New Medical and Injectable Treatments for LUTS/BPH – Anticholinergics,PDE-5, and Botox

Although alpha-blockers, 5-alpha-reductase inhibitors and prostatectomy are clearly efficacious treatment options for men with LUTS/BPH, these therapies are less than perfect. This has led to the investigation of new treatment options for men with LUTS/BPH. Three of these new treatment options include anticholinergics, phosphodiesterase-5-inhibitors (PDE5I), and botulinum toxin A (BoNT-A). Of these, anticholinergics and PDE5I have demonstrated a clear efficacy in appropriately selected patients. On the other hand, despite initial promising data , recent studies have not supported a clear efficacy with intraprostatic BoNT-A. The literature on anticholinergics, PDE5I, and BoNT-A is reviewed. Areas for future research within the field are then presented along with guidelines for prescribing these therapies.     

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.     

The Link Between Benign Prostatic Hyperplasia and Sexual Dysfunction

Benign prostate hyperplasia (BPH) occurs in up to 50 % of men by age 50, and the incidence increases with age. The rate of erectile dysfunction (ED) in patients with BPH ranges from 30 to 70 %, but can be as high as 90.5 % in males aged over 50 years. BPH/lower urinary tract symptoms (LUTS) and sexual dysfunction (SD) can have a substantial negative impact on a man’s quality of life (QoL). Symptom severity and impact on QoL in each condition increase when LUTS and ED coexist. Age and erection change in patients with LUTS could also correlate with ejaculation dysfunction. However, urologists and primary care physicians appear to under-recognize SD in men with BPH/LUTS. We review the mechanisms of action, association, and effect of treatment between BPH and ED.     

广州地区老年科良性前列腺增生的诊断治疗现状

目的 了解广州地区老年科门诊伴有下尿路症状的良性前列腺增生(LUTS/BPH)患者的基本情况及诊治状况. 方法 对广州地区三家三级甲等医院的老年科门诊进行调查,对诊断为LUTS/BPH的患者进行生活的基本状况的问卷调查,同时对门诊医师开具的检查和治疗药物进行分析统计. 结果 6140例男性门诊患者中1824例拟诊LUTS/BPH,占29.7%.在有效回收的调查问卷的134例患者中,国际前列腺症状评分(IPSS)轻、中及重度者分别占24.5%、72.5%及3.0%.血清前列腺特异性抗原(PSA)异常率为37.3%.患者最常接受的检查是直肠指检(96.8%)、PSA(88.7%)和经腹B超(84.8%).医师开具的药物最常见为单独使用5-α还原酶抑制剂(44.7%);其次为α-受体拮抗剂及5-α还原酶抑制剂联合使用(24.7%)及其他(植物用药)(16.7%).单独使用α-受体拮抗剂和单独使用植物制剂的比例相近(分别为6.8%和7.1%). 结论 LUTS/BPH是老年科男性患者最常见的疾病之一.医师开具的检查不尽合理,对常规的病史询问、IPSS评分等重视不够,医师开具的治疗药物基本合理.     

Early Efficacy of an α1 Adrenoceptor Antagonist,Naftopidil, against Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia

Objectives: The present study investigated the early efficacy of naftopidil against lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Methods: Subjects comprised patients with LUTS suggestive of BPH who were followed prospectively for 8 weeks. Inclusion criteria were: (i) international prostate symptom score (IPSS) ≥8; (ii) no previous treatment for BPH; and (iii) eligibility for naftopidil monotherapy. IPSS and quality of life index were evaluated, and uroflowmetry and residual urine volume were determined optionally. In the previous study, patients who demonstrated a decrease in total American Urological Association symptom score of 25% or more from baseline were considered responders. The ratio of onset of efficacy of naftopidil was calculated by the ratio of the number of responder in each group with the starting dose. Results: Naftopidil efficacy was analyzed for 243 patients. Significant improvement of IPSS was achieved within 1–3 days after medication. Starting dosage and average dosage were identified as factors associated with the period until onset of naftopidil efficacy. Onset of efficacy was significantly quicker with a starting dosage of 50 mg/day as compared with 25 mg/day (P = 0.0047). However, ratios of onset of efficacy with starting dosages of 25, 50 and 75 mg/day were 77.9, 76.7 and 85.7%, respectively, showing no significant difference between groups (P = 0.7463). Duration to onset of efficacy with naftopidil dosage ≥50 mg/day was 11.2 days, significantly early compared to dosage <50 mg/day. Incidence of adverse effect was 3.8%. Conclusion: Naftopidil showed early effects against LUTS suggestive of BPH within a few days.     

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.     

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.     

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.     

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.     

Estrogen and androgen signaling in the pathogenesis of BPH

Estrogens and androgens have both been implicated as causes of benign prostatic hyperplasia (BPH). Although epidemiological data on an association between serum androgen concentrations and BPH are inconsistent, it is generally accepted that androgens play a permissive role in BPH pathogenesis. In clinical practice, inhibitors of 5α-reductase (which converts testosterone to the more potent androgen dihydrotestosterone) have proven effective in the management of BPH, confirming an essential role for androgens in BPH pathophysiology. To date, multiple lines of evidence support a role for estrogens in BPH pathogenesis. Studies of the two estrogen receptor (ER) subtypes have shed light on their differential functions in the human prostate; ERα and ERβ have proliferative and antiproliferative effects on prostate cells, respectively. Effects of estrogens on the prostate are associated with multiple mechanisms including apoptosis, aromatase expression and paracrine regulation via prostaglandin E2. Selective estrogen receptor modulators or other agents that can influence intraprostatic estrogen levels might conceivably be potential therapeutic targets for the treatment of BPH.     

The use of baseline clinical measures to predict those at risk for progression of benign prostatic hyperplasia

Although histologic changes of benign prostatic hyperplasia (BPH) begin in men when they are in their thirties, symptomatic BPH characterized by lower urinary tract symptoms (LUTS) typically do not develop for several decades. Progression of BPH may lead to significant voiding symptoms, acute urinary retention, and the need for prostate surgery. However, developing LUTS is not inevitable for men with histologic evidence of BPH. The ability to predict those men who are risk for BPH progression is increasingly important because of recent evidence provided by the Medical Therapy of Prostate Symptoms study. This landmark study demonstrated that 5α-reductase inhibitors, alone or in combination with selective α-blockers, can delay or prevent the progression of BPH. In addition, the most important and consistent predictive factors for BPH progression are baseline prostatespecific antigen and prostate volume. Integration of these clinical parameters into clinical practice is influencing the decision regarding which men should observe or initiate treatment. This article highlights recent studies regarding the use of baseline clinical parameters on predicting BPH progression.     

180例离退休干部下尿路症状与尿流率的相关性探讨

目的 探讨离退休干部良性前列腺增生(BPH)患者下尿路症状(LUTS)与前列腺体积(PV)、最大尿流率(QMAX)的关系. 方法 随机选取180例经直肠指诊及经直肠前列腺超声(TRUS)确诊的离退休干部BPH患者,计算其国际前列腺症状评分(IPSS),记录PV及QMAX值,分析其相关性. 结果 (1)60～69岁、70～79岁、≥80岁3组离退休干部BPH患者IPSS评分分别为(9.1±0.7)分、(12.1±0.7)分、(14.0±1.3)分,PV分别为(40.6±1.9)ml、(42.4±1.9)ml、(48.7±2.8)ml,随年龄增加而增加(F值分别为5.705,2.983,P＜0.05).QMAX分别为(14.7±0.6)ml/s、(14.0±0.5)ml/s、(12.6±0.9)ml/s,随年龄增加而降低,但差异无统计学意义(F=2.131,P＞0.05),组间分析,60～69岁组与≥80岁组间差异有统计学意义(P=0.048).(2)随着LUTS加重,在IPSS评分＜7分、8～17分、＞20分组中,PV增加[分别为(39.2±18.1)ml、(45.7±16.9)ml、(47.9±16.5)ml],QMAX下降[(15.0±4.8)ml/s、(13.5±5.0)ml/s、(11.5±4.7)ml/s](F值分别为3.427,4.742,P＜0.05). 结论 离退休干部BPH患者LUTS不仅随年龄增加而加重,而且其严重程度随PV增加,随QMAX下降.对于PV增大的老年患者积极给予缩小体积的药物治疗有可能改善LUTS.     

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.     

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.     

Botulinum: A toxin for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms

Botulinum neurotoxin (BoNT) has been called the most poisonous poison and a potential bioterrorism weapon, and yet modern medicine has been able to harvest the elegant and specific activity of this toxin to treat a variety of medical conditions. BoNT application recently has been extended to prostate disorders, and this article reviews the literature on the mechanisms of action and clinical efficacy of BoNT treatment in the prostate. BoNT has demonstrated promising preliminary results for male lower urinary tract symptoms, and translational research suggests novel mechanism of action of BoNT in the prostate. It is important to remember that the application of BoNT in the prostate is not approved by the regulatory agencies and caution should be applied until larger randomized clinical studies are completed.     

辛伐他汀对代谢综合征并良性前列腺增生患者下尿路症状的影响

目的 观察辛伐他汀对代谢综合征(MS)并存良性前列腺增生症(BPH)患者的下尿路症状(LUTS)影响.方法 2011年2-6月我科门诊和住院患者中MS并存BPH继发LUTS患者共30例,检查并记录国际前列腺症状评分(IPSS)、生活质量评分(QOL)、最大尿流率(MFR)、前列腺体积、肝肾功能、尿常规后,随机分为两组:联合用药组给予辛伐他汀40 mg和坦索罗辛0.2 mg口服,每晚1次;单药组给予坦索罗辛0.2 mg口服,每晚1次,治疗8周后复诊,复查上述指标,对治疗的有效性和安全性进行评价.结果 联合用药组和单药组IPSS、QOL、和MFR与治疗前比较,差异均有统计学意义,前列腺体积差异无统计学意义.联合用药组治疗后IPSS评分变化值为(6.4±4.4)分,单药组为(4.2±3.3)分,两组比较差异有统计学意义(P＜0.05),联合用药组症状改善优于单药组.两组均无不良事件发生.结论 辛伐他汀对MS并存BPH患者的LUTS有改善作用,联合用药组耐受性良好,未出现明显不良事件.     

Recent Advances and Emerging Technology in the Surgical Management of BPH-Related Voiding Dysfunction

As transurethral resection of the prostate (TURP) continues to be the standard of care to alleviate voiding dysfunction in men with benign prostatic hyperplasia (BPH), novel techniques are being addressed to promote operative efficacy and long-term results for improved voiding. This review addresses recent literature over the past year on various transurethral technologies and procedures as well as the developing practice of prostatic arterial embolization (PAE) to improve lower urinary tract symptoms in the setting of BPH. The transurethral technologies include bipolarity, which has come to the forefront in the resection of large prostates as it reduces the risk of TUR syndrome, and plasmakinetic enucleation and diode laser enucleation which have both recently been demonstrated to improve tissue resection for larger prostate glands. The Oyster Procedure, described below, is a specific method of adenoma resection which has been demonstrated to be effective in the treatment of large obstructing prostates. HoLEP, which has been established as an effective tool for large prostates, has now been described to be useful in patients requiring retreatment of LUTS secondary to BPH. Prostatic artery embolization (PAE) has recently come to the forefront of a minimally invasive alternative to TURP with a reduction of symptoms and recovery time in patients who have had unsuccessful or refractory treatments for LUTS. While TURP aids in improving voiding dysfunction, it is known to affect sexual function. New implants, such as those explained in the UroLift procedure below, can improve LUTS while preserving sexual function. Finally, The GreenLight laser prostatectomy has now been demonstrated to be safe and effective in an office setting with conscious sedation, thereby reducing surgical risk with anesthesia for those with comorbidities. The studies discussed in this review focus on improving procedures for treating larger prostates, prostates with prior surgical interventions or refractory BPH, patients who wish to maintain sexual function, and assessing interventions for the elderly and those with comorbidities. As new technologies continue to expand, their use among both novice and experienced surgeons will be vital to advancing the treatments for BPH.     

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.