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.     

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.     

Combination 5-α-reductase inhibitors and α-blockers for treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia

Open or transurethral resection of the prostate was once the only option for men afflicted with symptomatic benign prostatic hyperplasia (BPH). In the past 10 to 15 years, however, medical management has become a common step in the treatment of BPH, often postponing or eliminating the need for surgical intervention. The two drug classes used in the medical management of BPH are α-blockers and 5-α-reductase inhibitors. This paper reviews major studies related to the use of these medications in combination and discusses patient populations best served by combination therapy.     

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.     

The role of 5-α-reductase inhibition as monotherapy in view of the MTOPS data

Medical treatment for the symptoms of benign prostatic hyperplasia (BPH) consists of α blockers and 5-α -reductase inhibitors. Data suggest that 5-α -reductase inhibitors can prevent progression of BPH and reduce the risk of BPH-related surgery, especially in men with large-volume prostates. Results from the largest randomized, prospective, placebo-controlled trial, the Medical Therapy of Prostatic Symptoms trial, have been presented. These results support the notion of using 5-α-reductase inhibitors for the prevention of BPH progression and BPH-related surgery. Furthermore, long-term 5-α -reductase inhibitor monotherapy, although slow in onset, is a viable therapy for symptom relief in men with mild to moderate symptoms.     

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.     

老年良性前列腺增生症单药治疗无效的危险因素

目的通过分析α-受体阻滞剂治疗老年良性前列腺增生症(BPH)无效的危险因素,明确初诊老年BPH的药物选择。方法回顾研究96例老年BPH患者,其中单用α-受体阻滞剂坦索罗新治疗组42例,与5α-还原酶抑制剂非那雄胺联合治疗组54例,比较两组国际前列腺症状评分(IPSS)、生活质量指数(QOL)、最大尿流速(Qmax)、残余尿量(PVR)、前列腺体积及血清前列腺特异性抗原(PSA)。结果联合用药与单药治疗组比较,前列腺体积、Qmax和IPSS具有统计学差异;多元回归分析显示IPSS(P<0.001)及前列腺体积(P<0.05)与老年BPH单药治疗无效密切相关。结论老年BPH患者单药及联合治疗均能改善病情,对于初诊时具有较高的IPSS评分及严重的前列腺体积增大者应给予药物联合治疗。     

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.     

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.     

Clinical aspects and molecular genetics of the persistent Müllerian duct syndrome

OBJECTIVE The 5α-reductase inhibitor, finasteride, provides a logical medical treatment for benign prostatic hyperplasia (BPH). However, the effects of chronic finasteride treatment on prostatic androgen levels, 5α-reductase activity and tissue prostatic specific antigen (PSA) have not been studied. We have examined prostate tissue androgen concentrations and 5α-reductase activity of the gland in men with BPH treated with the drug for 3 months. DESIGN AND PATIENTS Twenty-eight patients with clinically diagnosed BPH, awaiting transurethral resection of the prostate, were entered in a double-blind placebo controlled study. Nineteen patients were randomly allocated to treatment with finasteride (5 mg daily) and 9 received placebo for 3 months. MEASUREMENTS Prostate specimens were collected immediately following surgery and analysed for testosterone, dihydrotestosterone (DHT), androstenedione, 5α-reductase activity and PSA. Blood specimens obtained before the start and immediately following treatment were also tested for steroid hormone concentrations and PSA levels. RESULTS There was no significant difference in the median levels of intraprostatic testosterone (P = 0.77), DHT(P= 0.46) and androstenedione (P = 0.09) between the finasteride and placebo groups. However, the 5α-reductase activity of the placebo group (237.9 pmol DHT/g tissue/30 min) was approximately 10 times that of the finasteride group (21.5 pmol DHT/g tissue/30 min; P = 0.0008). Although we were unable to detect any differences in the PSA concentrations of the prostate glands, there was a significant difference (P = 0.0002) in the median percentage change of serum PSA concentrations for the two patient groups. Serum DHT levels were also depleted (P = 0.038) whilst serum testosterone was increased (P = 0.054) in the finasteride patients when compared to the placebo group. Furthermore our study demonstrated no correlation between the in vitro 5α-reductase activity of the gland and tissue DHT concentrations. CONCLUSIONS Whilst finasteride treatment induced a reduction in serum dihydrotestosterone and prostatic specific antigen levels with a concomittant increase in blood testosterone concentrations, the impact of the drug on tissue androgen concentrations varied considerably from one patient to another. The differential effect of the drug on tissue androgen concentrations suggests that in the human prostate there are possibly more than one isoform of 5α-reductase responsible for the accumulation of DHT in the gland.     

老年人良性前列腺增生与心血管疾病的关系

目的 了解老年良性前列腺增生(BPH)患者临床特点及用药情况,探讨BPH与心血管疾病的关系. 方法 搜集本院老年病科100例BPH患者临床资料,采用国际前列腺症状评分表(IPSS)、生活质量量表(QOL)对患者进行评价,所有患者均详细询问心血管病史,并检测前列腺特异性抗原(PSA)水平,采用腹部超声测量前列腺体积(PV). 结果 老年BPH患者PV和PSA随年龄增长而升高;疾病严重程度以中度(IPSS 8～19分)多见;BPH患者高血压、冠心病和糖尿病患病率高,冠心病者PV显著高于非冠心病者(P＜0.05);我院BPH患者服用5-α还原酶抑制剂和α-受体阻滞剂者多见,治疗依从性好. 结论 老年BPH患者严重程度与年龄、冠心病发病相关;药物干预治疗以5-α还原酶抑制剂使用率最高.     

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.     

Prostate diseases--role of sex steroids and their inhibitors

The normal prostate as well as prostatic diseases are influenced by androgens. The exact reason for an altered and uncontrolled response to androgens, whether benign as in benign prostate hyperplasia (BPH) or malignant as in the case of prostate cancer (PC), is not known in detail. Nevertheless, restriction of androgen receptor activation by reduction of available androgens is of great clinical value in both diseases. In BPH the inhibition of the conversion of testosterone into 5α-dihydrotestosterone (DHT) by 5α-reductase (5AR) is highly efficient and used in general practice, while the situation in PC is more complex. Specific inhibition of 5AR does not provide as efficient relief of symptoms as general androgen deprivation therapy (ADT), and the use of 5ARI for PC prevention is still under debate. Further, the altered steroid metabolism in castration resistant prostate cancer (CRPC) together with the complex paracrine signalling between different androgen responsive cell types, make the development of more specific drugs targeting androgen receptor signalling both more relevant and challenging.     

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.     

5α-reductase inhibitors in benign prostatic hyperplasia and prostate cancer risk reduction

Androgens play a key role in the development and maintenance of normal and aberrant prostatic growth. It is now understood that DHT is the primary androgen in the prostate; DHT is synthesized from testosterone under the catalysis of the 5α-reductase isoenzymes. Inhibition of these isoenzymes therefore represents a rational approach for the development of pharmacological therapy for BPH and prostate cancer. This led to the discovery and clinical development of first finasteride, a type-2 5ARI, and subsequently dutasteride, a dual 5ARI. Both compounds have demonstrated benefits in the treatment of symptomatic BPH and in the prevention of long-term disease progression. Both agents are safe and well tolerated, and are therefore suitable for long-term clinical use. Finasteride has also demonstrated efficacy in the primary risk reduction of prostate cancer, while the ongoing REDUCE study is evaluating the effects of dutasteride in a similar setting, but with a different risk profile. The effect of dutasteride in reducing progression in low-risk, localized prostate cancer is also being investigated in the ongoing REDEEM study. Given that type-1 5α-reductase appears to play a role in the development and progression of prostate cancer, these ongoing studies will add much to our understanding of dual 5α-reductase inhibition in the prostate cancer setting.

Conflict of interest

Dr Rittmaster is an employee of GlaxoSmithKline.     

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.     

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.     

老年科良性前列腺增生的诊治现状

目的 了解良性前列腺增生(benign prostate hyperplasia,BPH)在老年科的诊断和治疗现状,促进BPH诊断和治疗的规范化.方法 抽取我国23个城市的老年科门诊BPH患者,完成老年科BPH门诊登记调查表.问卷内容包括患者的基本情况、诊疗情况和治疗效果.结果 对4001份调查问卷的分析显示,患者平均国际前列腺症状评分(IPSS)(18.8±5.9)分,中、重度症状患者分别占53.8％和42.0％.并存疾病的患病率依次为高血压(63.9％)、冠心病(40.4％)、糖尿病(32.4％)和高脂血症(25.7％).BPH相关并发症的发生率依次为尿路感染(21.0％)、尿路结石(8.3％)、反复血尿(1.8％)、肾积水(1.7％)和疝气(0.6％).医师采用的诊疗手段中,未进行直肠指诊的占27.2％,未进行血清前列腺特异性抗原(PSA)检查的占89.5％.在药物治疗的患者中,68.1％的患者处方中有a受体阻滞剂,92.9％的处方中有5α还原酶抑制剂,11.8％的处方中有中药和植物制剂,0.4％的处方中有M受体阻滞剂.首次处方中,单药治疗的占51.1％,2种药物联合治疗的占46.6％.在中重度症状患者中,遵医嘱规律服药的占60.6％,已停药的占13.9％.需要调整处方的原因依次为药物疗效差(23.4％)、不良反应多(5.4％)、价格昂贵(3.5％)、服用不方便(2.9％)等.结论 老年科门诊BPH患者以中重度症状为主,BPH治疗的同时还需考虑并存的疾病和BPH相关并发症;医师需进一步认识直肠指诊和PSA检查的重要性,联合治疗对于改善患者下尿路症状效果显著,长期治疗效果更好.     

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.     

中国11城市老年科门诊良性前列腺增生现状调查

目的 了解中国老年科门诊伴有下尿路症状的良性前列腺增生(LUTS/BPH)患者的诊断及治疗现状,以及患者对于这一疾病的认知及需求. 方法 2008年2～9月在全国11个城市的34个老年科门诊进行调查.先对在调查时间内前来老年科门诊就诊的全部男性患者进行LUTS/BPH病史的询问.然后在LUTS/BPH患者中选择部分患者进行详细的问卷调查及BPH相关检查.结果 在调查过程中,共有31 371位男性患者来老年科门诊就诊,14 748(47.0%)例有LUTS/BPH病史.其中10 678例(72.4%)曾接受或正在接受药物或手术治疗,4070例(27.6%)第1次诊断LUTS/BPH或以往曾诊断LUTS/BPH但未行药物或手术治疗.患者最常接受的检查是尿常规检查.血清前列腺特异抗原(PSA)检查和经腹前列腺超声检查.在接受药物治疗情况调查的3542例患者中,1155例(32.6%)采用5α还原酶抑制剂单独药物治疗,1239例(35.0%)采用5α还原酶抑制剂+α受体阻滞剂联合药物治疗.对检查及治疗满意的患者分别为1796例(84.5%)和1678例(79.0%). 结论 LUTS/BPH是老年科门诊常见疾病,目前临床应用的检查及药物治疗方案与国际上有一定差异,需要对患者进行相关疾病知识的普及.