinary tract symptoms (LUTS) are commonly observed in men afflicted with BPH. Evidence suggests that warm needling therapy could be applied clinically to relieve the LUTS associated with BPH, particularly in China, where experienced practitioners are readily available. In this review, the safety and effects of warm needling therapy are assessed in the context of treatment for LUTS associated with BPH.Methods:First, data for relevant randomised controlled trials and the initial periods of randomised cross-over trials will be obtained from four English databases (MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and Allied and Complementary Medicine Database) and six Chinese databases (China National Knowledge Infrastructure, Wanfang Database, SinoMed, Chongqing VIP Chinese Science and Technology Periodical Database, China Master''s Theses Full-text Database and China Doctoral Dissertations Full-text Database). The primary outcomes analysed in this protocol are improvements in urological symptoms as measured by recognized urological symptom scores, while secondary outcomes include improvement of urine flow rate measures, residual urine volume, nocturia, prostate size, and quality-of-life score. In addition, safety outcomes will be analysed by assessing incidences of adverse events. Two reviewers will independently assess and select studies, extract data and assess the risk of bias. Data synthesis and risk bias assessment will be performed with Review Manager software (version 5.3).Results:This systematic review provides a synthesis to assess the therapeutic efficacy of warm needling therapy for LUTS associated with BPH.Conclusion:The present study will provide a clinically relevant evaluation of the current state of evidence regarding the therapeutic efficacy of warm needling therapy for LUTS associated with BPH.Ethics and dissemination:Ethical approval is not required for this review, because private information will not be collected from the included participants. The results of the study will be published in a peer-reviewed journal.Registration number:PROSPERO CRD42020198360.     

Anticholinergics in men: Does the evidence support combination therapy?

Benign prostatic hyperplasia (BPH) is common in men older than age 50, and the symptoms occurring from bladder outlet obstruction (BOO) commonly overlap with lower urinary tract symptoms (LUTS) experienced in overactive bladder (OAB). Anticholinergics are often withheld from men with BOO. This article reviews seven randomized controlled trials (RCTs) and a meta-analysis study examining anticholinergic use in men with LUTS associated with OAB and BPH. There is growing evidence that anticholinergics are a suitable, safe treatment in men with persistent LUTS associated with BOO, refractory to α-blockers. Only four of 750 men treated with anticholinergics in the seven RCTs reviewed had acute urinary retention. Further well-designed, placebo-controlled RCTs are required to assess the efficacy and long-term safety outcomes of combination therapy. However, it appears feasible to effectively use adjunctive anticholinergic therapy in men with LUTS/BPH and no significant increase in postvoid residual volume.     

Medical therapy options for aging men with benign prostatic hyperplasia: focus on alfuzosin 10 mg once daily

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging men and can significantly affect quality of life. Men with bothersome LUTS/BPH often present with various other age-related conditions, including sexual dysfunction, heart disease, hypertension, diabetes, and the metabolic syndrome, which can complicate management decisions. Therefore, healthcare providers should be familiar with first-line treatment options for LUTS/BPH and their differing safety profiles, particularly with respect to cardiovascular and sexual function side effects. This article presents a review of first-line medical therapy options for managing aging men with LUTS/BPH and patient considerations when evaluating and selecting these therapies, with a focus on the clinical efficacy and cardiovascular and sexual function safety profiles of the uroselective α₁-adrenergic receptor antagonist alfuzosin 10 mg once daily. Alfuzosin improves LUTS, peak urinary flow rates, and disease-specific quality of life, reduces the long-term risk of overall BPH progression, and is well tolerated in aging men, with minimal vasodilatory and sexual function side effects, even in those with comorbidities. Alfuzosin is well tolerated when used in combination with antihypertensive medications and phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction. The long-term clinical efficacy and good cardiovascular and sexual function safety profile of alfuzosin can contribute to an improved quality of life for aging men with LUTS/BPH.     

Medical Treatment of BPH: An Update on Results

Benign prostatic hyperplasia (BPH) is a common condition in older men, resulting in chronic lower urinary tract symptoms (LUTS) that are bothersome and cause impaired physiological and functional well-being and interference with activities of daily living. BPH is rarely life-threatening, but it can lead to acute urological problems, for example acute urinary retention (AUR). The clinical manifestations of BPH include LUTS, poor bladder emptying, urinary retention, detrusor instability, urinary tract infection, hematuria, and renal insufficiency. Surgery remains the most effective treatment for complicated or severe symptomatic BPH, especially where medical treatment has failed. Its invasive nature and potential side-effects have led to the development of potentially less traumatic techniques and the widespread adoption of medical strategies. Medical management continues to evolve and refinements are aimed at achieving reduced frequency of dosage and achieving minimal side-effects, while maintaining clinical efficacy. In the current era of male health promotion the number of men who seek and receive treatment for uncomplicated BPH continues to rise. Thus the medical management of BPH is likely to continue playing an important role in the future.     

PDE5-Is for the Treatment of Concomitant ED and LUTS/BPH

Epidemiologic data in adult men exhibit a strong relationship between erectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), indicating that men affected by ED should also be investigated for LUTS/BPH and those presenting with storage or voiding LUTS should be investigated for co-morbid ED. Common pathophysiolgical mechanisms underlying both LUTS/BPH and ED, including alteration of NO/cGMP or RhoA/Rho-kinase signaling and/or vascular or neurogenic dysfunction, are potential targets for proposed phosphodiesterase type 5 inhibitors (PDE5-Is). Several randomized controlled trials and only a few reviews including all commercially available PDE5-Is demonstrated the safety and efficacy of these drugs in the improvement of erectile function and urinary symptoms, in patients affected either by ED, LUTS, or both conditions.     

Management of overactive bladder and lower urinary tract symptoms in men

According to prevailing clinical wisdom, most male lower urinary tract symptoms have been ascribed to disorders of the bladder outlet and the prostate gland in particular. Therefore, most pharmacologic therapy and surgical therapy has been directed toward the prostate. However, emerging laboratory and clinical data suggest that the bladder may be an important factor in the genesis of male lower urinary tract symptomatology, often independent of bladder outlet disorders. Overactive bladder, a diagnosis given to women with urinary frequency, urgency, and nocturia, clearly also occurs in men. In this context, and with the proliferation of various terminology changes describing lower urinary tract function, it is increasingly important to use precise and correct terminology when referring to male voiding symptoms and their treatment. Further, the traditional application of pharmacologic therapy for male lower urinary tract symptoms (LUTS) is undergoing changes, with antimuscarinics being used in some men with LUTS either alone or in combination with other oral therapies such as α-blockers. The therapy for LUTS in men will continue to evolve as newer agents in various pharmacologic classes become available.     

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.     

Relationship among serum testosterone, sexual function, and response to treatment in men receiving dutasteride for benign prostatic hyperplasia

CONTEXT: Although benign prostatic hyperplasia (BPH) is an androgen-dependent disorder, little is known regarding the influence of serum testosterone levels on sexual or prostate function or clinical response to dutasteride. OBJECTIVE: The objective of the study was to explore these relationships in a large cohort of men treated with dutasteride for BPH. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: Among 4254 men with BPH participating in 2-yr placebo-controlled dutasteride trials, 27% had a pretreatment serum testosterone less than 300 ng/dl. These 1162 men were divided into seven groups based on their serum testosterone level (<150, 150-174, 175-199, 200-224, 225-249, 250-274, and 275-299 ng/dl) and compared with men with normal baseline serum testosterone (BST; > or = 300 ng/dl). Questionnaires were used to assess sexual function, prostate-specific antigen (PSA), and prostate volume to assess androgenic stimulation of the prostate and the American Urological Association Symptom Index to assess clinical responses. RESULTS: Although lower BST was associated with increased sexual dysfunction, this increase was not seen until BST was less than 225 ng/dl. There was no decrease in baseline PSA and prostate volume at low BST levels. Dutasteride was effective at decreasing PSA and prostate volume and improving BPH symptoms at all BST levels. CONCLUSIONS: In men with BPH, the frequency of sexual dysfunction increases at serum testosterone concentrations less than 225 ng/dl. However, PSA and prostate volume were similar at all testosterone levels, explaining why BPH can occur in men that would otherwise be considered hypogonadal. The fact that dutasteride is also effective in men with normal and low testosterone levels suggests that the high levels of 5alpha-reductase and dihydrotestosterone in the prostate allow the development and progression of prostatic hyperplasia, even at low circulating testosterone levels.     

Tadalafil Administered Once Daily for Treatment of Lower Urinary Tract Symptoms in Korean men with Benign Prostatic Hyperplasia: Results from a Placebo‐Controlled Pilot Study Using Tamsulosin as an Active Control

Objectives: Assess the efficacy and safety of once‐daily tadalafil or tamsulosin versus placebo during 12 weeks on lower urinary tract symptoms (LUTS) in Korean men with benign prostatic hyperplasia (BPH). Methods: Following a 4‐week placebo run‐in period, 151 Korean men were randomly assigned to receive once‐daily tadalafil 5 mg, tamsulosin 0.2 mg, or placebo for 12 weeks. Results: The International Prostate Symptom Score (IPSS) least squares mean changes from baseline to endpoint were numerically but not significantly improved in the tadalafil (?5.8) and tamsulosin (?5.4) groups compared with placebo (?4.2, P > 0.05). Decreases in IPSS obstructive and irritative subscores, IPSS Quality of Life score, and BPH Impact Index from baseline to endpoint were largest in the tadalafil group followed by tamsulosin, though none separated significantly from placebo. Increases in maximum urinary flow rate were small and not significantly different than placebo; the increase was largest in the tadalafil group (2.5 mL/sec), followed by the placebo (2.3 mL/sec) and tamsulosin (2.1 mL/sec) groups. The percentage of subjects reporting at least one treatment‐emergent adverse event was 26.5, 13.7 and 3.9% in the tamsulosin, tadalafil and placebo groups, respectively. Conclusions: In this pilot study in Korean men, those with BPH and treated with tadalafil 5 mg or tamsulosin 0.2 mg once daily experienced a reduction in LUTS, which was numerically (but not statistically) significant compared with the placebo. Tadalafil was well tolerated and few subjects discontinued the study due to treatment‐emergent adverse events. Larger studies in Asian men with BPH and LUTS treated with phosphodiesterase type 5 inhibitors are needed.     

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.     

Efficacy of Additional Dutasteride on Lower Urinary Tract Symptoms in Patients with Alpha‐1 Blocker‐Resistant Benign Prostatic Hyperplasia

Objective: We investigated the effects of dutasteride on urination and quality of life (QOL) in patients diagnosed with benign prostatic hyperplasia (BPH) who showed poor improvement in lower urinary tract symptoms (LUTS) with alpha‐1 blockers. Methods: We retrospectively analyzed 108 patients with BPH who took dutasteride for more than 3 months from October 2009 to October 2011. The patients showed poor improvement in LUTS despite administration of alpha‐1 blockers for more than 3 months; all had an International Prostate Symptom Score (IPSS) of eight or greater. We investigated changes in prostate‐specific antigen and prostate volume and performed uroflowmetry and medical interviews to assess IPSS‐QOL score and BPH impact index (BII). Results: Mean prostate volume was 52.8 ± 22.2 mL, and the mean period of dutasteride administration was 284 ± 118 days. Prostate volume decreased 24.1% from baseline to 6 months after administration. Voiding symptoms and storage symptoms showed improvements with longer administration periods, but only nocturia showed no clear improvement. There was a 0.9‐point decrease in BII after 6 months. There was no statistically significant association between the rate of prostate volume reduction and improvement in voiding and storage symptoms. Conclusion: Additional administration of dutasteride to patients with alpha‐1 blocker‐resistant BPH led to improvements in all voiding and storage symptoms except nocturia, and showed no correlation between the prostate volume reduction rates and improvement in LUTS.     

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.     

Management of Lower Urinary Tract Symptoms in Men

Abstract. This clinical update, written for the non‐urologist, aims to highlight the important concepts behind understanding and treating men with uncomplicated lower urinary tract symptoms (LUTS). In the last five years there have been important changes in the preferred terminology and guidelines for managing men with voiding symptoms. In particular, the assessment of a patient's degree of bother is the most important factor when making management decisions for men with uncomplicated LUTS. Although this clinical update does not attempt to address the management of prostate cancer it does include some brief guidelines on prostate specific antigen (PSA) testing. The following information is based on the NH&MRC Clinical Practice Guidelines, published 1996 [1]. It is acknowledged that opinion remains divided among urologists concerning some of these guidelines.