Our Drug review describes the recommended

management of lower urinary tract symptoms

due to benign prostatic hyperplasia in general

practice, followed by an analysis of prescrip-

tion data and sources of further information.

Until recently, a man presenting to his doctor withurinary symptoms was immediately labelled as

having benign prostatic hyperplasia (BPH), with anassumption as to the aetiology of his symptoms.Subsequently, the term ‘lower urinary tract symp-toms’ (LUTS) was introduced to dispel the percep-tion that male urinary symptoms invariably arise from

the prostate. The publication by the NationalInstitute for Health and Clinical Excellence (NICE)in May 2010 of The Management of Lower Urinary TractSymptoms in Men clinical guideline is a landmark inthe recognition of the term ‘LUTS’ as the firstnational guideline to address this umbrella conceptrather than focussing on BPH alone.1 The guidelinecovers the management of a man presenting withLUTS from initial assessment, usually in a primary-care setting, all the way through to complex surgicalmanagement.

Given that there are now many excellent resourcesavailable for guidance (see Figure 1),2 the aim of thisreview is to focus on tips and pitfalls in the manage-ment of LUTS, especially those nonsurgical aspects ofthe condition that can easily be managed by GPs.

16 Prescriber 19 June 2011 www.prescriber.co.uk

Drug review BPH

Management of lower urinary

tract symptoms due to BPHRoger Kirby MA, MD, FRCS(Urol)

SP

L

CPD questions available for this article. See page 24

www.prescriber.co.uk Prescriber 19 June 2011 17

BPH

overactivebladder

review at 6–12weeks review at 3–6 months

LUTS patient

GP:• history including symptomsassessment (IPSS)

• examination and DRE • urinalysis/MSU• PSA

• PSA elevated for age• DRE abnormal/ofconcern

• haematuria• elevated urea/ creatinine

• palpable bladder• recurrent UTI• abnormal cytology• severe symptoms

unresponsiveor recurrent

UTI

yes

yes

nocturia?

no

yes

nocturnalpolyuria

no yes

prostaticobstruction?

no

bothersome LUTS?

yes

risk factors for

progression?

large prostate(>30cc) or highPSA (>1.4ng/ml)

• lifestyleadvice

• alpha-blocker

yes no

risk factors for

progression?

large prostate (>30cc)or high PSA(>1.4ng/ml)

no

• lifestyle advice • 5-alpha red uct ase

inhibitor, alpha-blocker orcombination

• lifestyleadvice

• 5-alphareductase inhibitor

lifestyleadvice

Figure 1. British Association of Urological Surgeons (BAUS) guideline for the treatment of lower urinary tract symptoms; after reference 2

nonocturnalpolyuria?

treat

urinary tractinfection

urological referral

LUTS = lower urinary tract symptomsIPSS = International Prostate Symptom Score

Common causesThe commonest urological conditions presenting withLUTS are BPH and overactive bladder (OAB) syn-drome. These conditions have a high prevalence in thecommunity, with studies estimating that over one-thirdof men aged 50 or over suffer from significant symptomsfrom BPH – this would equate to approximately 3.2 mil-lion men in the UK alone. There is no doubt, however,that there are a huge number of men with significantLUTS who are not receiving optimal treatment. This isfor a variety of reasons, including failure to present toa healthcare professional (‘these symptoms are just anormal feature of ageing’), delayed presentation, dis-missal of symptoms at initial assessment, misdiagnosis,incorrect choice of treatment, cessation of treatmentdue to side-effects, and not referring to secondary carefor failed treatment at a primary-care level.

AssessmentGPs are now encouraged to make a full assessment ofthe patient presenting with LUTS through history tak-ing, general and clinical examination and a numberof simple investigations.

Many men with LUTS can be effectively managedin a primary-care setting. There has been a tendencyto refer patients with LUTS for urological assessment,particularly due to fear of missing a patient withprostate cancer. The guideline makes it clear that, pro-vided an adequate assessment is carried out, medicalmanagement can be safely instituted in a communitysetting without the need for immediate specialistinvolvement. It is only those patients with complex pre-sentations or who fail to respond to initial therapy thatshould be referred for specialist urological assessment.

Care, however, is required to ensure that a diagno-sis of prostate cancer or carcinoma-in-situ (CIS) of thebladder is not overlooked. For this reason a digital rec-tal examination (DRE), a prostate specific antigen(PSA) determination and dipstick with subsequent cys-toscopy or cytological examination of the urine shouldbe considered, as appropriate, in addition to the usualflowmetry and ultrasonic measurement of the postvoidresidual (PVR) volume of urine.

Medical managementRecent advances in medical therapy have revolu-tionised the care of LUTS patients, with a dramaticreduction in the number of patients requiring surgicaltreatment. It has also transformed the specialty of urol-ogy from an exclusively surgical specialty to one inwhich a large number of patients can be successfullymanaged in the community.

Overactive bladderMedical management of OAB is with anticholinergicdrugs, expecting a fairly rapid improvement in symp-toms. Side-effects from these drugs are relatively com-mon and may lead to discontinuation of treatment –it is vital that GPs therefore warn patients of possibleadverse effects, such as dry mouth and blurred vision,and encourage patients to re-attend should theseoccur. Different patients respond in different ways toanticholinergics, so if side-effects are experienced onone formulation, a trial with another is worthwhile.

Benign prostatic hyperplasiaTwo drug groups form the mainstay of managementof men with symptoms caused by BPH – alpha-block-ers, eg tamsulosin, alfuzosin, doxazosin, etc, and 5-alpha-reductase inhibitors (5ARIs), eg finasteride ordutasteride (Avodart).Alpha-blockers are generally regarded as the first-line

medical therapy for LUTS suggestive of BPH.3 Theywork by relaxing the smooth muscle of the bladderneck and prostate (see Figure 3). All alpha-blockersare similarly effective in LUTS, but older, less ‘uro -selective’ alpha-blockers such as doxazosin or terazosinhave different side-effect profiles that may limit theiruse. Alpha-blockers have a rapid onset of action andare generally well tolerated. Tiredness, dizziness andpostural hypotension may occur; moreover, they havenot been shown to lower the risk of long-term progres-sion of LUTS, eg deterioration in symptoms, acute uri-nary retention (AUR) or BPH-related surgery.5ARIs decrease the size of the prostate through

inhibition of the conversion of testosterone to its activemetabolite dihydrotestosterone. They are most useful

18 Prescriber 19 June 2011 www.prescriber.co.uk

BPH

Figure 2. A transabdominal ultrasound scan showing a benignly

enlarged prostate indenting the base of the bladder and a con-

siderable postvoid residual urine volume

in patients with significant risk factors for ‘progres-sion’, eg large prostates on DRE (estimated >30g), aPSA >1.4ng per ml (a surrogate marker of prostate vol-ume in the absence of prostate cancer), severe symp-toms and in older men.4

Combination therapy with an alpha-blocker and5ARI is recommended for patients with both moderateto severe symptoms and significant risk factors for pro-gression. Recent data from two four-year studies of com-bination therapy in men with significant risk factors hasshown combination therapy to be more effective thaneither alpha-blocker or 5ARI monotherapy in control-ling symptoms and reducing acute retention surgery.5,6

Anticholinergic drugs also have a role in the manage-ment of men with BPH; for many years, however, cli-nicians have been cautious about prescribing this classof drugs in men considered to have BPH due to a per-ceived high risk of precipitating AUR. Studies haveshown, however, that this risk is actually very low unlesspatients have severe voiding symptoms or high post-micturition residual volumes (>200ml).

Anticholinergics are particularly useful for the treat-ment of storage symptoms that have failed to respondto treatment with an alpha-blocker. These storage symp-toms are far more troublesome than voiding symptomsdue to the effect they have on a patient’s quality of life– thus improving voiding symptoms may lower theInternational Prostate Symptom Score (IPSS) and givean impression of success, but unless these symptoms offrequency, urgency and nocturia are addressed patientswill experience little improvement in quality of life.

For patients identified with nocturnal polyuria ontheir frequency volume chart (defined as passing morethan one-third of total daily urine output during thenight), if simple measures such as evening fluid restric-tion fail the guideline recommends that first-line treat-ment is a loop diuretic, eg furosemide 40mg taken at4pm. This aims to produce a diuresis during theevening, thus decreasing the number of nocturnalvoids. Desmopressin (synthetic antidiuretic hormone)is a second-line therapy, but should be prescribed withcaution and with careful monitoring of serum sodiumin the early phase of therapy in patients over the ageof 65 years to prevent the development of dilutionalhyponatraemia.

Who and when to referBy no means every patient with LUTS resulting fromBPH needs to be referred to a urologist. Those withcomplications from BPH and those who fail to respondto medical therapy will, however, need specialist eval-uation. The indications for referral include: AUR,haematuria, recurrent UTIs, bladder stones, elevatedPSA indicating a risk of prostate cancer (usually >4.0ngper ml), positive urine cytology indicating a risk oftransitional cell carcinoma (TCC) or CIS, and failureto respond adequately to medical therapy.

Surgical treatment optionsTransurethral resection of the prostate (TURP) is stillthe dominant surgical treatment option, althoughnewer techniques such as Holmium laser enucleation

20 Prescriber 19 June 2011 www.prescriber.co.uk

BPH

Figure 3. Mode of action of alpha-blockers, 5-alpha-reductase inhibitors, loop diuretics and anticholinergics in treating BPH

loop diuretics create a

diuresis in the evening (for

nocturnal polyuria)

alpha-blockers relax the smooth

muscle of the bladder neck and

prostate

5-alpha-reductase inhibitors

reduce the size of the prostate

anticholinergic drugs relax the

detrusor muscle reducing bladder

contractions and increasing capacity

of the prostate (HoLEP) are increasingly popular. Thisprocedure has good results in the literature; however,there is a steep learning curve for surgeons withHoLEP and thus it should only be performed in cen-tres specialising in the technique.7,8

For smaller prostates an alternative surgical proce-dure is transurethral incision of the prostate (TUIP),and for very large prostates (>100g) an open prostat -ectomy may occasionally be required. Bleeding andurethral strictures are the main side-effects. Erectiledysfunction and urinary incontinence should be veryrare after surgery for BPH. Newer laser techniques,such as green light laser (GLL), do not as yet have asufficient evidence base to be recommended by NICEbut are increasingly employed in the USA and else-where, especially since the introduction of the higher-powered device with a modified laser fibre.

Minimally invasive techniques such as microwavetherapy (TUMT) or needle ablation (TUNA) are notrecommended due to high failure and re-operationrates, which greatly decrease cost-effectiveness.

ConclusionsLUTS resulting from BPH are extremely common inmen beyond middle age.9 Traditionally, patients suffer-ing from this disorder have been primarily referred toa urologist for specialist surgical care; however, this par-adigm is now changing and more and more men arebeing managed in primary care by GPs with an interestin men’s health. The forthcoming shift of purchasingpower to GPs is only likely to promote this trend.

While overall this is likely to be in the best interestof patients, GPs will need to be cautious to avoid over-looking a more serious and sinister diagnosis ofprostate or bladder cancer. They will also need to beprompt in referring those men who are failing torespond to first-line medical therapy, as well as thosewho are developing complications of their BPH.

References1. NICE. Management of lower urinary tract symptoms in men.Clinical Guideline 97. May 2010.2. Speakman MJ, et al. BJU Int 2004;93:985–90.3. Kaplan S. BJU Int 2008;102 Suppl 2:3–7.4. Roehrborn CG, et al. Urology 2004;63:709–15.5. Roehrborn C, et al. J Urol 2008;179(2):616–21.6. McConnell JD, et al, N Engl J Med 2003;349:2387–98.7. Gilling P. BJU Int 2008;101:131–42.8. Hoekstra RJ, et al. BJU Int 2010;106:822–6.9. Kirby RS, et al. Fast facts: Benign prostatic hyperplasia. 6th ed.Abingdon: Health Press, 2009.

Roger Kirby is professor of urology and director of TheProstate Centre, London

22 Prescriber 19 June 2011 www.prescriber.co.uk

BPH

BPH

Prescription review

Prescribing of drugs used to treat BPH continuesto increase, growing by over 20 per cent since 2007

but with a similar fall in costs to £78.2 million in 2010.Alpha-blockers – which, with the exception of alfu-zosin and tamsulosin, are also prescribed for hyper-tension – accounted for over 80 per cent of volumeand cost of BPH drugs, whereas the two 5-alpha-reduc-tase inhibitors accounted for less than 20 per cent. Two drugs make up the bulk of prescribing for alpha-blockers. Doxazosin use has changed little but prescrib-ing of tamsulosin has increased by 15–18 per cent peryear in each of the last five years, though total spendingon this drug is now less than half of the 2005 level. Prescribing of dutasteride has also been rising ata rate of 15–17 per cent since 2006, faster than finas-teride in the past two years (11 per cent). Followingprice cuts, spending on finasteride is now about one-quarter what it was in 2007 whereas cost growth hasresumed for dutasteride, with spending in 2010 up11 per cent on 2009.

Alpha-blockers*

alfuzosin 668 10 474

doxazosin 5 927 29 335

indoramin 122 1 654

prazosin 81 464

tamsulosin 3 480 20 409

terazosin 155 870

5-alpha-reductase inhibitors

dutasteride 407 9 088

finasteride 1 779 5 706

Combined formulation

dutasteride/tamsulosin 9 201

*includes all formulations, some of which are prescribed forother indications

Items (000) Cost (£000)

Table 1. Number of prescriptions and costs for drugs used inBPH in England, 2010

24 Prescriber 19 June 2011 www.prescriber.co.uk

BPH

1. One of these statements about men presenting with LUTS inprimary care is false – which is it?a. Over one-third of men aged 50 or over suffer from significant

symptoms from BPHb. Tests to rule out a diagnosis of prostate cancer include a digi-

tal rectal examination, a PSA determination and cystoscopy orcytological examination of the urine, as appropriate

c. The reasons why men with significant LUTS may not receiveoptimal treatment include failure to present to a health pro-fessional

d. Only patients with complex presentations should be referredfor specialist urological assessment

2. Which one of these statements about the medical manage-ment of LUTS suggestive of OAB is false?a. Storage symptoms are far more troublesome than voiding

symptomsb. Patients should be encouraged to reattend if they experience

side-effects with an anticholinergicc. If side-effects occur with one anticholinergic, there is no point

in trying a different one because the response will be the samed. A fairly rapid improvement in OAB symptoms should be

expected with anticholinergic drug treatment

3. Which one of these statements about alpha-blockers isfalse?a. They are generally regarded as the first-line medical therapy

for LUTS suggestive of BPHb. They are similarly effective in LUTSc. Older, less ‘uroselective’ alpha-blockers such as doxazosin or

terazosin have side-effect profiles that may limit their use inLUTS

d. They have a slow onset of action and are generally poorly tol-erated

4. One of these statements about the treatment of LUTS sugges-tive of BPH is false - which is it?a. Combination therapy with an alpha-blocker and a 5ARI is rec-

ommended for patients with mild LUTSb. 5ARIs are considered most useful in patients with significant risk

factors for progressionc. Combination therapy is more effective than monotherapy with

either an alpha-blocker or a 5ARI in controlling symptoms andreducing acute retention surgery over four years

d. Risk factors for progression of BPH include a large prostate onDRE, a PSA >1.4ng per ml, severe symptoms and older age

5. Regarding other aspects of the treatment of LUTS suggestiveof BPH, which one of these statements is false?a. The risk of precipitating AUR with anticholinergic drugs is very

low in the absence of severe voiding symptoms or high post-micturition residual volumes

b. Anticholinergics are not useful for treating storage symptomsthat have failed to respond to an alpha-blocker

c. Patients with nocturnal polyuria should be offered furosemide,to be taken at 4pm, if evening fluid restriction fails

d. Treatment with desmopressin requires careful monitoring ofserum sodium in the early phase of therapy in patients over theage of 65 years

6. Which of these statements about referral and surgery forpatients with LUTS is false?a. Indications for referral include recurrent UTIs and haematuriab. Holmium laser enucleation of the prostate should only be per-

formed in centres specialising in the techniquec. An alternative surgical procedure for large prostates is

transurethral incision of the prostated. Minimally invasive techniques such as microwave therapy or

needle ablation have high failure and reoperation rates

CPD: recommended treatment of BPHAnswer these questions online at Prescriber.co.uk and receive acertificate of completion for your CPD portfolio. Utilise theLearning into Practice form to record how your learning has con-tributed to your professional development.

ResourcesGuidelineNICE. Management of lower urinary tract symptoms in men.Clinical Guideline 97. May 2010.

Groups and organisationsBodytalk Online. www.bodytalk-online.com. Websitewith audio tapes that you can hear online. DoctorHilary Jones explains a wide range of medical condi-tions, including prostate enlargement.

Men’s Health Matters. www.menshealthmatters.co.uk.

British Prostatitis Support Association. www.bps-assoc.org.uk.

Men’s Health Forum. Tel: 020 7922 7908; www.menshealthforum.org.uk.

Prostate Action (formerly Prostate UK). Tel: 020 87887720. www.prostateaction.org.uk.

Prostate Help Association (PHA). www.prostatehelp.me.uk.