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Keywords:

  • α1-blockers;
  • benign prostatic hyperplasia;
  • guideline;
  • lower urinary tract symptoms;
  • men

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

Abstract:  This article is a shortened version of the clinical guideline for lower urinary tract symptoms (LUTS), which has been developed in Japan for symptomatic men aged 50 years and over irrespective of presumed diagnoses. The guideline was formed on the PubMed database between 1995 and 2007 and other relevant sources. The causes of male LUTS are diverse and attributable to diseases/dysfunctions of the lower urinary tract, prostate, nervous system, and other organ systems, with benign prostatic hyperplasia, bladder dysfunction, polyuria, and their combination being most common. The mandatory assessment should comprise medical history, physical examination, urinalysis, and measurement of serum prostate-specific antigen. Symptom and quality of life questionnaires, bladder diary, residual urine measurement, urine cytology, urine culture, measurement of serum creatinine, and urinary tract ultrasonography would be optional tests. The Core Lower Urinary Tract Symptom Score Questionnaire may be useful in quickly capturing important symptoms. Severe symptoms, pain symptoms, and other clinical problems would indicate urological referral. One should be careful not to overlook underlying diseases such as infection or malignancy. The treatment should be initiated with conservative therapy and/or medicine such as α1-blockers. Treatment with anticholinergic agents should be reserved only for urologists, considering the risk of urinary retention. The present guideline should help urologists and especially non-urologists treat men with LUTS.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

A number of clinical guidelines are now available for lower urinary tract disorders; however, these are designed for a specific disorder/disease thus not applicable to patients with no definite diagnosis, multiple diseases, or diseases for which no guidelines are available. Considering that most patients visit physicians with complaints of lower urinary tract symptoms (LUTS) and the etiology of LUTS would be more complicated in aged men due to the prostate pathology, a guideline for male LUTS has been developed in Japan to help urologists and especially non-urologists. This article is the English translation of a shortened version of the guideline for convenience of readers worldwide.

Targeted patients and anticipated users

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

The guideline is targeted to men aged 50 years and over complaining of any LUTS. The anticipated users include urologists, non-urological physicians, nurses, and other health providers who may be involved in the care of such men. The clinical algorithm and treatment options are prepared primarily for non-urologists.

Methodology

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

The guideline was developed by the committee members recommended by the Japanese Society of Neurogenic Bladder and endorsed by the Japanese Urological Association. To prepare the guideline, the members meticulously reviewed relevant references that were retrieved via the PubMed database between 1995 and 2007. Other sources included the Japanese Guideline for Benign Prostatic Hyperplasia,1 the Japanese Clinical Guideline for Overactive Bladder,2 the guidelines on benign prostatic hyperplasia published by the American Urological Association and the European Association of Urology (http://www.auanet.org/guidelines/bph.cfm; http://www.uroweb.org/fileadmin/user_upload/Guidelines/11%20BPH.pdf), and the meeting report of the International Consultation on Urological Diseases (ICUD) on male lower urinary tract disorder.3

Definition of LUTS

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

Male LUTS are diverse in nature and may reflect underlying disorders of the prostate and lower urinary tract organs. LUTS comprise important elements in the diagnosis and assessment of severity and therapeutic outcomes. Precise use of terminology should facilitate clinical and scientific communications on LUTS.

The 2002 standardization committee report on terminology from the International Continence Society (ICS)4 defined three important LUTS categories: storage symptoms, voiding symptoms, and post-micturition symptoms. Storage symptoms include increased daytime frequency, nocturia, urgency, urinary incontinence (stress urinary incontinence, urge urinary incontinence, mixed urinary incontinence, enuresis, nocturnal enuresis, continuous urinary incontinence, other type of urinary incontinence), and bladder sensation (normal, increased, reduced, absent, non-specific). Voiding symptoms cover slow stream, splitting or spraying, intermittent stream, hesitancy, straining, and terminal dribble. Post-micturition symptoms indicate feeling of incomplete emptying and post-micturition dribble. Other related symptoms are pain symptoms of the genitourinaty tract (bladder pain, urethral pain, vulval pain, scrotal pain, perineal pain, and pelvic pain). Symptom syndromes serve to group some of these symptoms exemplified by overactive bladder syndrome (OAB) and lower urinary tract symptoms suggestive of bladder outlet obstruction.

Male LUTS and female LUTS are essentially the same; however, men are more likely to complain of voiding symptoms than women, and are less likely to experience urinary incontinence. LUTS comprise the important elements for diagnosis, treatment selection, and assessment of clinical severity or therapeutic efficacy, since they are closely related with the degree of bothersomeness or quality of life (QOL) impairment.5–7 Research on relative importance of symptoms indicated that storage symptoms exert greater bother on patients' QOL than voiding symptoms.8–10 Contrarily, LUTS have low specificity to underlying disorders and are unreliable for the correct diagnosis, and storage and voiding symptoms do not necessarily reflect disorders of storage and voiding function, respectively.11 There is weak or almost no correlation between LUTS and other clinical indicators such as prostate volume, urinary flow rate, residual urine volume, or the degree of infravesical (outflow) obstruction.12,13 Within the individuals of the particular disorder, however, LUTS and urodynamic findings are modestly correlated.14

Related terminology

Prostatism

The term ‘prostatism’ has been used widely on the assumption that LUTS in middle-aged and older men are related to the prostate, although this is not necessarily the case.15 It is recommended that this term not be used to avoid misunderstanding.

Infravesical (outflow) obstruction

This implies increased resistance of urinary flow downstream of the bladder as a result of benign prostatic hyperplasia, urethral stricture or other conditions. Bladder outlet obstruction (BOO) is an almost identical term.

Urinary retention and overflow incontinence

Urinary retention signifies a condition in which the patient is unable to pass urine despite a large amount of urine having accumulated in the bladder (300 mL or more, for example). Such patients may be incontinent, since intravesical pressure exceeds the urethral closure pressure, leading to urinary leakage (overflow incontinence). These terms are not recommended by the ICS report;4,16 however, urinary incontinence associated with chronic urinary retention must not be overlooked.

Epidemiology and QOL

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

In Japan, 78% of males aged 60 years and older complain of some kind of LUTS. The most common symptom in men is nocturia followed by daytime frequency. The presence of LUTS shares risk factors with chronic lifestyle diseases and erectile dysfunction. LUTS, storage symptoms in particular, can impair QOL.

The representative epidemiological survey on LUTS in Western individuals is the EPIC Study.17 The study, which recruited 19 165 subjects aged 18 to 80 years, found that 62.5% of men and 66.6% of women were symptomatic, respectively. The most common symptom was nocturia in both men and women, and almost all symptoms were more prevalent with advanced age. In Japan, a survey involving 4480 men and women aged 40 years and older was reported in 2003.18 The frequencies of all LUTS increased with age, and approximately 78% of individuals aged over 60 years experienced some kind of LUTS. Weak stream and feeling of incomplete emptying were more common in men, while stress urinary incontinence was more common in women. The most prevalent symptom was nocturia followed by daytime frequency. Health seeking behavior was low (18.0%), with men (27.4%) visiting physicians more often than women (9.0%).

The risk factors for LUTS include heart disease, diabetes, hypertension, hyperlipidemia, obesity, alcohol consumption, smoking, and lack of exercise. These lifestyle factors are also related to the so-called lifestyle diseases.19–22 Recent epidemiological researches indicate a robust linkage between LUTS and erectile dysfunction.23

Investigations on QOL in men with LUTS have been almost limited to benign prostatic hyperplasia. Analyses using the Short Form-36 and other generic QOL questionnaires24 or disease-specific instruments have uniformly shown that LUTS, storage symptoms in particular, have negative effects on QOL,25 and that medical therapy26 and surgical interventions27 improve the lowered QOL. Few investigations have looked into the relationship between LUTS and QOL. A Japanese epidemiological study18 indicates that 14.7% of people have their daily life affected by some kind of LUTS in various domains including mental health, vitality, physical activity, and social activities. Assessment of QOL impairment would be crucial in determining the severity of therapeutic outcomes for male LUTS.

Etiology and pathogenesis

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

The causes of LUTS in middle-aged and older men are diverse, including lower urinary tract, prostate, nervous system, systemic diseases, and other pathological conditions (Table 1). The most common causes would be benign prostatic hyperplasia, overactive bladder, underactive bladder, cerebrovascular disorder, polyuria, and their combination. In many instances, multiple causes are involved or no specific causes can be definitely identified.

Table 1.  Possible diseases/disorders for male lower urinary tract symptoms (LUTS)
1.Prostate and lower urinary tract
Prostate: benign prostatic hyperplasia, prostatitis, prostate cancer
Bladder: bacterial cystitis, interstitial cystitis, bladder cancer, bladder stones, bladder diverticulum, overactive bladder, other (aging)
Urethra: urethritis, urethral stricture
2.Nervous system
Cerebral: cerebral infarction, dementia, Parkinson's disease, multiple system atrophy, brain tumor
Spinal cord: spinal cord injury, multiple sclerosis, spinal cord tumor, spinal infarction, spinal degenerative disease, spina bifida
Peripheral nerves: diabetic neuropathy, post-pelvic surgery
Other: aging, autonomic hyperactivity
3.Miscellaneous
Drug-related, Polyuria, Sleep disorder, Psychogenic

Prostate and lower urinary tract

Benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is highly prevalent in aged men and associated with various combinations of voiding and storage symptoms.28 Presumably, BOO by the enlarged prostate accounts for LUTS in BPH; however, the severity of LUTS are not necessarily correlated with the degree of BOO or the prostate volume.12 Bladder overactivity in BPH would be explained by denervation hypersensitivity,29 modulated detrusor properties,30 increased release of urothelial neurotransmitters (e.g. ATP, NO, prostaglandin, acetylcholine),31 or increased afferent stimulation from the urethra.32

Other prostate diseases

Prostatitis:  Prostatitis, acute or chronic, may occur in men of any age.33 Pain and/or discomfort, in addition to storage and voiding symptoms, are perceived in the lower abdomen, perineum, and other areas of the pelvis. Chronic prostatitis and interstitial cystitis are symptomatically alike and postulated for common etiologies.34

Prostate cancer:  No specific LUTS is known to prostate cancer, especially in its early stage. LUTS can be a clue to prostate cancer detection; prostate cancer was reportedly detected in 7.2% of men complaining of LUTS.35

Diseases and pathological conditions of the bladder

Bacterial cystitis:  Bacterial cystitis is commonly associated with frequency, urgency and pain. It is rarely identified in isolated forms in men and may coexist with bladder stones or BPH.

Interstitial cystitis:  Interstitial cystitis is predominant in women yet not uncommon in men. Typical clinical features include normal urinalysis and severe LUTS including frequency, urgency, bladder hypersensitivity, and bladder pain. It is sometimes misdiagnosed as chronic prostatitis.36

Bladder cancer:  Bladder cancer, carcinoma in situ in particular, produces storage symptoms.

Bladder stones:  Storage symptoms are common in men with bladder stones. Abrupt interruption of urinary stream may occur when the stones block the bladder outlet. Associated infection may cause painful micturition.

Bladder diverticulum:  A large bladder diverticulum is associated with a substantial amount of residual urine, which may result in slow urinary stream or urinary tract infection.

Overactive bladder:  OAB syndrome is a constellation of symptoms constituting urgency, usually associated with daytime frequency and nocturia, with or without urgency incontinence. Obvious local pathologies (bladder cancer, bladder stones, infection, etc.) should be exluded.4 OAB is caused by diverse conditions including BPH, neurological disorders, and unknown etiologies (idiopathic).

Other (aging):  Underactive bladder is often found in the elderly.37 Recurrent or persistent voiding symptoms after surgical resection of the prostate are commonly explained by detrusor acontractility.38 Decreased smooth muscle, increased fibrotic changes, and detrusor overactivity are associated with advancing age.39,40

Urethral diseases

Urethritis:  Urethral pain and discharge are common complaints in urethritis.

Urethral stricture:  Urethral stricture can occur as a sequela of urethritis or urethral injury. Voiding symptoms such as weak urinary stream or straining are often described.

Nervous system

Cerebral

Cerebrovascular disorder:  Forebrain lesions tend to cause storage symptoms, while brainstem lesions cause voiding symptoms.41 Lowered mobility by paralyzed extremities may cause functional urinary incontinence.

Dementia:  Impaired function of the forebrain may deregulate inhibition of micturition and produce OAB symptoms. Cognitive deficits sometimes result in functional urinary incontinence.

Parkinson's disease:  Parkinson's disease is often associated with various LUTS, with storage symptoms predominant rather than voiding symptoms.

Multiple systemic atrophy:  LUTS are often complained of at an early stage, which mostly comprise OAB symptoms.

Brain tumor:  The type and sequence of LUTS are variable, depending on the tumor location.

Spinal cord

Spinal cord lesions should be classified into supra-nuclear, nuclear, and infra-nuclear lesions. Supra-nuclear lesions are often associated with detrusor overactivity and detrusor sphincter dyssynergia (DSD), which may cause high infravesical pressure, leading to deterioration of the upper urinary tract. The other lesions usually accompany detrusor underactivity with varying degrees of urethral closing function.

Spinal cord injury:  Total or partial abolishment of voiding function and urinary sensation develop in the acute phase, which restore in due time to varying degrees of dysfunctions.

Multiple sclerosis:  This demyelinating disease, more common in women, brings a variety of symptoms due to variable etiologies including detrusor overactivity, detrusor sphincter dyssynergia and underactive bladder. In Japan, voiding symptoms are reportedly more common than storage symptoms.

Spinal cord tumor, spinal vascular disorder:  LUTS and functional impairment vary depending on the affected site.

Spinal degenerative disease:  Spinal canal stenosis and disc herniation compress nerves, producing various LUTS. Urinary retention may result from an acute phase of herniation.

Spina bifida:  Spina bifida is a congenital anomaly in unifying the vertebral arch, and when occurring at the lumbosacral level, results in vesico-rectal dysfunction. The dysfunction and associated LUTS are diverse in combination and severity.

Peripheral nerves

Neuropathy peripheral to the sacral micturition center impairs contractility of the detrusor and causes voiding symptoms.

Diabetes mellitus:  Degenerated autonomic nerves in the bladder wall as a consequence of diabetic neuropathy cause detrusor underactivity and voiding symptoms. Patients may be unaware of dysfunction or symptoms because of the weakening urinary sensation.42

Pelvic surgery:  Pelvic surgery may injure the nerves and blood vessels supplying the lower urinary tract. Detrusor underactivity, low-compliance of the bladder and imcompetent urethra are common urodynamic abnormalities, resulting in various LUTS including urinary incontinence.

Others

Aging of the central nervous system:  With advancing age, the number of dopamine D1 and D2 receptors decreases in the corpus striatum. The production and release of acetylcholine in the brain and the number of correspondent receptors diminishes with age.43,44 These changes are likely to cause overactive bladder symptoms and may explain age-related increases in those symptoms.

Autonomic hyperactivity:  The activity of the sympathetic nervous system is upregulated with aging, and this may contribute to the prevalence of LUTS in aged populations. Spontaneously hypertensive rats are found to have elevated noradrenaline levels in the bladder, urethra and prostate, marked proliferation of the glandular component of the prostate, a threefold increase in the urinary frequency, and increased nerve growth factor in the bladder.45–47

Other conditions

Drug-associated

A variety of medicines including anticholinergics, antispasmodics, antiparkinsonian drugs, antihistamines, and psychotic drugs influence lower urinary tract function and may cause LUTS.

Polyuria

Increased urinary frequency is often caused by polyuria due to diabetes mellitus, diabetes insipidus, or over-drinking. Nocturnal polyuria is an important etiology for nocturia and potentially results from congestive heart failure, renal failure, overactivity of the autonomic nervous system, obstructive sleep apnea, lost diurnal variation of antidiuretic hormone secretion, or excessive consumption of water, caffeine, or alcohol.48

Sleep disorder

Sleep disorder results in frequent arousal and consequent frequent voiding during the night. It is also a cause of nocturnal polyuria.49

Psychogenic

Lower urinary tract symptoms can be caused by psychogenic reasons. The worsening and improvement of symptoms should be closely correlated with psychogenic episodes with no detectable organic disorders.

Diagnosis

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

Diagnosis of male LUTS requires evaluation for subjective aspects (symptoms and quality of life issue) and objective aspects (physiological function of lower urinary tract). One should be careful not to overlook underlying diseases such as infection or malignancy.

Clinical history

Focused questions on LUTS should be made for the present symptoms, the time-course of the symptoms including factors that may influence the symptoms, and the effect of the symptoms on the patient's QOL. The Core Lower Urinary Tract symptoms Score (CLSS)50 would be a simple and valuable instrument for capturing the whole profile of LUTS without significant omission. Non-urological medical histories to be asked include neurological disease, diabetes mellitus, lower abdominal surgeries, and medications used.

Symptom and QOL questionnaires

Men are more likely to complain of voiding symptoms, although it is storage symptoms that are more bothersome.8,18 It is difficult to diagnose the underlying condition of the lower urinary tract from the symptoms alone.51 Symptoms are usually assessed by questionnaires. Valid symptom questionnaires for BPH include the American Urological Association (AUA) Symptom Score,52 the International Prostate Symptom Score (IPSS),53 and the Benign Prostatic Hyperplasia Impact Index (BII).54 Incontinence Impact Questionnaire (IIQ),55 Incontinence Quality of Life Instrument (I-QOL),56 King's Health Questionnaire (KHQ),57 International Consultation on Incontinence Questionnaire (ICIQ),58 ICIQ Short Form (ICIQ-SF),59 Overactive Bladder Questionnaire (OAB-q),60 and the Overactive Bladder Symptom Score (OABSS),61 are used to evaluate urinary incontinence or OAB symptoms. Symptoms associated with interstitial cystitis are evaluated by the Interstitial Cystitis Symptom Index (ICSI), the Interstitial Cystitis Problem Index (ICPI),62 and the Pain Urgency Frequency Score (PUF).63 The National Institute of Health–Chronic Prostatitis Symptom Index (NIH–CPSI) is used for chronic prostatitis.64 Questionnaires that are not disease-specific, and thus are usable for patients with no definite diagnosis or multiple conditions include the International Consultation on Incontinence Modular Lower Urinary Tract Symptoms Questionnaire (ICIQ-MLUTS)65 and the Core Lower Urinary Tract Symptoms Score (CLSS).50 In particular, the CLSS is a simple questionnaire with questions addressing 10 important symptoms, and should be useful for the basic assessments.

Physical findings

The lower abdomen, pelvis, and external genitalia should be inspected for any abnormalities including neurological ones. Lower abdominal distension suggests urinary retention. Enlarged, indurated and painful prostate may imply BPH, prostate cancer and prostatitis, respectively.

Bladder diary

Bladder diary is the recording of micturition time and voided volume throughout the day and night. This is particularly useful for measuring the precise voiding frequency, functional bladder capacity and urine production. The recording period is preferably 3 to 7 days.66 Nocturnal polyuria is defined as nocturnal urine volume ≥20% (<65 years old) or ≥33% (≥65 years) of the 24 h urine volume, or ≥10 mL/kg bodyweight.67 A maximum voided volume ≤4 mL/kg bodyweight is regarded as a small functional bladder capacity.67

Urine tests

Urinalysis should be examined for all patients.68 Hematuria needs urological consultation. Pyuria should be treated with antimicrobial agents as presumptive urinary tract infection. Treatment-resistant pyuria should be referred to a urologist. Urine cytology is indicated when bladder cancer is suspected.

Blood tests

Serum creatinine measurement is recommended as a screening test for renal dysfunction. Prostate-specific antigen (PSA) is highly sensitive to prostate cancer,69 and recommended for all men complaining of LUTS.

Residual urine test and ultrasonography

Residual urine is urine remaining in the bladder immediately after voiding. Trans-abdominal ultrasonography rather than catheter insertion is less invasive, and thus recommended as the measurement method. A clinically significant amount of urine (>100 mL, for example) necessitates further urological evaluation. Abdominal ultrasonography may reveal tumors, stones, and other abnormalities in the kidneys, prostate and bladder.

Urinary flow measurement

Uroflowmetry measures the volume of urine voided per unit of time. It is a simple and non-invasive test for voiding function.

Other tests

Other tests include endoscopy, imaging tests such as computed tomography scanning and excretory urography, and urodynamic investigations. These should be considered at urological referral.

Testing and diagnostic procedures

The basic assessment 1 (present illness, past history, physical examination, urinalysis, and serum PSA measurement) is mandatory in all cases. The basic assessment 2 (symptom and QOL questionnaires, bladder diary, residual urine measurement, urine cytology, urine culture, serum creatinine, and urinary tract ultrasonography) is selected on an individual basis. Men with severe symptoms or bladder pain should be referred to a urologist. Nocturia, if present as the predominant symptom, should be managed according to the Clinical Guidelines for Nocturia. Before starting treatment, some of the basic assessment 2 should be conducted; measurement of residual urine is most recommended. Patients who failed to respond to the initial treatment should be referred to a urologist.

Treatment

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

The causes of male LUTS in middle-aged and elderly men can be classified into diseases or dysfunction of the prostate, bladder, urethra, or other organs. Treatment should be optimized to the condition being treated.

Grades of recommendation for treatments

The guidelines deal primarily with treatments that are used by general physicians rather than urological specialists. The grade of recommendation (Table 2) was determined for each treatment by examining not only the level of evidence (Table 3) but the variability of efficacy, magnitude of efficacy, clinical applicability, morbidity and cost. The levels of evidence and grades of recommendation for individual treatments are shown in Table 4.

Table 2.  Grade of recommendation
GradeNature of recommendation
AHighly recommended
BRecommended
CNo clear recommendation possible
 C1Can be considered
 C2Not recommended
DRecommend not to do
Reserved 
Table 3.  Levels of evidence
Level of evidenceType of evidence
1Evidence obtained from multiple randomized controlled trials (RCTs)
2Evidence obtained from a single RCT or low quality RCTs
3Evidence obtained from non-randomized controlled studies
4Evidence obtained from observational studies or case series
5Evidence obtained from case studies or expert opinions
Table 4.  Treatments for male lower urinary tract symptoms (LUTS)
Treatment methodLevel of evidenceGrade of recommendation
  • Assumed that treatment is provided by general physicians rather than urological specialists. Indwelling catheter and clean intermittent catheterization are not included in this table because they should be undertaken under the guidance of urologists.

  • ‡Not approved for clinical use in Japan.

  • §

    §Reserved for urologists only.

  • ¶The same level of evidence for efficacy and lack of efficacy.

α1-adrenoceptor antagonists (α1-blockers)  
 Prazosin1C1
 Terazosin, Urapidil, Tamsulosin, Naftopidil1A
 Silodosin2B
 Alfuzosin1Not approved
Anti-androgens  
 Chlormadinone, allylestrenol3C1
 Finasteride, Dutasteride1Not approved
Other oral medications  
 Paraprost, Eviprostat, Cernilton, Chinese herbal medicines, flavoxate3–5C1
 Tricyclic antidepressants5C2
 Anticholinergics1Reserved§
 Cholinergics1Reserved
 Sildenafil, Tadalafil2Not approved
Combination therapy with α1-blockers  
 Chlormadinone3C1
 Finasteride1Not approved
 Anticholinergics1Reserved
Electrical or magnetic stimulation  
 Interferential low-frequency therapy3C1
 Others3Not approved
Conservative therapy  
 Lifestyle modification2A
 Saw palmetto1Not definable
 Supplements other than saw palmetto5C2
 Conservative therapy for prostatitis5C1

Pharmacotherapy

α1-adrenoceptor antagonists (α1-blockers)

There is ample evidence to support the efficacy and safety of α1-blockers for BPH, indicating that α1-blockers would be the first choice medicine for male LUTS.

α1-Blockers relieve outlet obstruction by inhibiting contraction mediated by prostatic α1 adrenaline receptors (α1-AR), thereby ameliorating symptoms of BPH. The magnitude of efficacy of various α1-blockers would be 16–25% (2.0–2.5 mL/s) increase in the maximum flow rate and 30–40% (4–6 points) reduction of average IPSS. The well-known adverse reactions such as postural hypotension and asthenia are as uncommon as placebo (4–10%) for alfuzosin and tamsulosin.70–72 Other adverse events include ejaculatory dysfunction and intraoperative floppy iris syndrome (IFIS).73

Prazosin: Grade of recommendation: C1Clinical studies have been conducted on prazosin since before 1995, providing adequate evidence to support efficacy for BPH (1). Compared with newer α1-blockers, however, adverse events such as postural hypotension are more frequent with prazosin (1).

The efficacy of prazosin has been confirmed in a Western large-scale, placebo-controlled, randomized controlled trial (RCT), and in a Japanese RCT.74,75 However, hypotension and other adverse reactions are more common than newer agents.

Terazosin: Grade of recommendation: AThere is adequate evidence to support the efficacy of terazosin for BPH (1).The incidence of orthostatic hypotension and other adverse reactions may be relatively high (1).

Improvement in IPSS and urinary flow rate was significantly better for terazosin than a placebo or finasteride, and similar to tamsulosin. However, vascular adverse reactions may be more common than with tamsulosin and other α1-blockers.76 A Japanese study found no significant difference between terazosin and tamsulosin in improvement of symptoms or urinary flow rate or in the incidence of adverse events.77 Significant symptomatic improvement has been demonstrated for chronic prostatitis in a placebo-controlled RCT.78

Urapidil: Grade of recommendation: AThere is adequate evidence to support the efficacy of urapidil for BPH and neurogenic bladder (1).

Urapidil significantly improved residual urine and maximum flow rates than placebo in an RCT on BPH.79 The efficacy of urapidil for neurogenic bladder has also been confirmed in a placebo-controlled RCT.80

Tamsulosin: Grade of recommendation: AThere is adequate evidence to support efficacy for BPH, including long-term efficacy (1). Adverse reactions, including postural hypotension, were uncommon (1).

A Japanese RCT of tamsulosin on BPH demonstrated its superiority to a placebo, and found the optimal dosage to be 0.2 mg/day.81 Western studies have yielded an optimal dosage of 0.4 mg/day.82,83 Long-term studies showed that efficacy and safety were unchanged over treatment durations exceeding 3 years (at longest 9 years).84

Naftopidil: Grade of recommendation: AThere is adequate evidence to support the efficacy of naftopidil for BPH (1).

The efficacy of naftopidil for BPH has been demonstrated in RCTs in comparison with placebo and other agents.85,86 Comparisons between naftopidil and tamsulosin have found no discernible differences between the two agents.87,88

Silodosin: Grade of recommendation: BThere is evidence to support the efficacy of silodosin for BPH, albeit limited to a single Japanese study (2).

Silodosin is a selective α1A-subtype blocker developed in Japan. An RCT indicated significantly larger decreases in IPSS and QOL score for silodosin compared with placebo.89 Of adverse events, ejaculatory dysfunction was reported by 25% of subjects, although this was the cause of discontinuation in only 2.9%.89

Alfuzosin: Grade of recommendation: Not approvedThere is adequate evidence to support the efficacy of alfuzosin for BPH and chronic prostatitis (1). Alfuzosin is widely used in Western countries, but is at the clinical trial stage in Japan.

In placebo-controlled RCTs alfuzosin produced significant improvements in symptoms and urinary flow rate.90,91 The efficacy is roughly comparable with tamsulosin.92 The reported incidences of adverse events are similar to those seen with other α1-blockers.92 Significant symptomatic improvements were reported for chronic prostatitis.93

Anti-androgens

Antiandrogens inhibit the action of androgens on the prostate, thereby shrinking the prostate and lessening the symptoms associated with BPH. One should be careful for to overlook prostate cancer, since PSA is decreased by approximately 50%.

Chlormadinone, allylestrenol: Grade of recommendation: C1Evidence to support the efficacy of chlormadinone and allylestrenol for BPH is less than adequate (3). Reported adverse events included hepatic dysfunction, erectile dysfunction, loss of libido, and gynecomastia (3).

In an RCT comparing chlormadinone and Eviprostat (Mn-ethamsylate and plant extracts) for BPH, symptomatic improvement was reported by 90% and 70% of subjects, and prostate volumes decreased in 50% and 0%, respecitvely.94 There was no significant difference for efficacy between chlormadinone and allylestrenol.95 Reported adverse events included hepatic dysfunction, erectile dysfunction, loss of libido, and gynecomastia.

Finasteride, dutasteride: Grade of recommendation: Not approvedThere is adequate evidence to support the efficacy of finasteride and dutasteride for BPH (1). Adverse reactions affecting sexual function are relatively rare (1). However, neither agent has been approved in Japan.

Finasteride and dutasteride are 5α-reductase inhibitors that prevent the activation of testosterone. Finasteride significantly reduced prostate volumes and improved symptoms in subjects with prostate volumes exceeding 40 mL.96 It also reduced the relative risk of acute urinary retention and surgery by 57–59% and 36–55%, respectivley.97 Dutasteride, a more potent inhibitor of testosterone activation, proved to be similarly efficacious for symptomatic and uroflowmetric improvement.98

Combination therapy involving α1-blockers plus anti-androgens: Grade of recommendation: C1 (chlormadinone), Not approved (finasteride)Evidence to support efficacy in BPH is adequate for finasteride (1), but not for chlormadinone (3).

In a 16-week RCT in which BPH men were randomized to tamsulosin, chlormadinone, or combination, significantly better symptomatic improvement was seen in the tamsulosin group and combination group than in the chlormadinone group, and the uroflowmetric improvement was greatest in the combination group.99 However, a 52-week RCT with these three arms failed to show significant inter-group differences in symptomatic improvement.100 The addition of finasteride to doxazosin could not confirm benefits of the combination therapy in 1-year RCTs.101 When the study period was extended to 4.5 years, the combination therapy significantly decreased the risk of acute urinary retention and surgical intervention.102

Anticholinergics: monotherapy and combination with α1-blockers

Grade of recommendation: ReservedThere is adequate evidence to support the efficacy and safety of anticholinergics for male OAB symptoms (1). The efficacy and safety of anticholinergic agents have not been confirmed in Japanese men, however, the risk of urinary retention remains to be a concern (5). Treatment with anticholinergic agents should be reserved only for urologists.

For OAB symptoms α1-blockers are effective as monotherapy,103 although their efficacy is limited for patients with detrusor overactivity.104 Anticholinergics are most commonly used for OAB symptoms, and the reported incidence of acute urinary retention is <1%, which is comparable to placebo.105 The efficacy and safety of anticholinergic monotherapy have also been confirmed in the treatment of BPH associated with OAB.106 Combined therapy of anticholinergics and α1-blockers improved storage symptoms, with urinary retention being extremely rare over the 12-week observation period.107–109 A Japanese study also found that combination therapy improved storage symptoms, especially urgency, in BPH.110 In a 12-week trial of combination therapy in men with LUTS, the benefits were significantly greater in the combination therapy group, with only a mild increase in residual urine volumes, and a 1% incidence of urinary retention, with no difference between groups.111

It should be noted, however, that most of these studies were conducted with Caucasian men with strict exclusion criteria, specialists' supervision, and relatively short-term observational period. There remains a concern about exacerbation of voiding difficulty and possible urinary retention by a wider and longer use of anticholinergics with or without α1-blocker in the practical clinical setting.

Other oral medications

Paraprost, Eviprostat, Cernilton (cernitine pollen extract), Chinese herbal medicines (Hachimi-jio-gan, Gosha-jinki-gan), Flavoxate: Grade of recommendation: C1Efficacy of these agents is suggested for symptoms of BPH and chronic prostatitis, although evidence is scant (3–5). Adverse events are rare and mild.

Several studies have suggested efficacy for these agents, but they had small sample sizes, limited efficacy, and lack of reproducibility of results in multiple studies.86,112,113–115

Tricyclic antidepressants: Grade of recommendation: C2Evidence to support efficacy is scant (5). Adverse events include arrhythmia and drowsiness.

Theoretically, imipramine is potentially effective for various forms of urinary incontinence, but no studies have convincingly demonstrated its efficacy.

Cholinergics: monotherapy or combination with α1-blockers: Grade of recommendation: ReservedEvidence to support the efficacy of cholinergic agents in underactive bladder is lacking (1). Japanese and overseas studies have demonstrated the usefulness in certain patient groups only (3). Serious adverse reactions may occur, especially in elderly individuals. Treatment with cholinergic agents should be reserved for a urologist.

A recent review article found no evidence of a therapeutic effect on voiding diffuculty.116 Combination therapy with α1-blockers significantly improved symptoms and urinary flow in underactive bladder.117 Adverse reactions include abdominal pain and diarrhea, as well as the risk of a cholinergic crisis.

Phosphodiesterase-type 5 inhibitors: Grade of recommendation: Not approvedThese drugs are intended for treatment of erectile dysfunction, but adequate evidence exists to support their efficacy in male LUTS (2). They are not approved in Japan.

In a placebo-controlled RCT in middle-aged and elderly men with erectile dysfunction and LUTS, sildenafil and tadalafil significantly improved symptoms.118,119

Electrical and magnetic stimulation therapy

Grade of recommendation: C1 (electrical stimulation), Not approved (magnetic stimulation)

There is evidence of efficacy but it is far from adequate (3). Adverse events are almost completely absent.

In comparison with placebo, electrical and magnetic stimulations showed significantly higher efficacy for OAB symptoms and urgency incontinence.120–122 Other studies have shown equivalent efficacy to oxybutynin.123,124 The efficacy of interferential low-frequency therapy has also been demonstrated in an RCT.125 However, there are no investigations in male patients only, and its long-term effects remain uncertain.

Conservative therapies

Lifestyle modification

Grade of recommendation: AThere is evidence supporting the efficacy of lifestyle modification (2). Adverse events are almost completely absent, and the financial burden is low.

In a study where men with BPH were allocated to either transurethral resection of the prostate (TURP) or to lifestyle modifications only (restrictions on fluid intake and information on provision), voiding symptoms improved in over one-quarter of subjects in the latter group.126 The benefits of behavioral therapy for elderly subjects with LUTS, including female subjects, have been demonstrated in an RCT.127 The therapy included moderate physical activity, amelioration of constipation, and avoidance of sitting for extended periods or exposing the lower body to cold tempreture.128

Supplements and alternative remedies

Saw palmetto (Serenoa repens): Grade of recommendation: ReservedThere is adequate evidence to support efficacy for BPH, but there is also adequate evidence for its lack of efficacy (1). No serious adverse events are known.

A meta-analysis found saw palmetto to be effective in the treatment of BPH.129 A placebo-controlled RCT found absolutely no difference in efficacy between saw palmetto and a placebo, however.130 A separate review article also raised doubts about its efficacy.131

Supplements other than saw palmetto: Grade of recommendation: C2There is no evidence to support efficacy (5).

Treatments requiring urological expertise

Grade of recommendation: Reserved

These therapies should either be performed under supervision by urologists or by urologists in person.

Indwelling catheter and clean intermittent catheterization (CIC):  An indwelling catheter is frequently used as a treatment for urinary retention where other therapies cannot be carried out or are unsuccessful. However, long-term use of an indwelling catheter impairs QOL, and increases the risk of urethral injury, urinary tract infection, and bladder stones. An RCT comparing clean intermittent catheterization (CIC) with an indwelling catheter demonstrated a significantly lower incidence of symptomatic urinary tract infection in the CIC group.132

Surgical treatment for BPH:  Transurethral resection of the prostate (TURP) is the surgical gold standard for BPH.133 Possible complications include bleeding, TUR syndrome (hyponetremia and water intoxication), and postsurgical urethral stricture. Less invasive surgical methods are under development, with laser resection and ablation appearing particularly promising.

Algorithm

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References

Figure 1 shows an algorithm for management of lower urinary tract symptoms in males.

image

Figure 1. Algorithm for management of lower urinary tract symptoms in males: (a) This algorithm is applicable to middle-aged or older men who present with some kind of LUTS. (b) The basic assessment 1, mandatory in all cases, comprises present illness, past history, physical examination, urinalysis, and measurement of serum PSA. The basic assessment 2 is selected on an individual basis. It includes symptom and QOL questionnaires, bladder diary, and residual urine measurement, as well as urine cytology, urine culture, measurement of serum creatinine, and urinary tract ultrasonography. (c) If the symptoms are severe or include bladder pain, the patient should be referred to a urologist. If the predominant symptom is nocturia, the Clinical Guidelines for Nocturia should be consulted. The CLSS questionnaire (Table 5) may be useful in capturing important symptoms and their effects on QOL. (d) If any of these problems are revealed, the patient should be referred to a urologist. (e) Pyuria without fever is likely indicative of urinary tract infection and should be treated with appropriate antimicrobials. Note that urinary tract infection in men is sometimes associated with underlying diseases. (f) When the assessments reveal no problems, the patient should be asked for his desire for therapy. (g) At this stage the LUTS would be most probably attributable to BPH, bladder dysfunction, or both. Before initiating treatment, it is preferable that some of the tests of the basic assessment 2 be conducted, such as symptom and QOL questionnaires, bladder diary, and residual urine measurement. Of these, residual urine measurement is highly recommended. Patients who do not respond to the initial treatment should be referred to a urologist. (h) Re-assessment should be conducted on a regular basis, where changing, discontinuing or reducing the medications should be considered.

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Table 5.  Core Lower Urinary Tract Symptom Score (CLSS) Questionnaire : Please circle the number that applies best to your urinary condition during the last week.
 0123
Q1: How many times do you typically urinate from waking in the morning until going to sleep at night?0–78–910–1415+
Q2: How many times do you typically urinate from going to sleep at night until waking in the morning?012–34+
How often do you have the following symptoms?NeverRarelySometimesOften
Q3: A sudden strong desire to urinate, which is difficult to postpone0123
Q4: Leaking of urine because you cannot hold it in0123
Q5: Leaking of urine when you cough, sneeze, or strain0123
Q6: Slow urinary stream0123
Q7: Need to strain when urinating0123
Q8: Feeling of incomplete emptying of the bladder after passing urine0123
Q9: Pain in the bladder0123
Q10: Pain in the urethra0123
CLSS (Sum of Q1–10) ___________
From symptoms 1–10, please circle the numbers corresponding to no more than three symptoms you find bothersome.
Q1Q2Q3Q4Q5Q6Q7Q8Q9Q10Not applicable
Of the symptoms you chose above, please circle the number of the symptoms that you find most bothersome (1 only).
Q1Q2Q3Q4Q5Q6Q7Q8Q9Q10Not applicable
If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?
DelightedPleasedMostly satisfiedAbout equally satisfied and dissatisfiedMostly dissatisfiedUnhappyTerrible
0123456

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Targeted patients and anticipated users
  5. Methodology
  6. Definition of LUTS
  7. Epidemiology and QOL
  8. Etiology and pathogenesis
  9. Diagnosis
  10. Treatment
  11. Algorithm
  12. References
  • 1
    The Research Group on the Standardization of Urological Treatment. EBM-based Guidelines for the Treatment of Benign Prostatic Hyperplasia. The Research Group on the Standardization of Urological Treatment, Jiho, Tokyo, 2001.
  • 2
    The Research Group on the Standardization of Urological Treatment. EBM-based Guidelines for Urinary Incontinence. The Research Group on the Standardization of Urological Treatment, Jiho, Tokyo, 2004.
  • 3
    McConnell J, Abrams P, Denis L, Khoury S, Roehrborn C (eds). Male Lower Urinary Tract Dysfucntion Evaluation and Management, Edition 21. Health Publications, Paris, 2006.
  • 4
    Abrams P, Cardozo L, Fall M et al. The standardisation of terminology of lower urinary tract function: report from the standardization sub-committee of the International Continence Society. Neurourol. Urodyn. 2002; 21: 16778.
  • 5
    Welch G, Weinger K, Barry MJ. Quality-of-life impact of lower urinary tract symptom severity: results from the Health Professionals Follow-up Study. Urology 2002; 59: 24550.
  • 6
    Boyle P, Robertson C, Mazzetta C et al. The relationship between lower urinary tract symptoms and health status: the UREPIK study. BJU Int. 2003; 92: 57580.
  • 7
    Engström G, Henningsohn L, Steineck G, Leppert J. Self-assessed health, sadness and happiness in relation to the total burden of symptoms from the lower urinary tract. BJU Int. 2005; 95: 81015.
  • 8
    Peters TJ, Donovan JL, Kay HE et al. The International Continence Society ‘Benign Prostatic Hyperplasia’ Study: the bothersomeness of urinary symptoms. J. Urol. 1997; 157: 8859.
  • 9
    Homma Y, Yamaguchi O, Hayashi K, the members of the Neurogenic Bladder Society Committee. Epidemiologic survey of lower urinary tract symptoms in Japan. Urology 2006; 68: 5604.
  • 10
    Araki I, Tsuchida T, Nomura T et al. Differential impact of lower urinary tract symptoms on generic and disease-specific quality of life in men and women. Urol. Int. 2008; 81: 605.
  • 11
    Madersbacher S, Pycha A, Klingler CH, Schatzl G, Marberger M. The International Prostate Symptom Score in both sexes: a urodynamics-based comparison. Neurourol. Urodyn. 1999; 18: 17382.
  • 12
    De La Rosette JJ, Witjes WPJ, Schäfer W et al. Relationships between lower urinary tract symptoms and bladder outlet obstruction: results from the ICS-‘BPH’ Study. Neurourol. Urodyn. 1998; 17: 99108.
  • 13
    Yano M, Kitahara S, Yasuda K et al. A pilot study evaluating a new questionnaire for prostatic symptom scoring, the SPSS, and its sensitivity as constructed to objective measures of outflow obstruction. Int. J. Urol. 2004; 11: 28894.
  • 14
    Seki N, Yunoki T, Tomoda T, Takei M, Yamaguchi A, Naito S. Association among the symptoms, quality of life and urodynamic parameters in patients with improved lower urinary tract symptoms following transurethral resection of the prostate. Neurourol. Urodyn. 2008; 27: 2225.
  • 15
    Chai TC, Belville WD, McGuire EJ, Nyquist L. Specificity of the American Urological Association voiding symptom index: comparison of unselected and selected samples of both sexes. J. Urol. 1993; 150: 171013.
  • 16
    Honma Y, Nishizawa O, Yamaguchi O. The standardization of terminology of lower urinary tract function. Report from the Standardisation Sub-committee of the International Continence Society. J. Neurogenic Bladder Soc. 2003; 14: 27889.
  • 17
    Irwin DE, Milsom I, Hunskaar S et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Eur. Urol. 2006; 50: 130615.
  • 18
    Honma Y, Kakizaki H, Gotoh M, Takei M, Yamanishi T, Hayashi K. Epidemiologic survey on urination. J. Neurogenic Bladder Soc. 2003; 14: 26677.
  • 19
    Wong SY, Woo J, Hong A, Leung JCS, Kwok T, Leung PC. Risk factors for lower urinary tract symptoms in southern Chinese men. Urology 2006; 68: 100914.
  • 20
    Ponholzer A, Temml C, Wehrberger C, Marszalek M, Madersbacher S. The association between vascular risk factors and lower urinary tract symptoms in both sexes. Eur. Urol. 2006; 50: 5816.
  • 21
    Joseph MA, Harlow SD, Wei JT et al. Risk factors for lower urinary tract symptoms in a population-based sample of African-American men. Am. J. Epidemiol. 2003; 157: 90614.
  • 22
    Roberts RO, Jacobsen SJ, Rhodes T et al. Cigarette smoking and prostatism: a biphasic association? Urology 1994; 43: 797801.
  • 23
    Rosen R, Altwein J, Boyle P et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur. Urol. 2003; 44: 63749.
  • 24
    Quek KF. Factors affecting health-related quality of life among patients with lower urinary tract symptoms. Int. J. Urol. 2005; 12: 10326.
  • 25
    Okamura K, Usami T, Nagashima K, Maruyama S, Mizuta E. ‘Quality of life’ assessment of urination in elderly Japanese men and women with some medical problems using International Prostate Symptom Score and King's Health Questionnaire. Eur. Urol. 2002; 41: 41119.
  • 26
    O'leary MP, Roehrborn C, Andriole G, Nickel C, Boyle P, Höfner K. Improvements in benign prostatic hyperplasia-specific quality of life with dutasteride, the novel dual 5 α-reductase inhibitor. BJU Int. 2003; 92: 2626.
  • 27
    Gacci M, Bartoletti R, Figlioli S et al. Urinary symptoms, quality of life and sexual function in patients with benign prostatic hypertrophy before and after prostatectomy: a prospective study. BJU Int. 2003; 91: 196200.
  • 28
    Hyman MJ, Groutz A, Blaivas JG. Detrusor instability in men: correlation of lower urinary tract symptoms with urodynamic findings. J. Urol. 2001; 166: 5503.
  • 29
    Speakmann MJ, Brading AF, Gilpin CJ, Dixon JS, Gilpin SA, Gosling JA. Bladder outflow obstruction – a cause of denervation supersensitivity. J. Urol. 1987; 138: 14616.
  • 30
    Seki N, Karim OM, Mostwin JL. The effect of experimental urethral obstruction and its reversal on changes in passive electrical properties of detrusor muscle. J. Urol. 1992; 148: 195761.
  • 31
    Andersson K-E, Hedlund P. Pharmacologic perspective on the physiology of the lower urinary tract. Urology 2002; 60 (Suppl 5A): 1320.
  • 32
    Yokoyama O, Nagano K, Kawaguchi K, Ueki O, Ohkawa M. The influence of prostatic urethral anesthesia in overactive detrusor in patients with benign prostatic hyperplasia. J. Urol. 1994; 151: 15546.
  • 33
    Collins MM, Stafford RS, O'Leary MP, Barry MJ. How common is prostatitis? A national survey of physician visits. J. Urol. 1998; 159: 12248.
  • 34
    Miller JL, Rothman I, Bavendam TG, Berger RE. Prostatodynia and interstitial cystitis: one and the same? Urology 1995; 45: 58790.
  • 35
    Ichikawa T, Takao A, Nakayama Y, Saegusa M, Aramaki K. Sexual functions in men with micturition disorder. Jpn J. Urol. 2001; 92: 4649.
  • 36
    Novicki DE, Larson TR, Swanson SK. Interstitial cystitis in men. Urology 1998; 52: 6214.
  • 37
    Ameda K, Sullivan MP, Bae RJ, Yalla SV. Urodynamic characterization of nonobstructive voiding dysfunction in symptomatic elderly men. J. Urol. 1999; 162: 1426.
  • 38
    Thomas AW, Cannon A, Bartlett E, Ellis-Jones J, Abrams P. The natural history of lower urinary tract dysfunction in men: minimum 10-year urodynamic followup of transurethral resection of prostate for bladder outlet obstruction. J. Urol. 2005; 174: 188791.
  • 39
    Lepor H, Sunaryadi I, Hartanto V, Shapiro E. Quantitative morphometry of the adult human bladder. J. Urol. 1992; 148: 41417.
  • 40
    Madersbacher S, Kilingler HC, Schatzl G, Stulnig T, Schmidbauer CP, Marberger M. Age related urodynamic changes in patients with benign prostatic hyperplasia. J. Urol. 1996; 156: 16627.
  • 41
    Sakakibara R, Fowler CJ, Hattori T. Voiding and MRI analysis of the brain. Int. Urogynecol. J. Pelvic Floor Dysfunct. 1999; 10: 1929.
  • 42
    Kaplan SA, Te AE, Blavas JG. Urodynamic findings in patients with diabetic cystopathy. J. Urol. 1995; 153: 3424.
  • 43
    Wang Y, Chan GLY, Holden JE et al. Age-dependent decline of dopamine D1 receptors in human brain: a PET study. Synapse 1998; 30: 5661.
  • 44
    Morgan DC, May PC. Age-related changes in synaptic neurochemistry. In: SchneiderEL, RoweJW (eds). Handbook of the Biology of Aging, 3rd edn. Academic Press, San Diego, CA, 1990; 21954.
  • 45
    Tong YC, Hung YC, Lin SN, Cheng JT. The norepinephrine tissue concentration and neuropeptide Y immunoreactivity in genitourinary organs of the spontaneously hypertensive rat. J. Auton. Nerv. Syst. 1996; 56: 2158.
  • 46
    Golomb E, Rosenzweig N, Eilam R, Abramovici A. Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J. Androl. 2000; 21: 5864.
  • 47
    Steers WD, Clemow DB, Persson K, Sherer TB, Andersson K-E, Tuttle JB. The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males. Exp. Physiol. 1999; 84: 13747.
  • 48
    Gourova LW, Van De Beek C, Spigt MG, Nieman FHM, Van Kerrebroeck PEVA. Predictive factors for nocturia in elderly men: a cross-sectional study in 21 general practices. BJU Int. 2006; 97: 52832.
  • 49
    Asplund R. Nocturia, nocturnal polyuria, and sleep quality in the elderly. J. Psychosom. Res. 2004; 56: 51725.
  • 50
    Homma Y, Yoshida M, Yamanishi T, Gotoh M. Core Lower Urinary Tract Symptom score (CLSS) questionnaire: a reliable tool in the overall assessment of lower urinary tract symptoms. Int. J. Urol. 2008; 15: 81620.
  • 51
    Abrams P, Donovan JL, De La Rosette JJ, Schäfer W, the ICS-‘BPH’ Study Group. International Continence Society ‘Benign Prostatic Hyperplasia’ Study: background, aims, and methodology. Neurourol. Urodyn. 1997; 16: 7991.
  • 52
    Barry MJ, Fowler FJ Jr, O'Leary MP et al. The American Urological Association Symptom Index for benign prostatic hyperplasia. J. Urol. 1992; 148: 154957.
  • 53
    Cockett ATK, Khoury S, Aso Y, Chatelain C, Griffiths K, Murphy G (eds). Proceedings of the Second International Consultation on Benign Prostatic Hyperplasia. Scientific Communication International, Jersey, 1993.
  • 54
    Barry MJ, Fowler FJ Jr, O'Leary MP et al. Measuring disease-specific health status in men with benign prostatic hyperplasia. Med. Care 1995; 33 (Suppl): AS14555.
  • 55
    Shumaker SA, Wyman JF, Uebersax JS, McClish D, Fantl JA, Continence Program in Women (CPW) Research Group. Health-related quality of life measures for women with urinary incontinence: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Qual. Life Res. 1994; 3: 291306.
  • 56
    Wagner TH, Patrick DL, Bavendam TG, Martin ML, Buesching DP. Quality of life of persons with urinary incontinence: development of a new measure. Urology 1996; 47: 6772.
  • 57
    Kelleher CJ, Cardozo LD, Khullar V, Salvatore S. A new questionnaire to assess the quality of life of urinary incontinent women. Br. J. Obstet. Gynaecol. 1997; 104: 13749.
  • 58
    Avery K, Donovan J, Peters TJ, Shaw C, Gotoh M, Abrams P. ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence. Neurourol. Urodyn. 2004; 23: 32230.
  • 59
    Karantanis E, Fynes M, Moore KH, Stanton SL. Comparison of the ICIQ-SF and 24-hour pad test with other measures for evaluating the severity of urodynamic stress incontinence. Int. Urogynecol. J. Pelvic Floor Dysfunct. 2004; 15: 11116.
  • 60
    Coyne K, Revicki D, Hunt R et al. Psychometric validation of an overactive bladder symptom and health-related quality of life questionnaire: the OAB-q. Qual. Life Res. 2002; 11: 56374.
  • 61
    Homma Y, Yoshida M, Seki N et al. Symptom assessment tool for overactive bladder syndrome-overactive bladder symptom score. Urology 2006; 68: 31826.
  • 62
    O'Leary MP, Sant GR, Fowler FJ Jr, Whitmore KE, Spolarich-Kroll J. The interstitial cystitis symptom index and problem index. Urology 1997; 49: (Suppl 5A): 5863.
  • 63
    Parsons CL, Dell J, Stanford EJ et al. Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Urology 2002; 60: 5738.
  • 64
    Litwin MS, McNaughton-Collins M, Fowler FJ et al. The National Institute of Health Chronic Prostatitis Symptom Index: development and validation of new outcome measure. J. Urol. 1999; 162: 36975.
  • 65
    Abrams P, Avery K, Gardener N, Donovan J on behalf of the ICIQ Advisory Board. The International Consultation on Incontinence Modular Questionnaire: http://www.iciq.net. J. Urol. 2006; 175: 10636.
  • 66
    Homma Y, Ando T, Yoshida M et al. Voiding and incontinence frequencies: variability of diary data and required diary length. Neurourol. Urodyn. 2002; 21: 2049.
  • 67
    Homma Y, Yamaguchi O, Kageyama S, Nishizawa O, Yoshida M, Kawabe K. Nocturia in the adult: classification on the basis of largest voided volume and nocturnal urine production. J. Urol. 2000; 163: 77781.
  • 68
    Gerber GS, Brendler CB. Evaluation of the urologic patient: history, physical examination, and urinalysis. In: WalshPC, RetikAB, VaughanEDJr, WeinA (eds). Campbell's Urology, 8th edn. Saunders, Philadelphia, PA, 2002; 83110.
  • 69
    Carvalhal GF, Smith DS, Mager DE, Ramos C, Catalona WJ. Digital rectal examination for detecting prostate cancer at prostate-specific antigen levels of 4 ng/ml or less. J. Urol. 1999; 161: 8359.
  • 70
    Djavan B, Marberger M. A meta-analysis on the efficacy and tolerability of α1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur. Urol. 1999; 36: 113.
  • 71
    AUA Practice Guidelines Committee. AUA. Guideline on management of benign prostatic hyperplasia (2003). Chapter 1: diagnosis and treatment recommendations. J. Urol. 2003; 170: 53047 (Guideline).
  • 72
    Tsujii T; on behalf of BPH Medical Therapy Study Group. Comparison of prazosin, terazosin and tamsulosin in the treatment of symptomatic benign prostatic hyperplasia: a short-term open, randomized multicenter study. Int. J. Urol. 2000; 7: 199205.
  • 73
    Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J. Cataract Refract. Surg. 2005; 31: 66473.
  • 74
    Chapple CR, Stott M, Abrams PH, Christmas TJ, Milroy EJG. A 12-week placebo-controlled doubleblind study of prazosin in the treatment of prostatic obstruction due to benign prostatic hyperplasia. Br. J. Urol. 1992; 70: 28594.
  • 75
    Yamaguchi O, Shiraiwa Y, Kobayashi M et al. Clinical evaluation of effects of prazosin in patients with benign prostatic obstruction. A double-blind, multi-institutional, Paraprost-controlled study. Urol. Int. 1990; 45 (Suppl 1): 406.I
  • 76
    Wilt TJ, Howe W, MacDonald R. Terazosin for treating symptomatic benign prostatic obstruction: a systematic review of efficacy and adverse effects. BJU Int. 2002; 89: 21425.
  • 77
    Okada H, Kamidono S, Yoshioka T et al. A comparative study of terazosin and tamsulosin for symptomatic benign prostatic hyperplasia in Japanese patients. BJU Int. 2000; 85: 67681.
  • 78
    Cheah PY, Liong ML, Yuen KH et al. Terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome: a randomized, placebo controlled trial. J. Urol. 2003; 169: 5926.
  • 79
    Kawabe K, Tsuchida S, Shimazaki J, Morita T, Yasuda K, Kageyama S. Effect on urapidil on benign prostatic hypertrophy: a multicenter, double-blind study. Urol. Int. 1993; 50: 2732.
  • 80
    Yamanishi T, Yasuda K, Homma Y, Kawabe K, Morita T. A multicenter placebo-controlled, doubleblind trial of urapidil, an α-blocker, on neurogenic bladder dysfunction. Eur. Urol. 1999; 35: 4551.
  • 81
    Kawabe K, Ueno A, Takimoto Y, Aso Y, Kato H; YM617 Clinical Study Group. Use of an α1-blocker, YM617, in the treatment of benign prostatic hypertrophy. J. Urol. 1990; 144: 90812.
  • 82
    Abrams P, Schulman CC, Vaage S; the European Tamsulosin Study Group. Tamsulosin, a selective α1c-adrenoceptor antagonist: a randomized, controlled trial in patients with benign prostatic ‘obstruction. Br. J. Urol. 1995; 76: 32536.
  • 83
    Lepor H, for the Tamsulosin Investigator Group. Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Urology 1998; 51: 892900.
  • 84
    Kawabe K, Homma Y, Kubota K, Sozu T, the Tamsulosin Long-term Study Group. How frequent are invasive therapies required in patients receiving tamsulosin for benign prostatic hyperplasia? A retrospective long-term study. Int. J. Urol. 2006; 13: 12731.
  • 85
    Yamaguchi O, Fukaya Y, Shiraiwa Y et al. Clinical evaluation of naftopidil (KT-611) in micturition disorder associated with benign prostatic hyperplasia: a double- blind comparative study using prazosin hydrochloride as a comparator. J. Clin. Ther. Med. 1992; 8: 699722.
  • 86
    Yamanishi T, Yasuda K, Kamai K et al. Single-blind, randomized controlled study of the clinical and urodynamic effects of an α-blocker (naftopidil) and phytotherapy (eviprostat) in the treatment of benign prostatic hyperplasia. Int. J. Urol. 2004; 11: 5019.
  • 87
    Gotoh M, Kamihira O, Kinukawa T, Ono Y, Ohshima S, Origasa H, on behalf of the Tokai Urological Clinical Trial Group. Comparison of tamsulosin and naftopidil for efficacy and safety in the treatment of benign prostatic hyperplasia: a randomized controlled trial. BJU Int. 2005; 96: 5816.
  • 88
    Nishino Y, Masue T, Miwa K, Takahashi Y, Ishihara S, Deguchi T. Comparison of two α1-adrenoceptor antagonists, naftopidil and tamsulosin hydrochloride, in the treatment of lower urinary tract symptoms with benign prostatic hyperplasia: a randomized crossover study. BJU Int. 2006; 97: 74751.
  • 89
    Kawabe K, Yoshida M, Homma Y, for the Silodosin Clinical Study Group. Silodosin, a new α1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int. 2006; 98: 101924.
  • 90
    MacDonald R, Wilt TJ. Alfuzosin for treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia: a systematic review of efficacy and adverse effects. Urology 2005; 66: 7808.
  • 91
    Shah T, Palit V, Biyani S, Elmasry Y, Puri R, Flannigan GM. Randomised, placebo controlled, double blind study of alfuzosin SR in patients undergoing trial without catheter following acute urinary retention. Eur. Urol. 2002; 42: 32932.
  • 92
    Lapitan MCM, Acepcion V, Mangubat J. A comparative study on the safety and efficacy of tamsulosin and alfuzosin in the management of symptomatic benign prostatic hyperplasia: a randomized controlled clinical trial. J. Int. Med. Res. 2005; 33: 56273.
  • 93
    Mehik A, Alas P, Nickel JC, Sarpola A, Helström PJ. Alfuzosin treatment for chronic prostatitis/chronic pelvic pain syndrome: a prospective, randomized, double-blind, placebo-controlled, pilot study. Urology 2003; 62: 4259.
  • 94
    Yoshida H, Haraguchi T, Ogawa Y. Clinical effect of chlormadinone acetate on benign prostatic hyperplasia: a study on changes in the morphology and organ weight of the prostate (3 months) by ultrasonic tomography. Acta Urol. Jpn 1983; 29: 141926.
  • 95
    Shida K, Kakei R, Koyanagi T et al. Clinical effect of allylestrenol on benign prostatic hyperplasia in a double-blind study. Acta Urol. Jpn 1986; 32: 62548.
  • 96
    Boyle P, Gould AL, Roehrborn CG. Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 1996; 48: 398405.
  • 97
    Roehrborn CG, Bruskewitz R, Nickel GC et al. Urinary retention in patients with BPH treated with finasteride or placebo over 4 years. Characterization of patients and ultimate outcomes. Eur. Urol. 2000; 37: 52836.
  • 98
    Debruyne F, Barkin J, Van Erps P, Reis M, Tammela TLJ, Roehrborn C, on behalf of the ARIA3001, ARIA3002 and ARIB3003 Study Investigators. Efficacy and safety of long-term treatment with the dual 5α-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia. Eur. Urol. 2004; 46: 48895.
  • 99
    Okada H, Kawaida N, Ogawa T, Arakawa S, Matsumoto O, Kamidono S. Tamsulosin and chlormadinone for the treatment of benign prostatic hyperplasia. The Kobe University YM617 Study Group. Scand. J. Urol. Nephrol. 1996; 30: 37985.
  • 100
    Otani M, Kikuchi K, Tsuchiya A et al. A randomized, long-term comparative study of α1-blocker monotherapy and α1-blocker/anti-androgen combination therapy in patients with benign prostatic hyperplasia: focusing on the improvement of I-PSS. Acta Urol. Jpn 2000; 46: 7917.
  • 101
    Kirby RS, Roehrborn C, Boyle P et al. Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) Trial. Urology 2003; 61: 11926.
  • 102
    McConnell JD, Roehrborn CG, Bautista OM et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N. Engl. J. Med. 2003; 349: 238798.
  • 103
    Yasuda K, Yamanishi T, Kawabe K, Ohshima H, Morita T. The effect of urapidil on neurogenic bladder: a placebo controlled double-blind study. J. Urol. 1996; 156: 112530.
  • 104
    Lee JY, Kim HW, Lee SJ, Koh JS, Suh HJ, Chancellor MB. Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder. BJU Int. 2004; 94: 81720.
  • 105
    Roehrborn CG, Abrams P, Rovner ES, Kaplan SA, Herschorn S, Guan Z. Efficacy and tolerability of tolterodine extended-release in men with overactive bladder and urgency urinary incontinence. BJU Int. 2006; 97: 10036.
  • 106
    Abrams P, Kaplan S, De Koning Gans HJ, Millard R. Safety and tolerability of tolterodine for the treatment of overactive bladder in men with bladder outlet obstruction. J. Urol. 2006; 175: 9991004.
  • 107
    Lee K-S, Choo M-S, Kim D-Y et al. Combination treatment with propiverine hydrochloride plus doxazosin controlled release gastrointestinal therapeutic system formulation for overactive bladder and coexisting benign prostatic obstruction: a prospective, randomized, controlled multicenter study. J. Urol. 2005; 174: 13348.
  • 108
    Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder. A randomized controlled trial. JAMA 2006; 296: 231928.
  • 109
    Blake-James BT, Rashidian A, Ikeda Y, Emberton M. The role of anticholinergics in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a systematic review and metaanalysis. BJU Int. 2006; 99: 8596.
  • 110
    Maruyama O, Kawachi Y, Hanzawa K et al. Naftopidil monotherapy vs naftopidil and an anticholinergic agent combined therapy for storage symptoms associated with benign prostatic hyperplasia: a prospective randomized controlled study. Int. J. Urol. 2006; 13: 12805.
  • 111
    Kaplan SA, Walmsley K, Te AE. Tolterodine extended release attenuates lower urinary tract symptoms in men with benign prostatic hyperplasia. J. Urol. 2005; 174: 22736.
  • 112
    Yamaguchi O, Shiraiwa Y, Kobayashi M et al. Clinical evaluation of effects of prazosin in patients with benign prostatic obstruction. A double-blind, multi-institutional, Paraprost-controlled study. Urol. Int. 1990; 45 (Suppl 1): 406.
  • 113
    MacDonald R, Ishani A, Rutks I, Wilt TJ. A systematic review of Cernilton for the treatment of benign prostatic hyperplasia. BJU Int. 1999; 85: 83641.
  • 114
    Elist J. Effects of pollen extract preparation Prostat/Poltit on lower urinary tract symptoms in patients with chronic nonbacterial prostatitis/chronic pelvic pain syndrome: a randomized, double-blind, placebo-controlled study. Urology 2006; 67: 603.
  • 115
    Dahm TL, Ostri P, Kristensen JK et al. Flavoxate treatment of micturition disorders accompanying benign prostatic hypertrophy: a double-blind placebo-controlled multicenter investigation. Urol. Int. 1995; 55: 2058.
  • 116
    Barendrecht MM, Oelke M, Laguna MP, Michel MC. Is the use of parasympathomimetics for treating an underactive urinary bladder evidence-based? BJU Int. 2007; 99: 74952 (Review).
  • 117
    Yamanishi T, Yasuda K, Kamai T et al. Combination of a cholinergic drug and an α-blocker is more effective than monotherapy for the treatment of voiding difficulty in patients with underactive detrusor. Int. J. Urol. 2004; 11: 8896.
  • 118
    McVary KT, Monnig W, Camps JL Jr, Young JM, Tseng LJ, Van Den Ende G. Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial. J. Urol. 2007; 177: 10717.
  • 119
    McVary KT, Roehrborn CG, Kaminetsky JC et al. Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J. Urol. 2007; 177: 14017.
  • 120
    Yamanishi T, Yasuda K, Sakakibara R, Hattori T, Suda S. Randomized, double-blind study of electrical stimulation for urinary incontinence due to detrusor overactivity. Urology 2000; 55: 3537.
  • 121
    Yamanishi T, Yasuda K, Sakakibara R, Hattori T, Ito H, Murakami S. Pelvic floor electrical stimulation in the treatment of stress incontinence: an investigational study and a placebo controlled double-blind trial. J. Urol. 1997; 158: 212731.
  • 122
    Suzuki T, Yasuda K, Yamanishi T et al. Randomized, double-blind, sham-controlled evaluation of the effect of functional continuous magnetic stimulation in patients with urgency incontinence. Neurourol. Urodyn. 2007; 26: 76772.
  • 123
    Yamanishi T, Sakakibara R, Uchiyama T et al. Comparative study of the effects of magnetic versus electrical stimulation on inhibition of detrusor overactivity. Urology 2000; 56: 77781.
  • 124
    Soomro NA, Khadra MH, Robson W, Neal DE. A crossover randomized trial of transcutaneous electrical nerve stimulation and oxybutynin in patients with detrusor instability. J. Urol. 2001; 166: 1469.
  • 125
    Yasuda K, Kawabe K, Sato A et al. A double-blind cross-over comparative study of TEU-20 interferential low-frequency device for urinary frequency, urgency, and incontinence. Jpn J. Urol. Surg. 1994; 7: 297324.
  • 126
    Wasson JH, Reda DJ, Bruskewitz RC, Elinson J, Keller AM, Henderson WG, for the Veterans Affairs Cooperative Study Group on Transurethral Resection of the Prostate. A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. N. Engl. J. Med. 1995; 332: 759.
  • 127
    Van Eijken M, Wensing M, De Konink M et al. Health education on self-management and seeking health care in older adults: a randomised trial. Patient Educ. Couns. 2004; 55: 4854.
  • 128
    Managing incontinence due to detrusor instability. Drug Ther. Bull. 2001; 39: 5964 (Review).
  • 129
    Fong YK, Milani S, Djavan B. Role of phytotherapy in men with lower urinary tract symptoms. Curr. Opin. Urol. 2005; 15: 458 (Review).
  • 130
    Bent S, Kane C, Shinohara K et al. Saw palmetto for benign prostatic hyperplasia. N. Engl. J. Med. 2006; 354: 55766.
  • 131
    Avins AL, Bent S. Saw palmetto and lower urinary tract symptoms: what is the latest evidence? Curr. Urol. Rep. 2006; 7: 2605 (Review).
  • 132
    Turi MH, Hanif S, Fasih Q, Shaikh MA. Proportion of complications in patients practicing clean intermittent self-catheterization (CISC) vs indwelling catheter. J. Pak. Med. Assoc. 2006; 56: 4014.
  • 133
    MacDonagh RP, Cliff AM, Speakman MJ, O'Boyle PJ, Ewings P, Gudex C. The use of generic measures of health-related quality of life in the assessment of outcome from transurethral resection of the prostate. BJU Int. 1997; 79: 4018.