UAA Consensus on the Management of BPH/Male - UAANET guidelines.pdf · - 1 - UAA Consensus on the...

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UAA Consensus on the

Management of BPH/Male

LUTS (1st Edition)

Edited and written by Masayuki Takeda,

Md Afiquor Rahman, M A Salam, Masaki Yoshida, Hideki Kobayashi,

Norifumi Sawada, Momokazu Gotoh, Koji Yoshimura, Jun Hyuk

Hong, Kyu-Sung Lee, Joon Chul Kim, Rohan Malek, Selvalingam

Sothilingam, Jose Albert C.Reyes III, Kok Bin Lim, Keong Tatt Foo,

Colin Teo, Shih-Ping Liu, Shing-Hwa Lu, Chih-Shou Chen, Sathit

Ruangdilokrat, Wachira Kochakarn and other UAA Guideline

members.

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Foreword

These Proceedings represent the consensus and recommendation

of Benign Prostatic Hyperplasia (BPH)/Male Lower Urinary Tract

Symptoms (LUTS) by the 16 countries that met in Pattaya, Thailand

at the occasion of the 11th Asian Congress of Urology, on August

22nd 2012, and in Hong Kong on November 10th 2012.

On behalf of Urological Association of Asia (UAA), we would like to

thank the chairman, the committee members, and Ms. Angie See,

Executive Secretary of UAA Central Office.

We also would like to thank JUA, AUA, EAU, and ICUD for kind

allowance to use some parts of their Guidelines.

This is the 1st Clinical Guideline published by UAA, hence, is a

milestone for UAA.

UAA Representatives Keong Tatt Foo, Osamu Ogawa, Masayuki Nakagawa

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Contents

Preface

COI (Conflict of interest)

Methodology

Committee Members

1. Algorithm

2. CQ(Clinical Question)s

3. Introduction

4. Definition, and Terminology of Benign Prostatic Hyperplasia

(BPH) and related disorders

5. Risk factors

6. Epidemiology & Natural history

7. Pathophysiology

8. Complications by BPH

9. Diagnosis & Investigation of BPH/Male LUTS

10. Recommendation grade for treatment: Pharmacological &

Conservative Treatments

11. Recommendation grade for treatment: Surgery

12. Abbreviations

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Preface

1. Purposes of guideline: Practical Consensus Statement on the Management

of BPH/Male LUTS

2. Target doctors: Both Urologists and General Practitioners

3. Target patients: 40 years or older male patients with BPH/LUTS

4. Ownership and responsibility of this guideline: UAA

Conflict of interest

All members of the BPH/Male LUTS working group have provided disclosure

statements on all relationships that they have and that might be perceived to be

a potential source of conflict of interest. This information is kept on file in the

Urological Association of Asia Central Office database. These guidelines

document was developed with the financial support of the Urological Association

of Asia. No external sources of funding and support have been involved.

The UAA is a non-profit organization and funding is limited to administrative

assistance and travel and meeting expenses. No honorarium or other

reimbursements.

Methodology

1. The BPH/Male LUTS Guidelines have been developed by committee

members recommended by the Urological Association of Asia (UAA).

2. The members have meticulously reviewed relevant references, retrieved via

the PubMed and MEDLINE databases, published between 1966 through

Dec 31st, 2011.

3. The search strategy includes the Medical Subject Headings (MeSH) for BPH

and LUTS: “Prostatic Hyperplasia”[MeSH] AND Benign; “Urinary tract”

4. [MeSH] AND Symptoms AND Lower. Other key words for searching

references will be selected by each committee.

5. Other sources of information include

1) JUA clinical guidelines for benign prostatic hyperplasia,

2) The BPH Guidelines 2010 published by The American Urological

Association (AUA)

3) Guidelines on the Treatment of Non-neurogenic Male LUTS2011

The European Association of Urology (EAU),

4) The meeting reports of the 6th International Consultation on

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New Developments in Prostatic Cancer and Prostatic Diseases.

“MALE LOWER URINARY TRACT DYSFUNCTION; Evaluation

and Management”

6. Level of Evidence & Grade of Recommendation for each treatment will be

made according to the following strategy. The recommendations of the

treatments are based on a non-structured literature search, which has been

previously shown, and labeled with a Level of Evidence (LE), according to a

classification system modified from the Oxford Centre for Evidence-based

Medicine Levels of Evidence*, ranging from LE:1 (highest evidence level) to

LE:5 (case study or expert opinion).

*Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001).

Produced by Bob Phillips, et al., Since November 1998.

http://www.cebm.net/index.aspx?o=1025 [accessed March 2012].

7. For each subsection, the conclusion(s) drawn from the relevant articles and

evidence levels have been judged using a Grade of Recommendation (GR),

ranging from a strong recommendation (Grade A) to recommendation not to

do (Grade D).

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As presented above, Level of Evidence for each reference will be made

according to the following strategy in CQ6-14(pages 24-48), however, Level of

Evidence will not be shown for each reference in either “Chapter 10.

Recommendation grade for treatment: Pharmacological & Conservative

Treatments”, or in “Chapter 11.Recommendation grade for treatment: Surgery”.

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Committee Members of Guideline (should be correctly written)

1. UAA Representative

Prof. Keong Tatt Foo, Prof. Osamu Ogawa, Prof. Masayuki Nakagawa

2. 8 core member countries: Korea, Taiwan, Japan, Singapore, Malaysia,

Thailand, Bangladesh, Philippines

3. Members from 16 countries (Alphabetical orders)

Bangladesh Dr. Md Afiquor Rahman, Dr. M A Salam

Cambodia Dr. Prak Seng Hour

China Dr. Song Bo

Hong Kong Dr. Steve Chan, Dr. In Chak Law

India Dr. R M Meyyappan

Indonesia Dr. Chaidir Arif Mochtar

Iran Dr. Seyed Mohammad Kazemeyni

Japan Dr. Momokazu Gotoh, Dr. Hideki Kobayashi

Dr. Masayuki Nagakawa, Dr. Osamu Ogawa

Dr. Norifumi Sawada, Dr. Masayuki Takeda

Dr. Masaki Yoshida, Dr. Koji Yoshimura

Korea Dr. Jun Hyuk Hong, Dr. Kyu-Sung Lee

Dr. Joon Chul Kim

Malaysia Dr. Zulkifli Md Zainuddin, Dr. Rohan Malek

Dr. Selvalingam Sothilingam

Philippines Dr. Eduardo R Gatchalian, Dr. Jose Albert C.Reyes III

Singapore Dr. Kok Bin Lim, Keong Tatt Foo,

Dr. Colin Teo

Sri Lanka Dr. Srinath Chandrasekera

Taiwan Dr. Shih-Ping Liu, Dr. Shing-Hwa Lu

Dr. Chih-Shou Chen

Thailand Dr. Sathit Ruangdilokrat, Dr. Wachira Kochakarn

Vietnam Dr. Vu Le Chuyen

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1. Algorithms

Algorithms are made for general practitioner (GP; a) and Urologist (b-d),

separately.

1.1Treatment Algorithm of Male LUTS for General Practitioner (GP)

*Neurological disorders, Pelvic surgery, Radiation Therapy, DM, Drugs

**In patients with life expectancy of less than 10 years, or without indication for

prostatic cancer treatment, serum PSA may not be routinely measured.

(See page 22, in Chapter 2. CQ5)

***Assessment of shape and size of prostate is recommended.

(See page 15 in Chapter 2. CQ2)

GP: General practitioner

DRE: digital rectal examination

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1.2 Treatment Algorithm of Male LUTS; Basic Options for Urologist

Using Medical/ Conservative Treatments

*In patients with life expectancy of less than 10 years, or without indication for

prostatic cancer treatment, serum PSA may not be routinely measured.

(See page 22 in Chapter 2. CQ5, and page 93 in Chapter 9. Diagnosis &

Investigation for BPH/Male LUTS)

**Assessment of shape and size of prostate is recommended.

*** IPP=1 and good flow is good indication.

IPP=3 and poor flow is a potential risk for urinary retention.

IPP: Intravesical prostatic protrusion.

(See page 15 in Chapter 2. CQ2, and page 74–75 in Chapter 7.

Pathophysiology of BPH)

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1.3 Specialized Management for Persistent Bothersome LUTS after

Basic Management for Urologist

BOO: Bladder outlet obstruction

PFS: Pressure-flow study

*Urethrocystoscopy is indicated if urethral stricture or bladder neck sclerosis is

suspected.

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1.4Treatment Algorithm of Bothersome Male LUTS Refractory to

Medical/Conservative Treatment or Absolute Surgical Indications

for Urologist

TURP: Transurethral resection of the prostate

TUIP: Transurethral incision of the prostate

TUEB: Transurethral enucleation of the prostate using bipolar electrode

TUERP: Transurethral enucleation and resection of the prostate

(either using bipolar or monopolar electrode)

TUVP: Transurethral vaporization of the prostate

PVP: Photoselective vaporization of the prostate

HoLAP: Holmium laser ablation of the prostate

HoLEP: Holmium laser enucleation of the prostate

TUMT: Transurethral microwave thermotherapy of the prostate

TUNA: Transurethral needle ablation of the prostate

CIC: Clean intermittent catheterization

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2. Clinical Question (CQ)

Masayuki Takeda, M.D., Ph.D., Hideki Kobayashi, M.D., Ph.D.,

Norifumi Sawada, M.D., Ph.D., Masaki Yoshida, M.D., Ph.D., Koji

Yoshimura, M.D., Ph.D., Momokazu Gotoh, M.D., Ph.D., Japan.

As described in page 5, the recommendations of the treatments (CQ6-14)

are based on a non-structured literature search, which has been previously

shown, and labeled with a Level of Evidence (LE), according to a classification

system modified from the Oxford Centre for Evidence-based Medicine Levels of

Evidence, ranging from LE:1 (highest evidence level) to LE:5 (case study or

expert opinion). However, Grade of Recommendations for examinations and

methods for diagnosis (CQ1-CQ5) are made by the consensus of the committee

members, not solely according to the above strategy.

CQ1

What questionnaires should be recommended for initial evaluation of BPH/Male

LUTS ?

Answer:

IPSS: Recommendation Grade A

QOL in IPSS: Recommendation Grade A

Frequency volume chart (FVC) or Bladder diary: Recommendation Grade B

The OABSS: Recommendation Grade B

Systematic diagnostic work-up should be begun by history, validated symptom

questionnaires. International Prostate Symptom Score (IPSS) and QOL score

are the most prevalent, highly validated questionnaire for BPH patients [1-4].

Freuqeuncy volume chart (time and volume of voids and including any episodes

of incontinence) or a bladder diary (a 24 hour recording of your liquid intake and

urine output) is recommended for men with daytime or nocturnal frequency.

Nocturnal polyuria (> 33% of the 24-hour urine excretion overnight) can be made

only by a bladder diary, whereas the diagnosis of all other forms of

non-neurogenic benign forms of LUTS in men aged 40 years or older is mainly

made by exclusion.

The diary records individual voiding prospectively, enabling the accurate

evaluation of voiding time, individual volumes voided, and total urinary

volume. This information is useful for the differential diagnosis of urinary

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frequency, which can be classified as a decrease in the volume voided, polyuria,

or both [5–7]. Ideally, the diary should be kept over a period of 3–7 days,

although keeping the diary for over 1 or 2 days may be sufficient [8–11].

The OABSS, the sum score of four symptoms (daytime frequency, nighttime

frequency, urgency, and urgency incontinence), has been developed and

validated [12, 13]. OABSS can be applied efficiently to the evaluation of OAB in

patients with BPH [14].

The different QOL instruments are discussed in relation to their correlation with

symptom evaluation in studies of treatment options for BPH, however, there is

neither agreement nor data to decide which QOL instrument is preferable.

The most widely used QOL instrument is the disease-specific QOL, single

question added to the IPSS, and BPH Impact Index (BII). Symptom-specific QOL

is also used. Disease-specific QOL domains (interference with daily activities)

tend to improve more with treatment interventions than general health measures

(i.e. general well-being). Symptom-specific QOL of BPH patients cannot be

estimated by physically measurable variables [15–17].

References of CQ1

1. Bolognese JA, Kozloff RC, Kunitz SC, Grino PB, Patrick DL, Stoner E.

Validation of a symptoms questionnaire for benign prostatic hyperplasia.

Prostate 1992; 21: 247–54.

2. Epstein RS, Deverka P, Chute CG et al. Validation of a new quality of life

questionnaire for benign prostatic hyperplasia. J. Clin. Epidemiol. 1992; 45:

1431–45.

3. Bosch JL, Hop WC, Kirkels WJ, Schroder FH. The International Prostate

Symptom Score in a community-based sample of men between 55 and 74

years of age: prevalence and correlation of symptoms with age, prostate

volume, flow rate and residual urine volume. Br. J. Urol., 1995; 75: 622–30.

4. Netto Junior NR, D'Ancona CA, De Lima ML. Correlation between the

International Prostatic Symptom Score and a pressure-flow study in the

evaluation of symptomatic benign prostatic hyperplasia J. Urol., 1996; 155:

200–2.

5. Homma Y, Araki I, Igawa Y et al. Clinical guideline for male lower urinary

tract symptoms. Int. J. Urol. 2009; 16: 775–90.

6. Homma Y, Kawabe K, Tsukamoto T et al. Estimate criteria for efficacy of

treatment in benign prostatic hyperplasia. Int. J. Urol. 1996; 3: 267–73.

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7. Abrams P, Chapple C, Khoury S, Roehrborn C, De la Rosette J. Evaluation

and treatment of lower urinary tract symptoms in older men. J. Urol. 2009;

181: 1779–87.

8. EAU Guidelines on the Management of Male Lower Urinary Tract Symptoms

(LUTS), incl. Benign Prostatic Obstruction (BPO)

(http://www.uroweb.org/gls/pdf/12_Male_LUTS_LR%20May%209th%20201

2.pdf)

9. Weiss JP, Van Kerrebroeck PE, Klein BM, Norgaard JP. Excessive nocturnal

urine production is a major contributing factor to the etiology of nocturia. J.

Urol. 2011; 186: 1853–63.

10. Vaughan CP, Endeshaw Y, Nagamia Z, Ouslander JG, Johnson TM. A

multicomponent behavioural and drug intervention for nocturia in elderly

men: rationale and pilot results. BJU Int. 2009; 104: 69–74.

11. Gisolf KW, Van Venrooij GE, Eckhardt MD, Boon TA. Analysis and reliability

of data from 24-hour frequency-volume charts in men with lower urinary tract

symptoms due to benign prostatic hyperplasia. Eur. Urol. 2000; 38: 45–52.

12. Homma Y, Yoshida M, Seki N et al. Symptom assessment tool for overactive

bladder syndrome – overactive bladder symptom score. Urology 2006; 68:

318–23.

13. Homma Y, Kakizaki H, Yamaguchi O et al. Assessment of overactive bladder

symptoms: comparison of 3-day bladder diary and the overactive bladder

symptoms score. Urology 2011; 77: 60–4.

14. Tsujimura A, Takao T, Miyagawa Y et al. Survey of overactive bladder

symptoms influencing bother before and after treatment with tamsulosin

hydrochloride in Japanese patients with benign prostatic hyperplasia.

Urology 2011; 78: 1058–62.

15. Batista-Miranda JE, Diez MD, Bertran PA, Villavicencio H. Quality-of-life

assessment in patients with benign prostatic hyperplasia: effects of various

interventions, Pharmacoeconomics 2001; 19: 1079–90.

16. Arai Y, Ishitoya S, Okubo K, Suzuki Y. Transurethral interstitial laser

coagulation for benign prostatic hyperplasia: treatment outcome and quality

of life. Br. J. Urol. 1996; 78: 93–8.

17. Yoshimura K, Arai Y, Ichioka K, Terada N, Matsuta Y, Okubo K.

Symptom-specific quality of life in patients with benign prostatic hyperplasia.

Int. J. Urol. 2002; 9: 485–90.

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CQ2

Should ultrasonography be recommended for the anatomical evaluation of

BPH ?

Answer:

Ultrasonography (IPP, Prostate volume) is recommended for the

anatomical evaluation of the prostate (Recommendation Grade A).

Compared with a digital rectal examination and other imaging tests,

ultrasonography is more accurate and minimally invasive [1–3]. Transabdominal

ultrasonography is easily performed and readily able to detect both bladder

pathology, and kidney lesion, whereas trans-rectal ultrasonography permits the

detailed imaging of the inner structures. The type of ultrasonography performed

depends on the equipment available, as well as on the objective of the

examination. PV is predictive of both clinical progression and the therapeutic

outcomes of surgical or medical treatment [4, 5].

Urethrography provides information in the post prostatectomy patients with

residual symptoms [6, 7].

Intravesical Protrusion of Prostate (IPP) is the distance measured from the tip of

the protruding lobes to the base of the prostate at the circumference of the

bladder, seen in the sagittal view on transabdominal ultrasonography.

A grading system for IPP is well established. Grade 1 IPP is 5mm or less, grade

2 IPP is more than 5mm to 10mm, grade 3 IPP is more than 10mm. Recent

studies have shown good correlation between IPP grade and urodynamic

evidence of obstruction [8–10].

For the estimation of histologically measured components, various ultra-

sonographic parameters obtained by transrectal method (TRUS) were effectively

compared with using ultrasonic power Doppler imaging (PDI) of the prostate [7].

CT scans and MR imaging are expensive and have no routine use in evaluating

patients with BPH [6].

Ultrasound derived measurements of bladder and detrusor wall thickness, and

ultrasound estimated bladder weight is potential noninvasive clinical tools for

assessing the lower urinary tract [11, 12].

Retrograde urethrography has no routine use except for the case highly

suspicious of urethral stricture.

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References of CQ2





3. Abrams P, Chapple C, Khoury S, Roehrborn C, De la Rosette J. Evaluation

and treatment of lower urinary tract symptoms in older men. J. Urol. 2009;

181: 1779–87.

4. Marks LS, Roehrborn CG, Wolford E, Wilson TH. The effect of dutasteride

on the peripheral and transition zones of the prostate and the value of the

transition zone index in predicting treatment response. J. Urol. 2007; 177:

1408–13.

5. Peeling WB. Diagnostic assessment of benign prostatic hyperplasia.

Prostate Suppl, 1989; 2: 51–68.

6. Scheckowitz EM, Resnick MI. Imaging of the prostate. Benign prostatic

hyperplasia. Urol. Clin. North. Am. 1995; 22: 321–32.

7. Hayami S, Ushiyama T, Kurita Y, Kageyama S, Suzuki K, Fujita K. The value

of power doppler imaging to predict the histologic components of benign

prostatic hyperplasia. Prostate 2002; 53: 168–74.

8. Foo KT. Decision making in the management of benign prostatic

enlargement and the role of transabdominal ultrasound. Int. J. Urol. 2010;

17: 974–9.

9. Chia SJ, Heng CT, Chan S, Foo KT. Correlation of intravesical prostatic

protrusion with bladder outlet obstruction. BJU Int. 2003; 91: 371–4.

10. Nose H, Foo KT, Lim KB, Yokoyama T, Ozawa H, Kumon H. Accuracy of two

noninvasive methods of diagnosing bladder outlet obstruction using

ultrasonography: intravesical prostatic protrusion and velocity-flow video

urodynamics. Urology 2005; 65: 493–7.

11. Lovvik A, Yaqub S, Oustad H, Sand TE, Nitti VW. Can noninvasive

evaluation of benign prostatic obstruction be optimized? Curr. Opin. Urol.

2012; 22: 1-6.

12. Bright E, Oelke M, Tubaro A, Abrams P. Ultrasound estimated bladder

weight and measurement of bladder wall thickness – useful noninvasive

methods for assessing the lower urinary tract? J. Urol. 2010; 184: 1847–54.

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CQ3

Should evaluation of upper urinary tract be recommended in the initial evaluation

of all BPH/Male LUTS patients?

Answer:

Routine evaluation of the upper urinary tract is not recommended in the

initial evaluation.

It is recommended for men with abnormal urinalysis, a large amount of

PVR, renal insufficiency, symptoms suggestive of upper urinary tract

disorder (stone, cancer, infection and so on ) or a history of other

urological diseases (Recommendation Grade B).

A structured MEDLINE review of the literature on the association between BPH

and CRF from 1966 to 2003 was performed. The extent of the association

between BPH and CRF is unknown and more community based, observational

studies are needed. However, an association exists and it should be considered

in men presenting with obstructive BPH or CRF [1].

Discharges for primary BPH with acute renal failure increased >400% (OR 4.28,

95% CI 3.22-5.71, P-trend <0.001) from 1998 to 2008 in USA. Severe AEs of

BPH persist despite widespread use of oral therapies in the USA [2]

Renal ultrasonography in 556 men with BPH detected hydronephrosis, renal

cysts, and renal cancer in 2.5, 11.7 and 0.18% of men, respectively [3].

According to those data, evaluation of the upper urinary tract is not to be

performed routinely. It is recommended for men with abnormal urinalysis, a large

amount of PVR, renal insufficiency, or a history of other urological diseases.

In these cases, ultrasonography is recommended as the initial method of

assessment [4, 5].

References of CQ3

1. Rule AD, Lieber MM, Jacobsen SJ. Is benign prostatic hyperplasia a risk

factor for chronic renal failure? J. Urol. 2005; 173: 691–96.

2. Stroup SP, Palazzi-Churas K, Kopp RP, Parsons JK. Trends in adverse

events of benign prostatic hyperplasia (BPH) in the USA, 1998 to 2008. BJU

Int. 2012; 109: 84–7.

3. Koch WF, Ezz el Din K, De Wildt MJAM, Debruyne FMJ, De la Rosette

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JJMCH. The outcome of renal ultrasound in the assessment of 556

consecutive patients with benign prostatic hyperplasia. J. Urol. 1996; 155:

186–9.





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CQ4

In which case should urodynamic study (except for uroflowmetry ) be

recommended ?

Answer:

Urodynamic examinations, including PFS and CMG, are recommended to

delineate BOO, DU, and DO. PFS and CMG should be performed in whom

DU or DO is suspected due to failure to respond to medication/surgery, or

neurogenic lower urinary tract dysfunction is suspected

(Recommendation Grade B).

In this section, pressure flow study (PFS) and filling cystometry (CMG) are

included in the terminology of urodynamic study (UDS). TURP is effective,

especially for patients with BOO. From symptoms alone, it is not possible to

diagnose BOO. PFS and symptom profiles measure different aspects of the

clinical condition that should be viewed separately in the evaluation and

treatment decision of the patient presenting with lower urinary tract symptoms [1].

BOO and detrusor underactivity (DU) can be correctly evaluated, and outcome

of surgery may be predicted by PFS. Detrusor overactivity (DO) can be

evaluated by CMG. However, routine CMG or routine PFS is not necessary for

initial diagnosis of BPH [2]. BOO, DU, and DO are all important prognostic

variables for the surgical outcomes of BPH [3].

The surgical indication should be circumspect for patients who do not have BOO

but have DO [2]. Symptom improvement is less likely for men with no or

equivocal BOO compared with men with evident BOO [4].

Both DU without BOO and DO without BOO strongly predict treatment failure for

TURP [5]. The presence of a higher degree of BOO is associated with

improvements in both symptoms and QOL [6].

A significant proportion (23%) of the patient with symptomatic BPH was

urodynamically unobstructed group to which prostatectomy should not be

offered. To identify unobstructed patients, PFS is recommended in all BPH

patients with dominant irritative symptoms [7].

PFS can be used to allocate patients with LUTS due to suspected BOO into

different treatment arms with good clinical outcome and less complications [8].

While uroflowmetry cannot replace PFS in the diagnosis of BOO, it can provide a

valuable improvement over symptoms alone in the diagnosis of the cause of

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lower urinary tract dysfunction in men presenting with LUTS.

Predicting BOO using simpler parameters such as uroflowmetry and PV may be

a viable alternative because of the invasiveness of PFS and CMG [9].

The ICS-'BPH' Study provided performance statistics for Qmax with respect to

BOO: such statistics may be used to define more accurately the presence or

absence of BOO in men presenting with LUTS [10].

References of CQ4

1. De la Rosette JJ, Witjes WP, Schafer W et al. Relationships between lower

urinary tract symptoms and bladder outlet obstruction: results from the

ICS-"BPH" study. Neurourol. Urodyn. 1998; 17: 98–108.

2. Tanaka Y, Masumori N, Itoh N, Furuya S, Ogura H, Tsukamoto T. Is the

short-term outcome of transurethral resection of the prostate affected by

preoperative degree of bladder outlet obstruction, status of detrusor

contractility or detrusor overactivity? Int. J. Urol. 2006; 11: 1398–04.

3. Thomas AW, Cannon A, Bartlett E, Ellis-Jones J, Abrams P. The natural

history of lower urinary tract dysfunction in men: the influence of detrusor

underactivity on the outcome after transurethral resection of the prostate

with a minimum 10-year urodynamic follow-up. BJU Int. 2004; 93: 745–50.

4. Van Venrooij GE, Von Melick HHE, Boon TA. Comparison of outcomes of

transurethral prostate resection in urodynamically unobstructed or equivocal

men. Urology 2003; 62: 672–6.

5. Machino R, Kakizaki H, Ameda K et al. Detrusor instability with equivocal

obstruction: a predictor of unfavorable symptomatic outcomes after

transurethral prostatectomy. Neurourol. Urodyn. 2002; 21: 444–9.

6. Seki N, Takei M, Yamaguchi A, Naito S. Analysis of prognostic factors

regarding the outcome after a transurethral resection for symptomatic

benign prostatic enlargement. Neurourol. Urodyn. 2006; 25: 428–32.

7. Cetinel B, Turan T, Talat Z, Yalcin V, Alici B, Solok V. Update evaluation of

benign prostatic hyperplasia: when should we offer prostatectomy? Br. J.

Urol. 1994; 74: 566–71.

8. Knutson T, Pettersson S, Dahlstrand C. Pressure-flow studies for patient

selection in the treatment of symptomatic BPH – a one-year follow-up study.

Scand. J. Urol. Nephrol. 2001; 35: 470–75.

9. Homma Y. Pressure flow studies in benign prostatic hyperplasia: to do or not

to do for the patient? BJU Int. 2001; 87: 19–23.

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10. Reynard JM, Yang Q, Donovan JL et al. The ICS-'BPH' Study: uroflowmetry,

lower urinary tract symptoms and bladder outlet obstruction. Br. J. Urol.

1998; 82: 619–23.

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CQ5

Should serum PSA be measured in BPH/Male LUTS patients?

Answer:

In the patients at risk of prostate cancer, measurement of serum PSA

concentration is strongly recommended (Recommendation Grade A).

However, factors affecting on serum PSA concentration, such as enlarged

prostate volume, urinary retention, prostatitis/UTI, and treatment with

5ARIs should be considered.

In patients with life expectancy of less than 10 years, or without indication

for prostatic cancer treatment, serum PSA may not be routinely measured.

As higher serum PSA concentrations are indicative of prostate cancer [1–3]),

and useful for estimation of enlarged prostate volume [4]. Not only prostate

cancer, serum PSA concentrations are increased in men with enlarged adenoma,

urinary retention, prostatitis, and massage of prostate [5]. On the other hand,

anti-androgens or 5ARIs can reduce the PSA concentrations by approximately

50% [6–10]. In patients treated with the drugs, careful follow-up of serum PSA

concentrations should be needed.

References of CQ5



2. Abrams P, Chapple C, Khoury S, Roehrborn C, De la Rosette J, the

International Scientific Committee and members of the committees, 6th

International Consultation on New Developments in Prostate Cancer and

Prostate Diseases. Evaluation and treatment of lower urinary tract

symptoms in older men. J. Urol. 2009; 181: 1779–87.

3. EAU Guidelines on the management of male lower urinary tract symptoms

(LUTS), incl. benign prostatic obstruction (BPO).

(http://www.uroweb.org/gls/pdf/12_Male_LUTS_LR%20May%209th%20201

2.pdf)

4. Gupta A, Aragaki C, Gotoh M et al. Relationship between prostate specific

antigen and indexes of prostate volume in Japanese men. J. Urol. 2005;

173: 503–6.

5. Gretzer MB, Partin AW. Prostate cancer tumor markers. In: Wein AJ,

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Kavoussi LR, Novick AC, Partin AW, Peters CA (eds). Campbell-Walsh

Urology. 9th ed., Philadelphia, Saunders, 2007; 2896.

6. D’Amico AV, Roehrborn CG. Effect of 1 mg/day finasteride on concentrations

of serum prostate specific antigen in men with androgenic alopecia: a

randomised controlled trial. Lancet Oncol. 2007; 8: 21–5.

7. Tsukamoto T, Endo Y, Narita M. Efficacy and safety of dutasteride in

Japanese men with benign prostatic hyperplasia. Int. J. Urol. 2009; 16: 745–

50.

8. Andriole GL, Kirby R. Safety and tolerability of the dual 5α-reductase

inhibitor dutasteride in the treatment of benign prostatic hyperplasia. Eur.

Urol. 2003; 44: 82–8.

9. Andriole GL, Marberger M, Roehrborn CG. Clinical usefulness of serum

prostate specific antigen for the detection of prostate cancer is preserved in

men receiving the dual 5α-reductase inhibitor dutasteride. J. Urol. 2006; 175:

1657–62.

10. Marks LS, Andriole GL, Fitzpatrick JM, Schulman CC, Roehrborn CG. The

interpretation of serum prostate specific antigen in men receiving

5α-reductase inhibitors: a review and clinical recommendations. J. Urol.

2006; 176: 868–74.

- 24 -

CQ6

Is long-term treatment with 1 blocker recommended ?

Answer:

Many studies have been reported regarding the efficacy and safety of α1

blockers up to1 year. However, there is a relative paucity of long-term data

over 3 years regarding the maintained efficacy of these drugs

(Recommendation Grade A).

Most long-term studies for the efficacy of α1 blockers are open-label extension

studies of the previous short-term trials [1, 2] or retrospective studies in clinical

practice. The studies showed that the efficacy and safety of α1 blockers up to1

year. In long-term studies (over 3 years; range 4–10 years), the withdraw rates

were approximately 18, 64, and 36–80% of patients in 2, 3, and >4 years after

starting of the studies, respectively [3–6]. The risk factors for treatment failure

were severe LUTS, low urinary flow rate, large prostate volume (>30–40 mL),

large PVR or a history of urinary retention, concomitant OAB symptoms,

urodynamically proven BOO, and insufficient effects with short-term therapy [5–

7]. In the comparative long-term studies of mono- and combination treatment

with α1 blockers and 5ARI, the efficacy of α1 blockers appears to be maintained

over at least 4 years [8, 9]. However, the combination therapy was significantly

effective as compared with α1 blocker mono-therapy. It may suggest that the

long-term efficacy of α1 blockers mono-therapy of is not sufficient. Alpha-1

blockers do not prevent acute urinary retention in long-term studies, so that

eventually some patients will have to be surgically treated [8].

References of CQ6

1. Kawabe K, Yoshida M, Arakawa S, Takeuchi H. Silodosin Clinical Study

Group. Long-term evaluation of silodosin, a new α1A-adrenoceptor selective

antagonist for the treatment of benign prostatic hyperplasia: phase III

long-term study. Jap. J. Urol. Surg. 2006; 19: 153–64. (4)

2. Marks LS, Gittelman MC, Hill LA, Volinn W, Hoel G. Silodosin in the

treatment of the signs and symptoms of benign prostatic hyperplasia: a

9-month, open-label extension study. Urology 2009; 74: 1318–24. (4)

3. Narayan P, Evans CP, Moon T. Long-term safety and efficacy of tamsulosin

for the treatment of lower urinary tract symptoms associated with benign

- 25 -

prostatic hyperplasia. J. Urol. 2003; 170: 498–502. (5)

4. Schulman CC, Lock TMTW, Buzelin J-M, Boeminghaus F, Stephenson TP,

Talja M. European Tamsulosin Study Group: Long-term use of tamsulosin to

treat lower urinary tract symptoms/benign prostatic hyperplasia. J. Urol.

2001; 166: 1358–63. (5)

5. Masumori N, Hashimoto J, Itoh N, Tsukamoto T, the Sapporo Medical

University Naftopidil Study Group. Short-term efficacy and long-term

compliance/treatment failure of the α1 blocker naftopidil for patients with

lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

Scand. J. Urol. Nephrol. 2007; 41: 422–9. (5)

6. De la Rosette JJ, Kortman BBM, Rossi C, Sonke GS, Floratos DL, Kiemeney

LALM. Long-term risk of re-treatment of patients using a-blockers for lower

urinary tract symptoms. J. Urol. 2002; 167: 1734–9. (5)

7. Kawachi Y, Sakurai T, Sugimura S et al. Long-term treatment and prognostic

factors of a1-blockers for lower urinary tract symptoms associated with

benign prostatic hyperplasia: a pilot study comparing naftopidil and

tamsulosin hydrochloride. Scand. J. Urol. Nephrol. 2010; 44: 38–45. (3)

8. 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: 2387–98. (1)

9. Roehrborn CG, Siami P, Barkin J et al. The effects of combination therapy

with dutasteride and tamsulosin on clinical outcomes in men with

symptomatic benign prostatic hyperplasia: 4-year results from the CombAT

study. Eur. Urol. 2010; 57: 123–31. (1)

- 26 -

CQ7

Is long-term treatment with 5ARI recommended ?

Answer:

5ARIs should be offered to men who have moderate-to-severe lower

urinary tract symptoms and enlarged prostates (≥ 30 mL) or elevated

serum PSA concentrations (> 1.4 – 1.6 µg/L). Efficacy for subjective and

objective parameters of long-term treatment is reported. Long term

treatment of 5ARIs can also prevent disease progression with regard to

acute urinary retention and the need for surgery (Recommendation Grade

B).

After 2 to 4 years of treatment, 5ARIs reduce LUTS (IPSS) by approximately

15-30%, decrease prostate volume by approximately 18-28% and increase

Qmax of free uroflowmetry by approximately 1.5-2.0 mL/s in patients with LUTS

due to prostate enlargement [1–10].

Comparative studies with α1 blockers have demonstrated that 5ARIs reduce

symptoms more slowly and, for finasteride, less effectively [1, 2, 7]. A long-term

trial with dutasteride in symptomatic men with a prostate volume ≥ 30 mL

(average prostate volume in the CombAT trial was approximately 55 mL)

showed that the 5ARI reduced LUTS in these patients at least as much or even

more effectively than tamsulosin [8, 9]. The greater the baseline prostate volume

(serum PSA concentration), the faster and more pronounced the symptomatic

benefit of dutasteride [11]. 5ARIs, but not α1 blockers, reduce the long-term (> 1

year) risk of acute urinary retention or need for surgery [5, 7, 11, 12]. Prevention

of disease progression by 5ARIs is already detectable with prostate sizes

considerably smaller than 40 mL [9, 10, 12]. The precise mechanism of action of

5ARIs in reducing disease progression is unclear, but it was demonstrated that

reductions of voiding parameters after computer-urodynamic re-evaluation in

men who were treated at least 3 years with finasteride [13, 14, 15].

References of CQ7

1. Lepor H, Williford WO, Barry MJ et al. The efficacy of terazosin, finasteride,

or both in benign prostatic hyperplasia. N. Engl. J. Med. 1996; 335: 533–9.

(1)

- 27 -

2. Kirby R, Roehrborn CG, 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: 119–26. (1)

3. Andersen JT, Ekman P, Wolf H et al. Can finasteride reverse the progress of

benign prostatic hyperplasia? A two-year placebo-controlled study. The

Scandinavian BPH Study Group. Urology 1995; 46: 631–7. (1)

4. Nickel JC, Fradet Y, Boake RC et al. Efficacy and safety of finasteride

therapy for benign prostatic hyperplasia: results of a 2-year randomised

controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy

Canadian Two year Study. CMAJ 1996; 155: 1251–9. (1)

5. McConnell JD, Bruskewitz R, Walsh P et al. The effect of finasteride on the

risk of acute urinary retention and the need for surgical treatment among

men with benign prostatic hyperplasia. N. Engl. J. Med. 1998; 338: 557–63.

(1)

6. Marberger MJ, on behalf of the PROWESS Study Group. Long-term effects

of finasteride in patients with benign prostatic hyperplasia: a double-blind,

placebo-controlled, multicenter study. Urology 1998; 51: 677–86. (1)

7. McConnell JD, Roehrborn CG, Bautista O et al. Medical Therapy of Prostatic

Symptoms (MTOPS) Research Group. The long-term effect of doxazosin,

finasteride, and combination therapy on the clinical progression of benign

prostatic hyperplasia. N. Engl. J. Med. 2003; 349: 2387–98. (1)

8. Roehrborn CG, Boyle P, Nickel JC et al. Efficacy and safety of a dual

inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign

prostatic hyperplasia. Urology 2002; 60: 434–41. (1)

9. Roehrborn CG, Siami P, Barkin J et al. The effects of dutasteride, tamsulosin

and combination therapy on lower urinary tract symptoms in men with

benign prostatic hyperplasia and prostatic enlargement: 2-year results from

the CombAT study. J. Urol. 2008; 179: 616–21. (1)



symptomatic benign prostatic hyperplasia: 4-year results from the

CombATstudy. Eur. Urol. 2010; 57: 123–31. (1)

11. Debruyne FM, Jardin A, Colloi D et al. Sustained-release alfuzosin,

finasteride and the combination of both in the treatment of benign prostatic

hyperplasia. Eur. Urol. 1998; 34: 169–75. (1)

- 28 -

12. Roehrborn CG, Siami P, Barkin J et al. The influence of baseline parameters

on changes in International Prostate Symptom Score with dutasteride,

tamsulosin, and combination therapy among men with symptomatic benign

prostatic hyperplasia and enlarged prostate: 2-year data from the CombAT

Study. Eur. Urol. 2009; 55: 461–71. (1)

13. Roehrborn CG. BPH progression: concept and key learning from MTOPS,

ALTESS, COMBAT, and ALF-ONE. BJU Int. 2008; 101 (Suppl 3): 17–21. (1)

14. Kirby RS, Vale J, Bryan J, Holmes, K, Webb, JA. Long-term urodynamic

effects of finasteride in benign prostatic hyperplasia: a pilot study. Eur. Urol.

1993; 24: 20–6. (3)

15. Tammela TLJ, Kontturi MJ. Long-term effects of finasteride on invasive

urodynamics and symptoms in the treatment of patients with bladder outflow

obstruction due to benign prostatic hyperplasia. J. Urol. 1995; 154: 1466–9.

(3)

- 29 -

CQ8

Is anticholinergic monotherapy recommended for BPH/OAB patient ?

Answer:

Monotherapy of anticholinergic drugs might be considered in men with

moderate to severe lower urinary tract symptoms who have predominantly

bladder storage symptoms. However, careful follow-up is recommended in

men with bladder outlet obstruction. Low grade IPP with good flow rate is

indication for anti-cholinergic monotherapy (Recommendation Grade B)

The efficacy of the anticholinergic drugs was tested as a single agent in adult

men with bladder storage symptoms (OAB symptoms) but without bladder outlet

obstruction. In open-label trials with tolterodine, daytime frequency, nocturia,

urgency incontinence, and IPSS were all significantly reduced compared to

baseline values after 12-25 weeks [1, 2]. In an open-label study with α1 blocker

non-responders, each storage and voiding symptom of IPSS was improved

during tolterodine treatment [1]. Randomized, placebo-controlled trials

demonstrated that tolterodine can significantly reduce urgency incontinence and

daytime or 24-hour frequency compared to placebo. It was also demonstrated

that urgency related voiding is significantly reduced by tolterodine [3–5].

Treatment outcome analyzed by PSA-concentration (prostate volume),

tolterodine significantly reduced daytime frequency, 24h voiding frequency and

IPSS storage symptoms only in those men with PSA concentrations below 1.3

ng/mL indicating that men with smaller prostates might profit more from

anticholinergic drugs [6]. Increase of post-void residual urine in men without

bladder outlet obstruction is minimal and not significantly different compared to

placebo (0 to 5 mL vs. -3.6 to 0 mL). However, fesoterodine 8 mg showed higher

post-void residuals (+20.2 mL) compared to placebo (-0.6 mL) or fesoterodine 4

mg (+9.6 mL) [7]. The incidence of urinary retention in men treated with

tolterodine without bladder outlet obstruction was comparable with placebo (0 to

1.3 vs. 0 to 1.4%). In men under fesoterodine 8 mg treatment, 5.3% had

symptoms suggestive of urinary retention that was higher compared to placebo

or fesoterodine 4 mg (0.8% each). In men with bladder outlet obstruction,

anticholinergic drugs are not recommended due to the theoretical decrease of

bladder strength which might be associated with post-void residual urine [8] or

urinary retention. In addition, long-term studies on the efficacy of muscarinic

- 30 -

receptor antagonists in men with LUTS/BPH are still missing, therefore, these

drugs should be prescribed with caution, and regular re-evaluation of IPSS and

post-void residual urine is advised. For patients complaining nocturia, not OAB,

desmopressin is effective for nocturia due to nocturnal polyuria [9–12].

References of CQ8

1. Kaplan SA, Walmsley K, Te AE. Tolterodine extended release attenuates

lower urinary tract symptoms in men with benign prostatic hyperplasia. J.

Urol. 2005; 174: 2273–5. (4)

2. Höfner K, Burkart M, Jacob G, Jonas U. Safety and efficacy of tolertodine

extended release in men with overactive bladder symptoms and presumed

non-obstructive benign prostatic hyperplasia. World J. Urol. 2007; 25: 627–

33. (3)

3. Kaplan SA, Roehrborn CG, Chancellor M, Carlsson M, Bavendam T, Guan Z.

Extended-release tolterodine with or without tamsulosin in men with lower

urinary tract symptoms and overactive bladder: effects on urinary symptoms

assessed by the International Prostate Symptom Score. BJU Int. 2008; 102:

1133–9. (2)

4. Kaplan SA, Roehrborn CG, Dmochowski R, Rovner ES, Wang JT, Guan Z.

Tolterodine extended release improves overactive bladder symptoms in men

with overactive bladder and nocturia. Urology 2006; 68: 328–32. (1)

5. Dmochowski R, Abrams P, Marschall-Kehrel D, Wang JT, Guan Z. Efficacy

and tolerability of tolterodine extended release in male and female patients

with overactive bladder. Eur. Urol. 2007; 51:1054–64. (1)

6. Roehrborn CG, Kaplan SA, Kraus SR, Wang JT, Bavendam T, Guan Z.

Effects of serum PSA on efficacy of tolterodine extended release with or

without tamsulosin in men with LUTS, including OAB. Urology 2008; 72:

1061–7. (1)

7. Herschorn S, Jones JS, Oelke M, MacDiarmid S, Wang JT, Guan Z. Efficacy

and tolerability of fesoterodine in men with overactive bladder: a pooled

analysis of 2 phase III studies. Urology 2010; 75: 1149–55. (1)

8. 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: 999–1004. (1)

- 31 -

9. Mattiasson A, Abrams P, Van Kerrebroeck P, Walter S, Weiss J. Efficacy of

desmopressin in the treatment of nocturia: a double-blind placebo-controlled

study in men. BJU Int. 2002; 89: 855–62. (1)

10. Van Kerrebroeck P, Rezapour M, Cortesse A, Thuroff J, Riis A, Norgaard JP.

Desmopressin in the treatment of nocturia: a double blind placebo-controlled

study. Eur. Urol. 2007; 52: 221–9. (1)

11. Weatherall M. The risk of hyponatremia in older adults using desmopressin

for nocturia: a systematic review and meta-analysis. Neurourol. Urodyn.

2004; 23: 302–5. (1)

12. Wang CJ, Lin YN, Huang SW, Chang CH. Low dose oral desmopressin for

nocturnal polyuria in patients with benign prostatic hyperplasia: a

double-blind, placebo controlled, randomized study. J. Urol. 2011; 185: 219–

23. (1)

- 32 -

CQ9

In which case should combination use of α1 blocker and 5ARI be

recommended ?

Answer:

Combination use of 1 blocker and 5 alpha-reductase inhibitors (5ARIs)

are recommended for symptomatic BPH, especially for patients with a

relatively large-sized prostate. (Recommendation Grade A)

Non-selective 1 blockers have a potentially higher risk of orthostatic

hypotension.

The Medical Therapy of Prostatic Symptoms (MTOPS) study was a double-blind

trial involving 3047 men to compare the effects the effects of placebo, doxazosin,

finasteride and combination therapy on measures of the clinical progression of

BPH [1]. Inclusion criteria were age ≥50, IPSS ≥8 and a maximum urinary flow

rate between 4 and 15 mL/s, and the mean follow-up was 4.5 years. The

reduction in risk of clinical progression associated with combination therapy

(66%) was significantly greater than that associated with doxazosin (39%,

p<0.001) or finasteride (34%, p<0.001) alone. The improvement in symptoms

scores of combination therapy (-7.4 at 4 years) was significantly greater than

doxazosin (-6.6, p=0.006) and finasteride (-5.6, p<0.001) alone. The rates of

adverse events were higher in combination therapy group than in each single

treatment groups, in the aspects of abnormal ejaculation, peripheral edema and

dyspnea.

The Combination of Avodart® and Tamsulosin (CombAT) study was a 4-yr.,

multicenter, randomized, double-blind, parallel-group study in 4844 men ≥50

years of age with a clinical diagnosis of BPH, IPSS ≥12, prostate volume ≥30mL,

PSA 1.5-10 ng/mL and maximum urinary flow rate >5 and ≤15 mL/s with

minimum voided volume ≥125mL [2]. At 4 yr., combination therapy was

significantly superior to both monotherapies at reducing the relative risk of BPH

progression (31% from dutasteride, 44% from tamsulosin), and provided

significantly greater symptom benefit (-6.3) than dutasteride (-5.3, p<0.001) and

tamsulosin (-3.8, p<0.001) alone. The occurrence of drug-related adverse

events was significantly greater in the combination group. However, withdrawal

rates due to drug-related adverse events were similar across treatment groups

(4-6%). These observations were also similar in Asian men [3].

- 33 -

In both trials, post hoc analyses showed that patients with larger prostate volume

(≥25 mL in MTOPS study, and ≥40 mL in CombAT study) at baseline had a

greater benefit in reduction of clinical progression from combination therapy than

those with small prostate [4, 5].

Analyses on cost-effectiveness of combination therapy using Norwegian model

estimated that incremental cost-effectiveness ratios, which means the cost per

quality-adjusted life-years (QALYs) gained, are higher in combination therapy

than in alpha blocker monotherapy both at 4 years and at the lifetime. However,

the incremental QALYs gained for combination therapy are twice those of

blocker monotherapy. If willingness to pay per QALY gained is above €6000,

fixed-dose combination therapy with dutasteride becomes the preferred

treatment [6].

References of CQ9



of benign prostatic hyperplasia. N. Engl. J. Med. 2003; 349: 2387–98. (1)




study. Eur. Urol. 2010; 57: 123–31. (2)

3. Chung B-H, Roerhborn CG, Siami P et al. Efficacy and safety of dutasteride,

tamsulosin and their combination in a subpopulation of the CombAT study:

2-year results in Asian men with moderate-to-severe BPH. Prostate Cancer

Prostatic. Dis. 2009; 12: 152–9. (1)

4. Kaplan SA, McConnell JD, Roerhborn CG, Meehan AG, Lee MW, Noble WR.

Combination therapy with doxazosin and finasteride for benign prostatic

hyperplasia in patients with lower urinary tract symptoms and a baseline

total prostate volume of 25 mL or greater. J. Urol. 2006; 175: 217–21. (1)

5. Roehrborn CG, Barkin J, Siami P et al. Clinical outcomes after combined

therapy with dutasteride plus tamsulosin or either monotherapy in men with

benign prostatic hyperplasia (BPH) by baseline characteristics: 4-year

results from the randomized, double-blind Combination of Avodart and

Tamsulosin (CombAT) trial. BJU Int. 2011; 107: 946–54. (1)

6. Johansen TEB, Baker TM, Black LK. Cost-effectiveness of combination

therapy for treatment of benign prostatic hyperplasia: a model based on the

- 34 -

findings of the Combination of Avodart and Tamsulosin trial. BJU Int. 2012;

109: 731–8.

- 35 -

CQ10

In which case should combination use of 1 blocker and anticholinergic drug be

recommended ?

Answer:

Patients with LUTS/BPH associated with OAB are recommended to use

combination of 1 blocker and anticholinergic drug. There are sufficient

evidences supporting the efficacy and safety of combination therapy with

1 blocker and anticholinergic drug for LUTS/BPH associated with OAB.

Especially, the patients still having OAB symptoms after 1 blockers

treatment are good candidates for the combination treatment.

(Recommendation Grade B). Low grade IPP with good flow is an indication

for combination therapy.

It is suggested that 50-70 % of patients with BPH have OAB symptoms [1]. For

male OAB symptoms, monotherapy with 1 blockers is effective and may be a

first line treatment [2], although the efficacy of 1 blockers is limited for patients

with detrusor overactivity [3]. Several reports suggested that combined therapies

with anticholinergic drugs and 1 blockers are more effective than monotherapy

with 1 blockers in improving storage symptoms, with urinary retention being

rare [4–13]. Meta-analysis of the combination therapy showed that the therapy

did not affect to urinary flow rate, increased average post-void residual urine by

11.6mL, and caused urinary retention just 0.3% [14]. Urodynamic study showed

that combination therapy increased bladder volume at the first involuntary

contraction and maximum bladder capacity [7]. Although the combination

therapy did not cause the change of total IPSS, it improved the storage

sub-score [8]. There remains a concern about the exacerbation of voiding

difficulties and possible urinary retention in a practice setting [2]. Grade 3 IPP is

risk factor for possible urinary retention with combination therapy.

References of CQ10

1. Yamaguchi O, Nishizawa O, Takeda M et al. Clinical guidelines for

overactive bladder. Int. J. Urol. 2009; 16: 126–42. (guideline)


tract symptoms. Int. J. Urol. 2009; 16: 775–90. (guideline)

3. Lee JY, Kim HW, Lee SJ, Koh JS, Suh HJ, Chancellor MB. Comparison of

- 36 -

doxazosin with or without tolterodine in men with symptomatic bladder outlet

obstruction and an overactive bladder. BJU Int. 2004; 94: 817–20. (2)

4. Chapple C, Herschorn S, Abrams P, Sun F, Brodsky M, Guan Z. Tolterodine

treatment improves storage symptoms suggestive of overactive bladder in

men treated with α-blockers. Eur. Urol. 2009; 56: 534–43. (1)

5. MacDiarmid SA, Peters KM, Chen A et al. Efficacy and safety of

extended-release oxybutynin in combination with tamsulosin for treatment of

lower urinary tract symptoms in men: randomized, double-blind,

placebo-controlled study. Mayo Clin. Proc. 2008; 83: 1002–10. (1)

6. Kaplan SA, McCammon K, Fincher R, Fakhoury A, He W. Safety and

tolerability of solifenacin add-on therapy to α-blocker treated men with

residual urgency and frequency. J. Urol. 2009; 182: 2825–30. (1)

7. Athanasopoulos A, Gyftopoulos K, Giannistas K, Fisfis J, Perimenis P,

Barbalias G. Combination treatment with an α-blocker plus an anticholinergic

for bladder outlet obstruction: a prospective, randomized, controlled study. J.

Urol. 2003; 169: 2253–6. (2)

8. Lee KS, Choo MS, Kim DY 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: 1334–8. (2)

9. 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: 2319–28. (1)

10. Maruyama O, Kawauchi Y, Hanazawa 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: 1280–5. (2)

11. Yokoyama T, Uematsu K, Watanabe T et al. Naftopidil and propiverine

hydrochloride for treatment of male lower urinary tract symptoms suggestive

of benign prostatic hyperplasia and concomitant overactive bladder: a

prospective randomized controlled study. Scand. J. Urol. Nephrol. 2009; 43:

307–14. (2)

12. Nishizawa O, Yamaguchi O, Takeda M, Yokoyama O, for the TAABO Study

Group. Randomized controlled trial to treat benign prostatic hyperplasia with

- 37 -

overactive bladder using an alpha-blocker combined with anticholinergics.

LUTS 2011; 3: 29–35. (2)

13. Yamaguchi O, Kakizaki H, Homma Y et al. Solifenacin as add-on therapy for

overactive bladder symptoms in men treated for lower urinary tract

symptoms – ASSIST, randomized controlled study. Urology 2011; 78: 126–

33. (1)

14. 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 systemic review and meta-analysis. BJU Int.

2007; 99: 85–96. (1)

- 38 -

CQ11

In which case should surgical intervention be recommended ?

This CQ should be modified into 2 categories;

In which case should surgical intervention be recommended ?

1. Absolute indications ?

2. Relative indications ?

Answer:

Absolute indications are patients with refractory urinary retention,

recurrent UTI, vesical stone, renal insufficiency, refractory gross

hematuria (Recommendation Grade A) .

Relative indications are patients unresponsive to medical treatment, or

patients who cannot maintain medical treatments due to adverse events,

or patients who are not satisfied with medical treatments.

Pressure-flow study is recommended in order to rule out detrusor

underactivity and overactivity. IPP should be correctly evaluated when

surgery is planned.

Recurrent spontaneous urinary retention after failure of trials without catheter is

an indication of surgical intervention (see CQ13). Similarly, surgery would be

better to be considered in patients with hydronephrosis and/or renal function

impairment due to chronic bladder outlet obstruction (BOO) from BPH, gross

hematuria, bladder stone and recurrent urinary tract infection, whereas these

indications are empirical and not supported by clinical evidences [1].

Patients resistant to medical treatment are relative symptom-based indication of

surgery. However, male lower urinary tract symptoms are not always associated

with BOO or BPH [2]. Approximately 15% of patients undergoing surgery do not

profit in improvement of symptoms [3, 4]. Pressure-flow study (PFS) is an

important examination to provide objective information [4–6], and BOO, detrusor

underactivity (DU) and detrusor overactivity (DO) are key conditions to predict

outcome of surgery. However, it is still under debate whether this examination is

essential for judge of surgery [7, 8]. Although BOO is not an essential condition

for TURP, the degree of symptom improvement in patients without BOO is

approximately 70% of that in patients with BOO [6, 9]. DU, DO and absence of

BOO are independent risk factors for poor outcome of surgery [10].

- 39 -

Nocturia is the symptom least sensitive to treatment for BPH [11, 12]. When

nocturia remains as a main symptom after medical treatment for BPH, conditions

other than BPH, such as lowering functional bladder capacity, polyuria, nocturnal

polyuria and sleep disturbance, should be ruled out before decision of surgical

intervention. Frequency volume charts are recommended to use to detect such

conditions.

References of CQ11

1. Jang DG, Yoo C, Oh Y et al. Current status of transurethral prostatectomy: a

Korean multicenter study. Korean J. Urol. 2011; 52: 406–9. (4)

2. Hald T. Urodynamics in benign prostatic hyperplasia: a survey. Prostate

1989; 2 (Suppl): 69–77. (review)

3. Emberton M, Fordham M, Harrison M et al. The effect of prostatectomy on

symptom severity and quality of life. Br. J. Urol. 1996; 77: 233–47. (4)

4. Hakenberg OW, Pinnock CB, Marshall VR. The follow-up of patients with

unfavourable early results of transurethral prostatectomy. BJU Int. 1999; 84:

799–804. (4)

5. Javle P, Jenkins SA, Machin DG, Parsons KF. Grading of benign prostatic

obstruction can predict the outcome of transurethral prostatectomy. J. Urol.

1998; 160: 1713–7. (4)

6. Robertson AS, Griffiths C, Neal DE. Conventional urodyamics and

ambulatory monitoring in the definition and management of bladder outlet

obstruction. J. Urol. 1996; 155: 506–11. (4)

7. Homma Y. Pressure-flow studies in benign prostatic hyperplasia: to do or not

to do for the patient? BJU Int. 2001; 87: 19–23. (review)

8. McConnell JD. Why pressure-flow studies should be optional and not

mandatory studies for evaluating men with benign prostatic hyperplasia.

Urology 1994; 44: 156–8. (editorial)

9. Van Venrooij GEPM, Van Melick HHE, Boon TA. Comparison of outcomes of

transurethral prostate resection in urodynamically obstructed versus selected

urodynamically unobstructed or equivocal men. Urology 2003; 62: 672–6. (4)

10. Seki N, Takei M, Yamaguchi A, Naito S. Analysis of prognostic factors

regarding the outcome after a transurethral resection for symptomatic benign

prostatic enlargement. Neurourol. Urodyn. 2006; 25: 428–32. (4)

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11. Homma Y, Yamaguchi T, Kondo Y, Horie S, Takahashi S, Kitamura T.

Significance of nocturia in the International Prostate Symptoms Score for

benign prostatic hyperplasia. J. Urol. 2002; 167: 172–6. (4)

12. Yoshimura K, Ohara H, Ichioka K et al. Nocturia and benign prostatic

hyperplasia. Urology 2003; 61: 786–90. (4)

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CQ12

Which interventions are recommended for urinary retention in BPH patients ?

Answer:

Initially, immediate bladder decompression by catheterization should be

performed. Treatment with 1 blockers before a trial without catheter

(TWOC) is recommended after that. Surgical intervention for BPH is

required for patients with a TWOC failure. Duration of catheterization

should be shortened to reduce the comorbidity.

(Recommendation Grade B)

Acute urinary retention (AUR) due to BPH should be initially managed by

immediate bladder decompression. Urethral catheterization is exclusively more

chosen by urologists or emergency room physicians than suprapubic

catheterization world widely [1], and suprapubic catheterization is associated

with significantly high rate of hematuria, impossible catheterization and catheter

obstruction [2].

A trial without catheter (TWOC) is the next step. Treatment with 1 blockers for

2-3 days before catheter removal should be strongly recommended, since it

significantly increases success rate of TWOC [1, 3, 4]. Duration of

catheterization should be shortened, since catheterization for 4 days or longer is

associated with significantly higher rate of asymptomatic bacteriuria, lower

urinary tract infection, urine leak, catheter obstruction and prolongation of

hospitalization for adverse events [1]. After failure of first TWOC, second and

third TWOC can succeed. However, the rate of success of second and third

TWOC is not high and most patients with TWOC failure require surgical

intervention [1]. Even after success of TWOC, half patients require surgical

intervention during long-term follow-up [5].

Risk factors for failure of TWOC are older age (≥70y, OR 1.4), spontaneous AUR

(OR 1.4), large amount of drained volume (≥1000mL, OR 1.6), severe LUTS

before AUR (OR 1.6) and large prostate volume (>50mL, OR 1.6) [1].

References of CQ12

1. Fitzpatrick JM, Desgrandchamps F, Adjali K et al. Management of acute

urinary retention: a worldwide survey of 6074 men with benign prostatic

hyperplasia. BJU Int. 2012; 109: 88–95. (4)

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2. Desgrandchamps F, De la Taille A, Doublet JD. The management of acute

urinary retention in France: a cross-sectional survey in 2618 men with benign

prostatic hyperplasia. BJU Int. 2006; 97: 727–33. (4)

3. Lucas MG, Stephenson TP, Nargund V. Tamsulosin in the management of

patients with acute urinary retention from benign prostatic hyperplasia. BJU

Int. 2005; 95: 354–7. (2)

4. McNeill SA, Hargreave TB, Roehrborn CG. Alfuzosin 10mg once daily in the

management of acute urinary retention: results of a double-blind

placebo-controlled study. Urology 2005; 65: 83–9. (1)

5. Lo KL, Chan MC, Wong A, Hou SM, Ng CF. Long-term outcome of patients

with a successful trial without catheter after treatment with an

alpha-adrenergic receptor blocker for acute urinary retention caused by

benign prostatic hyperplasia. Int. Urol. Nephrol. 2009; 42: 7–12. (4)

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CQ13

Which therapies are recommended for BPH patients who are not fit for surgery

due to severe comorbidities ?

Answer:

For surgery-unfit patients, alternative therapies are recommended

according to individual medical and social conditions of patients. Each

option, such as urethral stent placement, intermittent catheterization,

urethral catheter placement, suprapubic cystostomy placement, and other

minimal invasive surgical therapies (TUMT, TUNA), have their respective

benefits and drawbacks. (Recommendation Grade C1)

There are patients with severe LUTS or complications of BPH in whom medical

therapy fails and for whom surgery is deemed a high risk. Alternative options for

such unfit patients include urethral stent placement, intermittent catheterization,

intra-prostatic ethanol injection, intra-prostatic botulinum toxin injection, urethral

catheter placement and suprapubic cystostomy placement.

Various types of urethral stent are available, and they can be used temporarily

(such as ProstakathTM, ProstaCoilTM and MemokathTM) or permanently (such as

MemokathTM , UroLumeTM and MemothermTM). Placement of stents is generally

safe and significantly improves obstructive symptoms [1]. However, the rate of

complications including removal due to stent malposition/migration, gross

hematuria, vesical irritability, symptomatic urinary tract infection, and stone

formation is not low during follow-up [2–5].

Clean intermittent catheterization is another option for surgery-unfit BPH. There

are few evidences of superiority of intermittent catheterization to continuous

catheterization for BPH patients. However, there are several RCTs showing

superiority of intermittent catheterization with regard to bacteriuria and urinary

tract infection in other diseases [6, 7]. Therefore, if possible, this technique

should be considered. Dementia, motor paralysis of upper limbs and visual

impairment do not allow patients to perform self-catheterization.

When medical and/or social condition cannot afford intermittent catheterization,

continuous indwelling of urethral catheter could be considered, while this method

is liable to various complications, including acquired hypospadias,

cutaneourethral fistula, and vesical stone formation [8]. Suprapubic cystostomy

has a further higher rate of stone formation than urethral catheterization [9].

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Intraprostatic ethanol injection [10] and botulinum toxin injection [11] are

promising alternatives for surgery-unfit patients, while they are considered still

experimental. Transurethral microwave thermotherapy (TUMT) and transurethral

needle ablation (TUNA) are indicated in high risk patients especially having

bleeding tendency and volume overload [12]. These kinds of treatment can be

performed without anesthesia. Due to less improvement of symptoms [13], when

compared to standard treatment and introduction of any kind of laser therapy,

TUMP is performed less frequent during the last decade. TUNA is considered

contraindicated in prior radiation to pelvic organ due to higher risk of rectal fistula

[14].

References of CQ13

1. Vander Brink BA, Rastinehad AR, Badlani GH. Prostatic stents for the

treatment of benign prostatic hyperplasia. Curr. Opin. Urol. 2007; 17: 1–6.

(review)

2. Braf Z, Chen J, Sofer M, Matzkin H. Intraprostatic metal stents (Prostakath®

and Urospiral®): more than 6 years’ clinical experience with 110 patients. J.

Endourol. 1996; 10: 555–8. (4)

3. Gesenberg A, Sintermann R. Management of benign prostatic hyperplasia in

high risk patients: long-term experience with the Memotherm stent. J. Urol.

1998; 160: 72–6. (4)

4. Perry MJA, Roodhouse AJ, Gidlow AB, Spicer TG, Ellis BW.

Thermo-expandable intraprostatic stents in bladder outlet obstruction: an

8-year study. BJU Int. 2002; 90: 216–23. (4)

5. Masood S, Djaladat H, Kouriefs C, Keen M, Palmer JH: The 12-year outcome

analysis of an endourethral wallstent for treating benign prostatic hyperplasia.

BJU Int 2004; 94: 1271–4 (4)

6. Van den Brand IC, Castelein RM. Total joint arthroplasty and incidence of

postoperative bacteriuria with an indwelling catheter or intermittent

catheterization with one-dose antibiotic prophylaxis: a prospective

randomized trial. J. Arthroplasty 2001; 16: 850–5. (2)

7. Hakvoort RA, Thijs SD, Bouwmeester FW et al. Comparing clean intermittent

catheterisation and transurethral indwelling catheterisation for incomplete

voiding after vaginal prolapse surgery: a multicentre randomized trial. BJOG

2011; 118: 1055–60. (1)

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8. Igawa Y, Wyndaele JJ, Nishizawa O. Catheterization: possible complications

and their prevention and treatment. Int. J. Urol. 2008; 15; 481–5. (review)

9. Mitsui T, Minami K, Furuno T, Morita H, Koyanagi T. Is suprapubic cystostomy

an optimal urinary management in high quadriplegics? A comparative study

of suprapubic cystostomy and clean intermittent catheterization. Eur. Urol.

2000; 38: 434–8. (3)

10. Grise P, Plante M, Palmer J, Martinez-Sagarra J, Hernandez C, Schettini M.

Evaluation of the transurethral ethanol ablation of the prostate (TEAP) for

symptomatic benign prostatic hyperplasia (BPH): a European multi-center

evaluation. Eur. Urol. 2004; 46: 496–501. (4)

11. Brisinda G, Cadeddu F, Vanella S, Mazzeo P, Marniga G, Maria G. Relief by

botulinum toxin of lower urinary tract symptoms owing to benign prostatic

hyperplasia: early and long-term results. Urology 2009; 73: 90–4. (4)

12. De la Rosette J, Laguna MP, Gravas S, De Wildt MJ. Transurethral

microwave thermotherapy: the gold standard for minimally invasive therapies

for patients with benign prostatic hyperplasia ? J. Endourol. 2003; 7: 245–51.

(survey)

13. Zlotta AR, Giannakopoulos X, Machlum O, Ostrem T, Schulman CC.

Long-term evaluation of transurethral needle ablation of the prostate (TUNA)

for the treatment of symptomatic benign prostatic hyperplasia: clinical

outcome up to 5 years from 3 centers. Eur. Urol. 2003; 44: 89–93. (4)

14. Gravas S, Laguna MP, De la Rosette JJ. Efficacy and safety of intraprostatic

temperature controlled microwave thermotherapy in patients with benign

prostatic hyperplasia: results of a prospective, open-label, single-center

study with 1-year follow-up. J. Endourol. 2003; 17: 425–30. (4)

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CQ14

What therapeutic strategies are recommended to avoid sexual dysfunction as an

adverse event?

Answer:

Watchful waiting (active surveillance) could be considered for avoidance

of any sexual dysfunction. Alpha 1 blockers could be recommended for

patients who care erectile dysfunction. Tamsulosin and silodosin are liable

to ejaculation dysfunction. 5 alpha-reductase inhibitors could cause

erectile dysfunction and decrease of libido.

Phosphodiesterase type 5 inhibitor, Tadalafil, has been approved for

BPH/Male LUTS in USA and some Asian countries in 2011. Tadalafil is

effective in both LUTS and ED, but has not been approved in most Asian

countries.

Surgical therapy can induce ED, and it generally result in ejaculation

dysfunction. Although the incidence of sexual adverse events by

minimally invasive treatments, such as transurethral microwave therapy

(TUMT) and transurethral needle ablation (TUNA), is lower, these types of

treatment cannot always avoid adverse events on sexual function.

(Recommendation Grade B)

If a patient has only mild lower urinary tract symptoms owing to BPH and cares

sexual dysfunction due to interventional therapy, watchful waiting is a potential

option.

Alpha 1 blockers, such as alfuzosin and doxazosin, have generally beneficial

effects on erectile function [1–4]. Further, the incidence of erectile dysfunction

(ED) induced by 1 blockers is not so high (0.6-12%) and similar to that by

placebo [4]. Therefore, 1 blockers can be recommended to use for patients

who care ED. Although non-selective A1Bs, such as alfuzosin and doxazosin,

have no increased risk of ejaculation dysfunction (EjD) (0-1.3%) [5], 1 blockers

selective for alpha-1A adrenoreceptor, including tamsulosin (~30%) [5] and

silodosin (~28%) [6] are associated with increased risk of EjD. 5 alpha-reductase

inhibitors (5ARIs), finasteride and dutasteride, can induce several types of

sexual dysfunction, i.e. ED, EjD, and decrease of libido [7, 8]. The incidence of

drug-related sexual adverse events decreases with longer duration of therapy [9,

10]. Phosphodiesterase type 5 inhibitors, such as sildenafil, vardenafil and

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tadalafil, have promising effects both on lower urinary tract symptoms due to

BPH and erectile function [11, 12]. However, this type of drugs is approved for

treatment for LUTS in no Asian countries.

The incidence of ED by open prostatectomy and transurethral resection of the

prostate (TURP) is reported 3 to 20% [13, 14]. However, similar percentages of

patients could experience the improvement of erectile function by TURP

[14] .These standard surgical treatments inevitably result in EjD (~80%) [14].

Surgeries using holmium: YAG-laser (ablation; HoLAP, resection: HoLRP,

enucleation: HoLEP) or KTP-laser (vaporization; PVP) have similar effect on

sexual function to TURP [13].On the other hand, several minimally invasive

methods, such as transurethral microwave therapy (TUMT) and transurethral

needle ablation (TUNA), have lower incidence of adverse events on sexual

function [14].

References of CQ14

1. Rosen R, Seftel A, Roehrborn CG. Effects of alfuzosin 10mg once daily on

sexual function in men treated for symptomatic benign prostatic hyperplasia.

Int. J. Impot. Res. 2007; 19: 480–5. (1)

2. Kim MK, Cheon J, Lee KS et al. An open, non-comparative, multicentre study

on the impact of alfuzosin on sexual function using the Male Sexual Health

Questionnaire in patients with benign prostatic hyperplasia. Int. J. Clin. Pract.

2010; 64: 345–50. (4)

3. Kirby RS, O’Leary MP, Carson C. Efficacy of extended-release doxazosin

and doxazosin standard in patients with concomitant benign prostatic

hyperplasia and sexual dysfunction. BJU Int. 2005; 95: 103–9. (1)

4. Demir O, Ozdemir I, Bozkurt O, Asian G, Esen AA. The effect of

alpha-blocker therapy on erectile functions in patients with lower urinary tract

symptoms due to benign prostatic hyperplasia. Asian J. Andol. 2009; 11:

716–22. (4)

5. AUA Clinical Guidance, Management of BPH (Revised 2010), Final

Appendices

(http://www.auanet.org/content/clinical-practice-guidelines/clinical-guidelines.

cfm?sub=bph) (Guideline)

6. Marks LS, Gittelman MC, Hill LA, Volinn W, Hoel G. Rapid efficacy of highly

selective alpha 1A-adrenoreceptor antagonist silodosin in men with signs

and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3

http://www.auanet.org/content/clinical-practice-guidelines/clinical-guidelines.cfm?sub=bph

http://www.auanet.org/content/clinical-practice-guidelines/clinical-guidelines.cfm?sub=bph

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studies. J. Urol. 2009; 181: 2634–40. (1)

7. McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL.

The effect of finasteride on the risk of acute urinary retention and the need for

surgical treatment among men with benign prostatic hyperplasia. N. Engl. J.

Med. 1998; 338: 557–63. (1)

8. Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G. Efficacy and

safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in

men with benign prostatic hyperplasia. Urology 2002; 60: 434–41. (1)

9. Wessells H, Roy J, Bannow J, Grayhack J, Matsumoto AM, Tenover L.

Incidence and severity of sexual adverse experiences in finasteride and

placebo-treated men with benign prostatic hyperplasia. Urology 2003; 61:

579–84. (1)

10. Schulman C, Pommerville P, Hofner K, Wachs B. Long-term therapy with the

dual 5alpha-reductase inhibitor dutasteride is well tolerated in men with

symptomatic benign prostatic hyperplasia. BJU Int. 2005; 97: 73–80. (1)

11. Broderick GA, Brock GB, Roehrborn CG, Watts SD, Elion-Mboussa A,

Viktrup L. Effects of tadalafil on lower urinary tract symptoms secondary to

benign prostatic hyperplasia in men with or without erectile dysfunction.

Urology 2010; 75: 1452–8. (1)

12. Porst H, Kim ED, Casabe AR et al. Efficacy and safety of tadalafil once daily

in the treatment of men with lower urinary tract symptoms suggestive of

benign prostatic hyperplasia: results of an international randomized,

double-blind, placebo-controlled trial. Eur. Urol. 2011; 60: 1105–13. (1)

13. Larson TR. Current treatment options for benign prostatic hyperplasia and

their impact on sexual function. Urology 2003; 61: 692–8. (review)

14. Frieben RW, Lin HC, Hinh PP, Berardinelli F, Canfield SE, Wang R. The

impact of minimally invasive surgeries for the treatment of symptomatic

benign prostatic hyperplasia on male sexual function: a systematic review.

Asian J. Androl. 2010; 12: 500–8. (review)

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3. Introduction


Norifumi Sawada, M.D., Ph.D., Masaki Yoshida, M.D., Ph.D., Koji

Yoshimura, M.D., Ph.D., Momokazu Gotoh, M.D., Ph.D., Japan.

An increase in the prevalence of lower urinary tract symptoms (LUTS) with age

in men [1] is seen, and which is important given the increase in the aging

population [2]. Because of the great prevalence of benign prostatic hyperplasia

(BPH) in elderly men, which is as high as 40% in men in their fifth decade and

90% in men in their ninth decade [3], the most important and prevalent cause of

LUTS in men over 40 years is generally believed to be the enlarging

prostate/BPH. Although BPH is a histologic diagnosis that refers to the

proliferation of smooth muscle and epithelial cells within the prostatic transition

zone [4, 5], benign prostatic enlargement (BPE), or benign prostatic obstruction

(BPO) are often used in the same way as BPH in the clinical setting. Recently,

the causes of aging male LUTS are known to be multifactorial, and LUTS may

be linked to the prostate (BPH-LUTS), bladder (detrusor overactivity-overactive

bladder syndrome [OAB], detrusor underactivity), kidney/heart (nocturnal

polyuria), or brain (sleep disorder) [6]. Usually, more than one of those factors is

present, in a patient complaining of LUTS. According to such situation, the title of

the 1st UAA Guideline has been determined as “BPH/Male LUTS”, not solely

“BPH”, and the Purposes of this guideline is to summarize Practical Consensus

Statement on the Management of BPH/Male LUTS from UAA. Target doctors are

both Urologists and non-Urologists/General Practitioners, and target patients are

40 years or older male patients with BPH/LUTS. Traditionally in Asian countries,

socio-cultural atmosphere of accepting lower urinary tract symptoms (LUTS) as

a natural part of aging process has been dominant. However, far Eastern

countries like Japan, Korea and Taiwan have already become an “aging society”

and the ever-growing public interest in their health and well-being, public

awareness towards BPH has been increasing rapidly along with the number of

patients who visit hospitals seeking medical care for LUTS. Thus, it can be

expected that BPH will soon become a major issue with regard to public health

and welfare in all Asian countries, as is already the situation for many Western

countries. The UAA Guideline on Male LUTS mainly covers LUTS secondary to

benign prostatic enlargement (BPE) or benign prostatic obstruction (BPO),

detrusor overactivity or overactive bladder (OAB), and nocturia due to nocturnal

polyuria. Other causes of male LUTS are covered by separate EAU Guidelines.

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3.1 Multifactorial Etiology of LUTS

3.2 Multifactorial conditions for LUTS

- 51 -

References

1. Platz EA, Joshu CE, Mondul AM, Peskoe SB, Willett WC, Giovannucci E.

Incidence and Progression of Lower Urinary Tract Symptoms in a Large

Prospective Cohort of United States Men. J. Urol. 2012; 186: 496–501.

2. World Population Ageing 1950–2050. 2002 [cited May 2012]; United Nations

Department of Economic and Social Affairs Population Division]. Available

from: http://www.un.org/esa/population/publications/worldageing

19502050/

3. Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development of human

benign prostatic hyperplasia with age. J. Urol. 1984; 132: 474–9.

4. Lee C, Kozlowski J, Grayhack J. Intrinsic and extrinsic factors controlling

benign prostatic growth. Prostate 1997; 31: 131–8.

5. Auffenberg G, Helfand B, McVary K. Established medical therapy for benign

prostatic hyperplasia. Urol. Clin. North. Am. 2009; 36: 443–59.

6. Chapple CR, Roehrborn CG. A shifted paradigm for the further

understanding, evaluation, and treatment of lower urinary tract symptoms in

men: focus on the bladder. Eur. Urol. 2006; 49: 651–8.

7. Oelke M, Bachmann A, Descazeaud A et al. EAU Guideline Male LUTS

2012. Guidelines on Management of Male Lower Urinary Tract Symptoms

(LUTS) LUTS: lower urinary tract symptoms, incl. Benign Prostatic

Obstruction (BPO) BPO: benign prostatic obstruction.

(http://www.uroweb.org/guidelines/online-guidelines/)

http://www.un.org/esa/population/publications/worldageing

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4. Definition, and terminology of benign prostatic hyperplasia

(BPH) and related disorders

Salam, M.A., MD, Md Afiquor Rahman, MD

In the past, a number of terms such as prostatism, symptomatic benign prostatic

hyperplasia (BPH), and clinical BPH have been used to describe symptoms

related to micturition in older men. Currently, the traditional belief that urinary

symptoms in elderly men were always assumed to be directly or indirectly

related to prostate has been challenged. The term lower urinary tract symptoms

(LUTS) has been adopted and several consensus and guidelines committees

have attempted to define the appropriate terminology for categorizing the

pathophysiological conditions underlying male LUTS [1–5].

4.1 The term lower urinary tract symptoms (LUTS; as defined by the

International Continence Society) are the subjective indicator of a disease or

change in condition as perceived by the patient, caregiver or partner and may

lead him/her to seek help from health care professionals. LUTS can be classified

as storage, voiding, and post micturition symptoms.

4,2 Bladder storage (irritative) symptoms are experienced during the

storage phase of the bladder and include: increased daytime frequency, nocturia,

urgency, and urinary incontinence.

4.3 Voiding (obstructive) urinary symptoms are experienced during the

voiding phase and include: slow urinary stream, splitting or spraying of the

urinary stream, intermittent urinary stream, hesitancy, straining to void, and

terminal dribbling.

4.4 Post micturition symptoms include feeling of incomplete emptying and

postmicturition dribbling.

4.5 Benign prostatic hyperplasia (BPH) represents a histologic diagnosis

that refers to the proliferation of smooth muscle and epithelial cells within the

prostatic transition zone. Benign prostatic hyperplasia or BPH is a term used

(and reserved for) the typical histological pattern, which defines the disease.

BPH progression is a dynamic process that includes deterioration of LUTS and

- 53 -

health related quality of life, increased prostatic size, acute urinary retention

(AUR), and BPH-related surgery. Renal insufficiency and recurrent urinary tract

infections as additional measures of BPH progression have also been

considered. However, these outcomes are rarely observed [6–9].

4.6 Benign prostatic enlargement (BPE) is defined as prostatic enlargement

due to histologic benign prostatic hyperplasia. The term “prostatic enlargement”

should be used in the absence of typical prostatic histology

4.7 Bladder outlet obstruction (BOO) is the generic term for obstruction

during voiding and is characterized by increased detrusor pressure and reduced

urine flow rate. Therefore, the term BOO requires urodynamic confirmation

4.8 Benign prostatic obstruction (BPO) is bladder outlet obstruction (needs

urodynamic evaluation) and may be diagnosed when the cause of outlet

obstruction is known to be benign prostatic enlargement, due to histologic

benign prostatic hyperplasia.

The relationship between LUTS, BPH, BPE, BOO and BPO is complex and not

fully understood. Because the prevalence of histological BPH and LUTS is

age-related, it was often assumed that they were causally related, but recent

evidence indicate that male LUTS may result from a complex interplay of

pathophysiological influences, including prostatic pathology and bladder

dysfunction. However, BPH is the primary cause of LUTS in older men.

Most men with enlarged prostates may not have any symptoms at all. BPO may

occur in some but not all men with BPH and LUTS. The elderly men with BPH

may not develop BOO which is characterized by increased detrusor pressure

and reduced urine flow rate. Many men develop BPO without evidence of

histologically proven BPH. BOO due to BPE may have both static (increased

tissue mass) and dynamic (increased smooth muscle tone) components in the

prostate leading to variable lower urinary tract symptoms. BOO due to BPE or

BPH may lead to overactivity of the detrusor muscle leading to irritative

symptoms predominantly. This situation may not be clarified with conventional

investigations of BPH. An urodynamic studies will settles the issue by confirming

the overactivity of the bladder is due to benign prostatic obstruction [10, 11].

- 54 -

References

1. Abrams P, Cardozo L, Fall M et al. Standardisation Sub- Committee of the

International Continence Society. The standardisation of terminology in

lower urinary tract function: report from the standardisation sub-committee of

the International Continence Society. Urology 2003; 61: 37–49.

2. Arrighi HM, Metter EJ, Guess HA, Fozzard JL. Natural history of benign

prostatic hyperplasia and risk of prostatectomy, the Baltimore Longitudinal

Study of Aging. Urology 1991; 35 (Suppl): 4–8.


understanding, evaluation, and treatment of lower urinary tract symptoms in

men: focus on the bladder. Eur. Urol. 2006; 49: 651–8.

4. Chute CG, Panser LA, Girman CJ et al. The prevalence of prostatism: a

population based survey of urinary symptoms. J. Urol. 1993; 150: 85–9.

5. Emberton M, Andriole GL, De la Rosette J et al. Benign prostatic

hyperplasia: a progressive disease of aging men. Urology 2003; 61: 267–73.

6. Issa MM, Fenter TC, Black L, Grogg AL, Kruep EJ. An assessment of the

diagnosed prevalence of diseases in men 50 years of age or older. Am. J.

Manag. Care 2006; 12: S83–9.

7. Jacobsen SJ, Girman CJ, Guess HA, Rhodes, T, Oesterling JE, Lieber MM.

Natural history of prostatism: longitudinal changes in voiding symptoms in

community dwelling men. J. Urol. 1996; 155: 595–600.



of benign prostatic hyperplasia. N. Engl. J. Med. 2003; 349: 2387–98.

9. Roberts RO, Jacobsen SJ, Jacobsen D, Rhodes T, Girman CJ, Lieber MM.

Longitudinal changes in Roehrborn CG: Benign prostatic hyperplasia: an

overview. Rev. Urol. 2000; 7: S3–14.

10. Guidelines on the Management of Male Lower Urinary Tract Symptoms

(LUTS), incl. Benign Prostatic Obstruction (BPO), European Association of

Urology, 2012.

11. 2010 Update: Guidelines for the management of benign prostatic

hyperplasia. Can. Urol. Assoc. J. 2010; 4: 310–31.

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5 Risk Factors for BPH

Jose Albert C. Reyes III, MD, DPBU, FPUA, FPCS

Evidence suggests that modifiable factors such as obesity, diet, dyslipidemia,

hormonal imbalance, hypertension, metabolic syndrome, alcohol and smoking

contribute to the development of BPH and/or LUTS other than aging and

androgens [1].

5.1 Genetic Factors:

Partin and colleagues demonstrated a concordance for benign prostate disease

in monozygotic (MZ) and dizygotic (DZ) twins who served in the United States

military in World War II [2]. Genetic factors not only determine risk for

development of BPH but also affect its presentation and severity. Also, Meikle

and colleagues demonstrated that heritability appears to account for 82.6% of

the variability in symptom score in men older than 50 years in a study conducted

on twins. Table 1 summarizes Family History of Early-Onset BPH Increases Risk

of Clinical Significant BPH (Table 1) [3].

5,2 Dietary Factors:

Those with high intake of protein and polyunsaturated fatty acid appear to be at

greater risk of developing BPH [4].

Marchard et al evaluated the relation between consumption of high animal fat

products to BPH and prostate cancer. It was proposed that certain aspects of

western diet, low amount of fruits and vegetables and a higher proportion of

energy from animal fats, explain the epidemiologic evidence linking western

dietary patterns to a higher BPH risk [5, 6].

Daily fruit consumption was later then found out to be inversely related to risk of

BPH [7]. Furthermore, Galuzzi et al found that Southeast Asian men have a

lower prevalence and severity of autopsy-diagnosed BPH than age-matched

North American men [8], implying that ethnicity and geographical factors, such

as migration, can influence the growth of the normal human prostate during

midlife [9]. Chyou examined 33 food items in relationship to prostatectomy rates

and found only beef intake significantly associated [10].

Araki and associates reported increased clinical diagnosis of BPH in men with

higher milk consumption and lower consumption of green and yellow vegetables

[11]. Overall there is no convincing evidence for any individual diet factor to play

- 56 -

a major role in the development of LUTS/BPH.

5,3 Obesity, Hypertension, DM, Hypercholesterolemia and Sexual

Dysfunction:

The relationships between LUTS/BPH and obesity, BMI, and the metabolic

syndrome have recently been of great interest [12–15]. Autonomic hyperactivity

has been implicated in the development of both LUTS and ED in the aging male,

but conclusive clinical data are lacking [16]. In the EpiLUTS study both heart

diseases and hypertension were associated with more severe LUTS

constellations [17]. Dyslipidemia has also been associated with an increased risk

of BPH [18] (See Appendix- Table II). In a cohort in 1998 involving Swedish men

with BPH lower HDL, higher LDL, and higher triglycerides were associated with

increased prostate volume [19]. A pilot case-control study showed that higher

triglyceride levels, high waist-to-hip ratio, and lower HDL levels were associated

with BPH in North Indian population [20]. Hammarsten and Hogstedt examined

250 patients with LUTS and found non–insulin-dependent diabetes mellitus,

hypertension, tallness, obesity, high insulin level, and low high-density

lipoprotein cholesterol levels to be risk factors for the development of BPH and

suggested a causal relationship between high insulin levels and the

development of BPH and hypothesize increased sympathetic nerve activity in

men with BPH [21].

5.4 Other risk factors:

Physical activity thus appears to reduce the risks of BPH and LUTS. Similar

findings of increased likelihood of LUTS with increasing BMI and decreasing

likelihood with greater physical activity were also reported from the EpiLUTS

study [17]. Alcohol intake may lower incidence of BPH by decreasing plasma

testosterone production and increasing testosterone clearance. In an analysis of

the Prostate Cancer Prevention Trial, alcohol appears to have a somewhat

protective effect against BPH [22]. Studies on the relationship of liver cirrhosis

and BPH, revealed a lower incidence of BPH in men with cirrhosis [22–25].

However, multivariate analysis show and increase surgical risk for BPH in

patients taking in more than three glasses of alcohol per day [26, 27].

Cigarette smoking appears to have a protective effect on prostatism at certain

smoking intensities, but no effect or a deleterious effect at other intensities [28–

30]. Light or moderate smokers are less likely to have moderate to severe

- 57 -

prostatism, whereas heavy smokers are at least as likely to have moderate to

severe prostatism compared with never-smokers [31]. Cold medications

containing α-sympathomimetic drugs exacerbate LUTS by the expected effect

on the smooth muscles of the bladder outlet. Recently a careful analysis of the

data from the Olmsted County study demonstrated that daily use of

antidepressants, antihistamines, or bronchodilators is associated with a 2- to

3-point increase in the IPSS compared with age-matched nonusers and daily

use of antidepressants is associated with a decrease in the age-adjusted flow

rate [32].

It was reported that there is 49% reduction in risk for prostatectomy in widowed

versus single men [33]. Cross-sectional data from the Olmsted County study

suggest that the frequency of ejaculation has no effect on LUTS, peak urinary

flow rates, or prostate volume; the apparent protective association appears to be

an artifact caused by the confounding effects of age [34]. Impact of some

socioeconomic factors on LUTS and BPH had deepened with the help of two

studies, the European Prospective Investigation into Cancer and Nutrition

(EPIC) and the Epidemiology of Lower Urinary Tract Symptoms (EpiLUTS), and

the Boston Area Community Health (BACH) studies [35, 36]. Araki and

associates found higher rates of BPH in higher income groups [10], whereas, in

contrast, Glynn and coworkers reported higher rates of surgery in lower income

groups which could be because higher income groups might have better access

to health care whereas lower income groups might submit more readily to the

suggestion of a surgical procedure [37].

- 58 -

APPENDIX

Table I. Family History of Early-Onset BPH Increases Risk of Clinical

Significant BPH

Relatives with history of prostatectomy (open or transurethral)

for BPH

RELATIVE RISK of

CLINICAL BPH

All first-degree male relatives 4.4

Fathers of proband 3.5

Brothers of proband 6.1

[3]

Table II. Modifiable Risk Factor Associated with Decreased or Increased

Risk of LUTS and/or BPH

STUDY RISK FACTOR REFERENCE

CATEGORY

OR (95% CI)

Clinical BPH: Alcohol intake 0 g/day

Alcohol intake 30.1-50 g/day Walking 0 hr/wk

Walking ≥ 2 hr/wk

Massachus

etts Male

Aging Study

Clinical BPH (physical

activity 862 kcal/day or

greater

Physical activity 140

kcal/day

0.50 (0.3-0.9)

Clinical BPH (alcohol intake

60 g/day or greater)

TURP likelihood (alcohol

intake ≥60 g/day) Nocturia

(alcohol intake ≥60 g/day)

LUTS: Alcohol intake ≥1

drink/day

Never

Physical activity >6

times/wk

Physical activity 0

times/wk

NHANES III 0.59 (0.36-0.97)

0.49 (0.29-0.84)

DECREASED RISK OF BPH AND LUTS

Health

Professiona

ls Follow-up

0.59 (0.51-0.70)

0.73 (0.63-0.84)

PLCO Alcohol intake <5 g/day

Alcohol intake <5 g/day

Alcohol intake <5 g/day

0.60 (0.5-0.7)

0.40 (0.3-0.7)

0.80 (0.7-1.0)

- 59 -

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2. Partin AW, Page WF, Lee BR, Sanda MG, Miller RN, Walsh PC.

Concordance rates for benign prostatic disease among twins suggest

hereditary influence. Urology 1994; 44: 646–50.

3. Sanda MG, Beaty TH, Stutzman RE, Childs B, Walsh PC. Genetic

susceptibility of benign prostatic hyperplasia. J. Urol. 1994; 152: 115–9.

4. Suzuki S, Platz EA, Kawachi I, Willett WC, Giovannucci E. Intakes of energy

and macronutrients and the risk of benign prostatic hyperplasia. Am. J. Clin.

Nutr. 2002; 75: 689–97.

5. Heber D. Prostate enlargement: the canary in the coal mine? Am. J. Clin.

Nutr. 2002; 75: 605–6.

6. Rohrmann S, Giovannucci E, Walter CW, Platz EA. Fruit and vegetable

consumption, intake of micronutrients, and benign prostatic hyperplasia in

STUDY RISK FACTOR REFERENCE

CATEGORY

OR (95% CI)

LUTS: BMI 40 mg/kg2 or

less/

BMI less than 25 1.79 (0.90-3.56)

Diabetes No diabetes 1.25 (1.04-1.49)

Waist/hip ratio 0.94 or less Waist/hip ratio 0.85 or

less

1.32 (1.15-1.50)

LUTS: Diabetes No diabetes 1.67 (0.72-3.86)

Hypertension No hypertension 1.76 (1.20-2.59)

Increase in BMI between

age 25 yr + highest BMI ever

No increase 1.90 (0.89-4.05)

Waist circumference >102

cm

Waist circumference

<94cm

1.48 (0.87-2.54)

LUTS: Diabetes No diabetes 2.80 (1.10-7.10)

2.60 (1.01-6.70)

Fasting glucose >110 ng/dL Fasting glucose ≤110

ng/dL

3.52 (1.45-8.56)

Prostate ≥40 mL: BMI <25 kg/m2 2.25 (1.25-4.11)

BMI >35 mg/kg2 No diabetes 2.98 (1.70-5.23)

Diabetes Fasting glucose ≤110

ng/dL

Fasting glucose >110 ng/dL

NHANES III

BLSA

INCREASED RISK OF BPH AND LUTS

Hunt-2

- 60 -

US men. Am. J. Clin. Nutr. 2007; 85: 523–9.

7. Ranjan P, Dalela D, Sankhwar SN. Diet and benign prostatic hyperplasia:

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8. Magi-Galuzzi Cristina. The prevalence and extent of autopsy benign

prostatic hyperplasia is less in Southeast Asian men than North American

men. Annual Meeting of the American Urological Association: San Francisco,

CA. May, 2004

9. Jin B, Turner L, Zhou Z, Zhou EL, Handelsman DJ. Ethnicity and migration

as determinants of human prostate size. J. Clin. Endocrinol. Metab. 1999;

84: 3613–9.

10. Chyou PH, Nomura AM, Stemmermann GN, Hankin JH. A prospective study

of alcohol, diet, and other lifestyle factors in relation to obstructive uropathy.

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11. Araki H, Watanabe H, Mishina T, Nakao M. High-risk group for benign

prostatic hypertrophy. Prostate 1983; 4: 253–64.

12. Hammarsten J, Hogstedt B, Holthuis N, Mellstrom D. Components of the

metabolic syndrome – risk factors for the development of benign prostatic

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13. Rohrmann S, Smit E, Giovannucci E, Platz EA. Associations of obesity with

lower urinary tract symptoms and noncancer prostate surgery in the Third

National Health and Nutrition Examination Survey. Am. J. Epidemiol. 2004;

159: 390–7.

14. Gupta A, Gupta S, Pavuk M, Roehrborn CG. Anthropometric and metabolic

factors and risk of benign prostatic hyperplasia: a prospective cohort study of

Air Force veterans. Urology 2006; 68: 1198–205.

15. Kasturi S, Russell S, McVary KT. Metabolic syndrome and lower urinary tract

symptoms secondary to benign prostatic hyperplasia. Curr. Urol. Rep. 2006;

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16. McVary KT. Erectile dysfunction and lower urinary tract symptoms secondary

to BPH. Eur. Urol. 2005; 47: 838–45.

17. Coyne KS, Sexton CC, Thompson CL et al. The prevalence of lower urinary

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18. Parsons JK. Modifiable risk factors for benign prostatic hyperplasia and

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19. Hammarsten J, Hogstedt B, Holthuis N, Mellstrom D: Components of the

metabolic syndrome- risk factors for the development of benign prostatic

hyperplasia. Prostate Cancer Prostatic Dis. 1998;3:157–62.

20. Tewari R, Prabhat P, Natu SM et al. Association of benign prostatic

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growing dilemma. J. Mens Health 2011; 8: 66–71.

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metabolic syndrome- risk factors for the development of benign prostatic

hyperplasia. Prostate Cancer Prostatic. Dis. 1998; 3: 157–62.

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hepatic cirrhosis. Studies in 13 male patients. Ann. Intern. Med. 1973; 79:

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men who die of cirrhosis of the liver. Am. J. Clin. Pathol. 1950; 20: 814–28.

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whites in a prepaid health care plan. Am. J. Epidemiol. 1991; 134: 825–9.

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smoking and prostatism in a Japanese community. Prostate 1997; 30: 154–

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31. Roberts RO, Jacobsen SJ, Rhodes T et al. Cigarette smoking and

prostatism: a biphasic association? Urology 1994; 43: 797–801.

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33. Morrison AS. Risk factors for surgery for prostatic hypertrophy. Am. J.

Epidemiol. 1992; 135: 974–80.

34. Jacobsen SJ, Jacobson DJ, Girman CJ, Roberts RO, Lieber MM. Frequency

of sexual activity and prostatic health: fact or fairy tale? Urology 2003; 61:

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35. Rosen RC, Coyne KS, Henry, D, Link, CL, Cinar A, Aiyer LP. Beyond the

cluster: methodological and clinical implications in the Boston Area

Community Health survey and EPIC studies. BJU Int. 2008; 101: 1274–8.

36. Kaplan SA, Wein AJ, Staskin DR, Roehrborn CG, Steers WD. Urinary

retention and post-void residual urine in men: separating truth from tradition.

J. Urol. 2008; 180: 47–54.

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benign prostatic hyperplasia among volunteers in the Normative Aging Study.

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- 63 -

6. Epidemiology & Natural history

Shing-Hwa Lu, M.D., Ph.D., and Edward Chen, M.D., Ph.D.

The following 4 categories are discussed in this chapter.

6.1 Natural history before diagnosis

6.2 Factors affecting health-care seeking behavior

6.3 Prediction of symptomatic progression

6.4 Natural history after diagnosis

6.1 Natural history before diagnosis

Benign prostatic hyperplasia (BPH) is the most common nonmalignant condition

of the prostate occurring in ageing men. Even though BPH is a major public

health problem, causing high morbidity and substantial worsening in men's

quality of life [1]. The prevalence rates of BPH, depend very much on the

parameters used in a case definition [2], has been estimated on the basis of

results of community-based studies in Japan [3–5]. Six and 12% of Japanese

men in their sixties and seventies, respectively, meet all three of the following

criteria for BPH: (i) an international prostate symptom score (IPSS) >7; (ii)

prostate volume (PV) >20 mL; and (iii) peak urinary flow rate (Qmax) <10 mL/s.

Only 2% of men in their forties and fifties met the above criteria.

The principal risk factors for BPH are aging and normally functioning testicles.

Although no definitive genes responsible for BPH have been identified, a family

history of BPH and molecular abnormalities may increase the likelihood of its

development. Dietary factors, such as isoflavonoids and lignans in vegetables,

grains, and soy, may have a negative impact on the development of BPH [1].

Furthermore, recent studies have claimed a relationship between metabolic

syndrome and BPH [6–8].

The normal prostate reaches 20 plus or minus 6 g in men between 21 and 30

years old, and this weight remains essentially constant with increasing age

unless benign prostatic hyperplasia develops. The prevalence of pathological

benign prostatic hyperplasia is only 8 % at the fourth decade; however, 50 % of

the male population has pathological benign prostatic hyperplasia when they are

51 to 60 years old. The average weight of a prostate that is recognized at

autopsy to contain benign prostatic hyperplasia is 33 plus or minus 16 g. Only 4

% of the prostates in men more than 70 years old reach sizes greater than 100 g.

- 64 -

An analysis of a logistic growth curve of benign prostatic hyperplasia lesions

removed at prostatectomy indicates that the growth of benign prostatic

hyperplasia is initiated probably before the patient is 30 years old. The early

phase of benign prostatic hyperplasia growth (men between 31 and 50 years old)

is characterized by a doubling time for the tumor weight of 4.5 years. In the mid

phase of benign prostatic hyperplasia growth (men between 51 and 70 years old)

the doubling time is 10 years, and increases to more than 100 years in patients

beyond 70 years old [9]. BPH is a physiological process that occurs with aging,

regardless of race, ethnicity or region [9, 10].

Estimated prostate growth rates increased with increasing age. However, the

estimated average annual change was 1.6% across all age groups. Estimated

prostate growth rates were high depending on baseline prostate volume with

higher growth rates for men with larger prostates [11].

BPH can be characterized as a progressive disease in a certain proportion of

men older than 50 yr. Men with growing prostates are at a greater risk of

symptomatic deterioration. Men who have prostates that do not grow

significantly are more likely to improve symptomatically [12]. The prevalence of

LUTS in the general population is age-related [4, 13, 15]. Longitudinal studies

have shown an increase in IPSS with advancing age as a whole [12, 16, 17], but

with simultaneous decreases in IPSS in certain subgroups [16, 18], Qmax

decrease with aging [5, 19], and this may be attributable to BPO as well as

detrusor underactivity (DU). Longitudinal studies have confirmed age-related

increases in PV [11, 12], although in a small proportion of men PV has been

noted to decrease with aging [20]. Recent studies indicate that PV is likely to

increase in men in whom the prostate has a visible transition zone with a clear

border [21, 22]. and with a large transition zone volume on transrectal ultrasound

at baseline [23]. The relationship between LUTS, urinary flow rate and PV is

generally poor in men presenting at hospital, but it is modest among men in the

general population. Prostate enlargement is likely to be involved in the

progression of symptoms [12, 24].

6.2 Factors affecting health-care seeking behavior

A cross-sectional, population-based cohort study in Olmsted County revealed

that health-care seeking behavior was influenced by the severity of symptoms,

particularly if they were bothersome and interfered with an individual's daily

- 65 -

activities. While symptom severity is an important determinant of health

care-seeking behavior for men with urinary symptoms, some additional factor or

factors associated with age remain that may drive men to seek care for urinary

symptoms. These factors may prove important in understanding the small-area

variations in treatment of benign prostatic hyperplasia that have been noted by

others. Men aged 70 to 79 years were 4.6 times as likely (95% confidence

interval, 2.1 to 10.1) as men aged 40 to 49 years to have sought health care

because of urinary symptoms [25]. Seventy-six% of men who had sought

medical care had prostatic enlargement, depressed peak urine flow rates, or

moderate-severe symptoms (sensitivity). In contrast, only 55% of men who did

not seek health care for urinary symptoms had mild symptoms, normal prostatic

volume, and normal peak urine flow rates (specificity). Clinical, physiologic, and

anatomic measures of prostatism do not adequately distinguish the men who

seek medical care for their urinary symptoms from those who do not. There

remain some factor(s) that apparently lead some men with minor disease to

seek care and that prevent men with measurable disease from seeking care

[26 ].

Voiding symptoms may have impact on medical care-seeking behavior through

QOL impairment in Japanese men. The QOL score appeared to reveal more

pronounced differences between men in clinic and community setting than the

IPSS category [27]. Core Lower Urinary Tract Symptom Score (CLSS)

questionnaire is more comprehensive than IPSS questionnaire for symptom

assessment of men with various diseases/conditions, although both

questionnaires can capture LUTS with possible negative impact on QOL [28].

The IPSS alone does not appropriately evaluate female LUTS. The CLSS

questionnaire could provide a comprehensive and simple assessment of female

LUTS [29].

6.3 Prediction of symptomatic progression

From a systemic review of placebo arm of clinical trials on benign prostatic

hyperplasia (BPH), the disease progression was observed in terms of increasing

prostate volume and decreased maximal urinary flow rate (Qmax). In addition,

the progression increases the risk of acute urinary retention (AUR) and surgery

[30]. The community-based and randomized controlled studies identified some

clinical parameters which may be associated with clinical progression,

complications such as AUR and related surgeries [31–35].

- 66 -

Progression may be associated with higher International Prostate Symptom

Score (IPSS), lower Qmax, increased post void residual urine (PVR) and

enlarged prostate volume. From the Medical Therapy of Prostatic Symptoms

study (MTOPS), the clinical progression of placebo arm (n=737) is 17%, the

AUR is 2%, and invasive therapy due to benign prostatic hyperplasia is 5% [36].

The risks for clinical progression in the study may include age ≥62 years old,

prostate volume ≥31 mL, prostate specific antigen (PSA) ≥1.6 ng/mL, Qmax

<10.6 mL/s and PVR ≥39 mL [37]. However, practicing doctors are faced with

patients often representing with several unfavorable conditions not only a single

risk. On a systemic analysis of expert opinions, the considerable PVR (>150 mL),

poor Qmax (<10 mL/s) and severe symptoms (total IPSS: 20–35) are the most

dominant factors predicting an elevated risk of disease progression [38].

Enlarged prostate and high PSA was found to be good clinical predictor of AUR

and BPH related surgery [39]. In addition, the high PVR should be reconsidered

as a predictor of BPH progression through the interpretation of longitudinal

population-based and placebo arm of controlled studies.

6.4 Natural history of BPH after diagnosis

The best way to see the natural history of BPH after diagnosis is to understand

the fate of watchful-waiting or placebo treatment group. In a community based

longitudinal study which was followed for 12 years showed an average

increased IPSS of 0.18 points per year (0.05 for men at 50s to 0.44 at 70s).

There was also a decreased Qmax 2% per year and median prostate growth of

1.9% per year. In addition, the accumulative incidence of AUR was 2.7% over 4

years monitoring [40, 41]. In the placebo controlled arm of MTOPS study, the

evidence revealed that symptom deterioration (IPSS ≥4 points) was the most

prevalent progression event (79.5%), with an accumulative incidence of 14%

over a mean follow-up of 4.5 years [36].

From a cohort study in North America, the outcome of men with BPH depends

on the initial symptom severity. However, the course of symptoms may vary

among patients even with same initial symptom severity [42, 43]. In those who

with severe symptoms usually did not have improvement to only mild symptoms.

Almost half of patients with moderate symptoms still had moderate symptoms at

4 years follow-up, and eventually a quarter of them underwent surgery.

After the diagnosis of BPH, self-management intervention including lifestyle

modification and specific behavioral changes such as decreasing fluid intake at

- 67 -

bed time, avoiding caffeine and alcohol consumption may be the choices of

management strategy, and which offer a better clinical response. However, the

failure rate at 3, 6 and 12 months is higher in watchful-waiting patients (40.3% vs.

9.6%; 58.2% vs. 17.8%; 65.7% vs. 24.6%) as compared with active

management [44]. This evidence indicates the BPH possesses a deteriorated

clinical or symptomatic natural history itself and early treatment may be better if

patients have bothersome symptoms.

The PROWESS study group revealed that their patients with moderate

symptoms have significant greater improvement with finasteride as compared

with placebo group. The prostate volume decreased 15.3% in treatment group

as compared with placebo group which increased their prostate volume about

8.9% at 24 months [45]. From a nationally representative databases study, in

additional to the α blockers therapy, each 30-day delay treatment with

5α-reductase inhibitors may result in an increased overall clinical progression

(21.1%), AUR (18.6%) and prostate related surgery (26.7%) within 6 months of

follow-up [46]. This means, even under early treatment with α blocker, patients

still have a relative higher risk of symptomatic progression if they did not reduce

the prostate size. In the Veterans Affairs Cooperative Study, 24%

watchful-waiting group patients will undergo surgery within three years waiting

assignment [47]. Based on the natural history after diagnosis of BPH either with

or without medical treatment, the fact of clinical progression should raise the

alertness of clinicians and theses patients should be informed with these facts,

especially those who under watchful-waiting treatment.

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29. Fujimura T, Kume H, Tsurumaki Y et al. Core lower urinary tract symptom

score (CLSS) for the assessment of female lower urinary tract symptoms: a

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http://ovidsp.tx.ovid.com/sp-3.5.1a/ovidweb.cgi?&S=CMALFPPFNADDJOPDNCPKPALBNNLEAA00&Link+Set=S.sh.66%7c12%7csl_10

http://ovidsp.tx.ovid.com/sp-3.5.1a/ovidweb.cgi?&S=CMALFPPFNADDJOPDNCPKPALBNNLEAA00&Link+Set=S.sh.66%7c12%7csl_10

http://ovidsp.tx.ovid.com/sp-3.5.1a/ovidweb.cgi?&S=HHHJFPKBGGDDIPCHNCPKLGDCKCIBAA00&Complete+Reference=S.sh.37%7c48%7c1



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7. Pathophysiology of BPH

Keong Tatt Foo, M.D., Cheuk Fan Shum, M.D., and Colin Teo,

M.D.

BPH is a common disease affecting males above the age of 50 years. It was

reported that on autopsy study, 60% of patients above the age of 60 has BPH [1].

It is associated with a significant health impact, either as bothersome lower

urinary tract symptoms (LUTS) to patients, or less commonly as potentially

serious complications resulting from obstruction to urinary outflow.

It may not be easy to distinguish BPH from other lower urinary tract conditions in

aging males, since many of their symptoms overlap. Urgency symptoms from

detrusor overactivity after chronic obstruction may occur in many BPH patients,

but there are just as many BPH patients with bladder decompensation and

hypocontractility [2, 3].

The common belief that BPH is a diffused and generalized disease of the

prostate, resulting from some form of hormonal derangement that leads to

prostatic hyperplasia, enlargement of the overall prostatic size, compression of

the prostatic urethra, and a progressive obstruction to the bladder outlet, does

not reflect the entire pathophysiology of BPH.

7.1 Pathogenesis

Androgens must be present for prostate cells to grow. While androgens may not

directly cause BPH, they play an important permissive role. The observation that

castrated pre-pubertal boys do not develop BPH when they age illustrates the

presence of androgens is essential for BPH development. The main androgen,

testosterone, is converted by 5α reductase to dihydrotestosterone.

Dihydrotestosterone is 10-times more potent than testosterone due to its slower

dissociation from androgen receptors. Five-alpha reductase inhibitors suppress

this enzymatic conversion, resulting in decreased prostatic dihydrotestosterone

level, decreased prostatic volume, and symptomatic improvement.

Within the prostate, androgens bind to androgen receptors and initiate the

transcription of growth factors that are mitogenic to prostatic epithelial and

stromal cells. Such androgenic action can be both autocrine and paracrine in

stimulating stromal and epithelial cell growth and differentiation [4–6]. The

stromal to epithelial cell ratio is believed to be deranged in BPH. Normally, the

ratio is about 2:1, but this increases to more than 3:1 in BPH [7]. The altered

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stromal to epithelial interaction leads to the formation of microscopic nodules of

fibromuscular hyperplasia. These nodules are first formed in the transition zone

just below the smooth muscle collar of the preprostatic sphincter [8]. There are

also nodules forming within the periurethral glandular tissue in the smooth

muscle collar of the preprostatic sphincter. Within these nodules, fibroblasts

transform into smooth muscle cells within a matrix of connective tissues [9]. As

these nodules increase in number and size, they coalesce to form larger

adenoma. The lateral lobes of BPH are formed from the coalescence of

micronodules within the transition zone, whereas the middle lobe of BPH is

formed from micronodules within the periurethral sleeve of glandular tissue

posteriorly. The remainder of the prostate is then compressed outward to form a

false capsule posteriorly [10]. Therefore, BPH is a focal, stromal-induced

disease affecting the transition and periurethral zones with formation of

fibromuscular micronodules, which increase in size and number and coalesce

into the lateral and middle lobes [11].

Being nodular in nature, BPH adenoma can cause obstruction at the bladder

outlet and prostatic urethra depending on location, rather than size. A small

adenoma sited at the strategic bladder outlet, in the submucosal region can

cause significant obstruction, whereas one situated deeper in the stroma of the

gland would need to grow to a bigger size before it causes obstruction and

symptoms. As in the analogy of the garden hose, it is the distortion which is more

important factor that the compression of the prostatic urethra in BPH. Therefore,

if the term BPH is reserved for only histological diagnosis, for clinical BPH, it is

suggested that the term prostate adenomata (PA) which cause various degree of

obstruction would be appropriate. The term benign prostatic enlargement (BPE)

to indicate clinical BPH may not be appropriate, for often even when the gland is

small and not enlarged by definition, it can still cause significant obstruction

when the adenoma is sited at the strategic position causing distortion to urinary

flow.

7.2 Histopathology

On histological examination, benign prostatic hyperplasia (BPH) contains three

main components: 1. Epithelial cells (glandular tissue); it contains acini and

ducts. There are three major types of cells: Secretory epithelial cells, basal cells

and neuroendocrine cells. Epithelial cells surround the periphery of the acini and

secrete into the acini, and then secretions are drained into ducti and urethra. In

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the ablation of androgen, there occur a 90 % decrease in the number of

secretory cells, and an 80 % lessening in the volume of cells, 2. Luminal

surfaces in acini (glandular lumen), 3. Stroma; stromal tissue composed of

smooth muscle, connective tissue, fibroblasts, nerves, Iymphatic and blood

vessels [12]. The normal adult prostate contains about 20% epithelium, 30%

acinar lumens, and 50% stroma according to morphometric studies. As

mentioned above, the stromal to epithelial cell ratio is deranged in BPH.

Interestingly, it seems that men with symptomatic BPH have a significantly

higher proportion of stroma compared to men with asymptomatic BPH. The

nature of the predominant nodule in BPH may play a role in determining the

patients’ response to treatment. Smooth muscle predominant nodules respond

better to alpha antagonists, epithelial nodules to 5α reductase inhibitors, and

fibrous nodules to surgery.

The altered stromal to epithelial interaction seems to be mediated by various

growth factors. Androgen appears to act via transforming growth factor-alpha

(TGF-α) expression to regulate other growth factors, which in turn alter the

balance between cell growth and apoptosis within the micronodules. There are

five isoforms of TGF-α, of which three are found in mammals (α-1 to α-3), and

α-1 and α-2 have been investigated in BPH. TGFα-1 is under a negative

feedback by androgen, so a fall in androgen will lead to an increase in TGFα-1

expression [13]. Together with TGFα-2, they are inhibitory on epithelial and

stromal cell growth. On the other hand, basic fibroblast growth factor (bFGF) and

keratinocyte growth factor (KGF), both are mediated by transforming growth

factor-beta (TGF-β) stimulates epithelial and stromal cell growth [14]. Normally,

there is a fine balance between the actions of these growth factors. In BPH, the

fibroblast growth factors seem to override the transforming growth factors

[15]. The eventual formation of the lateral and median lobes distorts the prostatic

urethra, and produce bladder outlet obstruction.

7.3 Clinical Pathology

In the clinic, the prostatic adenomata (PA) and the distortion of the bladder neck

can be seen with trans-abdominal ultrasound (TAUS) of the prostate and bladder,

as intravesical prostatic protrusion (IPP). IPP is the distance measured from the

tip of the protruding lobes to the base of the prostate at the circumference of the

bladder, seen in the sagittal view on TAUS. A grading system for IPP is well

established. Grade 1 IPP is 5mm or less, grade 2 IPP is more than 5mm to

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10mm, grade 3 IPP is more than 10mm [16]. Recent studies have shown good

correlation between IPP grade and urodynamic evidence of obstruction. It had

been found that among patients with grade 1 IPP, only 21% were obstructed;

while up to 94% were obstructed among patients with grade 3 IPP [17]. The

positive predictive value was 94% and negative predictive value was 79%. In a

study comparing IPP and non-invasive Doppler ultrasound urodynamics in

diagnosing bladder outlet obstruction noninvasively, IPP was validated to be

strongly correlated to obstruction [18]. The sensitivity of the IPP grading was

90% for those with grade 3 IPP and a bladder obstructive Index (BOOI) of more

than 40. The specificity for those with grades 1 or 2 IPP, and a BOOI of 40 or

less was 60%. Rather than just the overall prostatic volume causing urethral

compression and obstruction, IPP also contributes to the degree of obstruction

due to urethral distortion by the PA.

Several studies have illustrated the natural history of clinical progression in BPH.

The placebo arm of the MTOPS study showed that the risk of clinical

progression was 4.5 per 100 man-years, representing a total risk of 17% at 4

years, including symptom deterioration in 14%, retention in 2%, and surgery in

5% [19]. Based on the Olmsted County Study and the Health Professionals

Follow-up study, the risk of retention was 6.8/1000 and of surgery was 4.5/1000

respectively [20, 21]. While the natural history of BPH is well established, the

challenge is to identify those patients that are likely to deteriorate. In this aspect,

IPP grading is a very useful clinical tool. Patients with grade 3 IPP are 7 times

more likely to progress than those with grade 1 IPP [22]. IPP also correlates well

with other parameters of obstruction in BPH, namely peak urinary flow rate, and

prostatic volume [23]. Therefore IPP is a good predictor of disease progression

in BPH.

7.4 Clinical Physiology

As the prostate is situated around the bladder neck, PA affect the functions of the

bladder first and then the kidneys.

The two basic functions of the bladder are storage and voiding.

The storage function can be suspected clinically to be affected if patients

developed frequency and urgency with small voided volumes. This can be

detected and measured with IPSS, and the voiding dairy, looking at frequency

and maximum voided volume (MVV). Storage function can be considered

significantly affected if MVV is less than 100ml and deterioration of IPSS by 4 or

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more points [24].

The voiding function can be assessed by simple TAUS measurement of the

post-void residue urine (PVR). PVR can vary depending on the fluid consumed

and the timing of the measurement. However, it can easily be re-measured by

asking the patient to pass urine again at the same visit. If necessary, the patient

can be asked to return for a subsequent test without the need to drink before the

test. Only persistently high PVR would be considered significant.

Obstruction can range from mild to severe. The degree of obstruction can be

easily measured by uroflowmetry. Maximum flow rate (Qmax) less than 10mL/s

has a 90% correlation with pressure-flow study (PFS) proven obstruction [25].

Poor flow rate can also be due to detrusor dysfunction secondary to a

neurogenic cause, diabetes or aging. This can be differentiated by measuring

the IPP. Only patients with low grade and poor flow would need to be further

investigated with PFS or flexible cystoscopy. For grade 3 IPP, even though the

uroflow may be good, more than 12mL/s, 65% were found to be still obstructed

on PFS [26].

When would obstruction be considered severe or significant for the clinician to

take more active measures? Obstruction would be significant if the functions of

the bladder are affected. Thus, when there is persistently high PVR, or poor MVV,

then obstruction can be considered clinically significant.

Normal PVR is less than 10mL, what would the cut off for PVR to be considered

clinically significant?

7.5 PVR and UTI:

A study in 2009 found that among 225 asymptomatic patients, thirty-one percent

had a positive urine culture, and they have higher mean PVR of 113mL,

compared to 41mL in those without infection (p<0.001) [27].

Another study in 2008 found that among 196 patients without UTI symptoms,

27% had positive urine culture, and their mean PVR was 257mL compared with

133mL in patients with negative cultures. The positive predictive value for

bacterial growth at PVR of 180mL or more, was 87% and the negative predictive

value was 94.7% [28]

7.6 PVR and AUR:

In a community based study of 477 men, it was found that patients with PVR of

more than 50mL were 2.5times more common in patient with prostate volume

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more than 30mL than those less than 30mL, and also 3 times more likely to have

acute urinary retention within 2 to 3 years [29].

In a study of 953 patients from pooled analysis of 11 alfusozin trials, it found that

PVR >100mL is statistically related to uroflow, at 60%, 47% and 39% with flow

rate of 8mL/s, 8 to 11mL/s and >11mL/s. In the follow up of 1 to 6 months, 7

patients developed acute urinary retention, and 6 out of these 7 patients had

PVR of more than 100mL at initial evaluation [30].

There is increasing evidence that dynamic variables such as PVR is important in

predicting complication of BPH in community studies and MTOPS. Patients who

had AUR had PVR above 100mL in all treatment groups, while those with no

AUR their PVR were below 100mL [31].

From the above studies, there is evidence that PVR is an important parameter to

assess in patients with BPH, and complications can result from PVR varying

from 50 to 180mL. A good cut off of PVR 100mL or more would be appropriate

and balanced in our assessment of BPH for further management.

PVR, which is a consequence of infravesical obstruction, is an important

predictor of complication of prostatic obstruction. Unlike IPP which is the cause

of bladder outlet obstruction, PVR is the consequence of obstruction, and

therefore it is inappropriate to use it to predict obstruction. However, it can be

used to predict complications from obstruction, like UTI, acute or chronic

retention of urine.

7.7 PVR and Chronic Retention of Urine:

A more serious complication is chronic retention of urine (CRU). CRU can be

defined as a distended painless palpable bladder associated with residual urine

>500mL and is often associated with bilateral hydronephrosis. Patients often

present with adult onset enuresis and chronic renal failure [32]. Typically,

patients do not have lower urinary tract symptoms, and therefore this group of

patients would be missed if only IPSS or QOL index are used during

management of BPH. A study in 2001 found that among 3277 patients

presenting with LUTS, only 0.02% had chronic retention [33]. This may not

reflect the true incidence as chronic retention usually do not present with

LUTS. As another study from Sri Lanka in Asia in 2004 found 30 patients with

chronic retention, within a period of 12 months, presenting with nocturnal

enuresis with or without hydronephrosis [34].

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7.8 Assessing Symptoms:

Thus, there are strong evidences that many BPH patients can have significant

obstruction with minimum urinary symptoms, and yet, suffer from serious

complications such as high pressure chronic retention, bilateral hydronephrosis

and renal impairment.

The International Prostate symptoms Score (IPSS) and the quality of life score

(QOL) has only weak correlation with the degree of obstruction and therefore

should not be used alone in the management of BPH.

7.9 Symptoms and Obstruction

Siris et al 1996 in a study of 75 men with “prostatism” and correlating with Qmax,

PVR and PFS found 33 men with severe symptoms and 42 men with mild or

moderate symptoms, 40 men had obstruction and 35 had equivocal or no

obstruction. The sensitivity and specificity of AUA symptoms index (precursor of

IPSS) for PFS definition of obstruction was 42.5% and 54.3%, the conclusion

was that symptoms score should not be used to gauge the degree of obstruction

[35].

Bosch JL et al 1995, in a study of community based subjects found 12% with

zero IPSS but 82% claimed to have “no voiding complain”. There was weak

co-relation between IPSS with PV (r=0.19), Qmax (r=-0, 18) and PVR

(r=0.25).The study concluded that the parameters in BPH should be considered

independently and that IPSS should not be used as a pre-selection criterion in

the determination of the prevalence of clinical BPH [36].

Wadie BS et al 2001 studied 460 men, and correlated the IPSS with PV, Qmax,

PVR and PFS and found no correlation with the total, obstructive or irritative

symptoms. They concluded that symptoms scores are qualitative and to use

them to quantify the degree of obstruction or evaluate therapy was questionable

[37].

Rosier PFWM et al 1996, in a study of 707 with LUTS, also found no co-relation

of IPSS with obstruction, patients with mild symptoms (0–7), 51% were still

obstructed, while those with severe symptoms 37% were not obstructed [38].

Chia SJ et al (2003) in a study of 200 patients with LUTS found that severe IPSS

(21–35), 57% were obstructed, while those with IPP more than 10mm (Grade3),

94% of patients were obstructed [17]. Lim LS et al (2010) also showed that there

is no correlation between severity of IPSS and IPP [22].

Using IPSS and QOL solely to decide on further management is too simplistic

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and this would lead to overtreatment and under treatment in some patients. BPH

as a clinical entity (clinical BPH) is a composite of the gland causing obstruction

and symptoms (Hald Diagram) [39]. Therefore all three components should be

included in the total holistic assessment of the patient with clinical BPH.

The global QOL is more important than the total IPSS. This is because if the

patient is not bothered by his symptoms, there may not be a need to treat him,

unless he has significant obstruction by the prostate gland.

Deterioration of IPSS by 4 or more points may be important in the follow up of

patients as it may suggest the development of detrusor instability or over active

bladder (OAB) as a result of progression of BPO.

7.10 Application of Pathophysiology to clinical Practice in Real Life

Therefore for further management of BPH, significant obstruction as defined

above with persistent PVR of >100mL, should be ruled out first before

considering symptoms. Basic principle is that treatment should be according to

the severity of the disease. The cause of the obstruction and symptoms is the

prostate adenoma (PA). However, it is not necessary to treat all patients just

because the adenoma is there. IPP is useful in diagnosing the adenoma and the

degree of IPP predicts obstruction and progression of the disease. Though IPP

predicts that 49% of patients with grade 3 IPP will deteriorate, 51% still do not

deteriorate with a mean follow up of 30 months [22]. Treating patients just

because he has a grade 3 IPP would lead to over treatment of this cohort of

patient. Therefore, treatment should take into account whether the PA has

resulted in significant obstruction and bothersome symptoms, that is according

to the severity of the disease.

7.11 Staging of BPH

The severity of the disease BPH can be classified according to the stage,

combining the presence or absence of significant obstruction or bothersome

symptoms [40]. As discussed above, persistent PVR >100mL can be used as a

cut off to define significant obstruction, which should prompt the clinician to take

more active action in the management of BPH. In real life practice, PVR varies

according to the amount of pre-micturition volume and the timing of performing

the measurement; therefore it is emphasized that the PVR must be persistent.

Thus if patient has PVR >100mL, he is asked to void again and measurement

retaken. Also the PVR is interpreted together with the Qmax which is generally

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below 10mL/s and high grade IPP. Thus clinical BPH can be classified as;

Stage I: patients with No Significant Obstruction and No Bothersome symptoms

Stage II: patients with No Significant Obstruction but has Bothersome symptoms

(Defined as QOL 3)

Stage III: patients with Significant Obstruction defined as persistent PVR>100mL

or MVV (maximum voided volume) less than 100mL, irrespective of symptoms.

Patients may have more irritative symptoms because of inability to store, or no

bothersome symptoms in spite of large residue urine which would lead to chronic

retention of Urine and UTI.

Stage IV: patients with acute retention of urine, chronic retention, bladder stones,

recurrent UTI and hematuria.

As in malignant disease, further management of clinical BPH would be

according to the grade and stage of the disease.

Stage I ,Grade 1 can generally be watch, Stage III, grade3 would need more

aggressive treatment with pharmacotherapy such as combined α blocker with

5α-reductase inhibitors, or option for surgery, depending on the patients general

well-being, age and preferences. Stage IV high grade prostate would need

surgery. Generally there is good concordance between the grade and stage, but

if there is discordance with high stage low grade prostate as seen in about 16%

(7/44) of our patients then further more invasive investigations with urodynamic

studies and or flexible cystoscopy are indicated.

With this classification, of 406 patients 59% of patients can be watched, 32%

treated with pharmacotherapy and 9% had surgery at initial evaluation [41]. In an

Asian study by MK Li, of 892 patients, 17% were watch, 72.8% had

pharmacotherapy and 10.2% had surgery [42].

Conclusion

With better understanding of the pathophysiology of clinical BPH, patients can

be diagnosed clinically with non-invasive ultrasound and classified according to

grade and stage. The grade predicts the obstruction and progression, while the

stage guide the treatment. This staging system for BPH disease severity is

proposed in the initial UAA Guideline, but is not widely accepted, nor

recommended in the Guidelines of EAU, or AUA, or JUA, yet.

The final choice would take into account patients age, co-morbidity and his

preferences. Treating the patients as a whole would lead to a more balanced

and cost effective management and this is especially so in our Asian region.

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Incidence rates and risk factors for acute urinary retention: the health

professionals followup study. J. Urol. 1999; 162: 376–82.

22. Lee LS, Sim HG, Lim KB, Wang D, Foo KT. Intravesical prostatic protrusion

predicts clinical progression of benign prostatic enlargement in patients on

nonsurgical treatment. Int. J. Urol. 2010; 17: 69–74.

23. Lieber MM, Jacobsen DJ, McGree ME, St Sauver JL, Girman CJ, Jacobsen

SJ. Intravesical prostatic protrusion in men in Olmsted Country, Minnesota.

J. Urol. 2009; 182: 2819–24.

24. Haylen BT, Yang V, Logan V, Husselbee S, Law M, Zhou J. Deos the

presenting bladder volume at urodynamics have any diagnostic relevance?

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25. Abrams P, Bruskewit R, De la Rossette JJ. The diagnosis of bladder outlet

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26. Henry Ho et al: IPP and patient with good flow: Eur. Urol. 2007; Suppl 6

abstract.

27. May M, Brookman-Amissah S, Hoschke B, Gilfrich C, Braun KP, Kendel F.

Post-void residual urine as a predictor of urinary tract infection—is there a

cutoff value in asymptomatic men? J. Urol. 2009; 181: 2540–4.

28. Truzzi JC, Almeida FM, Nunes EC, Sadi MV. Residual urinary volume and

urinary tract infection—when are they linked? J. Urol. 2008; 180: 182–5.

29. Kolman C, Girman CJ, Jacobsen SJ, Lieber MM. Distribution of post-void

residual urine volume in randomly selected men. J. Urol. 1999; 161: 122–7.

30. McNeill SA, Hargreave TB, Geffriaud-Ricouard C, Santoni J, Roehrborn CG.

Postvoid residual urine in patients with lower urinary tract symptoms

suggestive of benign prostatic hyperplasia: pooled analysis of eleven

controlled studies with alfuzosin. Urology 2001; 57: 459–65.

31. Emberton M: Definition of at-risk patients: dynamic variables: BJU Int. 2006;

97 (Suppl 2): 12–5; discussion 21–2.

32. George NJ, O'Reilly PH, Barnard RA, Blacklock NJ. High pressure chronic

retention. Br. Med. J. 1983; 286: 1780–83.

33. Sakamoto K, Blaivas JG. Adult onset nocturnal enuresis. J. Urol. 2001; 165:

1914–7.

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35. Sirls LT, Kirkemo AK, Jay J. Lack of correlation of the American Urological

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37. Wadie BS, Ibrahim EH, De la Rosette JJ, Gomha MA, Ghoneim MA. The

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38. Rosier PFWM, De Wildt MJAM, Wijkstra H, Debruyne FMJ, De la Rosette

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39. Hald T. Urodynamics in benign prostatic hyperplasia. A Survey. Prostate

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40. Foo KT. Current assessment and proposed staging of patients with benign

prostatic hyperplasia. Ann. Acad. Med. Singapore 1995: 24: 648–51.

41. Wang D, Foo KT. Staging of benign prostatic hyperplasia is helpful in

patients with lower urinary tract symptoms suggestive of benign prostatic

hyperplasia. Ann. Acad. Med. Singapore 2010; 39: 798–802.

42. Li MK, Lester G, Nelson P. An Asian multinational prospective observational

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comorbidities, lower urinary tract symptoms and sexual function. BJU Int.

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8. Complications of BPH


Masaki Yoshida, M.D., Ph.D., Koji Yoshimura, M.D., Ph.D., and

Momokazu Gotoh, M.D., Ph.D.

Many of the complications of progressive BPH are rare, and much of the

knowledge comes from studies of men presenting with such complications for

treatment (i.e., cases) rather than observing cohorts of men for the development

of complications. Severe symptoms, urinary retention, gross hematuria,

recurrent urinary tract infections, bladder calculi, and hydronephrosis or renal

insufficiency warrant transurethral incision, resection, vaporization, or open

prostatectomy (for very large neoplasms).

8.1 Mortality

Levi et al. have considered trends in mortality from BPH over the last decades in

Europe and, for comparative purposes, the USA and Japan. Between the early

1950s and the late 1990s, overall mortality from BPH in the European Union

(EU) fell from 5.9 to 3.5 per million, and the decline since the late 1950s was

over 96%. Comparable falls were observed in the USA and Japan, and BPH

mortality rates in the late 1990s were lower than in the EU (1.8/106 in the USA,

1.4 in Japan) [1, 2]. In the 1950s, death rates from BPH in the few Asian

countries that provided data were low on a worldwide scale (3-6/100 000 in

Hong Kong, 1-2 in Japan, and 1-7 in Singapore). Substantial reductions were

observed nonetheless over the last few decades, and rates in the late 1980s or

early 1990s were around 0-2/100 000 in these countries (three of the lowest

rates in the world). The reductions were observed in various age groups, but

were larger at younger ages [2, 3]. If the mortality rates from 1950 were applied

to 1990, 13,681 fewer deaths occurred in the United States alone than expected,

a major but unheralded health care achievement. The most probable

interpretation of these trends is that therapeutic improvements–including more

widespread and timely surgery, introduction of less invasive techniques, such as

transurethral prostatectomy, and possibly the development of medical

treatments–have had a favorable and substantial impact on BPH mortality.

There are, however, areas of the world, including several countries of Western

Europe and South America, where rates are still very high [4].

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8.2 Acute Urinary Retention

Acute urinary retention (AUR) is, for several reasons, one of the most significant

complications or long-term outcomes resulting from BPH.

The epidemiology of AUR is better understood in recent years and it has even

been demonstrated from randomized trials that, probably, a portion of AURs can

be prevented [5]. An AUR can occur spontaneously (that is without any external

triggering event) or can be provoked by triggers like general or regional

anesthesia, non-prostate-related surgery, transurethral instrumentation, certain

medications that have an effect on lower urinary tract function, excessive fluid

(particularly alcohol) intake and sexual activity. In older studies of the occurrence

of AUR the range of the incidence rates has varied widely between 4 and 130

per 1000 person-years [6]. In more recent studies, rates range from about 2 to

18 per 1000 person-years. It has in the past represented an immediate indication

for surgery. For this reason alone, AUR is both from an economic viewpoint as

well as from the viewpoint of the patient, an important and feared event, but, the

etiology of AUR is poorly understood. From a clinical and prognostic point of

view, spontaneous AUR should be separated from precipitated AUR, latter of

which refers to the inability to urinate after a triggering event such as non–

prostate-related surgery, catheterization, anesthesia, ingestion of medications

with sympathomimetic or anticholinergic effects or antihistamines, or others. All

other AUR episodes are classified as spontaneous [7]. The importance of

differentiating the two types of AUR becomes clear when evaluating the ultimate

outcomes of patients. After spontaneous AUR, 15% of patients had another

episode of spontaneous AUR and a total of 75% underwent surgery, whereas

after precipitated AUR only 9% had an episode of spontaneous AUR, and 26%

underwent surgery [7]. Since 49% of AUR cases amongst the LUTS/BPH

patients presented with AUR as the first symptom, i.e. without previous contacts

with a health care provider, it is clear that earlier patient identification is needed if

we aim to reduce the incidence of AUR by means of pharmacological treatment

[8]. Presently this type of risk assessment is only possible in men who have seen

a health care provider for an assessment.

8.3 Bladder Stones

The mechanism for bladder stone formation with BPH may the congestion of

urine (post-void residual urine). In a large autopsy study the prevalence of

bladder stones was 8 times higher in men with a histologic diagnosis of BPH

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(3.4%) compared with controls (0.4%) but no increased incidence of ureteral or

kidney stones were found [9]. Recurrence rate of stones after removal without

BPH surgery has been reported as 17.4% [10].

In a study comparing watchful waiting and TURP in men with moderate

symptoms, only 1 of 276 patients assigned to watchful waiting developed a

bladder stone in 3 years of follow-up [11]. The self-reported rate of a bladder

stone in a cross-sectional study in 2002 Spanish men was 0.7% [12] In clinical

practice the risk of bladder stone development is small and screening only

indicated if clinical circumstances warrant it (e.g., hematuria, stuttering of

urination).

8.4 Recurrent Urinary Tract Infections

The mechanisms of recurrent UTI in BPH are believed to be increased post-void

urine volume, and in case of urinary retention, urethral catheterization, however,

clear evidence is lacking. As the previous statement, surgical treatment is

generally reserved for those patients [13]. In older surgical series UTIs constitute

the main indication for surgical intervention in about 12% [14, 15]. The incidence

of UTIs in the placebo-treated patients was only 0.1/100 patient-years in the

MTOPs study [16].

8.5 Decompensated bladder

Irreversible loss of bladder (voiding) function sometimes occur in BPH patients.

However, when the process starts, whether it really is related to BPH and

obstruction, and when an intervention is necessary to prevent decompensating

with resultant inability to void is unclear. Decompensated bladder, or impaired

detrusor contractility may also occur as normal consequence of aging [17].

The critical question is whether delayed intervention might lead to progressive

irreversible loss of bladder function and misses a window for cure. There is no

direct evidence for this from longitudinal population or clinic patient studies.

However, one report with randomized comparison between initial TURP and

delayed TURP with initial conservative treatment showed that the conservative

arm to TURP later in the trial had not as significant an improvement in symptoms

and flow rate compared with those who underwent TURP at the beginning after

randomization [18].

8.6 Upper Urinary Tract Deterioration and Azotemia

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In general, the incidence of end stage renal failure in patients with BPH is rare

(lower than 1%), however, several guidelines recommend measurement of

serum creatinine as an initial evaluation [19]. BPH patients with renal impairment

often are complicated with DM or hypertension [20]. The Agency for Health Care

Policy and Research BPH guidelines reported a mean of 13.6% (range 0.3% to

30%) of patients presenting for TURP with evidence of renal failure based on

predominantly older studies. In the large database of patients who had upper

tract imaging before surgery, 7.6% of 6102 patients in 25 series had evidence of

hydronephrosis, of whom one third had renal insufficiency [21].

8.7 Hematuria

In BPH patients who have been indicated to surgery, 12 % showed macroscopic

hematuria [22]. It has always been recognized that patients with BPH might

develop gross hematuria and form clots with no other cause being identifiable.

One of the reasons may be upregulation of vascular endothelial growth factor

(VEGF) and increase in the density of microvessel density [23–25].

Precise population estimates and incidence rates are not available, and the

clinical management is dictated by the circumstances.

References

1. Washecka R, Rumancik, WM. Prostatic abscess evaluated by serial

computed tomography. Urol. Radiol. 1985; 7: 54–6.

2. Boyle P, Maisonneuve P, Steg A. Decrease in mortality from benign prostatic

hyperplasia: a major unheralded health triumph. J. Urol.1996; 155: 176–80.

3. Levi F, Lucchini F, Negri E, Boyle P, La Vecchia C. Recent trends in mortality

from benign prostatic hyperplasia. Prostate 2003; 56: 207–11.

4. La Vecchia C, Levi F, Lucchini F. Mortality from benign prostatic hyperplasia:

worldwide trends 1950-92. J. Epidemiol. Community Health 1995; 49: 379–

84.

5. Blanker MH, Groeneveld FP, Prins A, Bernsen RM, Bohnen AM, Bosch JL.

Strong effects of definition and nonresponse bias on prevalence rates of

clinical benign prostatic hyperplasia: the Krimpen study of male urogenital

tract problems and general health status. BJU Int. 2000; 85: 665–71.

6. Jacobsen S, Jacobson D, Girman C et al. Natural history of prostatism: risk

factors for acute urinary retention. J. Urol. 1997; 158: 481–7.

7. Roehrborn CG, Bruskewitz R, Nickel GC et al. Urinary retention in patients

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with BPH treated with finasteride or placebo over 4 years: characterization of

patients and ultimate outcomes. The PLESS Study Group. Eur. Urol. 2000;

37: 528–36.

8. Verhamme KM, Bosch RJ, Sturkenboom MC. Finasteride in benign prostatic

hyperplasia. N. Engl. J. Med. 2004; 350: 1359-1361; author reply 1359–61.

9. Grosse H. Frequency, localization and associated disorders in urinary

calculi: analysis of 1671 autopsies in urolithiasis. Z. Urol. Nephrol. 1990; 83:

469–74.

10. O’Connor RC, Laven BA, Bales GT, Gerber GS. Nonsurgical management of

benign prostatic hyperplasia in men with bladder calculi. Urology 2002; 60:

288–91.

11. Wasson JH, Reda DJ, Bruskewitz RC, Elinson J, Keller AM Henderson WG.

A comparison of transurethral surgery with watchful waiting for moderate

symptoms of benign prostatic hyperplasia. N. Engl. J. Med. 1995; 332: 75–9.

12. Hunter DJ, Berra-Unamuno A, Martin-Gordo A. Prevalence of urinary

symptoms and other urological conditions in Spanish men 50 years old or

older. J. Urol. 1996; 155: 1965–70.

13. Gerber GS. Benign prostatic hyperplasia in older men. Clin. Geriatr. Med.

1998; 14: 317–31.

14. Holtgrewe HL, Mebust WK, Dowd JB, Cockett AT, Peters PC, Proctor C.

Transurethral prostatectomy: practice aspects of the dominant operation in

American urology. J. Urol. 1989; 141: 248–53.

15. Mebust WK, Holtgrewe HL, Cockett AT, Peters PC. Transurethral

prostatectomy: immediate and postoperative complications: a cooperative

study of 13 participating institutions evaluating 3,885 patients. J. Urol. 1989;

141: 243–7.

16. McConnell JD, Roehrborn CG, Bautista OM et al. The long-term effects of

doxazosin, finasteride and the combination on the clinical progression of

benign prostatic hyperplasia. N. Engl. J. Med. 2003; 349: 2385–96.

17. Lepor H, Sunaryadi I, H, Sunaryadi I, Hartanto V, Shapiro E. Quantitative

morphometry of the adult human bladder. J. Urol. 1992; 148: 414–7.

18. Flanigan RC, Reda DJ, Wasson JH, Anderson RJ, Abdellatif M, Bruskewitz

RC. 5-Year outcome of surgical resection and watchful waiting for men with

moderately symptomatic benign prostatic hyperplasia: a Department of

Veterans Affairs cooperative study. J. Urol. 1998; 160: 12–6. discussion 16–

7.

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19. Homma Y, Gotoh M, Yokoyama O et al. Outline of JUA clinical guidelines for

benign prostatic hyperplasia. Int. J. Urol. 2011; 18: 741–56.

20. Gerber GS, Goldfischer ER, Karrison TG, Bales GT. Serum creatinine

measurements in men with lower urinary tract symptoms secondary to

benign prostatic hyperplasia. Urology 1997; 49: 697–702.

21. McConnell JD, Barry MJ, Bruskewitz RC. Benign prostatic hyperplasia:

diagnosis and treatment. Clinical practice guideline no. 8. Rockville, MD, U.S.

Department of Health and Human Services, Agency for Health Care Policy

and Research, Public Health Service, 1994. p. 1–17.

22. Mebust WK, Holtgrewe HL, Cockett AT, Peters PC. Transurethral

prostatectomy: immediate and postoperative complications. A 41.

cooperative study of 13 participating institutions evaluating 3885 patients. J.

Urol. 1989; 141: 243–7.

23. Foley SJ, Bailey DM. Microvessel disease in prostatic hyperplasia. BJU Int.

2000; 85: 70–3.

24. Pareek G, Shevchuk M, Armenakas NA et al. The effect of finasteride on the

expression of vascular endothelial growth factor and microvessel density: a

possible mechanism for decreased prostatic bleeding in treated patients. J.

Urol. 2003; 169: 20–3.

25. DiPaola RS, Kumar P, Hait WN, Weiss RE. State-of-the-art prostate cancer

treatment and research. a report from the Cancer Institute of New Jersey. N.

Engl. J. Med. 2001; 98: 23–33.

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9. Diagnosis & Investigation for BPH/Male LUTS

Rohan Malek, M.D., and Selvalingam Sothilingam, M.D.

Diagnosis of LUTS due to BPH should be considered in males above the age of

45 years presenting with lower urinary symptoms especially in the presence of

demonstrable enlargement of the prostate (BPE). Patients with lower urinary

tract symptoms suggestive of BPH seek medical advice because they are

bothered by their urinary symptoms [1, 2]. Patients may also present with

bladder outlet obstruction (BOO) at the first presentation. In Asia where

symptomatic patients may present late in the course of their disease, many of

them may present with complications from BPH such as hematuria, urinary tract

infection, urinary stones, renal failure and acute or chronic urinary retention.

Difficulties in translation of BPH guidelines into clinical practice are related to

lack of knowledge, differences in routine practices, beliefs, cost, availability and

reimbursement policies [3, 4]. Therefore the diagnosis and investigation of BPH

in Asia should take into account the wide variability of the socio economic

situation and the differing medical practices in Asian countries. It is

understandable that not all patients with LUTS would have access to urologists

or to centers with urological facilities, therefore these guidelines have been

formulated taking into account the minimum investigations that should be done

even at the level of the primary healthcare provider or general practitioner. There

are significant differences in the practice patterns between primary care

physicians and urologist in the evaluation of BPH [5].

9.1 Conditions not suitable for general physicians

It is recommended that patients seen by primary care physicians should be

referred to the urologist in the presence of the following: (Level IV evidence,

Grade C recommendation) [3, 6].

9.1.1 Urinary Retention

9.1.2 Palpable bladder

9.1.3 Urinary Incontinence

9.1.4 Hematuria

9.1.5 Proven urinary tract infection

9.1.6 Persistent bothersomeness

9.1.7 Bladder Stones

9.1.8 Hard Prostate

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9.1.9 PSA> 4 ng/mL(> 2 ng/mL , pts on 5ARI [7])

We propose that for Asia, investigations should be categorized as

9.2 Highly recommended (All Medical Practitioners)

9.3 Recommended in special settings (Urologist, Urological Centers)

9.4 Optional

All tests included in the highly recommended category are also recommended

by AUA, EUA, BAUS, 5th International Consultation on BPH, Australian NHMRC

and JUA [8–13].

9.2 Highly Recommended Tests

9.2.1 Medical history should be thorough taking into account duration,

severity of lower urinary tract symptoms and mandatory to include history of

incontinence and hematuria [14]. History should also take into consideration

patients’ general condition including neurologic and, psychiatric disorders,

diabetes mellitus and cardiac diseases. History of bowel habit is relevant and so

is patient’s mobility and social support. Important drug history should include use

of diuretics, antiplatelet /anticoagulants and antihypertensives. Previous urinary

tract intervention or urethral trauma should also be questioned. Family history is

equally important especially of prostate disease or prostate cancer. Patients

should also be questioned on erectile dysfunction.

9.2.2 Physical Examination includes general examination including

assessment of blood pressure and must include digital rectal examination [15],

neurological examination especially of the lower extremities and anal sphincter

tone. The digital rectal examination should comment on estimated prostate

volume, prostate surface and consistency. Lower abdominal examination to look

for palpable bladder should also be performed. Examination of genitalia is

equally important.

9.2.3 Symptoms Scores would be useful and the International Prostate

Symptom Score (IPSS) is most commonly used [14]. However it should be

validated according to the spoken and written language(s) of the respective

Asian countries. Using the IPSS symptom score, patients can be categorized as

having predominant voiding, storage or post micturition symptoms [16]. This can

guide in choosing therapeutic options and in follow up of patients after treatment.

QOL symptom score is useful to assess the bothersomeness of the LUTS. In

patients with significant storage symptoms, additional symptoms scores such as

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the OAB symptom score (OABSS) may be useful [12].

9.2.4 Urinalysis is recommended [17] to detect microscopic hematuria and

pyuria to exclude other urological conditions that can cause LUTS such as

urinary infection, urological malignancies and urinary stones [18].

9.2.5 Serum Creatinine, although not recommended in AUA, is

recommended here as initial assessment. In the context of the high incidence of

diabetes mellitus and stone disease in Asia, the rate of silent renal insufficiency

is expected to be high. This is more so in countries where access to medical

facilities is not readily available.

9.2.6 PSA is recommended in patients with more than 10 years life

expectancy or in patients in whom PSA will make a difference in management of

the prostate disease [4, 13]. Patients should be counseled adequately prior to

performing the PSA test. A baseline PSA would be useful in predicting patient’s

10 or 15 year risk of prostate cancer based on evidence from current literature.

There is evidently a relationship between PSA and prostate volume [19, 20].

Therefore PSA can also be used as a guide on identifying patients at risk for

BPH progression [21, 15].

9.2.7 Bladder diary is recommended in patients with predominantly storage

symptoms and in patients where nocturia appears to be most bothersome [22,

23], to exclude nocturnal polyuria.

9.3 Recommended in Special Settings

9.3.1 Uroflowmetry, where facilities are available can be done to assess

Qmax where a Qmax <10 mL/s may indicate a stronger need for surgical

intervention [24]. At least two readings would be preferable and the voided

volume should be more than 150 mL [25]. Furthermore a flat pattern on

uroflowmetry may alert the physician on the possibility of urethral stricture

disease.

9.3.2 Post Void Residual (PVR) urine is recommended after having done a

uroflowmetry. Although there is intra individual variations in the values and

problems in reproducibility, a high PVR may indicate bladder dysfunction and

poorer response to medical therapy [26] although there is no consensus on the

cutoff point [27].

9.3.3 Prostate Ultrasound either transabdominal or transrectal, is

recommended where facilities are available, in symptomatic patients to assess

prostate size and presence of Intravesical Prostatic Protrusion (IPP) to help

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decide on the most appropriate management for the patient [28, 29]. Patients

with IPP Grade 3 would be suitable candidates for surgical intervention [29].

It may also be useful to assess very large prostates when considering open

prostatectomy.

9.4 Optional

9.4.1 Upper Tract Imaging is recommended when there is microscopic or

macroscopic hematuria, renal insufficiency, in patients with chronic retention or

in patients with stone disease [18]. KUB X ray may routinely be done in countries

where stone disease is endemic.

9.4.2 Urodynamics can be performed for specific indication, i.e. in the very

young (< 50yrs) or old (> 80 yrs.) patients with LUTS [18], symptomatic patients

with Qmax >15 mL/s, patients with large PVR with no significant IPP, patients

suspected of having neurogenic bladder or after radical pelvic surgery and in

patients who have had surgery for BPH but are still symptomatic.

9.4.3 Transrectal Ultrasound biopsy of prostate is recommended for

indicated patients with PSA> 4ng/ml and or in those with suspicious DRE

findings where prostate cancer is suspected.

9.4.4. Cystoscopy is recommended in patients with hematuria, suspected

urethral stricture, before surgery, in patients who had prior lower tract surgery or

in BPH patients not responding to medical treatment [18].

Urine cytology is recommended in patients with hematuria or in BPH patients

not responding to medical treatment.

9.4.5 Retrograde Cystourethrography may be done in patients with history

and uroflow assessment suggestive of urethral stricture to provide further

information on length and site of urethral stricture.

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benign prostatic hyperplasia. J. Urol. 2006; 175: 196–9.

21. Rosette JDL. Optimising assessment and treatment decisions for men with

BPH. Eur. Urol. 2006; Suppl 5: 710–5.

22. Van Venrooij GE, Van Melick HH, Eckhardt MD, Boon TA. Diagnostic and

predictive value of voiding diary data versus prostate volume, maximal free

urinary flow rate, and Abrams-Griffiths number in men with lower urinary

tract symptoms suggestive of benign prostatic hyperplasia. Urology 2008;

71: 469–74.

23. Batista JE, Berges R, Kastler EC et al. Future directions in evaluating

nocturia and its impact in patients with LUTS/BPH. Eur. Urol. 2006; Suppl

5: 19–21.

24. Belal M, Abrams P. Noninvasive methods of diagnosing bladder outlet

obstruction in men. part 2: noninvasive urodynamics. J. Urol. 2006; 176:

29–35.

25. Van de Beek C, Stoevelaar HJ, McDonnell J, Nijs HG, Casparie AF,

Janknegt RA. Interpretation of uroflowmetry curves by urologists. J. Urol.

1997; 157: 164–8.

26. Speakman MJ. Integrating patient risk profiles in the treatment of lower

urinary tract symptoms suggestive of benign prostatic hyperplasia

(LUTS/BPH) in clinical practice. Eur. Urol. 2004; Suppl 3 (issue 4): 18–22.

27. Mochtar CA, Kiemeney LALM, Riemsdijk MMV, Laguna MP, Debruyne FM,

De la Rosette JJ. Post-void residual urine volume is not a good predictor of

the need for invasive therapy among patients with benign prostatic

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hyperplasia. J. Urol. 2006; 175: 213–6.

28. Mariappan P, Brown DJG, McNeill AS. Intravesical prostatic protrusion is

better than prostate volume in predicting the outcome of trial without

catheter in white men presenting with acute urinary retention: a prospective

clinical study. J. Urol. 2007; 178: 573–7.

29. Tan YH, Foo KT. Intravesical prostatic protrusion predicts the outcome of a

trial without catheter following acute urinary retention. J. Urol. 2003; 170:

2339–41.

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10. Recommended grade for treatment: Pharmacotherapy and

Conservative Management

Kyu-Sung Lee, M.D., Joon Chul Kim, M.D.

10.1 Pharmacotherapy

The recommendations of this guideline are based on a structured literature

search using articles in English language published in the PubMed/Medline

databases, published between 1966 through Dec 31st, 2011. Databases

between 1966 and 1st January 2010, is based on EAU database

(http://www.uroweb.org/gls/pdf/12_Male_LUTS_LR%20May%209th%202012.

pdf).

Drugs used for the treatment of various forms of male LUTS are listed in Table 1.

The level of evidence and the grade of recommendation (according to the

current classification) for the each drug treatment are summarized in Table 2.

Table 1. Key pharmacokinetic properties and standard doses of drugs in Asia

for the treatment of male LUTS.

α1 adrenoceptor antagonists (for treating symptoms of BPH)

Drug tmax

(hours)

t½

(hours)

Recommended daily dose

Alfuzosin IR 1.5 4–6 3 x 2.5 mg

Alfuzosin SR 3 8 2 x 5 mg

Alfuzosin XL 9 11 1 x 10 mg

Doxazosin IR 2–3 20 1 x 2–8 mg

Doxazosin GITS 8–12 20 1 x 4–8 mg

Naftopidil 2.2 13.2 1 x 25–75 mg

Silodosin 2.5 11–18 2 x 4mg, 1 x 8 mg

Tamsulosin MR 6 10–13 1 x 0.2–0.4 mg

Tamsulosin OCAS 4–6 14–15 1 x 0.4 mg (1x0.2mg in Japan)

Terazosin 1–2 8–14 1x 2, 5, 10 mg

5α-reductase inhibitors (for treating benign prostatic enlargement due to BPH)

Dutasteride 1–3 3–5 weeks 1 x 0.5mg

Finasteride 2 6–8 hours 1 x 5 mg

Anticholinergic drugs (for treating overactive bladder/storage symptoms)

Drug tmax

(hours)

t½

(hours)

Recommended daily dose

http://www.uroweb.org/gls/pdf/12_Male_LUTS_LR%20May%209th%202012.%20pdf

http://www.uroweb.org/gls/pdf/12_Male_LUTS_LR%20May%209th%202012.%20pdf

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Darifenacin ERa 7 12 1 x 7.5–15 mg

Fesoterodinea,b 5 7 1 x 4–8 mg

Oxybutynin IR 1 2-5 2-3 x 5 mg

Oxybutynin ER 4–6 13 1 x 5–30 mg

Propiverine IR 2 14–22 1–2 x 10–20 mg

Propiverine ER 10 20 1 x 30 mg

Solifenacin 3–8 45–68 1 x 5–10 mg

Imidafenacin 1.5 2.9 2 x 0.1-0.2 mg

Tolterodine IRa 1–2 2 2 x 2 mg

Tolterodine ERa 4 7–10 1 x 4 mg

Trospium IR 5 18 2 x 20 mg

Trospium ER 5 36 1 x 60 mg

PDE5 inhibitors (for treating male LUTS ± erectile dysfunction)

Sildenafil

1*

(0.5–2)

3–5 1 x 25–100 mg

Tadalafil 2

(0.5–12)

17.5 1 x 2.5–20 mg

Vardenafil 1*

(0.5–2)

4–5 2 x 10 mg

Udenafil 0.8–1.3 7.3–12 1 x 100 mg

Mirodenafil 1.3 2.5 1 x 50 mg

Botulinum toxin(for treating symptoms of BPH)

BotoxTM Not detected Not detected 100–300 U

DysportTM Not detected Not detected 300–600 U

Antidiuretics (for treating nocturia due to nocturnal polyuria

Desmopressin 1–2 3 1 x 0.1 – 0.4 mg orally before

sleeping

Table 2. Level of Evidence (LE) and Grade of Recommendation (GR) of drug

treatments of male LUTS

Drug treatment LE GR

1. α1 blockers should be offered to men with moderate-to-severe lower

urinary tract symptoms.

1 A

Long-term treatment with α1 blockers for BPH patients is effective bot 1 A

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h subjectively and objectively.

2. 5α-reductase inhibitors are appropriate and effective treatment

alternatives for men with LUTS secondary to BPH who have

demonstrable prostate enlargement. 5α-reductase inhibitors can

prevent disease progression with regard to acute urinary retention and

need for surgery. The treatment is not recommended for short-term

therapy (<1 year).

1 A

Long-term treatment with 5α-reductase inhibitors is effective and well

tolerated.

2 B

3 Anticholinergics might be considered in men with moderate to severe

lower urinary tract symptoms who have predominantly bladder

storage symptoms with or without α1 blockers.

1 B

Caution is advised in men with increased postvoid residual urine

volume.

4 C

4. PDE5 inhibitors reduce moderate to severe male lower urinary tract

symptoms.

1

A

5. Desmopressin can be used for the treatment of nocturia secondary to

nocturnal polyuria. Caution is advised in old men with hyponatremia

and impaired renal function. Serum sodium concentration level should

be monitored periodically.

1 A

6 Plant extracts reduce moderate to severe male lower urinary tract

symptoms. Although plant extracts agents show some promise for

symptom relief, their use remains controversial due to the lack of

established mechanisms of action, efficacy, and safety. Clinical trials

are often flawed, as most studies of small scale and short duration

are; they are not blinded or controlled, and most have no placebo

group.

3 C2

7 Combination treatment with α1 blocker together with 5α-reductase

inhibitor should be offered to men with moderate-to-severe lower

urinary tract symptoms, enlarged prostates (≥30 mL or ≥40 mL), and

reduced Qmax (men likely to develop disease progression).

Combination treatment is not recommended for short-term therapy

(<1 year).

1 A

8. Combination treatment with α1 blocker and anticholinergic might be 1 B

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considered in patients with moderate to severe lower urinary tract

symptoms if symptom relief has been insufficient with the

monotherapy of either drug.

Combination treatment should cautiously be prescribed in men who

are suspicious of having bladder outlet obstruction with increased

postvoid residual urine volume.

2 B

9 The combination of α1 blocker and PDE 5 inhibitor is well tolerated

and effective in improving lower urinary tract symptoms. However

caution is advised in men with hypotention.

2 A

10. Intra-prostatic botulinum toxin injections for lower urinary tract

symptoms due to benign prostatic obstruction or urinary retention are

still experimental. Intra-prostatic botulinum toxin injections should be

performed only in clinical trials.

3 C

10.1.1 α1 adrenergic receptor antagonists (α1 blocker）

Alpha1-blockers produce a significant symptom improvement compared to

placebo, which the average patient will appreciate as a moderate improvement

from baseline [1-4]. The minor differences in efficacy noted between

the different α1 blockers are not statistically (when tested) or clinically significant

[5]. Prostate size does not affect α1 blocker efficacy but patients with smaller

prostates (<40 mL) seem to have better efficacy compared to those with larger

glands [6]. α1 blockers do not reduce prostate size and do not prevent acute

urinary retention, so that eventually some patients will have to be surgically

treated [7]. Nevertheless, the efficacy of α1 blockers appears to be

maintained over at least4 years [8]. The most frequent side-effects of

α1 blockers are asthenia, dizziness and (orthostatic) hypotension [9].

Although a reduction in blood pressure may benefit hypertensive patients,

at least some of the observed asthenia and dizziness can be attributed to a

decrease in blood pressure [10,11].

A systematic review concluded that α1 blockers do not adversely affect libido,

have a small beneficial effect on erectile function, but sometimes cause

abnormal ejaculation [12].

Originally, the abnormal ejaculation was thought to be retrograde, but more

recent data demonstrate that it is due to emission failure [13-20].

Although abnormal ejaculation has been observed more frequently with

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tamsulosin [21-25], the apparently greater risk for abnormal ejaculation with

tamsulosin is intriguing as even more α1A-selective drugs, silodosin, carry a

greater risk [26-28].

References

1. Michel MC, Vrydag W. α1-,α2- and β-adrenoceptors in the urinary bladder,

urethra and prostate. Br. J. Pharmacol. 2006; 147 (Suppl 2): S88–S119.

2. Kortmann BBM, Floratos DL, Kiemeney LA, Wijkstra H, De la Rosette JJ.

Urodynamic effects of alpha-adrenoceptor blockers: a review of clinical trials.

Urology 2003; 62:1–9.

3. Barendrecht MM, Abrams P, Schumacher H, De la Rosette JJ, Michel MC.

Do α1-adrenoceptor antagonists improve lower urinary tract symptoms by

reducing bladder outlet resistance? Neurourol. Urodyn. 2008; 27: 226–30.

4. Djavan B, Chapple C, Milani S, Marberger M. State of the art on the efficacy

and tolerability of alpha1-adrenoceptor antagonists in patients with lower

urinary tract symptoms suggestive of benign prostatic hyperplasia. Urology

2004; 64:1081–8.

5. Nickel JC, Sander S, Moon TD. A meta-analysis of the vascular-related

safety profile and efficacy of α-adrenergic blockers for symptoms related to

benign prostatic hyperplasia. Int. J. Clin. Pract. 2008; 62: 1547–59.

6. Michel MC, Mehlburger L, Bressel HU, Goepel M. Comparison of tamsulosin

efficacy in subgroups of patients with lower urinary tract symptoms. Prostate

Cancer Prostatic. Dis. 1998; 1: 332–5.

7. Roehrborn CG. Three months’ treatment with the α1-blocker alfuzosin does

not affect total or transition zone volume of the prostate. Prostate Cancer

Prostatic. Dis. 2006; 9: 121–5.

8. McConnell JD, Roehrborn CG, Bautista O et al. The long-term effect of



9. Barendrecht MM, Koopmans RP, De la Rosette JJ, Michel MC. Treatment for

lower urinary tract symptoms suggestive of benign prostatic hyperplasia: the

cardiovascular system. BJU Int. 2005; 95 (Suppl 4): 19–28.

10. Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with

tamsulosin. J. Cataract Refract. Surg. 2005; 31: 664–73.

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11. Michel MC, Okutsu H, Noguchi Y et al. In vivo studies on the effects of

α1-adrenoceptor antagonists on pupil diameter and urethral tone in rabbits.

Naunyn-Schmiedeberg’s Arch. Pharmacol. 2006; 372: 346–53.

12. Van Dijk MM, De la Rosette JJ, Michel MC. Effects of α1-adrenoceptor

antagonists on male sexual function. Drugs 2006; 66: 287–301.

13. Brawer MK, Adams G, Epstein H. Terazosin in the treatment of benign

prostatic hyperplasia. Terazosin Benign Prostatic Hyperplasia Study Group.

Arch. Fam. Med. 1993; 2: 929–35.

14. Roehrborn CG, Oesterling JE, Auerbach S et al. The Hytrin Community

Assessment Trial study: a one-year study of terazosin versus placebo in the

treatment of men with symptomatic benign prostatic hyperplasia. HYCAT

Investigator Group. Urology 1996; 47: 159–68.

15. Wilt TJ, Howe RW, Rutks I et al. Terazosin for benign prostatic hyperplasia.

Cochrane Database Syst. Rev. 2002; (4):CD003851.

16. Jardin A, Bensadoun H, Delauche-Cavallier MC, Attali P. Alfuzosin for

treatment of benign prostatic hypertrophy. The BPH-ALF Group. Lancet

1991; 337: 1457–61.

17. Buzelin JM, Roth S, Geffriaud-Ricouard C, Delauche-Cavallier MC. Efficacy

and safety of sustained-release alfuzosin 5 mg in patients with benign

prostatic hyperplasia. ALGEBI Study Group. Eur. Urol. 1997; 31: 190–8.

18. Van Kerrebroeck P, Jardin A, Laval KU, Van Cangh P. Efficacy and safety of

a new prolonged release formulation of alfuzosin 10 mg once daily versus

alfuzosin 2.5 mg thrice daily and placebo in patients with symptomatic

benign prostatic hyperplasia. ALFORTI Study Group. Eur. Urol. 2000; 37:

306–13.

19. 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: 780–8.

20. Kirby RS, Andersen M, Gratzke P, Dahlstrand C, Hoye K. A combined

analysis of double-blind trials of the efficacy and tolerability of

doxazosin-gastrointestinal therapeutic system, doxazosin standard and

placebo in patients with benign prostatic hyperplasia. BJU Int. 2001; 87:

192–200.

21. Chapple CR, Wyndaele JJ, Nordling J, Boeminghaus F, Ypma AF, Abrams P.

Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. A

meta-analysis of two randomised, placebo-controlled, multicenter studies in

- 104 -

patients with benign prostatic obstruction (symptomatic BPH). European

Tamsulosin Study Group. Eur. Urol. 1996; 29: 155–67.

22. Lepor H. Phase III multicenter placebo-controlled study of tamsulosin in

benign prostatic hyperplasia. Tamsulosin Investigator Group. Urology 1998;

51: 892–900.

23. Chapple CR, Al-Shukri SH, Gattegno B et al. Tamsulosin oral controlled

absorption system (OCAS) in patients with lower urinary tract symptoms

suggestive of benign prostatic hyperplasia (LUTS/BPH): efficacy and

tolerability in a placebo and active comparator controlled phase 3a study.

Eur. Urol. 2005; Suppl 4 (issue 2): 33–44.

24. Wilt TJ, MacDonold R, Rutks I. Tamsulosin for benign prostatic hyperplasia.

Cochrane Database Syst. Rev. 2003; (1): CD002081.

25. Gotoh M, Kamihira O, Kinukawa T et al. Comparison of tamsulosin and

naftopidil for efficacy and safety in the treatment of benign prostatic

hyperplasia: a randomized controlled trial. BJU Int. 2005; 96: 581–6.

26. Kawabe K, Yoshida M, Homma Y, Silodosin Clinical Study Group. Silodosin,

a new α1A-adrenoceptor-selective antagonist for treating benign prostatic

hyperplasia: a results of a phase III randomized, placebo-controlled,

double-blind study in Japanese men. BJU Int. 2006; 98: 1019–24.

27. Marks LS, Gittelman MC, Hill LA, Volinn W, Hoel G. Rapid efficacy of the

highly selective alpha1A-adrenoceptor antagonist silodosin in men with

signs and symptoms of benign prostatic hyperplasia: pooled results of 2

phase 3 studies. J. Urol. 2009; 181: 2634–40.

28. Chapple CR, Montorsi F, Tammela TL et al. Silodosin therapy for lower

urinary tract symptoms in men with suspected benign prostatic hyperplasia:

results of an international, randomized, double-blind, placebo- and

active-controlled clinical trial performed in Europe. Eur. Urol. 2011; 59: 342–

52.

10.1.2 5α-reductase inhibitor (5ARI)

5α-reductase inhibitors (Finasteride inhibits type 1 only, Dutasteride inhibits both

type 1 and 2) reduce LUTS (IPSS; moderate to severe) by approximately 15–

30%, decrease prostate volume by approximately 18–28% and increase Qmax

of free uroflowmetry by approximately 1.5–2.0 mL/s in patients with LUTS due to

prostate enlargement [1-8]. 5ARIs, but not α1 blockers, reduce the long-term

- 105 -

(>1 year) risk of acute urinary retention or need for surgery [9-12].

The most relevant adverse effects of 5ARIs are related to sexual function and

include reduced libido, erectile dysfunction and, less frequently, ejaculation

disorders. The incidence of sexual dysfunction and other adverse events is low

and even decreased with trial duration [3].

5ARIs should not be used in men with LUTS secondary to BPH without prostatic

enlargement. Due to the slow onset of action, 5ARIs are only suitable for

long-term treatment (many years) [13-15].

Their effect on the serum PSA concentration needs to be considered for prostate

cancer screening.

Of interest, 5ARIs might reduce blood loss during transurethral prostate surgery,

probably due to their effects on prostatic vascularization [16].

Long-time use of 5ARIs can improve urodynamic parametes [17-18].

References

1. Andriole G, Bruchovsky N, Chung LW et al. Dihydrotestosterone and the

prostate: the scientific rationale for 5α-reductase inhibitors in the treatment

of benign prostatic hyperplasia. J. Urol. 2004; 172: 1399–1403.

2. Rittmaster RS, Norman RW, Thomas LN, Rowden G. Evidence for atrophy

and apoptosis in the prostates of men given finasteride. J. Clin. Endocrinol.

Metab. 1996; 81: 814–819.

3. Naslund MJ, Miner M. A review of the clinical efficacy and safety of

5α-reductase inhibitors for the enlarged prostate. Clin. Ther. 2007; 29: 17–

25.

4. Andersen JT, Ekman P, Wolf H et al. Can finasteride reverse the progress

of benign prostatic hyperplasia? A two-year placebo-controlled study. The

Scandinavian BPH Study Group. Urology 1995; 46: 631–7.

5. Nickel JC, Fradet Y, Boake RC et al. Efficacy and safety of finasteride

therapy for benign prostatic hyperplasia: results of a 2-year randomised

controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy

Canadian Two year Study. CMAJ 1996; 155: 1251–9.

6. Marberger MJ, on behalf of the PROWESS Study Group. Long-term effects

of finasteride in patients with benign prostatic hyperplasia: a double-blind,

placebo-controlled, multicenter study. Urology 1998; 51: 677–86.

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7. Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G l. Efficacy and

safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in

men with benign prostatic hyperplasia. Urology 2002; 60: 434–41.

8. Roehrborn CG, Lukkarinen O, Mark S, Siami P, Ramsdell J, Zinner N.

Long-term sustained improvement in symptoms of benign prostatic

hyperplasia with the dual 5alpha-reductase inhibitor dutasteride: results of

4-year studies. BJU Int. 2005; 96: 572–7.



men with benign prostatic hyperplasia. N. Engl. J. Med.1998; 338: 557–63.


ALTESS, COMBAT, and ALF-ONE. BJU Int. 2008; 101 (Suppl 3): 17–21.

11. McConnell JD, Roehrborn CG, Bautista O et al. Medical Therapy of

Prostatic Symptoms (MTOPS) Research Group. The long-term effect of





symptomatic benign prostatic hyperplasia: 4-year results from the

CombATstudy. Eur. Urol. 2010; 57: 123–31.

13. Boyle P, Gould AL, Roehrborn CG. Prostate volume predicts outcome of

treatment of benign prostatic hyperplasia with finasteride: meta-analysis of

randomised clinical trials. Urology 1996; 48: 398–405.

14. Roehrborn CG, Siami P, Barkin J et al. The influence of baseline

parameters on changes in International Prostate Symptom Score with

dutasteride, tamsulosin, and combination therapy among men with

symptomatic benign prostatic hyperplasia and enlarged prostate: 2-year

data from the CombAT Study. Eur. Urol. 2009; 55: 461–71.

15. Gittelman M, Ramsdell J, Young J, McNicholas T. Dutasteride improves

objective and subjective disease measures in men with benign prostatic

hyperplasia and modest or severe prostate enlargement. J. Urol. 2006;

176: 1045–50.

16. Donohue JF, Sharma H, Abraham R, Natalwala S, Thomas DR, Foster MC.

Transurethral prostate resection and bleeding: a randomised, placebo

controlled trial of the role of finasteride for decreasing operative blood loss.

J. Urol. 2002; 168: 2024–6.

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17. Kirby RS, Vale J, Bryan J, Holmes K, Webb JA. Long-term urodynamic

effects of finasteride in benign prostatic hyperplasia: a pilot study. Eur. Urol.

1993; 24: 20–6.

18. Tammela TLJ, Kontturi MJ. Long-term effects of finasteride on invasive

urodynamics and symptoms in the treatment of patients with bladder

outflow obstruction due to benign prostatic hyperplasia. J. Urol. 1995; 154:

1466–9.

10.1.3 Anticholinergics

Muscarinic freceptor subtypes, especially M3 is the most important for

urinary bladder detrusor function [1-5], and muscarinic receptor antagonists

are valuable treatment modality for overactive bladder [6,7]. For elderly

population, there are higher incidence of adverse evens than younger [8].

Anticholinergics might be considered in men with moderate to severe lower

urinary tract symptoms who have predominantly bladder storage symptoms,

however, potential risk for urinary retention is a concern withoutα1 blockers

[9-16]. Hence, combination treatments or α1 blocker add-on treatments

have been evaluated [17-20]. Especially it may benefit men with lower

PSA levels (smaller prostates) [21].

References

1. Chess-Williams R, Chapple CR, Yamanishi T, Yasuda K, Sellers DJ. The

minor population of M3-receptors mediate contraction of human detrusor

muscle in vitro. J. Auton. Pharmacol. 2001; 21: 243–8.

2. Matsui M, Motomura D, Karasawa H et al. Multiple functional defects in

peripheral autonomic organs in mice lacking muscarinic acetylcholine

receptor gene for the M3 subtype. Proc. Natl. Acad. Sci. USA 2000; 97:

9579–84.

3. Braverman AS, Doumanian LR, Ruggieri MR Sr. M2 and M3 muscarinic

receptor activation of urinary bladder contractile signal transduction. II.

denervated rat bladder. J. Pharmacol. Exp. Ther. 2006; 316: 875–80.

4. Wuest M, Kaden S, Hakenberg OW, Wirth MP, Ravens U. Effect of

rilmakalim on detrusor contraction in the presence and absence of

urothelium. Naunyn-Schiedeberg’s Arch. Pharmacol. 2005; 372: 203–12.

5. Kono M, Nakamura Y, Ishiura Y, Komatsu K, Kotani H, Namiki M. Central

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muscarinic receptor subtypes regulating voiding in rats. J. Urol. 2006; 175:

353–7.

6. Witte LP, Mulder WM, De la Rosette JJ, Michel MC. Muscarinic receptor

antagonists for overactive bladder treatment: does one fit all? Curr. Opin.

Urol. 2009; 19: 13–9.

7. Michel MC. A benefit-risk assessment of extended-release oxybutynin.

Drug Safety 2002; 25: 867–76.

8. Michel MC, Schneider T, Krege S, Goepel M. Does gender or age affect the

efficacy and safety of tolterodine? J. Urol. 2002; 168: 1027–31.


understanding, evaluation, and treatment of lower urinary tract symptoms

in men: focus on the bladder. Eur. Urol. 2006; 49: 651–8.



Urol. 2005; 174: 2273–5.

11. Höfner K, Burkart M, Jacob G, Jonas U. Safety and efficacy of tolertodine

extended release in men with overactive bladder symptoms and presumed

non-obstructive benign prostatic hyperplasia. World J. Urol. 2007; 25: 627–

33.

12. Kaplan SA, Roehrborn CG, Dmochowski R, Rovner ES, Wang JT, Guan Z.

Tolterodine extended release improves overactive bladder symptoms in

men with overactive bladder and nocturia. Urology 2006; 68: 328–32.

13. Dmochowski R, Abrams P, Marschall-Kehrel D, Wang JT, Guan Z. Efficacy

and tolerability of tolterodine extended release in male and female patients

with overactive bladder. Eur. Urol. 2007; 51: 1054–64.

14. Herschorn S, Jones JS, Oelke M, MacDiarmid S, Wang JT, Guan Z.

Efficacy and tolerability of fesoterodine in men with overactive bladder: a

pooled analysis of 2 phase III studies. Urology 2010; 75: 1149–55.

15. 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: 999–1004.

16. 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 incontinence. BJU Int. 2006; 97: 1003–6.

17. Kaplan SA, Roehrborn CG, Chancellor M, Carlsson M, Bavendam T, Guan

Z. Extended-release tolterodine with or without tamsulosin in men with

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lower urinary tract symptoms and overactive bladder: effects on Urinary

symptoms assessed by the International Prostate Symptom Score. BJU Int.

2008; 102: 1133–9.



symptoms and overactive bladder. JAMA 2006; 296: 2319–28.

19. Nishizawa O, Yamaguchi O, Takeda M, Osamu Yokoyama for the TAABO

Study Group: Randomized Controlled Trial to Treat Benign Prostatic

Hyperplasia with Overactive Bladder Using an Alpha-blocker Combined

with Anticholinergics, LUTS 2011; 3:39-40.

20. Yamaguchi O, Kakizaki H, Homma Y, et al. on behalf of the ASSIT Study

Group: Solifenacin as add-on therapy for overactive bladder symptoms-

ASSIST, randomized controlled study – Urology 2011; 78:126-33.




1061–7.

10.1.4 PDE5 inhibitor

Nitric oxide/cyclic GMP pathway is an important functional implication not

only in penile erectile function, but in prostate/bladder neck smooth muscle

function [1-5]. Further study revealed that phosphodiesterase (PDE) isoenz

ymes are present in the lower urinary tract and prostate in human [6, 7].

PDE5 inhibitors may well have a role in therapy for BPH/LUTS, for either of

LUTS or uroflow [8-14]. Among PDE5 inhibotors initially developed for

erectile dysfuntion, tadalafil has been shown to be effective for Male/LUTS

in USA, European countries, and Asia [15-21].

It is likely that PDE5 inhibitor treatment will be of value, especially for men with

LUTS and significant ED [22-24]. Other PDE5 inhibitors have been tried for

Male LUTS/BPH [25].

References

1. Andersson KE, Persson K. Nitric oxide synthase and the lower urinary

tract: possible implications for physiology and pathophysiology. Scand. J.

Urol. Nephrol. 1995; 175 (Suppl): 43-53.

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2. Burnett AL, Maguire MP, Chang TS, Ricker DD, Takeda M, Lepor H

Chamness S: Characterization and localization of nitric oxide synthase in

the human prostate. Urology, 45:435-439 (1995)

3. Takeda M, Tang R, Shapiro E, Burnett, A L, and Lepor H : Effects of nitric

oxide on human and canine prostates. Urology, 45:440-446 (1995)

4. Kedia GT, Ückert S, Jonas U, Kuczyk MA, Burchardt M. The nitric oxide

pathway in the human prostate: clinical implications in men with lower

urinary tract symptoms. World J. Urol. 2008; 26: 603–9.

5. Ückert S, Küthe A, Jonas U, Stief CG. Characterization and functional

relevance of cyclic nucleotide phosphodiesterase isoenzymes of the

human prostate. J. Urol. 2001; 166: 2484–90.

6. Ückert S, Oelke M, Stief CG, Andersson KE, Jonas U, Hedlund P.

Immunohistochemical distribution of cAMP- and cGMP phosphodiesterase

(PDE) isoenzymes in the human prostate. Eur. Urol. 2006; 49: 740–5.

7. Wright PJ. Comparison of phosphodiesterase type 5 (PDE5) inhibitors. Int.

J. Clin. Pract. 2006; 60: 967–75.

8. Sairam K, Kulinskaya E, McNicholas TA , Boustead GB, Hanbury DC.

Sildenafil influences lower urinary tract symptoms. BJU Int. 2002; 90:

836-9.

9. Mulhall JP, Guhring P, Parker M, Hopps C. Assessment of the impact of

sildenafil citrate on lower urinary tract symptoms in men with erectile

dysfunction. J. Sex. Med. 2006; 3: 662–7.

10. 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 randomised, double-blind trial. J. Urol.

2007; 177: 1071–7.

11. Kaplan SA, Gonzalez RR, Te AE. Combination of alfuzosin and sildenafil is

superior to monotherapy in treating lower urinary tract symptoms and

erectile dysfunction. Eur. Urol. 2007; 51: 1717–23.

12. Stief CG, Porst H, Neuser D, Beneke M, Ulbrich R. A randomised,

placebo-controlled study to assess the efficacy of twice-daily vardenafil in

the treatment of lower urinary tract symptoms secondary to benign

prostatic hyperplasia. Eur. Urol. 2008; 53: 1236–44.

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13. Güler C, Tüzel E, Dogantekin E, Kiziltepe G. Does sildenafil affect

uroflowmetry values in men with lower urinary tract symptoms suggestive

of benign prostatic enlargement? Urol. Int. 2008; 80: 181–5.

14. Guven EO, Balbay MD, Mete K, Serefoglu EC. Uroflowmetric assessment

of acute effects of sildenafil on the voiding of men with erectile dysfunction

and symptomatic benign prostatic hyperplasia. Int. Urol. Nephrol. 2009; 41:

287–92.

15. McVary KT, Roehrborn CG, Kaminetsky JC et al. Tadalafil relieves lower

urinary tract symptoms secondary to benign prostatic hyperplasia. J. Urol.

2007; 177: 1401–7.

16. Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L. Tadalafil

administered once daily for lower urinary tract symptoms secondary to

benign prostatic hyperplasia: a dose finding study. J. Urol. 2008; 180:

1228–34.

17. Bechara A, Romano S, Casabé A et al. Comparative efficacy assessment

of tamsulosin vs. tamsulosin plus tadalafil in the treatment of LUTS/BPH.

Pilot study. J. Sex. Med. 2008; 5: 2170–8.

18. Liquori G, Trombetta C, De Giorgi G et al. Efficacy and safety of combined

oral therapy with tadalafil and alfuzosin: an integrated approach to the

management of patients with lower urinary tract symptoms and erectile

dysfunction. preliminary report. J. Sex. Med. 2009; 6: 544–52.

19. Porst H, McVary KT, Montorsi F et al. Effects of once-daily tadalafil on

erectile function in men with erectile dysfunction and sign and symptoms of

benign prostatic hyperplasia. Eur. Urol. 2009; 56: 727–35.

20. Roehrborn CG, Kaminetsky JC, Auerbach SM, Montelongo RM,

Elion-Mboussa A, Viktrup L. Changes in peak urinary flow and voiding

efficiency in men with signs and symptoms of benign prostatic hyperplasia

during once daily tadalafil treatment. BJU Int. 2010; 105: 502–7.

21. Takeda M, Nishizawa O, Imaoka T, Morisaki Y, Viktrup L. Tadalafil for the

Treatment of Lower Urinary Tract Symptoms in Japanese Men with Benign

Prostatic Hyperplasia: Results from a 12-week Placebo-controlled

Dose-finding Study with a 42-week Open-label Extension. LUTS 2012; 4:

110–9.

22. Broderick GA, Brock GB, Roehrborn CG, Watts SD, Elion-Mboussa A,

Viktrup L. Effects of tadalafil on lower urinary tract symptoms secondary to

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benign prostatic hyperplasia in men with or without erectile dysfunction.

Urology 2010; 75: 1452–8.

23. Porst H, Kim ED, Casabe AR et al. Efficacy and safety of tadalafil once

daily in the treatment of men with lower urinary tract symptoms suggestive

of benign prostatic hyperplasia: results of an international randomized,

double-blind, placebo-controlled trial. Eur. Urol. 2011; 60: 1105–13.

24. Liu L, Zheng S, Han P, Wei Q. Phosphodiesterase-5 inhibitors for lower

urinary tract symptoms secondary to benign prostatic hyperplasia: a

systematic review and meta-analysis. Urology 2011; 77: 123–9.

25. Chung BH, Lee JY, Lee SH, Yoo SJ, Lee SW, Oh CY. Safety and efficacy of

the simultaneous administration of udenafil and an alpha-blocker in men

with erectile dysfunction concomitant with BPH/LUTS. Int. J. Impot. Res.

2009; 21: 122–8.

10.1.5 Desmopressin

Desmopressin acetate (desmopressin) is a synthetic analogue of AVP (AVP:

arginine vasopressin) with high V2 receptor affinity and antidiuretic properties.

It is the only registered drug for antidiuretic treatment. In contrast to AVP,

desmopressin has no relevant V1 receptor affinity and hypertensive effects [1,2].

The clinical effects - in terms of urine volume decrease and an increase in urine

osmolality - last for approximately 8-12 hours[2]. Desmopressin may be used by

intravenous infusion, nasal spray, tablet, or MELT formulation [3,4].

Desmopressin significantly reduced nocturnal diuresis, decreased the number of

nocturnal voids, and extended the time until the first nocturnal void [5-7].

The 24-hour diuresis remained unchanged during desmopressin treatment.

Desmopressin should be taken once daily before sleeping [8].

As the optimal dose differs between patients, desmopressin treatment should be

initiated at a low dose (0.1 mg/day) and may be gradually increased every week

until maximum efficacy is reached [9]. For elderly patients, efficacy and safety

have been shown [9-12], however, the most frequent adverse events were

headache, nausea, diarrhea, abdominal pain, dizziness, dry mouth, and

hyponatremia. Hyponatremia was observed mainly in patients aged 65

years[13-16].

Caution is advised in old men with hyponatremia and impaired renal function.

Serum sodium concentration level should be monitored periodically.

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References

1. Fjellestad-Paulsen A, Höglund P, Lundin S, Paulsen O. Pharmacokinetics

of 1-deamino-8-D-arginine vasopressin after various routes of

administration in healthy volunteers. Clin. Endocrinol. 1993; 38: 177–82.

2. Rembratt A, Graugaard-Jensen C, Senderovitz, Norgaard JP, Djurhuus JC.

Pharmacokinetics and pharmacodynamics of desmopressin administered

orally versus intravenously at daytime versus night-time in healthy men

aged 55-70 years. Eur. J. Clin. Pharmacol. 2004; 60: 397–402.

3. Van Kerrebroeck P, Rezapour M, Cortesse A, Thüroff J, Riis A, Norgaard JP.

Desmopressin in the treatment of nocturia: a double blind

placebo-controlled study. Eur. Urol. 2007; 52: 221–9.

4. Wang CJ, Lin YN, Huang SW, Chang CH. Low dose oral desmopressin for

nocturnal polyuria in patients with benign prostatic hyperplasia: a

double-blind, placebo controlled, randomized study. J. Urol. 2011; 185:

219–23.

5. Cannon A, Carter PG, McConnell AA, Abrams P. Desmopressin in the

treatment of nocturnal polyuria in the male. BJU Int. 1999; 84: 20–4.

6. Chancellor MB, Atan A, Rivas DA, Watanabe T, Tai HL, Kumon H.

Beneficial effect of intranasal desmopressin for men with benign prostatic

hyperplasia and nocturia: preliminary results. Tech. Urol. 1999; 5: 191–4.

7. Mattiasson A, Abrams P, Van Kerrebroeck P, Walter S, Weiss J. Efficacy of

desmopressin in the treatment of nocturia: a double-blind

placebo-controlled study in men. BJU Int. 2002; 89: 855–62.

8. Hvistendahl GM, Riis A, Norgaard JP, Djurhuus JC. The pharmacokinetics

of 400 µg of oral desmopressin in elderly patients with nocturia, and the

correlation between the absorption of desmopressin and clinical effect. BJU

Int. 2005; 95: 804–9.

9. Asplund R, Sundberg B, Bengtsson P. Desmopressin for the treatment of

nocturnal polyuria in the elderly: a dose titration study. Br. J. Urol. 1998; 82:

642–6.

10. Asplund R, Sundberg B, Bengtsson P. Oral desmopressin for nocturnal

polyuria in elderly subjects: a double-blind, placebo-controlled randomised

exploratory study. BJU Int. 1999; 83: 591–5.

11. Kuo HC. Efficacy of desmopressin in treatment of refractory nocturia in

patients older than 65 years. Urology 2002; 59: 485–9.

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12. Rembratt A, Norgaard JP, Andersson KE. Desmopressin in elderly patients

with nocturia: short-term safety and effects on urine output, sleep and

voiding patterns. BJU Int. 2003; 91: 642–6.

13. Lose G, Mattiasson A, Walter S et al. Clinical experiences with

desmopressin for long-term treatment of nocturia. J. Urol. 2004; 172:

1021–5.

14. Bae JH, Oh MM, Shim KS et al. The effects of long-term administration of

oral desmopressin on the baseline secretion of antidiuretic hormone and

serum sodium concentration for the treatment of nocturia: a circadian study.

J. Urol. 2007; 178: 200–3.

15. Weatherall M. The risk of hyponatremia in older adults using desmopressin

for nocturia: a systematic review and meta-analysis. Neurourol. Urodyn.

2004; 23: 302–5.

16. Rembratt A, Riis A, Norgaard JP. Desmopressin treatment in nocturia; an

analysis of risk factors for hyponatremia. Neurourol. Urodyn. 2006; 25:

105–9.

10.1.6 Plant extract/Herbal medicine

Phytotherapy comprises the medical use of various extracts of different

plants. The most important compounds are believed to be phytosterols,

ß-sitosterol, fatty acids, and lectins[1]. In vitro studies have shown that

plant extracts have so many functions. They have anti-inflammatory, anti-

androgenic, oestrogenic effects, decrease sexual hormone binding globulin

(SHBG), inhibit aromatase, lipoxy-genase, growth-factor stimulated

proliferation of prostatic cells, 1-adrenoceptors, 5-reductase, muscarinic

cholinoceptors, dihydropyridine receptors, or vanilloid receptors,

and improve detrusor function, neutralise free radicals [1-3]. In spite of

a lot of mechanisms of action, phytotherapy remains problematic to use be

cause of different concentrations of the active ingredient(s) in different

brands of the same phytotherapeutic agent [4,5].

Although plant extracts agents show some promise for symptom relief, their use

remains controversial due to the lack of established mechanisms of action,

efficacy, and safety [6-13].

Clinical trials are often flawed, as most studies are of small scale and short

Duration. They are not blinded or controlled, and most have no placebo group.

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Hence, meta-analyses of extracts of the same plant do not seem to be justified

and results of these analyses have to be interpreted with caution.

References

1. Madersbacher S, Berger I, Ponholzer A, et al. Plant extracts: sense or

nonsense? Current Opin Urol 2008;18:16-20.

2. Levin RM, Das AK. A scientific basis for the therapeutic effects of

Pygeum africanum and Serenoa repens. Urol Res 2000 ;28:201-9.

3. Buck AC. Is there a scientific basis for the therapeutic effects of serenoa

repens in benign prostatic hyperplasia? Mechanisms of action. J Urol

2004;172:1792-9.

4. Habib FK, Wyllie MG. Not all brands are created equal: a comparison of

selected compounds of different brands of Serenoa repens extract.

Prostate Cancer Prostatic. Dis. 2004; 7: 195–200.

5. Scaglione F, Lucini V, Pannacci M, Caronno A, Leone C. Comparison of

the potency of different brands of Serenoa repens extract on

5alpha-reductase types I and II in prostatic co-cultured epithelial and

fibroblast cells. Pharmacology 2008; 82: 270–5.

6. Wilt T, Ishani A, MacDonald R, Stark G, Mulrow C, Lau J.

Beta-sitosterols for benign prostatic hyperplasia. Cochrane Database of

Syst. Rev. 2000; (2): CD001043.

7. Berges RR, Windeler J, Trampisch HJ, Senge T. Randomised,

placebo-controlled, double-blind clinical trial of beta-sitosterol in patients

with benign prostatic hyperplasia. beta-sitosterol study group. Lancet

1995; 345: 1529–32.

8. Klippel KF, Hiltl DM, Schipp B. A multicentric, placebo-controlled,

double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment

of benign prostatic hyperplasia. Br. J. Urol. 1997; 80: 427–32.

9. Wilt T, Ishani A, MacDonald R, Rutks I, Stark G. Pygeum africanum for

benign prostatic hyperplasia. Cochrane Database Syst. Rev. 2002; (1):

CD001044.

10. Wilt T, MacDonald R, Ishani A, Rutks I, Stark G. Cernilton for benign

prostatic hyperplasia. Cochrane Database Syst. Rev. 2000; (2):

CD001042.

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11. Tacklind J, Mac Donald R, Rutks I, Wilt TJ. Serenoa repens for benign

prostatic hyperplasia. Cochrane Database Syst. Rev. 2009; (2):

CD001423.

12. Wilt T, MacDonold R, Rutks I. Tamsulosin for benign prostatic

hyperplasia. Cochrane Database Syst. Rev. 2002; Issue 4: CD002081.

13. Barry MJ, Meleth S, Lee JY et al. Effect of increasing doses of saw

palmetto extract on lower urinary tract symptoms: a randomized trial.

JAMA 2011; 306: 1344–51.

10.1.7 Combination treatment with α1 blocker and 5α-reductase

inhibitor

Several studies have investigated the efficacy of combination therapy against

the efficacy of an 1-blockers and 5-reductase inhibitors, or placebo alone.

Initial studies with follow-up periods between 6 and 12 months used symptom

(IPSS) change as their primary endpoint [1-3]. All of these trials demonstrated

that the 1-blocker was superior to finasteride in symptom reduction, whereas

the combination treatment was not superior to the 1-blocker alone. More

recently, 4-year data analysis from MTOPS(medical therapy of prostatic

symptoms) as well as the 2- and 4-year results from the CombAT (Combination

of Avodart® and Tamsulosin) trials, have been reported [4-6].

In contrast to earlier studies with only 6 to 12 months follow-up, long-term data

have demonstrated that combination treatment is superior to either monotherapy

with regard to symptom reduction and Qmax (maximum urinary flow rate during

free uroflowmetry) improvement and superior to 1-blocker in reducing the risk

of acute urinary retention and the need for surgery [4-6].

Regarding discontinuation of 1 blockes after long-term combination

therapy, almost three-quarters of patients reported no worsening of symptoms.

However, patients with severe symptoms (IPSS > 20) at baseline may benefit

from longer combination therapy [7]. LUTS after discontinuation of 1 blocker

was sustained at 3 months (IPSS difference 1.24) and 9 months (IPSS

difference -0.44) [8]. Dutasteride patients discontinued 1-blocker therapy 64%

faster than finasteride patients at any time point [9].

Combination therapy should only be used when long-term treatment

(more than 12 months) is intended. Combination therapy with α1 blocker and

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5α-reductase inhibitor should be used primarily in men who have moderate

to severe LUTS and are at risk of disease progression (higher prostate volume,

higher PSA concentration, advanced age, etc.).

The adverse events observed during combination treatment were typical of

an α1 blocker and 5ARI. The frequencies of adverse events were significantly

higher for combination therapy for most adverse events

References

1. Lepor H, Williford WO, Barry MJ et al. The efficacy of terazosin, finasteride,

or both in benign prostatic hyperplasia. N. Engl. J. Med. 1996; 335: 533-9.

2. Debruyne FM, Jardin A, Colloi D et al. Sustained release alfuzosin,

finasteride and the combination of both in the treatment of benign prostatic

hyperplasia. Eur. Urol. 1998; 34: 169–75.

3. Kirby R, Roehrborn CG, 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: 119–26.

4. McConnell JD, Roehrborn CG, Bautista O et al. The long-term effect of



5. Roehrborn CG, Siami P, Barkin J et al. The effects of dutasteride,

tamsulosin and combination therapy on lower urinary tract symptoms in

men with benign prostatic hyperplasia and prostatic enlargement: 2-year

results from the CombAT study. J. Urol. 2008; 179: 616–21.




study. Eur. Urol. 2010; 57: 123–31.

7. Barkin J, Guimarães M, Jacobi G, Pushkar D, Taylor S, Van Vierssen Trip

OB. Alpha-blocker therapy can be withdrawn in the majority of men

following initial combination therapy with the dual 5alpha-reductase

inhibitor dutasteride. Eur. Urol. 2003; 44: 461–6.

8. Nickel JC, Barkin J, Koch C, Dupont C, Elhilali M. Finasteride monotherapy

maintains stable lower urinary tract symptoms in men with benign prostatic

hyperplasia following cessation of alpha blockers. Can. Urol. Assoc. J.

2008; 2: 16–21.

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9. Issa MM, Lin PJ, Eaddy MT, Shah MB, Davis EA. Comparative analysis of

alpha-blocker utilization in combination with 5-alpha reductase inhibitors for

enlarged prostate in a managed care setting among Medicare aged men.

Am. J. Manag. Care 2008; 14 (5 Suppl 2): S160–6.

10.1.8 Combination treatment with α1 blocker and anticholinergic

Combination treatment with α1 blocker and anticholinergic might be

considered in patients with moderate to severe LUTS if symptom relief has

been insufficient with the monotherapy of either drug.

At least nine trials have been published investigating the efficacy of the

combination treatment with 1-blockers and muscarinic receptor antagonists in

adult male patients with LUTS LUTS: lower urinary tract symptoms [1-8].

These trials demonstrated that persistent LUTS can be significantly reduced by

the additional use of a muscarinic receptor antagonist especially if detrusor

overactivity had been demonstrated [1-8]. Patient reported QoL, treatment

benefit, symptom bother, or patient perception of bladder condition was

significantly improved in the combination treatment arm [9-13]. The combination

treatment significantly reduced urgency urinary incontinence episodes as well as

urgency and significantly increased QoL compared to α1 blockers or placebo

alone. Combination treatment should cautiously be prescribed in men who are

suspicious of having bladder outlet obstruction with increased postvoid residual

urine volume [13-15].

References

1. Saito H, Yamada T, Oshima H et al. A comparative study of the efficacy and

safety of tamsulosin hydrochloride (Harnal capsules) alone and in

combination with propiverine hydrochloride (BUP-4 tablets) in patients with

prostatic hypertrophy associated with pollakisuria and/or urinary

incontinence. Jpn. J. Urol. Surg. 1999; 12: 525–36.

2. 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 detrusor. BJU Int. 2004; 94: 817–20.

3. Lee KS, Choo MS, Kim DY et al. Combination treatment with propiverine

hydrochloride plus doxazosin controlled release gastrointestinal

therapeutic system formulation for overactive bladder coexisting benign

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prostatic obstruction: a prospective, randomised, controlled multicenter

study. J. Urol. 2005; 174: 1334–8.



symptoms and overactive bladder. JAMA 2006; 296: 2319–28.

5. MacDiarmid SA, Peters KM, Chen A et al. Efficacy and safety of

extended-release Oxybutynin in combination with tamsulosin for treatment

of lower urinary tract symptoms in men: randomised, double-blind,

placebo-controlled study. Mayo Clin. Proc. 2008; 83: 1002–10.

6. Athanasopoulols A, Gyftopoulos K, Giannitsas K, Fisfis J, Perimenis P,

Barbalias G. Combination treatment with an a-blocker plus an

anticholinergic for bladder outlet obstruction: a prospective, randomised,

controlled study. J. Urol. 2003; 169: 2253–6.



Urol.2005; 174: 2273–5.

8. Yang Y, Zhao SF, Li HZ et al. Efficacy and safety of combined therapy with

terazosin and tolterodine for patients with lower urinary tract symptoms

associated with benign prostatic hyperplasia: a prospective study. Chin.

Med. J. 2007; 120: 370–4.

9. Maruyama O, Kawachi Y, Hanazawa K et al. Naftopidil monotherapy vs

naftopidil and an anticholinergic agent combined therapy for storage

symptoms associated with benign prostatic hyperplasia: A prospective

randomised controlled study. Int. J. Urol. 2006; 13: 1280–5.




1061–7.

11. Kaplan SA, McCammon K, Fincher R, Fakhoury A, He W. Safety and

tolerability of solifenacin add-on therapy to alpha-blocker treated men with

residual urgency and frequency. J. Urol. 2009; 182: 2825–3.

12. NishizawaO, Yamaguchi O, Takeda M, Yokoyama O, for the TAABO Study

Group: Randomized Controlled Trial to Treat Benign Prostatic Hyperplasia

with Overactive Bladder Using an Alpha-blocker Combined with

Anticholinergics, LUTS, 2011; 3:39-40.

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13. Yamaguchi O, Kakizaki H, Homma Y et al. Solifenacin as add-on therapy

for overactive bladder symptoms in men treated for lower urinary tract

symptoms--ASSIST, randomized controlled study. Urology 2011; 78: 126–

33.

14. Chapple C, Herschorn S, Abrams P, Sun F, Brodsky M, Guan Z. Tolterodine

treatment improves storage symptoms suggestive of overactive bladder in

men treated with α-blockers. Eur. Urol. 2009; 56: 534–41.

15. Takeda M, Nishizawa O, Gotoh M, Yoshida M, Takahashi S, Masumori N:

Clinical Efficacy and Safety of Imidafenacin as Add-on Treatment for

Persistent Overactive Bladder Symptoms Despite a-Blocker Treatment in

Patients with BPH: the ADDITION STUDY. Urology; 82:887-93, 2013.

10.1.9 Combination treatment with α1 blocker and PDE 5 inhibitor

The combination of α1 blocker and PDE 5 inhibitor is well tolerated and

effective in improving lower urinary tract symptoms [1-4].

However caution is advised in men with hypotention. Further data on safety

and cost-effectiveness, especially for combination therapy, will be needed.

References

1. Bechara A, Romano S, Casabe A et al. Comparative efficacy assessment

of tamsulosin vs. tamsulosin plus tadalafil in the treatment of LUTS/BPH.

pilot study. J. Sex. Med. 2008; 5: 2170–8.

2. Greco KA, McVary KT. The role of combination medical therapy in be

nign prostatic hyperplasia. Int. J. Impot. Res. 2008; 20 (Suppl 3): S33

–43.

3. Martinez-Salamanca JI, Carballido J, Eardley I et al. Phosphodiesteras

e type 5 inhibitors in the management of non-neurogenic male lower

urinary tract symptoms: critical analysis of current evidence. Eur. Urol.

2011; 60: 527–35.

4. Giuliano F, Oelke M, Jungwirth A et al. Tadalafil once daily improves

ejaculatory function, erectile function, and sexual satisfaction in men

with lower urinary tract symptoms suggestive of benign prostatic hype

rplasia and erectile dysfunction: results from a randomized, placebo- a

nd tamsulosin-controlled, 12-week double-blind study. J. Sex. Med.

2013; 10: 857–65.

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10.1.10 Botulinum toxin (BTX-A)

BTX-A inhibits vesicular neurotransmitter transport from nerve terminal via

inhibition of SNAIR/SNAP proteins [1]. Two commercially available products

(BotoxTM, DysportTM) of type A Botulinum toxin are now available in USA

and European countries (Table 1). The possible mechanisms of the effect

of intraprostatic injection of BTX-A may be variable including apoptosis

[2-5]. In addition to initla short term effects on the small prostate [6-8],

long-termeffects on LUTS, prostate volume, and QOL, were evaluated

[9-14]. There are some evidences to support its efficacy [9-14], large volu

me RCTdata is lacking [15,16].

Intra-prostatic BTX injections for LUTSdue to benign prostatic obstruction

or urinary retention are still experimental.

References

1. Smith CP, Franks ME, McNeil BK et al. Effect of botulinum toxin A on the

autonomic nervous system of the rat lower urinary tract. J. Urol. 2003; 169:

1896–900.

2. Doggweiler R, Zermann DH, Ishigooka M, Schmidt RA. Botox-induced

prostatic involution. Prostate 1998; 37: 44–50.

3. Chuang YC, Huang CC, Kang HY et al. Novel action of botulinum toxin on

the stromal and epithelial components of the prostate gland. J. Urol. 2006;

175: 1158–63.

4. Chuang YC, Tu CH, Huang CC et al. Intraprostatic injection of botulinum

toxin type-A relieves bladder outlet obstruction in human and induces

prostate apoptosis in dogs. BMC Urology 2006; 6: 12.

5. Lin AT, Yang AH, Chen KK. Effects of botulinum toxin A on the contractile

function of dog prostate. Eur. Urol. 2007; 52: 582–9.

6. Kuo HC. Prostate botulinum A toxin injection – an alternative treatment for

benign prostatic obstruction in poor surgical candidates. Urology 2005; 65:

670–4.

7. Chuang YC, Chiang PH, Huang CC, Yoshimura N, Chancellor MB.

Botulinum toxin type A improves benign prostatic hyperplasia symptoms in

patients with small prostates. Urology 2005; 66: 775–9.

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8. Park DS, Cho TW, Lee YK, Lee YT, Hong YK, Jang WK. Evaluation of short

term clinical effects and presumptive mechanism of botulinum toxin type A

as a treatment modality of benign prostatic hyperplasia. Yonsei Med. J.

2006; 47: 706–14.

9. Chuang YC, Chiang PH, Yoshimura N, De Miguel F, Chancellor MB.

Sustained beneficial effects of intraprostatic botulinum toxin type A on

lower urinary tract symptoms and quality of life in men with benign prostatic

hyperplasia. BJU Int. 2006; 98: 1033–7.

10. Brisinda G, Cadeddu F, Vanella S, Mazzeo P, Marniga G, Maria G. Relief

by botulinum toxin of lower urinary tract symptoms owing to benign

prostatic hyperplasia: early and long-term results. Urology 2009; 73: 90–4.

11. Kuo HC, Liu HT. Therapeutic effects of add-on botulinum toxin A on

patients with large benign prostatic hyperplasia and unsatisfactory

response to combined medical therapy. Scand. J. Urol. Nephrol. 2009; 43:

206–11.

12. Nikoobakht M, Daneshpajooh A, Ahmadi H et al. Intraprostatic botulinum

toxin type A injection for the treatment of benign prostatic hyperplasia: initial

experience with Dysport. Scand. J. Urol. Nephrol. 2010; 44: 151–7.

13. Silva J, Silva C, Saraiva L et al. Intraprostatic botulinum toxin type A

injection in patients unfit for surgery presenting with refractory urinary

retention and benign prostatic enlargement. effect on prostate volume and

micturition resumption. Eur. Urol. 2008; 53: 153–9.

14. Silva J, Pinto R, Carvalho T et al. Intraprostatic botulinum toxin type A

injection in patients with benign prostatic enlargement: duration of the

effect of a single treatment. BMC Urology 2009; 9: 9.

15. Maria G, Brisinda G, Civello IM, Bentivoglio AR, Sganga G, Albanese A.

Relief by botulinum toxin of voiding dysfunction due to benign prostatic

hyperplasia: results of a randomised, placebo-controlled study. Urology

2003; 62: 259–64.

16. Crawford ED, Hirst K, Kusek JW et al. Effects of 100 and 300 units of

onabotulinum toxin A on lower urinary tract symptoms of benign prostatic

hyperplasia: a phase II randomized clinical trial. J. Urol. 2011; 186: 965–70.

10.1.11 β3-Adrenoceptor agonist, Mirabegron

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A β3-Adrenoceptor agonist, Mirabegron, alleviates symptoms of OAB while

having a mechanism of action that provides an alternative for patients who are

intolerant of or who have contraindications to anticholinergic agents [1]. The

place in therapy of mirabegron relative to anticholinergics in the treatment of

OAB secondary to BPH has not yet been established[ 2], however, urodynamic

safety for BPH/BOO has been confirmed[ 3].

References

1. Bridgeman MB, Friia NJ, Taft C, Shah M: Mirabegron: β3-adrenergic

receptor agonist for the treatment of overactive bladder, Ann Pharmacother,

2013;47:1029-38.

2. Otsuki H, Kosaka T, Nakamura K, Mishima J, Kuwahara Y, Tsukamoto T:

β3-Adrenoceptor agonist mirabegron is effective for overactive bladder that

is unresponsive to antimuscarinic treatment or is related to benign prostatic

hyperplasia in men, 2013;45:53-60.

3. Nitti V W, Rosenberg S, Mitceson D H, He W, Fakhoury A, Martin N:

Urodynamic safety of the 3-adrenoceptor agonist Mirabegron in males with

lower urinary tract symptomsa and bladder outlet obstruction, J Urol, 2013,

190:1320-7.

http://www.ncbi.nlm.nih.gov/pubmed?term=Otsuki%20H%5BAuthor%5D&cauthor=true&cauthor_uid=23212147

http://www.ncbi.nlm.nih.gov/pubmed?term=Kosaka%20T%5BAuthor%5D&cauthor=true&cauthor_uid=23212147

http://www.ncbi.nlm.nih.gov/pubmed?term=Nakamura%20K%5BAuthor%5D&cauthor=true&cauthor_uid=23212147

http://www.ncbi.nlm.nih.gov/pubmed?term=Mishima%20J%5BAuthor%5D&cauthor=true&cauthor_uid=23212147

http://www.ncbi.nlm.nih.gov/pubmed?term=Kuwahara%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=23212147

http://www.ncbi.nlm.nih.gov/pubmed?term=Tsukamoto%20T%5BAuthor%5D&cauthor=true&cauthor_uid=23212147

http://www.ncbi.nlm.nih.gov/pubmed/23212147

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10.2 Conservative Therapy

In this chapter, conservative therapies including lifestyle advises, watchful

waiting, indwelling catheter, and intermittent catheterization are discussed.

Transurethral microwave thermotherapy (TUMT), Transurethral needle ablation

(TUNA) and Prostate stent are discussed in the next chapter (Chapter 10:

Surgery.)

Table. Level of Evidence and Grade of Recommendations for Conservative

therapies

10.2.1 Life style advises/modifications

Lifestyle factors play some part in the pathogenesis of BPH and LUTS. Lifestyle

factors associated with increased risks of BPH and LUTS include obesity,

diabetes, and meat and fat consumption [1]. In contrast, factors associated with

decreased risks include exercise, and vegetable consumption. Modification of

these factors can provide the opportunity for treatment of BPH and LUTS. This

approach has noninvasiveness and low financial burden. Lifestyle advises and

recommended modifications for BPH and LUTS should probably include the

following [2, 3].

Modifications of fluid intake; Reduction of fluid intake at specific times is

necessary for patients with storage symptoms, and the recommended total daily

Level Grade

Lifestyle advises prior to or concurrent with treatment can provide the

opportunity for treatment of BPH and LUTS.

2 B

Men with mild symptoms are suitable for watchful waiting. 2 B

The use of chronic indwelling catheter is necessary for patients who

have refractory retention and high surgical risk.

5 C1

Intermittent catheterization is associated with less UTI compared to

indwelling catheter and early recovery of bladder function following

surgery for urinary retention.

2 B

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fluid intake for an average man with LUTS should be 1500–2000mL. For

nocturia, evening fluid restriction 2 hours prior to sleeping is appropriate.

Avoidance or moderation of certain dietary factors which may have a diuretic

and irritant effect such as caffeine, alcohol, and spices.

Use of relaxed voiding, double-voiding techniques and urethral milking to

prevent post micturition dribble.

Distraction techniques, such as penile squeeze, breathing exercises, perineal

pressure and mental ‘tricks’ to take the mind off the bladder and toilet, to help

control irritative symptoms.

Bladder re-training, by which men are encouraged to ‘hold on’ when they have

sensory urgency to increase their bladder capacity (to around 400mL) and the

time between voids.

Optimizing the time of administration medication or substituting drugs for others

that have fewer urinary effects.

Providing necessary assistance when there is impairment of dexterity, mobility or

mental state.

Avoid constipation.

Education and reassurance

(Level of evidence 2, grade recommendation B)

10.2.2 Watchful waiting

There is some evidence to support the efficacy of watchful waiting [4, 5]. Men

who have not bothersome or mild uncomplicated LUTS are suitable for watchful

waiting which is not medical or surgical treatment but include education,

reassurance, periodic monitoring, and lifestyle advice. Progression of symptoms

is rare [6] and delayed treatment intervention is still effective in those patients. A

large study comparing watchful waiting and transurethral resection of the

prostate in men with moderate symptoms showed that those who had

undergone surgery had improved bladder function over the watchful waiting

group. Thirty six percent of patients crossed over to surgery in 5 years, leaving

64% doing well in the watchful waiting group [7]. For adequate patient selection,

physicians have to consider clinical findings because prostate-specific antigen,

obstructive symptom score, and transitional zone volume were identified as

important risk factors of clinical progression [8]. Watchful waiting patients usually

are recommended reexamination every 12 months.

(Level of evidence 2, Grade of recommendation B)

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10.2.3 Complementary/alternative medicine (CAM)

Most complementary and alternative medicines for BPH are extracts of the roots,

the seeds, the bark, or the fruits of the various plants. Among these, the most

commonly used and investigated product is an extract of the berry of the saw

palmetto (Serenoa repens). However, recent clinical trials have questioned their

efficacy and increasing doses of a saw palmetto extract did not improve LUTS

more than placebo [9, 10]. Other products include extracts of the African plum

tree (Pygeum africanum), stinging nettle (Urtica dioica), pumpkin seed

(Curcubita pepo), South African star grass (Hypoxis rooperi) and rye pollen

(Secale cereal). Complementary and alternative medicines other than saw

palmetto and Urtica dioica do not have evidence to support efficacy and safety.

(Level of evidence 2, grade of recommendation D)

10.2.4 Urethral indwelling catheter/Suprapubic catheter

The use of chronic indwelling catheter is necessary for patients who have

refractory retention and high surgical risk. However, it is associated with several

complications and significant impairment of quality of life. Urethral indwelling

catheter is technically easier, less morbid compared to suprapubic

catheterization, but its disadvantages are higher risk of injury to the urethra and

bladder neck [11]. Selection of management for patients with chronic indwelling

catheter should depend on the long term comfort for the patient and a physician

mind-set.

Patients who are on the waiting for definitive surgery after acute urinary retention

(AUR) need to indwell catheter too. In prospective cross-sectional survey, the

initial management of AUR consisted of urethral indwelling catheter and

suprapubic catheter in 83% and 17% respectively [12].

(Level of evidence 5, grade recommendation C1)

10.2.5 Intermittent catheterization

Intermittent catheterization is an alternative to an indwelling catheter in patients

who are capable of catheterizing themselves. It is associated with less urinary

tract infection compared to indwelling catheter [13]. There is evidence for early

recovery of bladder function following surgery for urinary retention [14]. It can

have a good effect of quality of life, especially sexual life.

However it is not appropriate in advanced old aged patients who may lack the

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mobility, visual acuity, or cognitive ability to manage self-catheterization. In

addition, patients with severe prostate enlargement have difficulty in urethral

catheterization if they do not have special skills or equipments.

(Level of evidence 2, grade of recommendation B)

References

1. Parsons JK. Lifestyle factors, benign prostatic hyperplasia, and lower

urinary tract symptoms. Curr. Opin. Urol. 2011; 21: 1–4.

2. Brown CT, van der Meulen J, Mundy AR, O'Flynn E, Emberton M.

Defining the components of a self-management programme for men with

uncomplicated lower urinary tract symptoms: a consensus approach.

Eur. Urol. 2004; 46: 254–62; discussion 63.

3. Brown CT, Van Der Meulen J, Mundy AR, Emberton M. Lifestyle and

behavioural interventions for men on watchful waiting with

uncomplicated lower urinary tract symptoms: a national multidisciplinary

survey. BJU Int. 2003; 92: 53–7.

4. Netto NR Jr, De Lima ML, Netto MR, D'Ancona CA. Evaluation of

patients with bladder outlet obstruction and mild international prostate

symptom score followed up by watchful waiting. Urology 1999; 53: 314–

6.

5. Wasson JH, Reda DJ, Bruskewitz RC, Elinson J, Keller AM, Henderson

WG. A comparison of transurethral surgery with watchful waiting for

moderate symptoms of benign prostatic hyperplasia. The Veterans

Affairs Cooperative Study Group on Transurethral Resection of the

Prostate. N. Engl. J. Med. 1995; 332: 75–9.

6. Fitzpatrick JM. The natural history of benign prostatic hyperplasia. BJU

Int. 2006; 97 (Suppl 2): 3–6; discussion 21–2.

7. Flanigan RC, Reda DJ, Wasson JH, Anderson RJ, Abdellatif M,

Bruskewitz RC. 5-year outcome of surgical resection and watchful

waiting for men with moderately symptomatic benign prostatic

hyperplasia: a Department of Veterans Affairs cooperative study. J. Urol.

1998; 160: 12–6; discussion 6–7.

8. Djavan B, Fong YK, Harik M et al. Longitudinal study of men with mild

symptoms of bladder outlet obstruction treated with watchful waiting for

four years. Urology 2004; 64: 1144–8.

9. Barry MJ, Meleth S, Lee JY et al. Effect of increasing doses of saw

palmetto extract on lower urinary tract symptoms: a randomized trial.

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JAMA 2011; 306: 1344–51.

10. MacDonald R, Tacklind JW, Rutks I, Wilt TJ. Serenoa repens

monotherapy for benign prostatic hyperplasia (BPH): an updated

Cochrane systematic review. BJU Int. 2012; 109: 1756–61.

11. Katsumi HK, Kalisvaart JF, Ronningen LD, Hovey RM. Urethral versus

suprapubic catheter: choosing the best bladder management for male

spinal cord injury patients with indwelling catheters. Spinal Cord 2010;

48: 325–9.

12. Desgrandchamps F, De La Taille A, Doublet JD. The management of

acute urinary retention in France: a cross-sectional survey in 2618 men

with benign prostatic hyperplasia. BJU Int. 2006; 97: 727–33.

13. Patel MI, Watts W, Grant A. The optimal form of urinary drainage after

acute retention of urine. BJU Int. 2001; 88: 26–9.

14. Ghalayini IF, Al-Ghazo MA, Pickard RS. A prospective randomized trial

comparing transurethral prostatic resection and clean intermittent

self-catheterization in men with chronic urinary retention. BJU Int. 2005;

96: 93–7.

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11. Recommended grade for treatment : Surgery

Wachira Kochakarn, M.D., Ph.D.

Absolute indications for surgery in patients with BPH/LUTS/BPE/BOO are

refractory urinary retention, recurrent urinary tract infection from BOO, refractory

hematuria due to BPH, renal insufficiency from chronic BOO, vesical calculi or

diverticulum. According to aging not only in Western countries but Asian

countries, such BPH patients are often at high risk for surgical interventions.

According to Treatment Algorithm (Chapter 1. Algorithm, d.Treatment Algorithm

of Bothersome Male LUTS Refractory to Medical/Conservative Treatment or

Absolute Surgical Indications for Urologist), American Society of

Anesthesiologists Operative Risk Assessment of Physical Status Class,

treatment recommendation are summarized in the following Table.

Table. Treatment recommendation according to operative risk assessment, and

prostate volume.

Operative Risk

Assessment

Prostate Volume Remark Recommended

treatments

ASA PS class IV Conservative CIC , Indwelling

Catheterization etc.

ASA PS class III, on

anti-coagulation drug

Laser PVP, Thulium laser,

HoLAP, HoLEP

ASA PS class I or

class II

>80 ml Classical/

Laser

TURP, TUEB

PVP, Thulium laser,

HoLEP

ASA PS class I

or class II

30-80 ml Classical/

Laser /MIST

TURP, TUEB, PVP,

Thulium laser, HoLEP,

TUMT, TUNA

ASA PS class I

or class II

<30 ml Classical/

MIST

TURP,

TUIP

ASA: American Society of Anesthesia, PS; Performance Status,

MIST; Minimal invasive therapy

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11.1 Transurethral resection of prostate (TURP)

TURP is the gold standard of surgical treatment of symptomatic BPH. An

indication that is accepted for TURP is for moderate to severe symptoms and for

those who fail to respond to medical treatment or don’t accept to medical

therapy. Many changes have undergone to improve outcome of TURP and incur

less complications such as optic quality, light sources, surgical and anesthetic

technique [1].

The current indications for TURP are moderate to severe bothersome

symptoms, recurrent urinary retention, bladder stones, obstructive renal failure

and hematuria due to prostate gland enlargement. Due to improvement of

instrument and technique including continuous sheath, TURP can be performed

in bigger gland than prior reported. In fact, prostate gland of 120 g can be done

with a minimal complication [2].

Complications of TURP [3] are TURP syndrome (1.4%), bleeding need for blood

transfusion (<20%), urethral stricture (10%). Mortality is less than 1 %. Bipolar

TURP is believed for fewer complications, especially TURP syndrome and

urethral stricture but there are data giving support of less complications as well

as a cost-analysis [4-7].

(Level 1 Evidence, Grade A Recommendation)

11.2 Transurethral incision of prostate (TUIP)

TUIP is indicated for men who have moderate to severe symptoms but reveal

small prostate gland. The accepted indication for TUIP is less than 30 g.

Long-term symptomatic improvement in TUIP is similar to TURP but with less

incidence of retrograde ejaculation [8].

(Level 2 Evidence, Grade B Recommendation)

11.3 KTP (greenlight)

Laser vaporization is associated with a low risk of hemorrhage and can be

performed safely even on large prostates [9-11]. Photoselective vaporization

prostatectomy (PVP) or greenlight laser ia another optional treatment in men

with symptomatic BPH who might have bleeding tendency. RCT comparing to

TURP shows camparable shortterm outcome but higher in reoperation in PVP

[11]. There is significant blood loss and shorten catherterization in PVP group

when compared to standard TURP. High voltage PVP (120 watts) is

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recommended for use in a very large galnd due to less time consumed in using

80 watts PVP [12].

There is sufficient evidence for the effectiveness and sustainability of laser

vaporization of the prostate, although tissue sampling is impossible, unlike

TURP.


11.4 HoLEP

Holmium laser enucleation ( HoLEP) is recommended for large prostate gland of

more than 50 g with bleeding tendency, including patients who take

anticoagulant [13-16]. RCT comparing HoLEP to TURP has demonstrated

impressive outcomes, especially in term of Qmax at 12 months after treatment.

But HoLEP has overall complication less than TURP (8.1% v.s.16.2%) [13].


11.5 Open prostatectomy

Open prostatectomy remains indicated as one of the optional treatments of BPH,

especially too large for TURP for fear of incomplete resection, massive bleeding

and dilutional hyponatremia [17]. Open prostatectomy is also indicated for

concomitant pathologies needing a surgical approach such as vesical stones

and diverticula.

(Level 3 Evidence, Grade C1 Recommendation)

Special situations

We categorize patients into 2 groups; patients, who can’t stop

anti-coagulation and who are not fit for surgery/general anesthesia.

1) Patient, who can’t stop anti-coagulation

a. KTP (greenlight)


b. HoLEP


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2) Patient, who are not fit for surgery/general anesthesia

a. Transurethral microwave thermotherapy (TUMT) and Transurethral

needle ablation (TUNA)

Transurethral microwave thermotherapy (TUMT) and transurethral needle

ablation (TUNA) are indicated in high risk patients especially having bleeding

tendency and volume overload [18]. This kind of treatment can be performed

without anesthesia. Due to less improvement of symptoms [18] when compared

to standard treatment and introduction of any kind of laser therapy, TUMT is

performed less frequent during the last decade. TUNA is considered

contraindicated in prior radiation to pelvic organ due to higher risk of rectal fistula

[19].

(Level 1 Evidence, Grade C Recommendation)

b. Prostate stent

Prostate stents have been indicated in elderly men with significant comorbidities

which are therefore unfit for surgery [20,21]. Two types of stent are introduced

as temporary and permanent stent.

(Level 3 Evidence, Grade D Recommendation)

Reference

1. Koshiba K, Egawa S, Ohori M, Uchida T, Yokoyama E, Shoji K. Does

transurethral resection of the prostate pose a risk to life? 22-year outcome.

J. Urol.1995; 153: 1506–9

2. Rassweiler J, Teber D, Kuntz R, Hofmann R. Complications of transurethral

resection of the prostate (TURP) – incidence, management and prevention.

Eur. Urol. 2006; 50: 969–80.

3. Reich O, Gratzke C, Bachmann A et al. Morbidity, mortality and early

outcome of transurethral resection of the prostate: a prospective multicenter

evaluation of 10,654 patients. J. Urol. 2008; 180: 246–9.

4. Michielsen DP, Debacker T, De Boe V et al. Bipolar transurethral in saline an

alternative surgical treatment for bladder outlet obstruction? J. Urol. 2007;

178: 2035–9.

5. Ho HSS, Cheng CWS. Bipolar transurethral resection of prostate: a new

reference standard? Curr. Opin. Urol. 2008; 18: 50–5.

6. Issa MM. Technological advances in transurethral resection of the prostate:

bipolar versus monopolar TURP. J. Endourol. 2008; 22: 1578–95.

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7. Singh H, Desai MR, Shrivastav P, Vani K. Bipolar versus monopolar

transurethral resection of prostate: randomized controlled study. J.

Endourol. 2005; 19: 333–8.

8. Lourenco T, Shaw M, Fraser C, MacLennan G, N'Dow J, Pickard R. The

clinical effectiveness of transurethral incision of the prostate: a systematic

review of randomised controlled trials. World J. Urol. 2010; 28: 23–32.

9. Horasanli K, Silay MS, Altay B, Tanriverdi O, Sarica K, Miroglu C.

Photoselective potassium titanyl phosphate (KTP) laser vaporization versus

transurethral resection of the prostate for prostates larger than 70 mL: a

short-term prospective randomized trial. Urology 2008; 71: 247-51.

10. Tasci AI, Tugcu V, Sahin S, Zorluoglu F. Rapid communication:

photoselective vaporization of the prostate versus transurethral

resection of the prostate for the large prostate: a prospective

nonrandomized bicenter trial with 2-year follow-up. J. Endourol. 2008;

22:347-53.

11. Skolarikos A, Papachristou C, Athanasiadis G, Chalikopoulos D,

Deliveliotis C, Alivizatos G. Eighteen-month results of a randomized

prospective study comparing transurethral photoselective

vaporization with transvesical open enucleation for prostatic

adenomas greater than 80 cc. J. Endourol. 2008; 22: 2333-40.

12. Lourenco T, Pickard R, Vale L et al. Alternative approaches to endoscopic

ablation for benign enlargement of the prostate: systematic review of

randomized controlled trials. BMJ 2008; 337: a449.

13. Kuntz RM, Ahyai S, Lehrich K, Fayad A. Transurethral holmium laser

enucleation of the prostate versus transurethral electrocautery resection of

the prostate: a randomized prospective trial in 200 patients. J. Urol. 2004;

172: 1012–6.

14. Ahyai SA, Gilling P, Kaplan SA et al. Meta-analysis of functional outcomes

and complications following transurethral procedures for lower urinary tract

symptoms resulting from benign prostatic enlargement. Eur. Urol. 2010; 58:

384–97.

15. Iwamoto K, Hiraoka Y, Shimizu Y. Transurethral detachment

prostatectomy using a tissue morcellator for large benign prostatic

hyperplasia. J. Nippon Med. Sch. 2008; 75: 77–84.

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16. Hiraoka Y, Shimizu Y, Iwamoto K, Takahashi H, Abe H. Trial of complete

detachment of the whole prostate lobes in benign prostate hyperplasia by

transurethral enucleation of the prostate. Urol. Int. 2007; 79: 50–4.

17. Serretta V, Morgia G, Fondacaro L et al. Open prostatectomy for benign

prostatic enlargement in southern Europe in the late 1990s: a contemporary

series of 1800 interventions. Urology 2002; 60: 623–7.

18. De la Rosette J, Laguna MP, Gravas S et al. Transurethral microwave

thermotherapy: the gold standard for minimally invasive therapies for

patients with benign prostatic hyperplasia? J. Endourol. 2003; 17: 245–51.

19. Zlotta AR, Giannakopoulos X, Machlum O, Ostrem T, Schulman CC.

Long-term evaluation of transurethral needle ablation of the prostate (TUNA)

for the treatment of symptomatic benign prostatic hyperplasia: clinical

outcome up to 5 years from 3 centers. Eur. Urol. 2003; 44: 89–93.

20. Gravas S, Laguna MP, De la Rosette JJ. Efficacy and safety of intraprostatic

temperature controlled microwave thermotherapy in patients with benign

prostatic hyperplasia: results of a prospective, open-label, single-center

study with 1-year follow-up. J. Endourol. 2003; 17: 425–30.

21. Vanderbrink BA, Rastinehad AR, Badlani GH. Prostatic stents for the

treatment of benign prostatic hyperplasia. Curr. Opin. Urol. 2007; 17: 1–6.

- 135 -

12. Abbreviations used in the text

This list is not comprehensive for the most common abbreviations.

ASA American Society of Anesthesia

AVP Arginine vasopressin

AUA American Urological Association

BOO(I) Bladder outlet obstruction (index)

BPE Benign prostatic enlargement

BPH Benign prostatic hyperplasia

BPO Benign prostatic obstruction

cGMP Cyclic guanosine monophosphate

CIC Clean intermittent catheterization

CombAT Combination of avodart® and tamsulosin

DHT Dihydrotestosterone

DRE Digital rectal examination

EAU European Association of Urology

EBM Evidence-based medicine

ED Erectile dysfunction

EjD Ejaculation dysfunction

eNOS Endothelial nitric oxide synthase

ER Extended release

FVC Frequency volume chart

GITS Gastrointestinal therapeutic system

GP General practitioner

HoLAP Holmium laser ablation of the prostate

HoLEP Holmium laser enucleation of the prostate

IFIS Intra-operative floppy iris syndrome

IPP Intravesical protrusion of prostate

IPSS International prostate symptom score

IR Immediate release

KTP Potassium titanyl phosphate

LUTS Lower urinary tract symptoms

MIST Minimal invasive therapy

MR Modified release

MTOPS Medical therapy of prostatic symptoms

NAION Non-arteritic anterior ischemic optic neuropathy

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NO Nitric oxide

NOS NO synthases

nNOS Neuronal nitric oxide synthase

n.s. Not significant

OAB Overactive bladder

OCAS Oral controlled absorption system

PA Prostatic adenoma

PDE Phosphodiesterase

PFS Pressure-flow study

PS Performance Status

PSA Prostate specific antigen

PV Prostate volume

PVP Photoselective vaporization of the prostate

PVR Post-void residual urine

Qmax Maximum urinary flow rate during free uroflowmetry

QoL Quality of life

RR Relative risk

SHBG Sexual hormone binding globulin

SR Sustained release

tmax Time to maximum plasma concentration

t½ Elimination half-life

TUEB Transurethral enucleation of prostate using bipolar electrode

TUERP Transurethral enucleation and resection of the prostate

(either using bipolar or monopolar electrode)

TUIP Transurethral incision of the prostate

TUMT Transurethral microwave therapy

TUNA Transurethral needle ablation

TURP Transurethral resection of the prostate

TUVP Transurethral vaporization of the prostate

UTI Urinary tract infection

WW Watchful waiting

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