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URO6110.1177/2051415812473243Journal of Clinical UrologyParnham and Haq

Continuing Medical Education: Review

Journal of Clinical Urology
6(1) 2431
British Association of
Urological Surgeons 2013
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DOI: 10.1177/2051415812473243
uro.sagepub.com

Benign prostatic hyperplasia

Arie Parnham and Ahsanul Haq

Abstract
Male Lower Urinary Tract symptoms (LUTs) and Benign Prostatic Hyperplasia (BPH) provide a significant proportion
of the core urologists workload, and will continue to do so for the foreseeable future with an increasingly elderly
population. This review sets out to provide an overview of the current understanding around BPH and male LUTs as
well as investigations and treatment options.
Keywords
alpha-blockers, NICE, benign prostatic hyperplasia, combination therapy, EAU, lower urinary tract symptoms, post-void
residual, PSA, symptoms scores,TURP, 5--reductase inhibitors

Introduction
In todays expanding elderly population the significance of
benign prostatic hyperplasia (BPH) is becoming more important to the urologist. It has long been established that the prevalence of BPH increases with age, with 50% of men in their
50s and 88% of men in their 80s having histological evidence.1,2

Definitions
BPH refers to the histological process of hyperplasia of the
prostate. The now redundant term prostatism was used
broadly to cover the clinical, pathological and pathophysiological elements of BPH and lower urinary tract symptoms
(LUTS) and wrongly suggested organ and gender specificity.
In response Abrams and Chapple et al., proposed a series of
definitions which would more accurately reflect the clinical,
pathological and pathophysiological components (Table 1).3,4

Aetiology
It is felt that initially there is an increase in the number of
small stromal periurethral and transitional zone glandular
nodules secondary to embryonic reawakening.6,7 A second
phase is characterised by an increase in larger nodules, and
in the stromal-epithelial ratio.7,8
The exact molecular cause behind the development
of BPH is not fully understood although a complex
The platform for answering on-line CME questions will be released later
in 2013.

interaction of androgens, oestrogens, stromal epithelial

interactions, growth factors (epidermal growth factor
(EGF), insulin-like growth factor (IGF), keratinocyte
growth factor (KGF), transforming growth factor (TGF)-)
and neurotransmitters are implicated).9 Other risk factors
are identified in Table 2.
Approximately 25% of the prostate is composed of
smooth muscle under the control of the adrenergic nervous
system (1a receptors) and contributes actively and passively to the pathophysiology of BPH and is the focus of
some medical treatments.10
The portrayal of the clinical manifestations of BPH
(LUTS) simply being attributed to a mass effect and tonicity is somewhat simplistic and incorrect. The prostate itself
cannot be considered in isolation and changes to the bladder
must be considered to fully appreciate the clinical manifestations. Indeed there is an increase in the urethral pressure
but this leads to compensatory changes in bladder function
which is already affected by age-related changes and neurological degeneration. At first the bladder increases its detrusor action to compensate but over time will hypertrophy,

Department of Urology, Royal Preston Hosptial, Preston, UK.

Corresponding author:
Arie Parnham, Department of Urology, Royal Preston Hospital, Sharoe
Green Lane, Fulwood, Preston, PR2, 9HT, UK
Email: arie_parnham@hotmail.com

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Parnham and Haq

Treatment
Non-surgical
There are a number of conservative strategies aimed at patients
demonstrating mild to moderate LUTS. EAU and NICE agree
on the education of the patient, reassurance of benign disease
and periodic monitoring. Lifestyle advice should also be given
and can empower and relieve symptoms without the risks of
medical or surgical treatment (see Table 4).
Alpha-blockers (ARBs)
Mechanism. There are three forms of 1 adrenoreceptors: 1a, which is primarily found in the prostate,
1b in blood vessels and 1d in the bladder. Of the 1a
type there are at least four different subtypes: a14, with
a1 being the predominant variant found in the prostate
and heart. It was felt that the alpha blockers effect was
through the antagonism of noradrenaline on the 1a

27

adrenoreceptors in the prostate leading to a reduction in

prostatic tone and accordingly bladder outflow obstruction. Unfortunately ARBs have failed to demonstrate a

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Journal of Clinical Urology 6(1)

5 alpha reductase Inhibitors (5-ARI)

Mechanism. The effect of testosterone and dihydrotestosterone (DHT) on the prostate and development of BPH
has been well documented. The 5 reductase inhibitors
(5-ARI) competitively inhibit the 5-reductase enzyme
which converts testosterone to the more active DHT. Finasteride, however, unlike dutasteride, doesnt reduce DHT to
castrate levels as it blocks only the type 2 isoform.
Efficacy. The enlarged Prostate International Comparator Study (EPICs) demonstrated that in those studied (i.e.
patients over 50 years old with a Qmax < 15 ml/s, AUASI > 12 and prostate volume > 30 ml) over a 12-month
period of 5-ARI use, the mean reduction of prostate volume was 26.7 vs. 26.3% for finasteride and dutasteride,
respectively (p=0.65). Further there was a reduction of
AUA-SI of 5.5 for finasteride and 5.8 with dutasteride
(p=0.38).34
The Proscar Long-term Efficacy and Safety Study
(PLESS) (a double-blinded European randomised, placebo-controlled trial, using finasteride 5 mg once daily in
men with Qmax < 15 ml/sec, a residual volume of > 150
ml, moderate to severe symptoms and BPE on DRE),
found that there was a 55% and 57% relative risk reduction in men requiring surgery and having an episode of
acute urinary retention, respectively, in the finasteride
arm.35
Side effects. Side effects include reduced libido, erectile dysfunction and abnormal ejaculation.36
Combination therapy. There have been a number of studies
that have examined the possible benefits and potential difficulties in using combination therapy. Short-term studies
(52 weeks) such as the Veterans Affairs Co-operative and
the Prospective European Doxazosin and Combination
Therapy trial (PREDICT) have demonstrated that although
patients on both ARB monotherapy and combination therapy (ARB+5ARI) show a significant improvement in outcome measures, specifically flow rate and symptom scores
(IPSS), there is no significant difference between monotherapy or combination therapy.37,38
However, longer-term data from the Medical Therapy
of Prostatic Symptoms trial (MTOPs) show that combination therapy significantly reduced the risk of clinical progression when compared with placebo and monotherapy
over a mean 4.5-year follow-up.27 Further post-hoc analysis showed, however, the difference in effect became less
significant as prostate volume decreased to a point where
there was no statistical difference in prostates < 25 ml in
volume.39
The Combination of Avodart and Tamsulosin trial
(COMBAT) aimed to characterise the benefit of combination therapy in larger prostates and recruited men with
prostates over 30 ml in size with an IPSS of at least 12.40
The multicentre double-blinded trial accepted 4844 men
50 years old and was run for four years. It concluded that

combination therapy had a significantly greater improvement in symptom score as well as peak urinary flow rates
from baseline than dutasteride or tamsulosin, as well as
reducing the relative risk of acute urinary retention (AUR)
or BPH-related surgery over four years by 66% compared
with tamsulosin monotherapy. Unfortunately those on
combination therapy suffered from a higher frequency of
adverse events.

Other treatments
Antimuscarinics
In some cases a degree of bladder overactivity may coexist or masquerade as BOO and as such the standard
treatment measures may fail. Several small studies have
looked at the concomitant use of antimuscarinics in resistant cases and have demonstrated positive effects. The
only placebo-controlled, randomised trial comparing the
combination of ARB and antimuscarinics to individual
therapy, demonstrated that in isolation the therapies performed less well compared with placebo but in combination showed good efficacy in improving QoL scores.41
Concerns over precipitating an episode of AUR exist.
PVR has been shown to be statistically significantly
increased in those on both ARB and an antimuscarinic
compared with monotherapy or placebo, although none of
the patients in the dual therapy group went on to develop
clinical retention.42

Saw palmetto
Derived from the serenoa repens, saw palmetto is thought
to be the active ingredient. Apart from one systematic
review and meta-analysis in 1990 by Wilt et al., the
general consensus from more recent randomised controlled trials (RCTs) do not support the efficacy of saw
palmetto over placebo and hence its exclusion from
guidelines.43

Botulinum toxin
There have been promising small studies examining the use
of intraprostatic botulinum toxin use as well as NX-1207
which have shown a reduction in prostate volume and
symptom scores.44 The NICE recommendation is for its use
only as part of an RCT.

Surgical treatments
The transurethral resection of the prostate (TURP) continues to be the benchmark treatment of BOO and BPH. In a
systematic review, TURP has been shown on average to
improve the mean AUA/ IPSS score from 18.8 to 7.2
(62%) after 12 months post-op as well as improve Qmax

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Parnham and Haq

by 9.7 ml/s, a mean increase of 120%.45 Approximately
1015% of patients within 10 years will require further
intervention.46 The standard workup is similar to that of
medical treatment. Contention still exists in the role of
urodynamic assessment and although none of the current
guidelines recommend pressure flow studies there are certainly patients who merit further characterisation such as
patients <50 or >80 years old, those with previous unsuccessful invasive therapy, high post-void residuals (>300
ml) and previous pelvic surgery. Indications and morbidity are listed in Tables 5 and 6.
However, over the last 20 years the numbers of alternative surgical treatment options have flourished (Table 7) as
clinicians have endeavoured to treat increasingly more
complex elderly patients. The introduction of bipolar TURP
has improved the safety profile by removing the concern of
TUR syndrome. However, the majority of these falls short

of the benchmark of TURP and only holmium laser enucleation of the prostate (HoLEP) provides comparable outcomes and longevity.36
Table 5. Indications for TURP.36
Indications
LUTS refractory to medical therapy
Recurrent UTI
BPH- or BPE-related visible haematuria refractory to
treatment
Renal insufficiency secondary to BOO
Bladder stone(s)
Recurrent urinary retention
LUTS: lower urinary tract symptoms; UTI: urinary tract infection; BPH:
benign prostatic hyperplasia; BPE: benign prostatic enlargement; BOO:
bladder outlet obstruction.

Table 6. Complications of TURP.47

Intraoperative

Perioperative/early

Bleeding requiring
transfusion
TUR syndrome

010%
<1%

Long-term

Bladder tapenade

15%

Strictures

29%

Urinary retention
Urinary tract infection

39%
420%

Incontinence
Retrograde ejaculation
Bladder neck stenosis

<0.5%
90%
09%

TURP: transurethral resection of prostate; TUR: transurethral resection.

Table 7. Summary of available treatments and recommendations.5,36

Therapy

Action

TUMT
(transurethral
microwave
thermotherapy)

HoLEP (holmium
laser enucleation
of prostate)

Simple, safe, fewer

complications and
relatively quicker than
TURP. Can be performed
under local anaesthetic
Transurethral catheter delivers Simple, safe, fewer
low level radiofrequency
complications and
(460 kHz) to prostate via
relatively quicker than
deployable needles generating TURP. Can be performed
temperatures >100C
under local anaesthetic
End firing pulsed solid state
Similar outcomes
laser 2140 nm wavelength
to TURP. Fewer
removes the adenoma whole
complications than TURP

KTP laser
(potassium titanyl
phosphate)

Nd:YAG laser passed through

KTP crystal giving wavelength
of 532 nm

TUNA
(transurethral
needle ablation)

Pros

Transurethral antenna delivers

heat>45C to prostate through
microwave radiation 915/1296
MHz

Cons

NICE 2010 EAU 2011

Poorer outcomes and N

longevity than TURP

RA

Poorer outcomes and N

longevity than TURP

RA

Longer operating
S
time, steep learning
curve, high initial cost,
requires morcellation
to remove tissue
Easy to learn, safe, Similar Longer operative
RCT
outcomes to TURP
time, lack of
histological tissue for
evaluation, high cost,
lack of medium to
long-term data

RA

NICE: National Institute for Health and Clinical Excellence; EAU: European Association of Urology; TURP: transurethral resection of prostate; N: not
recommended; RA: recommended alternative where standard treatment not suitable; S: only at specialist centres; R: recommended; RCT: only as part
of a randomised controlled trial.

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Journal of Clinical Urology 6(1)

Conclusion
BPH is a complex condition with a yet to be fully understood pathophysiology. The diagnosis and treatment of the
condition has been refined and are moving to less invasive
but effective treatments.
Funding
This research received no specific grant from any funding agency
in the public, commercial, or not-for-profit sectors.

Conflict of interest
The authors declare that there are no conflicts of interest.

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