Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia

INTRODUCTION Benign prostatic hyperplasia (BPH) is a common disorder that

increases in frequency progressively with age in men older than 50 years (figure
1). The clinical manifestations and the diagnostic approach to patients suspected of
having BPH will be reviewed here. The epidemiology, pathogenesis and treatment
of this disorder, and lower urinary tract symptoms in men and acute urinary
retention are discussed separately. (See
" Ep id em iolo gy and p at hoge ne sis of be nig n p r os ta tic hype r pla s ia"
and " M ed ical tr ea tm en t of
b en ign p rost at ic hyp e rp lasia " and " Tr an s ure t hral p roce dur e s f or tr
e at ing b eni gn pr ost at ic
hyp er p lasia" and " Low er u rin ary t ract sy mp tom s in me n" and " Acut
e ur inar y r e te nt ion" .)
NATURAL HISTORY The prevalence of moderate-to-severe lower urinary tract
symptoms (LUTS) and decreased peak urinary flow rates increases with age, and
there is a modest correlation among LUTS, peak flow rates, and prostate volume.
(See "E p ide miolog y a nd
p at hoge ne sis of b e nig n p r ostat ic hype r pla s ia" , se ct ion on ' Pr eva
len ce' and " L owe r ur inar y t r act
sym pt o ms in m en ", se ction on 'P re vale nc e ' .)
In a small percentage of men, untreated BPH can cause acute urinary retention,
recurrent urinary tract infections, hydronephrosis, and even renal failure. It is
estimated that a 60 year old man with moderate-to-severe symptoms would have
a 13.7 percent chance of developing acute
urinary retention in the following 10 years. Age, symptoms, urinary flow rate, and
prostate volume are risk factors for acute urinary retention at least in populationbased studies, though not in all clinical trials [ 1 ]. Men with symptomatic BPH who
are not treated have about a 2.5 percent per-year risk of developing acute urinary
retention [2,3]. (See " Acute u rin ary r et en tion " .)

The natural history of BPH has been examined both in population-based studies
and by looking at outcomes in the placebo arms of clinical trials. However, studies
have found that outcomes among patients in the placebo arms of clinical trials
may not accurately reflect outcomes in the general population [ 4] . In clinical
trials, measurements of LUTS and peak urine flow tend to show a regression to the
mean; whereas, this is not seen with measurements of prostate volume and PSA
[ 5] . A systematic review of the placebo arms of 16 randomized trials of medical
treatment lasting for one to four years found that the risk of surgery ranged from 1
to
10 percent, and the risk of acute urinary retention ranged from 0.4 to 6.0 percent
[ 6 ]. Patients experience some progression in symptoms, increase in prostate
volume, and decrease in peak urine flow rate that can result in a need for
invasive treatment.
Men may or may not have progressive symptoms. In one study, for example, about
one-third of men had a 50 percent reduction in the severity of their symptoms of
urinary obstruction when followed with no treatment for 2.5 to 5 years after
symptom onset [7]. On the other hand, many men have progressive disease that
eventually requires treatment [8]. In a prospective study of
1057 men, over 30 years of follow-up, 527 (50 percent) were given a diagnosis of
BPH and 110 (10 percent) underwent prostatectomy [9]. The Health Professionals
Follow-up Study provides the largest and longest evaluation of LUTS in men ages
40 to over 75 [ 1 0 ]. Participants completed and mailed the International Prostate
Symptom Score (IPSS) (table 1) every two years from 1992 to 2008. The study
found that progression rates rise steeply as men age. Investigators in the Florey
Adelaide Male Ageing Study conducted a five-year follow-up of 780 men between
the ages of 35 and 80 years at baseline [11]. They found that storage and voiding
lower urinary tract symptoms progressed in 39.8 and 32.3 percent, and improved
in 33.1 and
23.4 percent, respectively. Older age, previous diagnosis of BPH or erectile
dysfunction, and lower high-density lipoprotein (HDL) cholesterol, testosterone, and
income predicted progression of LUTS. Increased physical activity and use of an
alpha-blocker and/or a 5-alpha- reductase inhibitor improved symptoms.

Investigators in the United States Osteoporotic Fractures in Men (MrOS) Study

evaluated men
65 every two years with the American Urological Association (AUA) symptom index
[12]. They started with 3594 men and evaluated 1740 men after eight years.
Seventy-three percent remained stable, 20 percent progressed, 6 percent
regressed, and 1 percent had a mixed response. Compared with men who were
stable, those that progressed were more likely to have mobility limitations (OR 2.0,
95% CI 1.00-3.8), poor mental health (OR 1.9, 95% CI 1.1-3.4), body mass index
25.0 kgm2 (OR 1.7, 95% CI 1.0-2.8), hypertension (OR 1.5, 95% CI 1.0-2.4), and
back pain (OR 1.5, 95% CI 1.0-2.4). Men who remitted, compared with progressing,
more often used central nervous system medications (OR 2.3, 95% CI 1.1-4.9) and
less often had a history of problem drinking (OR 0.4, 95% CI 0.2-0.9).
Prostate cancer BPH is not believed to be a risk factor for prostate cancer,
although studies have come to conflicting results [13]. BPH occurs primarily in the
central or transitional zone of the prostate, while prostate cancer originates
primarily in the peripheral part of the prostate. Determining a causal association
between BPH and prostate cancer is difficult because both
diseases are common in older men and because BPH may increase the likelihood
of a patient being tested for prostate cancer. However, an analysis from the
placebo arm of the Prostate Cancer Prevention Trial, where routine biopsies were
performed, did not find an association between BPH and an increased risk of
prostate cancer [14].
CLINICAL MANIFESTATIONS The clinical manifestations of BPH are lower urinary
tract symptoms (LUTS) that include storage symptoms (increased daytime
frequency, nocturia, urgency, and urinary incontinence), voiding symptoms (a slow
urinary stream, splitting or spraying of the urinary stream, intermittent urinary
stream, hesitancy, straining to void, and terminal dribbling), and irritative
symptoms (frequent urination, urinary urgency). These symptoms typically appear
slowly and progress gradually over a period of years. However, they are not specific
for BPH. Many conditions, including BPH, detrusor overactivity, nocturnal polyuria,
detrusor underactivity, neurogenic bladder dysfunction, urinary tract infection,
foreign body, prostatitis, urethral stricture, bladder tumor, and distal ureteral stone

can present with LUTS [15]. (See " L o w er ur ina ry tr act sym pt oms in m en
" , se cti on on 'S ym pt oms ' .)
The correlation between symptoms and the presence of prostatic enlargement on
rectal examination or by transrectal ultrasonographic assessment of prostate size is
poor. This discrepancy probably results from changes in bladder function that
occur with aging and from enlargement of the transitional zone of the prostate that
is not always evident on rectal examination [ 1 6 ].
Patients with BPH may also have hematuria. However, the presence of BPH should
not dissuade the clinician from further evaluation of hematuria, particularly since
older men are more likely to have serious disorders such as cancer of the prostate
or bladder. (See " Et iolog y
an d e valua tion o f he ma tur ia in a dult s" .)
DIAGNOSTIC APPROACH Before one concludes that a man's symptoms are
caused by BPH, other disorders that can cause similar symptoms should be
excluded by history, physical examination, and several simple tests. These
disorders include:
Urethral stricture

Bladder neck contracture

Carcinoma of the prostate

Carcinoma of the bladder

Bladder calculi

Urinary tract infection and prostatitis

Neurogenic bladder
Clinical guidelines were developed by the Agency for Health Care Policy and
Research, including a standardized questionnaire and recommendations regarding
the evaluation of men with symptoms of bladder outlet obstruction [17]. The
American Urologic Association (AUA)
updated these guidelines in 2010 [
8 ], which recommended optional steps for diagnosing and
treating lower urinary tract symptoms (LUTS). The European Association of Urology
(EAU) also has developed guidelines with recommended and optional evaluations,
and they differ somewhat from those of the AUA [15,19].
History The history may provide important diagnostic information. In addition to
questioning the man about obstructive urinary symptoms, it is important to ask
about the following:
History of type 2 diabetes, which can cause nocturia and is a risk factor for BPH
[ 20 ,2 1 ]

Symptoms of neurologic disease that would suggest a neurogenic bladder

Sexual dysfunction, which is correlated with LUTS [22-24]

General health and fitness for possible surgical procedures

Gross hematuria or pain in the bladder region suggestive of a bladder tumor or

calculi

History of urethral trauma, urethritis, or urethral instrumentation that could lead

to urethral stricture
Family history of BPH and prostate cancer

Treatment with drugs that can impair bladder function (anticholinergic drugs) or
increase outflow resistance (sympathomimetic drugs)
The EAU recommends a 24-hour voiding chart with assessment of frequency and
volume [15]. Lower urinary tract symptoms in men are discussed in detail
separately. (See " L owe r ur inar y
t ra ct symp tom s in me n". )
American Urologic Association symptom score The AUA symptom score was
developed to measure outcomes in studies of different treatments for BPH (table 2)
(calculator 1) [ 2 5 ]. It should be used to assess the severity of symptoms of BPH,
but not for differential diagnosis. It consists of seven questions: frequency, nocturia,
weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency,
each of which is scored on a scale of 0 (not present) to 5 (almost always present).
Symptoms are classified as mild (total score 0 to 7), moderate (total score 8 to 19)
and severe (total score 20 to 35).
The AUA symptom score is a useful way to assess symptoms over time in a
relatively quantitative way. In one study, for example, the mean score decreased
from 17.6 to 7.1 in four weeks in a group of men who underwent transurethral
prostatectomy [ 2 5 ]. Individual men answer the questions in a reproducible way,
and the results appear to be valid when the questionnaire is administered by an
interviewer to visually impaired and illiterate men [ 26 ]. However, it correlates
poorly with prostate size and peak urinary flow rates [ 2 7 -2 9] .

The International Prostate Symptom Score (IPSS) uses the same questions and
scale as the AUA symptom score and adds a disease-specific quality of life
question: "If you were to spend the rest of your life with your urinary condition the
way it is now, how would you feel about that?" [ 29 ].
It also has been shown that a voiding diary that includes nocturia, diuria and void
volume may provide more meaningful information of prostate volume and
maximum urinary flow rates than AUA symptom score [30]. A voiding diary has
been developed and validated by the International Consultation on Incontinence
[31].
Physical examination A digital rectal examination should be done to assess
prostate size (normal prostate size between 7 to 16 grams, with an average of 11
grams [32]) and consistency and to detect nodules, induration, and asymmetry, all
of which raise suspicion for malignancy (see " Cli nical pr e sent at ion and dia gn
osis of p r os tat e can cer ") . Rectal sphincter tone should be determined, and
a neurological examination performed.
RECOMMENDED TESTS The American Urologic Association (AUA) recommends a
urinalysis and a serum PSA for the routine management of patients with lower
urinary tract symptoms (LUTS) [18]. We also obtain a serum creatinine for assessing
renal function and evaluate for possible urinary obstruction.
Urinalysis Urinalysis should be obtained to detect the presence of urinary
infection or blood; the latter could indicate bladder cancer or calculi. It is unclear
whether benign hematuria is more common in patients with BPH than in agematched controls [ 3 3, 34 ]. However, the presence of BPH should not dissuade the
clinician from further evaluation of hematuria, particularly since older men are
more likely to have serious disorders such as cancer of the prostate or bladder.
(See "E t iology and e valua tion of he mat ur ia in a dult s ". )
Among those with gross hematuria in whom no cause other than BPH can be
identified,
f ina s te ri de often suppresses the hematuria [35,36].

Serum creatinine The American Urologic Association (AUA) does not recommend
obtaining a serum creatinine in the routine management of patients with BPH,
however, we generally obtain a serum creatinine as part of routine assessment.
The EAU considers this a cost-effective test [15]. A high serum creatinine may be
due to bladder outlet obstruction or to underlying renal or prerenal disease; it also
increases the risk for complications and mortality after prostatic surgery.
Ultrasonography of the bladder, ureters and kidneys is indicated if the serum
creatinine concentration is high. (See ' Ultr ason ogr ap hy an d p lai n ab dom
inal r adiog r aphs ' below.)
Serum prostate specific antigen Prostate cancer can cause obstructive
symptoms, although the presence of symptoms is not predictive of prostate cancer [
2 6 ]. Measurements of serum PSA may be used as a screening test for prostate
cancer in these men with BPH, preferably in men between the ages of 50 to 69
years and before therapy for BPH is discussed. Measurement of PSA is
recommended by the EAU [15]. The following points should be kept in mind when
serum PSA determinations are ordered and the results interpreted (see
" Me asur e me nt of p rost at e sp ecif ic ant ig en" ):

The specificity of the serum PSA assay is lower in men with obstructive symptoms
than in asymptomatic men [ 3 7 ]. In men with prostate enlargement, the serum
PSA value and prostate volume have a log-linear relationship [38,39], but there
are conflicting data on its utility for predicting development of LUTS [40,41]. Older
men tend to have a steeper rate of increase in prostate volume with increasing
serum PSA concentrations. Free PSA appears to have a higher correlation with
prostate volume than total PSA [42].
High values occur in men with prostatic diseases other than cancer, including
BPH.

Some men with prostatic cancer have serum PSA concentrations of 4.0 ng/mL (a
widely used cut-off value) or less. (See " S cr e eni ng f or pr ost ate ca nce
r" , sect ion on ' Ef f e ct of low er ing P S A

cut of f s'. )
A combination of digital rectal examination and serum PSA determination provides
the most acceptable means for excluding prostate cancer.
OPTIONAL TESTS Several other tests may be performed as part of the evaluation
of men
with BPH, however, the American Urologic Association (AUA) considers them
optional. Maximal urinary flow rate, post-void residual urine volume, and urine
cytology are useful in most men
with suspected BPH.
Maximal urinary flow rate Maximal urinary flow rates greater than 15 mL/sec
are thought to exclude clinically important bladder outlet obstruction. Maximal flow
rates below 15 mL/sec
are compatible with obstruction due to prostatic or urethral disease; however, this
finding is not diagnostic since a low flow rate can also result from bladder
decompensation. To reduce the variability in flow rates, the voided volume should
be more than 150 mL. A prevoid bladder volume of > 250 mL with a bladder scan
can help to insure that the void volume is > 150 mL [43]. Among men with BPH,
those with maximal flow rates less than 10 mL/sec have better outcomes after
surgical intervention than those with higher flow rates. Uroflowmetry is
recommended by the EAU [15].
Post-void residual urine volume Residual urine volume can be determined by inout catheterization, radiographic methods, or ultrasonography. The bladder scanner,
which can be used in an office, has made this measurement simple because it does
not require catheterization or radiologic assistance. Normal men have less than
12 mL of residual urine [44]. In addition to being a possible indicator of BPH, a large
residual volume is probably associated with increased risk of infection and is a
precursor to bladder decompensation. Measurement of the post-void residual urine
volume is recommended by the EAU [15].

In the past, large post-void residual urine volumes were considered to indicate the
presence of severe BPH requiring surgery; however, outcome studies supporting
this view are lacking. A Veterans Administration Cooperative Study comparing
transurethral prostatic resection and watchful waiting in 556 men with moderate
symptoms of BPH demonstrated that post-void
residual urine volume was not a predictor of surgical outcome [
5] .
Urine cytology Urine cytology may be helpful in men with predominantly
irritative symptoms. It may be considered in men with a smoking history, since this
is a risk factor for bladder cancer. (See "E p ide miolog y a nd risk fa ctor s of urot
he lial (t ra nsit ional cell ) car cinom a of t he
b ladd er " , sect ion on ' Ci gar e tt e smok e '. )
NOT RECOMMENDED TESTS The American Urologic Association does not
recommend the following tests in routine evaluation of BPH. However, they may be
useful in individual cases.
Pressure-flow studies Measurement of the pressure in the bladder during voiding
provides the most accurate means for determining bladder outlet obstruction;
however, this requires either transvesical or transurethral insertion of a catheter
into the bladder. In a study of 108
men with obstructive symptoms in whom urine flow rates were measured and
pressure-flow studies done, only three percent of those with maximal flow rates
below 12 mL/sec were misclassified [ 4 6 ]. This test is usually reserved for men
with urinary symptoms and maximal flow rates above 15 mL/sec and those in
whom the clinical manifestations are atypical and there is reason to suspect some
problem other than or in addition to BPH.
Urethrocystoscopy Urethrocystoscopy is not recommended for routine evaluation.
It can be useful in detecting calculi, urethral stricture, and bladder cancer. Some
urologists routinely perform urethrocystoscopy to assist in planning for surgical
therapy of men with BPH.

Intravenous urography The large number of normal tests (70 to 75 percent) and
low rate of detection of abnormalities that change treatment has reduced the
frequency with which intravenous urography is performed in men with obstructive
and irritative symptoms. In one report, for example, only two to three percent of
men had findings that changed treatment [ 4 7] . Hematuria, a history of renal
stones, urinary tract infection, or previous urinary tract surgery are indications for
intravenous urography.
Ultrasonography and plain abdominal radiographs Ultrasonography is useful in
men who have a high serum creatinine concentration or a urinary tract infection. It
can be coupled with plain radiographs of the kidneys, ureters, and bladder. If a
bladder calculus is diagnosed, it should be considered the result of bladder outlet
obstruction until proven otherwise.
Despite the fact that BPH occurs in the central or transitional zone of the prostate,
ultrasound measurements of central zone volume do not appear to correlate better
with lower urinary tract symptoms than measurements of total prostate volume
[48].
Total prostate volume can be measured by ultrasonography to assess disease
progression, and it is useful when considering medical treatment with a 5-alphareductase inhibitor or when considering surgery [40,49].
When prostate volume was compared with enucleated prostate weight in men with
BPH undergoing open prostatectomy, transrectal ultrasound slightly underestimated
volume by 4.4 percent (95% CI, 1.7-10.5), while transabdominal ultrasound
overestimated volume by 55.7 percent (95% CI, 31.8-79.6) [50]. This information
may be helpful in interpreting different types of ultrasound in order to determine
which patients should have open prostatectomies.
Newer technologies It also is possible that newer imaging modalities, such as
contrast- enhanced MRI and MR diffusion will be able to differentiate glandularductal versus stromal-low ductal tissues [51]. Such information may aid in the

detection of cancer and its grading. It is still unclear whether this information will
prove to be cost-effective.
INFORMATION FOR PATIENTS UpToDate offers two types of patient education
materials, "The Basics" and "Beyond the Basics." The Basics patient education
pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education
pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10th to 12th grade reading level and are best for patients who want indepth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also locate
patient education articles on a variety of subjects by searching on "patient info" and
the keyword(s) of interest.)
Basics topics (see "P at ie nt inf or mat ion: Be nig n p r ostat ic hype r pla sia
( en lar ge d pr os t ate ) ( T he
Ba sic s)")
Beyond the Basics topics (see " P at ien t inf orm at ion: B en ign p ros t at ic
hyp e rp las ia ( BPH )
( Be yond the B asics)")
SUMMARY AND RECOMMENDATIONS

The prevalence of moderate-to-severe lower urinary tract symptoms (LUTS) and

decreased peak urinary flow rates increases with age. Men may or may not have
progressive symptoms. (See ' Nat ur al histor y' above.)
The clinical manifestations of benign prostatic hyperplasia (BPH) are lower urinary
tract symptoms (LUTS) that include increased frequency of urination, nocturia,

hesitancy, urgency, and weak urinary stream. (See ' C linical ma nif est at ions'
above.)
History, physical examination, and laboratory tests can provide reasonable
certainty of the diagnosis. Urinalysis should be done and serum creatinine and PSA
should be measured in all patients with lower urinary tract symptoms. (See ' D iag
nosti c ap pr oach' above and
' Re co mm en de d t e sts' above.)

The American Urologic Association symptom score (table 2) (calculator 1)

(assessing for frequency, nocturia, weak urinary stream, hesitancy, intermittence,
incomplete emptying, and urgency) is useful for quantifying the patient's symptoms
after the diagnosis of BPH has been made. (See ' Ame r ican Urolog ic Associ ati
on sym pt om score ' above.)
Measurements of maximal urinary flow rate, post-void residual urine, and urine
cytology are optional, but are useful in most men. The performance of other tests
(pressure-flow studies, urethrocystoscopy, intravenous urography, ultrasonography,
and abdominal radiographs)
should be reserved for unusual patients and for those being considered for
invasive treatments.
(See ' Opt io na l t est s ' above.)
Medical treatment of benign prostatic hyperplasia

INTRODUCTION Benign prostatic hyperplasia (BPH) becomes increasingly

common as men age. BPH can lead to urinary symptoms of increased frequency
of urination, nocturia, hesitancy, urgency, and weak urinary stream. Symptomatic
patients may benefit from medical or surgical treatment.
The medical therapy of BPH will be reviewed here. The clinical manifestations and
diagnosis, epidemiology and pathogenesis, and surgical and other invasive

therapies of BPH are all discussed separately. (See "Clinical manifestations and
diagnostic evaluation of benign prostatic hyperplasia" and "Epidemiology and
pathogenesis of benign prostatic hyperplasia" and "Transurethral procedures for
treating benign prostatic hyperplasia".)
Treatment of lower urinary tract symptoms in men from etiologies other than BPH
is also discussed separately. (See
"Lower urinary tract symptoms in men".) INDICATIONS FOR THERAPY
Medical treatment The decision to medically treat benign prostatic hyperplasia
(BPH) balances the severity of the patient's symptoms with potential side effects of
therapy. Unless patients have developed bladder outlet obstruction, BPH only
requires therapy if symptoms have a significant impact on a patient's quality of life
[1]. Symptoms typically appear slowly and progress gradually over a period of
years. Even without therapy, many men will experience stabilization or
improvement in symptoms over time [2]. (See "Clinical manifestations and
diagnostic evaluation of benign prostatic hyperplasia", section on 'Natural history'.)
For patients that require treatment, it is reasonable to initiate a trial of medical
therapy for BPH when the clinician is comfortable that presenting signs and
symptoms are consistent with BPH. (See "Clinical manifestations and diagnostic
evaluation of benign prostatic hyperplasia", section on 'Diagnostic approach'.)
The American Urological Association (AUA) symptom score/International Prostate
Symptom Score (IPSS) (table 1) is easy and quick to complete and permits
quantitation of symptom severity and monitoring of symptom progression over
time.
Urologic referral prior to medical treatment Patients who develop complications of
bladder outlet obstruction may require invasive therapy and should be referred to a
urologist [2]. These complications include upper tract injury such as hydronephrosis
or renal insufficiency, or lower tract injury such as urinary retention, recurrent
infection, or bladder decompensation (eg, low pressure detrusor contractions; postvoid residuals of >25 percent of total bladder volume) [3].

(See "Acute urinary retention" and "Transurethral procedures for treating benign
prostatic hyperplasia".)
In addition to bladder outlet obstruction, there are several other situations in which
patients should be referred to a urologist for evaluation prior to the initiation of
medical therapy:
Symptoms in the setting of autonomic or severe peripheral neuropathy
Symptoms following invasive treatment of the urethra or prostate
Men <45 years old
Abnormality on prostate exam (nodule, induration, or asymmetry)
Presence of hematuria in the absence of infection
Men with incontinence
Severe symptoms (IPSS 20) (table 1)
BEHAVIORAL MODIFICATIONS In patients with symptoms of benign prostatic
hyperplasia (BPH) who do not have any discomfort from their symptoms and no
evidence of complications (such as bladder outlet obstruction, renal insufficiency, or
recurrent infection), pharmacologic treatment may not be necessary [1,4]. These
patients may be monitored and advised regarding behavioral modifications.
Behavioral modifications may be helpful for all patients. For example, patients may
benefit from voiding in the sitting position (rather than standing) [5]. Other
behavioral modifications include:
Avoiding fluids prior to bedtime or before going out
Reducing consumption of mild diuretics such as caffeine and alcohol

Double voiding to empty the bladder more completely.

In one randomized trial, men given an educational intervention that included
teaching of behavioral modifications were significantly less likely to experience
treatment failure (increase in IPSS or requirement for medication) compared with
men followed with watchful waiting alone [6].
They should also avoid medications that can exacerbate symptoms (eg, diuretics)
or those that induce urinary retention
(table 2).
INITIAL MEDICAL MONOTHERAPY In patients with mild (IPSS <8) to moderate
symptoms (IPSS 8-19) (table 1) of benign prostatic hyperplasia (BPH), we suggest
initial treatment with an alpha-1-adrenergic antagonist monotherapy.
Alpha-1-adrenergic antagonists provide immediate therapeutic benefits, while 5alpha-reductase inhibitors require long- term treatment for efficacy. Patients who
experience side effects, such as hypotension, with alpha-1-adrenergic antagonists
but still desire medical therapy for their BPH can be switched to 5-alpha-reductase
inhibitors for monotherapy. Treatment with 5-alpha-reductase inhibitors requires 6 to
12 months before symptom improvement. (See
'5-alpha-reductase inhibitors' below.)
Alternative options are available in specific populations of patients. Anticholinergic
agents can be used in men who have predominately irritant symptoms and
phosphodiesterase-5 inhibitors are an option in men who also have erectile
dysfunction. (See 'Anticholinergic agents' below and 'PDE-5 inhibitors' below.)
In men with severe symptoms (IPSS 20), it may be reasonable to initiate therapy
with a combination of an alpha-1- adrenergic antagonist and a 5-alpha-reductase
inhibitor. (See 'Alpha-1-adrenergicantagonistand 5-alpha-reductase inhibitor'
below.)

Alpha-1-adrenergic antagonists We suggest treatment with an alpha-1-adrenergic

antagonist for initial therapy of symptomatic BPH in most patients. Alpha-1adrenergic antagonists are the most commonly prescribed medication for BPH [7,8].
They act against the dynamic component of bladder outlet obstruction by relaxing
smooth muscle in the bladder neck, prostate capsule, and prostatic urethra.
Terazosin, doxazosin, tamsulosin, alfuzosin, and silodosin are long-acting alpha-1antagonists that have been approved by the Food and Drug Administration in the
United States and are also available in Europe for treatment of the symptoms of
BPH [1,4].
Efficacy and administration Alpha-1-adrenergic antagonists improve symptoms
of BPH. A meta-analysis of trials with alfuzosin, terazosin, doxazosin, or tamsulosin
with 6333 men in placebo-controlled trials and 507 men in comparative studies
found that these drugs were more effective than placebo and that the efficacy of
the drugs was similar [9]. In
the drug-treated men, the IPSS scores (table 1) decreased 30 to 40 percent, and
urinary flow rates increased 16 to 25 percent.
Alpha-1-adrenergic antagonists appear to be more effective than 5-alpha-reductase
inhibitors for short-term and long- term treatment of BPH. In a 2010 meta-analysis
comparing alpha-adrenergic antagonist monotherapy versus finasteride (a 5-alphareductase inhibitor), doxazosin and terazosin were more effective in improving
urinary symptoms compared with finasteride [10]. Tamsulosin and finasteride were
equally effective. (See '5-alpha-reductase inhibitors' below.)
The approved alpha-1-adrenergic antagonists (terazosin, doxazosin, tamsulosin,
alfuzosin, and silodosin) appear to have similar efficacy, although there have been
few direct comparisons [11,12]. Given the similar efficacy of all the approved alpha1-adrengergic antagonists, choice of agent may be based on cost, side effects
(particularly hypotension) and potential medication interactions (especially with
phosphodiesterase-5 inhibitors). More uroselective
alpha-1-receptor antagonists (alfuzosin, tamsulosin, and silodosin) may have less
hypotension associated with their use [13]. Prazosin, a short-acting alpha-1antagonist, is generally not used for BPH, due to need for frequent dosing and the

potential for more cardiovascular side effects. The selective alpha-1D antagonist,
naftopidil, may also be effective although long-term randomized controlled trials are
needed prior to recommendation for use [14].
Initiation and dose titration is shown in a table (table 3). Terazosin and doxazosin
generally need to be initiated at bedtime (to reduce postural lightheadedness soon
after starting the medication) and the dose should be titrated up over several
weeks. Patients who remain symptomatic on a submaximal dose of an alphaadrenergic antagonist, and are not experiencing adverse effects, should have the
dose increased. It may take one to two weeks for patients to see benefits,
particularly if titrating medications.
Medication therapy for BPH is generally ongoing. If there is a hiatus in drug
administration, retitration is usually required.
Side effects and interactions In a meta-analysis, alpha-adrenergic antagonists
differed in their side-effect profiles [9]. In clinical trials, the rates of withdrawal for
side effects were similar to placebo for alfuzosin and tamsulosin (4 to 10 percent),
while with terazosin and doxazosin an additional 4 to 10 percent of men withdrew
for side effects. Side effects and interactions that are important for alpha-1adrenergic antagonists include:
Hypotension - The most important side effects of alpha-1-adrenergic antagonists
are orthostatic hypotension and dizziness. Tamsulosin, alfuzosin, and silodosin have
lower potential to cause hypotension and syncope than either terazosin or
doxazosin [15-18]. Tamsulosin may further have slightly less effect on blood
pressure than alfuzosin [9]. These differential effects on blood pressure by different
alpha-1-antagonists may be due to their differential blocking of alpha-1A receptor
subtype [19]. Terazosin and doxazosin generally need to be initiated at bedtime (to
reduce postural lightheadedness soon after starting the medication) and the dose
should be titrated up over several weeks.
While the hypotensive effect can be useful in older men who have hypertension,
careful blood pressure monitoring is required in all patients. In elderly men who are

hypertensive but also experience orthostatic hypotension, tamsulosin may be a

reasonable option. Alpha-1-adrenergic antagonists may increase the incidence of
heart failure when used as monotherapy for hypertension. (See "Choice of drug
therapy in primary (essential) hypertension", section on 'Alpha blockers'.)
Interaction with phosphodiesterase-5 inhibitors - The hypotensive effects of
terazosin and doxazosin can be potentiated by concomitant use of the
phosphodiesterase-5 (PDE-5) inhibitors sildenafil or vardenafil. The risks with
tadalafil are less clear. Tamsulosin at a dose of 0.4 mg/day does not appear to
significantly potentiate the hypotensive effects of sildenafil [20].
We advise men to separate the doses of alpha-1-adrenergic antagonists and PDE-5
inhibitors by at least 4 hours. In general, we use tamsulosin, alfuzosin, and
silodosin in men who are also using PDE-5 inhibitors. However, we feel that men
who are on lower doses of terazosin or doxazosin and are not experiencing
orthostatic blood pressure changes can also take a PDE-5 inhibitor.
Ejaculatory Dysfunction - Tamsulosin and silodosin, in particular, can affect
ejaculation [21]. In one study, tamsulosin decreased mean ejaculate volume in more
than 90 percent of patients, with 35 percent having no ejaculate; this problem was
not observed with alfuzosin 10 mg [22]. Silodosin produces retrograde ejaculation
in approximately 28 percent of patients [17].
Other side effects - Other common side effects include headache, dizziness and
nasal congestion. Alpha-1-adrenergic antagonist use has also been associated with
intraoperative floppy iris syndrome during cataract surgery. (See "Cataract in
adults", section on 'Medications and IFIS'.)
Alternative medications We suggest alpha-1-adrenergic antagonists as initial
medical monotherapy for most patients with BPH. However, there may be some
patients who do not tolerate these agents secondary to side effects but still desire
to try medical therapy. 5-alpha-reductase inhibitors are an option in these patients.

Alternatively, anticholinergic agents are an option in men who have predominately

irritant symptoms and phosphodiesterase-5 inhibitors are an option in men who
also have erectile dysfunction.
5-alpha-reductase inhibitors In patients who desire medical therapy but cannot
tolerate alpha-1-adrenergic antagonists and do not have predominately irritant
symptoms or concomitant erectile dysfunction, treatment with a 5- alpha-reductase
inhibitor is reasonable. Patients should understand that treatment for 6 to 12
months is generally needed before prostate size is sufficiently reduced to improve
symptoms.
5-alpha-reductase inhibitors are more effective in men with larger prostates. They
act by reducing the size of the prostate gland and have demonstrated the
potential for long-term reduction in prostate volume and need for prostate surgery.
The type 2 form of 5-alpha-reductase catalyzes the conversion of testosterone to
dihydrotestosterone in the prostate, hair follicles, and other androgen-sensitive
tissues. 5-alpha-reductase inhibitors act by reducing the size of the prostate gland
and have demonstrated the potential for long-term reduction in prostate volume
and need for prostate surgery [10].
Efficacy There are two 5-alpha-reductase inhibitors approved in the United
States and Europe, finasteride and dutasteride. The Enlarged Prostate International
Comparator Study (EPICS), an industry-sponsored trial, compared treatment with
finasteride or dutasteride for 12 months [23]. The primary outcome reported,
reduction in prostate volume, was not significantly different for the two drugs. The
drugs were also not significantly different in the secondary endpoints of urinary
flow rate and urinary symptom scores, and adverse effects were similar.
Finasteride - In a randomized multicenter trial in men with BPH comparing
treatment with placebo or finasteride for 12 months, the men treated with 5
mg/day finasteride were found to have a 23 percent reduction in obstructive and
18 percent reduction in non-obstructive symptom scores, an increase in maximal
urinary flow rate, and a 19 percent reduction in mean prostatic volume [24].

The efficacy of finasteride appears to persist with long-term treatment. A trial of

over 3000 men who were treated daily with 5 mg of finasteride or placebo
demonstrated that the improvements in symptom scores, maximal urinary flow
rates, and prostate volume were maintained for more than four years [25].
Finasteride treatment decreased the probability of surgery (5 versus 10 percent, risk
reduction 55 percent) and acute urinary retention (3 versus 7 percent,
risk reduction 57 percent) (figure 1). Patients who remained on finasteride for six
years in an open-label extension of the study had sustained benefits [26].
Finasteride may also suppress gross hematuria that can occur in BPH; other causes
of hematuria (particularly prostate and bladder cancer) should first be ruled out
[27,28]. One randomized trial included 57 men with BPH, evidence of bleeding from
friable prostatic tissue on flexible cystoscopy, and chronic intermittent gross
hematuria with no other identifiable cause [27]. Compared with control, finasteride
was associated with a lower rate of recurrent hematuria (14 versus 63 percent) and
of surgery for bleeding (0 versus 26 percent). (See "Clinical manifestations and
diagnostic evaluation of benign prostatic hyperplasia", section on 'Urinalysis' and
"Etiology and evaluation of hematuria in adults".)
Dutasteride - A 2013 meta-analysis of four randomized trials in over 13,000 men
comparing dutasteride to placebo found that dutasteride improved symptom score
and maximum flow rate while decreasing prostate volume, episodes of acute
urinary retention, and need for surgical intervention [29]. The major side effect of
treatment with dutasteride was sexual dysfunction.
Administration Finasteride can be initiated and maintained at 5 mg once daily.
Dutasteride can be initiated and maintained at 0.5 mg once daily. In contrast to the
alpha-1-adrenergic antagonists, 5-alpha-reductase inhibitors do not require titration.
Treatment for 6 to 12 months is generally needed before prostate size is sufficiently
reduced to improve symptoms. Their ability to prevent acute urinary retention and
reduction in need for surgery require chronic treatment for more than a year.
If effective, such therapy is continued indefinitely in most patients with BPH, as
treatment discontinuation may lead to symptom relapse. In one observational

follow-up study of a randomized trial, prostate volume and symptoms were

monitored after discontinuation of therapy with either finasteride or dutasteride
[30]. At one year, prostate volume had increased by 19 to 21 percent, and
symptom scores had worsened.
Side effects
Concern regarding prostate cancer - In randomized trials, 5-alpha-reductase
inhibitors significantly decreased the incidence of prostate cancer. While concern
has been raised that 5-alpha-reductase inhibitors may increase the incidence of
high-grade lesions, many believe this finding is spurious. Because of this concern,
however, the United States Food and Drug Administration (FDA) recommends that
before starting 5-alpha reductase inhibitors for treatment of BPH, the patient should
be assessed for other urological conditions, including prostate cancer [31].
Prior to starting any treatment for BPH, we evaluate patients with a digital rectal
exam (DRE) and a serum prostate- specific antigen (PSA) [31]. While on treatment
with a 5-alpha-reductase inhibitor, we monitor annually with a DRE and a PSA.
Serum PSA is reduced about 50 percent in patients taking these drugs. (See
"Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia",
section on 'Recommended tests' and "Measurement of prostate specific antigen",
section on 'Medications'.)
5-alpha-reductase inhibitors and prostate cancer are discussed in detail elsewhere.
(See "Chemoprevention strategies in prostate cancer", section on '5-Alpha
reductase inhibitors'.)
Sexual disfunction - The major side effects of these drugs are decreased libido
and ejaculatory or erectile dysfunction [21]. These occurred in 4 to 6 percent of
men in a randomized trial of finasteride [24]. Rates of sexual dysfunction in a
primary care trial of finasteride were somewhat higher (13.8 percent for any
sexual adverse event), and this may be more reflective of clinical practice [32].
However, in a long-term trial of finasteride versus placebo in 3040 men with BPH,
adverse sexual effects were increased only during the first year of therapy [33]. A

meta-analysis found that of the risk ejaculatory dysfunction was similar with
finasteride and dutasteride [21].
PSA - PSA concentrations may decrease with 5-alpha-reductase inhibitor
treatment. If a patient is being screened for prostate cancer, medication effect from
5-alpha-reductase inhibitors should be taken into account when interpreting the
PSA. This is discussed in detail separately. (See "Measurement of prostate specific
antigen", section on 'Medications' and "Screening for prostate cancer", section on
'Measuring PSA'.)
Concern regarding bone loss - Finasteride does not cause loss of bone, perhaps
because serum estradiol concentrations do not change [34]. A case-control study
found no positive association between use of finasteride and hip fracture, and
actually found evidence of lower risk of fracture with finasteride use [35].
Anticholinergic agents Anticholinergic agents are an alternative monotherapy for
patients with predominately irritative symptoms (frequency, urgency, and
incontinence) related to overactive bladder (OAB) and without elevated post void
residuals (PVR) [1]. They are also used in combination therapy with alphaadrenergic agents for patients with persistent symptoms of BPH who have irritative
symptoms without elevated PVR. (See "Lower urinary tract symptoms in men",
section on 'Overactive bladder and detrusor overactivity' and 'Alpha-1-adrenergic
antagonist and anticholinergic' below.)
Tolterodine, oxybutynin, darifenacin, solifenacin, fesoterodine and trospium are
currently approved in the United States for OAB. Side effects may be minimized by
using a low dose of short-acting medications (eg, tolterodine 1 mg twice daily).
Alternatives include extended-release tolterodine, M3 selective drugs (eg,
darifenacin, solifenacin), or quaternary amines (eg, trospium).
Significant peripheral side effects limit drug tolerability and dose escalation. These
include inhibition of salivary secretion (dry mouth), blockade of the ciliary muscle of
the lens to cholinergic stimulation (blurred vision for near objects), tachycardia,
drowsiness, decreased cognitive function, and inhibition of gut motility and

constipation. Anticholinergic agents are contraindicated in patients with gastric

retention and angle closure glaucoma.
These medications are discussed in more detail separately. (See "Lower urinary
tract symptoms in men", section on
'Anticholinergics'.)
PDE-5 inhibitors While evidence regarding efficacy is limited, it is reasonable to
consider treatment with phosphodiesterase-5 (PDE-5) inhibitors in patients who
have erectile dysfunction and mild or moderate symptoms (IPSS
<20) of BPH. In the United States, tadalafil is approved by the Food and Drug
Administration for use in BPH. Daily dosing of tadalafil should not be prescribed in
men with a creatinine clearance <30 mL/min. As discussed above, PDE-5 inhibitors
can potentiate the hypotensive effects of alpha-1-adrenergic antagonists. (See
'Side effects and interactions' above.)
In a 2011 meta-analysis of five placebo-controlled randomized trials in men with
symptomatic BPH, patients treated with PDE-5 inhibitors had significant
improvement in IPSS after 12 weeks of therapy [36]. There was no significant
difference in urodynamic parameters. A subsequent randomized trial in men with
symptoms of BPH found that compared with placebo, both tadalafil and
tamsulosin improved maximum urine flow rates, as well as symptom scores (figure
2), though only tadalafil improved erectile dysfunction [37]. A 2013 pooled analysis
from four randomized trials that included 1500 men found that compared with
placebo, tadalafil improved IPSS and BPH impact index, irrespective of symptom
severity, age, testosterone level, or PSA-predicted prostate volume [38]. A post-hoc
analysis of these four trials also found that tadalafil 5 mg led to clinically
meaningful improvements (3 point or 25 percent improvement in IPSS score)
within one to four weeks for most patients [39].
COMBINATION THERAPY For patients with severe symptoms of benign prostatic
hyperplasia (BPH) (IPASS 20) (table 1) or who do not have adequate response to
maximal monotherapy with an alpha-adrenergic antagonist, we suggest
combination treatment with an alpha-adrenergic antagonist and 5-alpha-reductase
inhibitor.

For men with low post-void residual urine volumes and irritative symptoms (eg,
frequency, urgency) that persist during treatment with an alpha-adrenergic
antagonist, we suggest combination treatment with an anticholinergic agent. For
men who have persistent symptoms with anticholinergic monotherapy, we suggest
combination treatment with an alpha-adrenergic antagonist.
Alpha-1-adrenergic antagonist and 5-alpha-reductase inhibitor In patients with
severe symptoms of BPH (IPASS 20) (table 1), those who are known to have a
large prostate (>40 mL), and/or in those who do not get an adequate response to
maximal dose monotherapy with an alpha-adrenergic antagonist, we suggest
combination treatment with an alpha- adrenergic antagonist and a 5-alphareductase inhibitor.
Short-term therapy with combined alpha adrenergic antagonist and 5-alphareductase inhibitor therapy appears to be superior to either agent alone in men
with BPH and larger prostate glands [40], but not in men with only moderate BPH
[41-43]. Long-term combination therapy provides some added benefit even in men
with moderate BPH [44,45]. Earlier initiation of combination treatment can reduce
risks for clinical progression, acute urinary retention, and prostate surgery
compared with starting combination treatment at a later time [46].
While earlier randomized trials had found combined alpha-1-adrenergic antagonist
and 5-alpha-reductase inhibitor therapy was not superior to monotherapy with a
alpha-1-adrenergic antagonist [41,43], subsequent randomized trials have found a
benefit for long-term use of combination therapy [44,47]. In the Medical Therapy of
Prostatic Symptoms (MTOPS) trial, 3047 men with BPH were randomly assigned to
receive doxazosin, finasteride, combination therapy, or placebo [44]. Long-term
combination therapy improved symptoms and reduced the risk of clinical
progression by 66 percent, significantly greater than with either drug alone. In
addition, combination therapy or finasteride alone (but not doxazosin alone)
reduced the risk of acute urinary retention and the need for invasive therapy. The
number needed to treat to prevent one instance of overall clinical progression was
8.4 for combination therapy, 13.7 for doxazosin, and

15.0 for finasteride.

A 2010 systematic review of the literature concluded that the combination of
doxazosin and finasteride compared with doxazosin alone improves urinary
symptoms in men with medium (25 to <40 mL) and large (>40 mL) prostates in
the long-term [10]. The four year CombAT study provides additional evidence that
combination therapy is effective in men with larger prostates [47]. Subjects were
randomly assigned to therapy with dutasteride, tamsulosin, or both. Combination
therapy was superior to either monotherapy in reducing BPH symptoms and the
relative risk of BPH
clinical progression (figure 3). In reducing the relative risk of acute urinary retention
or BPH-related surgery, combination therapy was superior to tamsulosin
monotherapy, but not dutasteride monotherapy. More drug-related adverse events
were seen with combination therapy than with monotherapy. Dutasteride alone or
in combination with tamsulosin reduced the number of prostate biopsies by 40
percent and the relative risk of prostate cancer by 40 percent [48].
Alpha-1-adrenergic antagonist and anticholinergic For men with low post-void
residual (PVR) urine volumes and irritative symptoms (eg, frequency, urgency) that
persist during monotherapy with an alpha-1-adrenergic antagonist or
anticholinergic agent, we suggest combination treatment with an alpha-1adrenergic antagonists and an anticholinergic agent. (See "Lower urinary tract
symptoms in men", section on 'Anticholinergics' and "Lower urinary tract symptoms
in
men", section on 'BOO with low PVR'.)
A 2013 meta-analysis of seven randomized trials found that the combination of an
alpha-1-adrenergic antagonist with an anticholinergic significantly improved storage
voiding parameters compared with alpha-1-adrenergic antagonist therapy alone
[49]. The risk of side effects, increased PVR urine volume, decreased maximal
urinary flow rate, or acute urinary retention, was low, with only a 1 percent risk of
acute urinary retention. The NEPTUNE II study found that patients continued to
maintain benefits of combined therapy after the 12 week double-blind trial
throughout the open- label extension study period (one year) [50].

REFERRAL FOR INVASIVE THERAPY Patients who do not tolerate any of these
therapies can be observed off therapy and/or can be referred for surgical
management.
Patients who are on combination therapy and do not experience an adequate
response over 12 to 24 months may wish to consider surgical therapies as well.
Patients with progression of disease on therapy will generally require surgical
therapy. (See "Transurethral procedures for treating benign prostatic hyperplasia".)
HERBAL THERAPIES Data concerning efficacy of herbal therapies for BPH are
conflicting. Until additional studies of herbals are performed, we do not suggest
using these for the treatment of BPH.
Herbal therapies for BPH are commonly used in Europe. No herbal therapies have
been approved by the United States Food and Drug Administration for this purpose,
although many men probably try these treatments. There is a substantial placebo
effect associated with herbal therapy, as there is for most drugs used to treat BPH.
Additionally, concerns regarding standardization remain, particularly in the United
States. (See "Overview of herbal medicine and dietary supplements".)
While there is some evidence evaluating herbal therapies for BPH, questions
regarding safety and efficacy remain. Some of those that have been evaluated
include:
Saw palmetto - Saw palmetto is widely used for treatment of BPH, but there are
few data to support its efficacy. A
2012 systematic review of 32 randomized trials (N = 5666) in patients with BPH
comparing saw palmetto and placebo did not find any differences in urinary
symptom scores, measures of urinary flow, or prostate size [51].
Beta-sitosterol - A 2011 systematic review of 4 randomized trials concluded that
while evidence suggests that the plant extract beta-sitosterol improved symptoms
in men with BPH, the long-term effectiveness and safety was not known [52].

Cernilton - Cernilton, which is prepared from the rye grass pollen Secale cereale,
has been evaluated in four clinical trials [53]. It improved symptoms, but did not
affect urinary flow rates or residual urine or prostate volume.
Pygeum africanum - Pygeum africanum is an extract of bark from an African plum
tree. In a 2002 meta-analysis of 18 randomized controlled trials, active treatment
improved symptoms two times more frequently than placebo and increased peak
urinary flow rates 23 percent [54].
INFORMATION FOR PATIENTS UpToDate offers two types of patient education
materials, The Basics and Beyond the Basics. The Basics patient education
pieces are written in plain language, at the 5th to 6th grade reading level, and they
answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the
10th to 12th grade reading level and are best for patients who want in-depth
information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also locate
patient education articles on a variety of subjects by searching on patient info and
the keyword(s) of interest.)
Basics topics (see "Patient information: Benign prostatic hyperplasia (enlarged
prostate) (The Basics)")
Beyond the Basics topics (see "Patient information: Benign prostatic hyperplasia
(BPH) (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS
Benign prostatic hyperplasia (BPH) becomes increasingly common as men age.
BPH can lead to urinary symptoms
that may benefit from medical or surgical treatment. (See 'Introduction' above and
'Indications for therapy' above.)

In general, men who develop upper tract injury (eg, hydronephrosis, renal
dysfunction) or lower tract injury (eg, urinary retention, recurrent infection, bladder
decompensation) require invasive therapy. (See "Transurethral procedures for
treating benign prostatic hyperplasia".)
We suggest that all men with symptoms of BPH be instructed in behavior
modifications (Grade 2B). These should be tailored to symptoms but may include
avoiding fluids prior to bedtime or before going out, reducing consumption of
mild diuretics such as caffeine and alcohol, and double voiding to empty the
bladder more completely. They should also
avoid medications that can exacerbate symptoms (eg, diuretics) or induce urinary
retention (table 2). (See 'Behavioral modifications' above.)
For most men with mild to moderate symptoms of BPH whose symptoms have a
sufficient effect on quality of life, we suggest initial treatment with an alphaadrenergic antagonist alone (Grade 2A). The choice of alpha-adrenergic antagonist
may be made on the basis of cost and side-effect profile. (See 'Alpha-1-adrenergic
antagonists' above.)
In patients who desire medical therapy but cannot tolerate alpha-1-adrenergic
antagonists and do not have predominately irritant symptoms or concomitant
erectile dysfunction, treatment with a 5-alpha-reductase inhibitor is a reasonable
option. Treatment for 6 to 12 months is generally needed before prostate size is
sufficiently reduced to improve symptoms. Finasteride and dutasteride, appear to
have similar efficacy and similar adverse effects. (See '5- alpha-reductase
inhibitors' above.)
In men with low post-void residual urine volumes and irritative symptoms,
anticholinergics are an option for initial medical therapy. (See 'Anticholinergic
agents' above.)

In men who have mild to moderate symptoms of BPH and erectile dysfunction,
PDE-5 inhibitors are an option for initial medical therapy (See 'PDE-5 inhibitors'
above.)
In men with severe symptoms, those with a large prostate (>40 ml), and/or in
those who do not get an adequate response to maximal dose monotherapy with an
alpha-adrenergic antagonist, we suggest combination treatment with an alphaadrenergic antagonist and a 5-alpha-reductase inhibitor (Grade 2A). (See 'Alpha-1adrenergic antagonist and 5- alpha-reductase inhibitor' above.)
In men with low post-void residual urine volumes and irritative symptoms (eg,
frequency, urgency) that persist during treatment with an alpha-1-adrenergic
antagonist or anticholinergic agents, we suggest combination treatment with alpha1-adrenergic antagonists and anticholinergic agents (Grade 2C). (See
'Anticholinergic agents' above and "Lower urinary tract symptoms in men".)
Transurethral procedures for treating benign prostatic hyperplasia

INTRODUCTION Benign prostatic hyperplasia (BPH) becomes increasingly

common as men age. Men with clinically significant lower urinary tract symptoms
(LUTS) suggestive of BPH who do not find adequate relief with medical treatment
may benefit from transurethral resection or ablation to enlarge the urethral channel
to reduce the amount of prostate tissue around the urethra. Most procedures are
performed via the urethra (ie, transurethral) using a cystoscope. Transurethral
resection of the prostate (TURP) has been the main form of treatment for many
years in men with BPH, and remains the standard against which other treatments
should be compared. Most men who undergo TURP experience a marked decrease
in urinary symptom scores, and a substantial increase in maximal urinary flow
rates. However, the complications and cost associated with TURP have encouraged
development of several alternative methods
to remove or destroy prostatic tissue using a variety of energy sources.
Transurethral procedures for resection or ablation of prostate tissue, and other
therapies for the treatment of BPH will be reviewed here. The clinical

manifestations and management of BPH are reviewed elsewhere. (See "Clinical

manifestations and diagnostic evaluation of benign
prostatic hyperplasia" and "Medical treatment of benign prostatic hyperplasia".)
INDICATIONS FOR TREATMENT Benign prostate enlargement is the physical
enlargement of the prostate gland that is due to histologic changes known as
benign prostatic hyperplasia (BPH). (See "Epidemiology and pathogenesis of
benign prostatic hyperplasia".)
Bladder outlet obstruction due to BPH is frequently diagnosed clinically on the basis
of lower urinary tract symptoms which can present acutely, or, more often,
chronically. A decision to treat BPH is usually based upon the severity of symptoms
determined by either the American Urological Association Symptom Index (AUA-SI)
(table 1), or the International Prostate
Symptom Score (IPSS ) [1], which are very similar. In general, symptoms only
require therapy if they have a significant impact on a patient's quality of life.
Whether to proceed to surgical intervention is generally based upon the adequacy
of medical therapy, the development of complications, and patient preference,
rather than any specific urological parameter. The medical treatment of benign
prostatic hypertrophy is discussed separately. (See "Medical treatment of benign
prostatic hyperplasia".)
General indications for surgical intervention include:

Surgery offers the most effective resolution of bladder outlet obstruction

symptoms of the lower urinary tract suggestive of BPH, and can be offered to
patients with moderate-to-severe chronic symptoms who are bothered by their
symptoms. (See 'Chronic lower urinary tract symptoms' below.)
Surgery is generally recommended for patients with symptoms of acute urinary
retention that is refractory to medical therapy. (See 'Acute urinary retention'
below.)

Surgery is also the treatment of choice for patients who have renal insufficiency
secondary to BPH, whether due to acute urinary retention or lower urinary tract
symptoms, or if there is clear evidence of bladder outlet obstruction on urodynamic
evaluation.
Patients with a median lobe configuration are unlikely to respond to medical
therapy and should also preferentially be treated surgically. A median lobe
configuration represents a lobe of hyperplastic tissue that protrudes into the lumen
of the bladder producing a mechanical obstruction to urine flow by occluding the
bladder neck like a valve each time the bladder contracts during voiding. For
patients who fail medical therapy, we suggest prostate imaging, either using
transrectal ultrasound or by direct visualization (ie, cystoscopy) to evaluate the
patients anatomy. (See 'Anatomy of the prostate' below.)
Chronic lower urinary tract symptoms Lower urinary tract symptoms include
increased frequency of urination, nocturia, hesitancy, urgency, and weak urinary
stream. These symptoms typically appear slowly, and gradually progress over a
period of years. (See "Lower urinary tract symptoms in men".)
In general, these symptoms require treatment only if they have a significant impact
on a patient's quality of life [2,3]. For men with moderate symptoms, transurethral
resection of the prostate (TURP) may be more effective compared with watchful
waiting, but watchful waiting is still a reasonable alternative [4]. Watchful waiting
may be the best alternative for men with significant medical comorbidities. (See
"Medical treatment of benign prostatic hyperplasia" and
'Outcome comparisons' below.)
Surgical intervention is indicated if bladder outlet obstruction is creating a risk for
upper tract injury such as hydronephrosis or renal insufficiency, or lower tract
complications such as urinary retention, recurrent infection, or bladder
decompensation (eg, low pressure detrusor contractions, post-void residuals of >25
percent of total bladder volume) [2]. Most patients who develop complications will
require treatment, as will patients who develop bladder calculi or persistent gross
hematuria [5].

Acute urinary retention BPH is a common cause of acute urinary retention in

older men. Catheterization is the initial treatment, but subsequent treatment varies.
Although some urologists continue to favor surgery for men with acute urinary
retention due to BPH, most suggest a trial of catheter drainage combined with alpha
blockers, and cessation of any anticholinergic agents or opiates, followed by a
voiding trial. For patients with acute urinary retention who subsequently fail a
voiding trial one or more times, we suggest transurethral resection of the prostate
(bipolar TURP). (See "Acute urinary retention", section on 'Surgical therapy' and
"Acute urinary retention", section on 'Benign prostatic hyperplasia'.)
Many men who are able to void successfully after removal of the catheter
eventually have recurrent urinary retention. As an example, in one study of 228
men, 56 percent had a recurrence within a week after the initial episode and 68
percent within a year [6]. Factors predictive of recurrence included a retained
volume >500 mL and a maximum flow rate of <5 mL/min after the episode of
retention. Another important stratification of the risk for recurrent acute urinary
retention is whether or not the episode was spontaneous or precipitated by some
other event (eg, unrelated surgery, opioids, cold medication) [7].
The risk of developing acute urinary retention in men with BPH depends upon the
population studied. In one report of more than 3000 men with BPH who were
randomized to receive finasteride or placebo, the risk of needing surgery for BPH or
developing acute urinary retention over four years was 7 percent in the finasteride
and 4 percent in the placebo group (figure 1)
[8]. In this study, the baseline serum PSA concentration and prostate volume were
the best predictors of the development of acute urinary retention. (See "Medical
treatment of benign prostatic hyperplasia".)
PREPARATION Prior to surgical treatment of benign prostatic hyperplasia (BPH),
we obtain a serum prostate specific antigen (PSA), free and total, and although not
mandatory, we prefer to obtain a transrectal prostate ultrasound to assess the size
and configuration of the prostate. We also prefer to obtain a serum creatinine and
renal ultrasound to have baseline information about the kidneys and their

function. A urine culture should also be obtained. If there is any evidence of urinary
tract infection, it should be treated according to antimicrobial sensitivities. We
postpone the surgery until the urine is sterile.
Antimicrobial prophylaxis Antimicrobial prophylaxis is recommended for
procedures that manipulate the genitourinary tract [9]. Appropriate antibiotic
choices are given in the table (table 2).
Antithrombotic therapy About one third of patients requiring a transurethral
procedure for BPH are taking some form of antithrombotic therapy (eg, Vitamin K
antagonist, antiplatelet agents) [10,11]. The management of patients on
antithrombotic therapy undergoing a
transurethral procedure to manage BPH continues to evolve. Because of the risk of
perioperative bleeding associated with TURP, bridging anticoagulation (intravenous
heparin, low molecular-weight heparin), or temporary cessation of therapy is
generally used [12]. A decision to withhold antithrombotic therapy needs to
consider the relative risk of a significant adverse cardiovascular event versus the
risk of bleeding. Lower bleeding rates associated with non-TURP procedures may
influence the choice of procedure in patients for whom the risks of altering the
anticoagulation regimen are deemed too high (see 'Choice of procedure' below).
The details of perioperative antiplatelet/anticoagulation management are discussed
in detail elsewhere. (See 'Bleeding' below and "Perioperative medication
management", section on
'Medications affecting hemostasis' and "Perioperative management of patients
receiving anticoagulants" and 'Choice of procedure' below.)
An increased risk of bleeding with TURP has been found in most [11,13,14], but not
all studies [10]. In one large multicenter study, the outcomes of TURP in patients on
antithrombotic therapy (warfarin in 33 percent, antiplatelet agents in 23 percent,
and combined in 1.5 percent) were compared with those with no antithrombotic
therapy [11]. Bridging anticoagulation was used in 76 percent of patients on chronic
warfarin therapy. Patients in the antithrombotic therapy group had significantly
higher rates of bladder clots (13 versus 4.7 percent), transfusion (1.9 versus 1.0

percent), late hematuria (15.0 versus 8.4 percent), and thromboembolic events
(2.4 versus 0.7 percent), and a significantly longer duration of hospitalization (6.4
versus 4.7 days). Patients on antithrombotic therapy were significantly older (75
versus 71 year), had significantly larger prostate volume (56 versus 49 mL), and a
significantly higher rate of bladder catheterization prior to surgery (26 versus 17
percent). In contrast, a retrospective review of 305 patients did not find significant
differences in postoperative bleeding rates [10]. In this study, the incidence of
postoperative hemorrhage (early <14 days, and delayed 14 days) was not
significantly different between those in whom anticoagulants were ceased
preoperatively and then resumed postoperatively (generally within
3 to 5 days after TURP), and those not receiving any anticoagulants (10/108 versus
16/194). The overall rate of cardiovascular events was low (<1 percent) and not
significantly different between the groups.
Two studies using non-TURP resection or ablation procedures (eg, HoLEP,
photoselective vaporization [PVP]) found no significant differences in bleeding
comparing patients who were, or were not, on antithrombotic therapy [15,16].
Compared with TURP, non-TURP procedures are generally associated with lower
bleeding rates [13,17]. One small study compared the bleeding rates between TURP
(n = 57) and plasma vaporization (n = 54) [17]. Patients treated with plasma
vaporization required less bladder washout (2 versus 18 percent), and had a lower
incidence of late hematuria (4 versus 19 percent).
Patient counseling Prior to proceeding, the patient should be informed about
potential complications, including alterations in sexual function. (See 'Anatomy of
the prostate' below and 'Periprocedural morbidity and mortality' below.)
Patients undergoing resective procedures should also be informed that the material
sent for pathologic examination may reveal prostate carcinoma, which is detected
in about 5 percent of patients. (See 'Incidental prostate cancer' below and
'Periprocedural morbidity and mortality' below.)
ANATOMY OF THE PROSTATE The prostate gland is a firm walnut-shaped
structure located at the base of the urinary bladder; the apex is caudal and the
base cranial. The prostate is composed of both glandular and muscular tissue.

Secretions from the prostate, vas deferens, and seminal vesicle empty into the
prostatic urethra (ie, section of the urethra that traverses the prostate); each of
these structures contribute to the composition of the semen (figure 2).
The prostate gland is divided into three general zones (figure 3).

Peripheral Approximately 70 percent of the normal prostate gland is contained

within the peripheral zone.
Central The central zone comprises 25 percent of the volume of the normal
prostate. The stroma of the prostate gland is the most dense in this zone.
Transition The transition zone comprises 5 percent of the normal volume of the
prostate and is the site of benign prostatic hyperplasia.
During most transurethral procedures, primarily the transition zone is resected or
ablated. Because the resection is limited to the area between the bladder neck and
the verumontanum, the ejaculatory ducts should not be affected; however, they can
be injured, which can lead to discomfort during orgasm. (See 'Sexual
dysfunction' below.)
TRANSURETHRAL PROCEDURES Most procedures used to reduce the amount of
prostate tissue are performed via the urethra using a special cystoscope (ie,
resectoscope) (figure 4). The prostatic tissue can be removed (ie, resected) or
destroyed (ie, ablated) using a variety of techniques such as electrocautery
(diathermy), lasers, radiofrequency devices, and microwave devices.
Transurethral resection techniques include:

Transurethral resection of the prostate (TURP) (see 'Monopolar TURP' below and
'Bipolar
TURP' below)

Transurethral laser enucleation (see 'HoLEP and ThuLEP' below) Transurethral

ablation techniques include:
Plasma vaporization (the button procedure) (see 'Plasma vaporization ("button"
procedure)' below)
Photoselective vaporization (PVP) (see 'Photoselective vaporization (PVP)' below)

Radiofrequency ablation (see 'Other ablation techniques' below)

Microwave thermotherapy (see 'Other ablation techniques' below)

Transurethral incision (TUIP) (see 'Other ablation techniques' below) Hybrid

techniques have also been described [18-20].
Monopolar TURP TURP using monopolar electrocautery (monopolar TURP) has
been the mainstay of treatment of BPH for many years in men with chronic
symptoms. However, the rate at which monopolar TURP has been performed
declined 47.6 percent in the United States Medicare population between 2000 and
2008 due to the emergence of alternative techniques [21]. At our institution,
bipolar TURP and plasma vaporization (ie, the button procedure) have largely
replaced traditional monopolar TURP, and we speculate that bipolar TURP will
replace monopolar TURP in the near future. (See 'Bipolar TURP' below and
'Plasma vaporization ("button" procedure)' below.)
Transurethral resection of the prostate (TURP) using monopolar electrocautery is the
standard procedure used for treating BPH. It can be performed under general
anesthesia, neuraxial anesthesia (spinal, epidural), or regional nerve block. The
procedure takes about 60 to 90 minutes to perform, and generally requires a 24
hour postoperative observation period in the hospital due to the need to monitor

the patient for bleeding and/or electrolyte abnormalities. (See 'Postprostatectomy

syndrome' below.)
For a monopolar TURP, the resectoscope, which is loaded with a monopolar
diathermy loop, is introduced into the bladder (figure 4). Continuous irrigation using
a nonconductive solution (eg,
1.5% glycine in sterile water, mix of 2% sorbitol plus 0.54% mannitol) is used to
distend the bladder, and to wash away blood and prostate tissue fragments.
Under direct vision, strips of prostate tissue are resected one at a time and placed
temporarily into the bladder. The resection is continued until the entire region of
hyperplasia (ie, adenoma) is resected. Once the resection is completed, the prostate
chips are evacuated from the bladder and bleeding is controlled using
electrocautery. The prostatic fossa is left wide open, bounded by its capsule (figure
5). The cavity will be lined by a regenerated epithelial surface in 4 to 12 weeks.
Bipolar TURP Bipolar TURP uses bipolar electrocautery instead of the monopolar
electrocautery used with the standard TURP procedure, described above [22,23]. In
contrast to standard TURP, saline can be used as an irrigant (also known as TUR in
saline), eliminating the risk of hyponatremia (ie, postprostatectomy syndrome). The
advantages of bipolar electrocautery are discussed elsewhere. (See "Overview of
electrosurgery" and "Overview of electrosurgery", section on 'Bipolar
electrosurgery'.)
Plasma vaporization ("button" procedure) Plasma vaporization uses bipolar
electrocautery similar to bipolar TURP described above. High-frequency electric
current passing between two electrodes creates the resection loop, which
vaporizes the prostate tissue with minimal blood loss. It has the advantage of not
causing sloughing of the tissue and is associated with less blood loss than TURP. In
contrast to monopolar and bipolar TURP, no prostate tissue is available for
pathological analysis [24]. Saline is also used as an irrigating solution, minimizing
the risk of postprostatectomy syndrome. (See 'Postprostatectomy syndrome'
below.)

Differences in design of the available bipolar devices and type and arrangement
of electrodes has led to variable terminology including terms such as bipolar
vaporization, plasma kinetic vaporization, electrovaporization, and the button
procedure or technique [25].
Laser techniques Several techniques use laser energy to resect or ablate
hyperplastic prostate tissue [26]. Two emerging laser techniques have become
increasingly popular. These include photoselective vaporization and Holmium laser
enucleation of the prostate. (See
'Photoselective vaporization (PVP)' below and 'HoLEP and ThuLEP' below.)
The general procedure is similar to that of traditional (monopolar) TURP described
above; however, saline usually is used as an irrigation solution. PVP uses the laser
to vaporize the prostate tissue, similar to plasma vaporization, while HoLEP uses the
laser like a knife to enucleate the BPH adenoma, similar to the digital enucleation
that is performed during open prostatectomy; the adenoma is morcellated to allow
removal. HoLEP is technically more challenging to perform and is less frequently
used in the United States compared with PVP.
Photoselective vaporization (PVP) Photoselective vaporization (PVP, Greenlight
laser) of the prostate is based upon the concept of selective photothermolysis (ie,
selective thermal confinement of light-induced damage). The basic principles of
medical lasers are discussed elsewhere. (See "Basic principles of medical lasers",
section on 'Tissue ablation'.)
Selected wavelengths of laser light are targeted to different constituents of the
tissue to ablate the prostate tissue.
The KTP (potassium-titanyl-phosphate) laser (eg, GreenLight laser) uses a
wavelength of 532 nm (figure 6), which is near the peak absorption of blood
(figure 7) [27-35]. A disadvantage of the KTP laser is coagulative necrosis (not
vaporization) in poorly vascularized tissues.

Diode (semiconductor) lasers emit light at various wavelengths. The application of

diode lasers to the treatment of BPH is recent and comparisons with other
technologies are emerging [36-39].
The Holmium:Yttrium-Aluminium-Garnet (YAG) (2140 nm), Thulium:YAG (2014
nm), and Neodymium:YAG (1064 nm) lasers were initially developed to ablate
tissue (figure 6) [40], but these lasers were less effective at ablating prostate tissue
compared with the other lasers, since the wavelength of light used is near the peak
of water absorption (figure 7). Over time, these evolved with modifications to be
used primarily for enucleation [41,42]. (See 'HoLEP and ThuLEP' below.)
PVP can be performed under local/regional anesthesia as an outpatient procedure,
and an office-based procedure has been described [43]; however, we typically
perform these on an outpatient basis and observe the patient for one day. The main
disadvantage of PVP is that it takes more time than TURP, but, like other non-TURP
procedures, blood loss is less. In many instances, less prostatic tissue is removed
with PVP compared with TURP.
HoLEP and ThuLEP The wavelength of light emanating from the
Holmium:Yttrium- Aluminium-Garnet (YAG) (2140 nm wavelength) laser [44-47] and
Thulium:YAG (2014 nm wavelength) [42,48-50] lasers is near the peak of water
absorption (2100 nm), which necessitates direct contact of the laser for tissue
ablation. A modification of the standard Holmium and Thulium YAG lasers creates a
pulsating stream of bubbles from the tip, essentially turning the device into a laser
knife, which allows resection of tissue (ie, HoLEP: holmium laser enucleation of the
prostate; ThuLEP: thulium laser enucleation of the prostate) [41,45]. The procedure
is performed similar to bipolar TURP using the laser tip instead of a bipolar cautery
loop. Like TURP, tissue can be preserved for histologic examination. However, with
HoLEP and ThuLEP, the size of the prostate that can be treated is not restricted
[24].
Other ablation techniques Transurethral incision of the prostate (TUIP) can be
useful for selected patients with obstructive symptoms, who are not good
candidates for the procedures

described above. Although still described in the literature, few urologists use
radiofrequency ablation or microwave thermotherapy at this time.
Transurethral incision of the prostate (TUIP) Transurethral incision of the
prostate (TUIP) refers to a procedure in which a longitudinal incision is made in the
prostate gland, widening the bladder neck and prostatic urethra without removal of
any prostate tissue [51]. TUIP can be performed under general anesthesia or with a
regional block, and generally requires a 24 hour observation period in the hospital.
The resectoscope is loaded with monopolar or bipolar electrocautery and
introduced into the bladder under direct vision. Traditionally, glycine was used as
an irrigating solution; however, saline is more commonly used. Usually, two deep
incisions are made starting distal to each ureteral orifice and proceeding in a
retrograde
fashion through the bladder neck and the prostatic adenoma distally toward the
verumontanum
of the prostate. The incisions go down to, but not through, the capsule of the
prostate. Bleeding is controlled with electrocautery.
Radiofrequency ablation Transurethral radiofrequency ablation of the prostate
(formerly referred to as transurethral needle ablation [TUNA]) involves placing
needles (electrodes) into the prostate via the urethra using a cystoscope, usually
using only local anesthesia [52-54]. A radiofrequency generator transmits a high
frequency (in the radio range of frequencies, 300 kHz to 1 MHz) alternating current
through the needle to produce heat within the tissue, which induces a coagulative
necrosis.
Microwave thermotherapy Microwave thermotherapy involves heating prostatic
tissue to temperatures above 45C (113F) [54]. Microwave thermotherapy can be
delivered transurethrally (TUMT) or transrectally (TRMT) using only local anesthetic
on an outpatient basis. Microwave thermotherapy can cause serious thermal
injuries and related complications if not performed properly or in properly selected
candidates [55]. (See 'Choice of procedure' below.)

OTHER PROCEDURES Other minimally invasive procedures, including urethral

stenting and injection of botulinum toxin, have also been used to treat benign
prostatic hyperplasia (BPH) [56].
Urethral stenting Urethral stents may provide safe and effective therapy for
selected men, but long-term experience is limited. Insertion of a self-expandable
metallic stent immediately increased peak urine flow rates to more than 8 mL/sec
in 11 of 13 men with urinary obstruction in one study, but bladder calculi formed in
six men in whom the stent extended into the bladder over an average follow-up
period of 37 months [57]. Exuberant granulation tissue growth through and around
the stent causes secondary obstruction and difficulty in removing the stent, as well
as other complications. As such, this procedure has been abandoned by most
urologists.
Prostatic urethral lift A novel procedure, the prostatic urethral lift, appears to be
well tolerated and appears to be effective for treating BPH [58]. The device is
introduced into the urethra and used to compress the prostate tissue, thereby
increasing the urethral lumen and reducing obstruction to urine flow. Subsequently,
one or more implant(s) are delivered into the prostatic urethra to maintain urethral
patency. This technique may be an option for men who are poor candidates for
more invasive procedures. Although short-term results (out to 12 months)
demonstrating safety and efficacy are available [58], longer follow-up will be
needed to determine the durability of the device.
In the multicenter trial, 206 men who were at least 50 years old with American
Urological Association Symptom Index (AUASI) 13, a maximum flow rate 12 mL
per second, and prostate 30 to 80 cc were randomized 2:1 to prostatic urethral lift
or a sham procedure, which involved rigid cystoscopy with simulated active
treatment sounds [59]. The reduction in the AUASI was significantly greater in the
prostatic lift group relative to baseline compared with the sham group (11.1 versus
5.9) at 12 months follow-up. The magnitude of the improvement was similar to
those seen with other treatments. Peak urinary flow also significantly increased and
was sustained at 12 months follow up with no ejaculatory or erectile dysfunction.
Fifty-three men previously enrolled in the sham arm of this trial who met eligibility

criteria elected to enroll in the crossover portion of the study [60]. The prostatic lift
group similarly showed significantly improved symptom scores, urine flow, and
quality of life relative to baseline assessment compared with their prior sham
procedure results. The symptom score reduction in crossover prostatic lift patients
closely mimicked those of patients assigned to prostatic lift in the initial trial. The
improvements seen were likewise durable over the 12 months of follow-up.
OUTCOME COMPARISONS
Monopolar and bipolar TURP Monopolar TURP has been the mainstay of
treatment of benign prostatic hyperplasia (BPH) for many years in men with
chronic lower urinary tract symptoms, and remains the standard against which
other treatments should be compared. Urologic symptom improvements using
bipolar TURP are comparable to monopolar TURP, but bipolar TURP has a better
safety profile [22,23,25,61-65]. (See 'Monopolar TURP' above and 'Bipolar TURP'
above.)
Most men undergoing traditional, monopolar TURP experience a marked decrease
in urinary symptom score (table 1) and a substantial increase in maximal urinary
flow rates [1,4,66]. In a Veterans Administration (VA) trial that randomly assigned
556 men to no therapy (watchful waiting) or TURP, the following results were
noted at an average follow-up of 2.8 years [4]:
The primary outcome of treatment failure (death, repeated or intractable urinary
retention, residual urinary volume over 350 mL, the development of bladder
calculus, new and persistent incontinence, a high AUA symptom score, or a
doubling of the serum creatinine concentration) occurred less frequently in the
TURP group compared with watchful waiting (8 versus 17 percent). However, only
24 percent of men who were watched required surgery during the follow-up
period, although by the end of five years of follow-up, 36 percent had undergone
surgery [67].

TURP resulted in a greater decrease in residual urine volume (60 mL versus 41 mL

decrease with watchful waiting) and greater increase in maximal urinary flow rate
(6 versus 0.4 mL/sec).
The symptom score decreased from 14.6 to 4.9 in the surgery group and from
14.6 to 9.1 in the watchful-waiting group. The results in the watchful waiting group
suggest that men gradually adapt to the symptoms.
In metaanalyses of trials comparing monopolar and bipolar TURP, there was no
significant difference in terms of International Prostate Symptom Score (IPSS) or
health-related quality of
life (HRQL) score [63,64]. However, it should be noted that most of the included
trials had short- term follow-up 1 year. Compared with monopolar TURP, bipolar
TURP had a significantly lower risk for adverse events including transurethral
resection syndrome (risk ratio [RR] 0.12, 95% CI
0.05-0.31), clot retention (RR 0.48, 95% CI 0.30-0.77), and blood transfusion (RR
0.53, 95% CI
0.35-0.82) [63].
TURP versus non-TURP techniques There are a limited number of high-quality
trials comparing TURP with non-TURP procedures, or other minimally invasive
procedures [68-71]. Non-TURP procedures that remove a sufficient quantity of
prostate tissue, such as laser enucleation (HoLEP, ThuLEP), plasma vaporization
(button), and photoselective vaporization (PVP), have perioperative advantages
(eg, less bleeding, shorter hospital stay), and early results are comparable to TURP.
Although there are as yet no long-term data on efficacy for these procedures, it is
anticipated that results will be also be comparable to standard TURP.
Radiofrequency ablation and incision procedures are also associated with less blood
loss, and can often be performed as a day procedure, but the level of urinary
improvement is not as good as TURP, and retreatment is common.
Systematic reviews, metaanalyses, and trials comparing TURP with non-TURP
techniques are summarized below.

Plasma vaporization A metaanalysis of 20 randomized trials comparing plasma

vaporization (button procedure) with TURP found similar improvements in
maximum urinary flow rates and symptom scores [72]. Patients treated with
electrovaporization had lower transfusion requirements (0 versus 4 percent) and
shorter length of stay (1.7 versus 3.4 days), but were at higher risk for urinary
retention (8 versus 3 percent) and reoperation (5 versus 2 percent). Similar results
have been reported in later comparison trials [23,25,61,73]. In the largest of these
trials, which randomized 510 patients to plasma vaporization, bipolar TURP in
saline, or monopolar TURP, plasma vaporization was superior to monopolar TURP in
terms of blood loss, hospital stay, and urinary outcomes (international prostate
symptom score [IPSS], maximal flow rate) at 1, 3, 6, 12, and 18 months [23].
Photoselective vaporization A 2015 metaanalysis of trials comparing PVP with MTURP found similar IPSS scores (four trials), maximal flow rate (three trials), and
postvoid residual (two trials) [64]. Length of catheterization and length of stay
were shorter, and transfusion rate was lower in the PVP group.
Laser enucleation In a systematic review and metaanalysis of six trials
comparing HoLEP with monopolar TURP, there was longer operative time but fewer
immediate complications, less need for blood transfusion, shorter catheterization
duration, and shorter length of hospital stay with HoLEP compared with TURP [64].
At one-year followup, HoLEP had better efficacy than monopolar TURP in terms of
International Prostate Symptom Score (mean difference: -0.91 [95% CI -1.51 to
-0.32]), maximum flow rate (mean difference: 1.59 mL/s [95% CI 0.26-2.91]),
and postvoid residual (mean difference: -18.69 [95% CI -22.96 to -14.43]). Longerterm results
after three to eight years (two trials) still favored HoLEP. The quality of life scores
were not significantly different between the two groups. The metaanalysis was
limited by heterogeneity across trials.

A separate metaanalysis also found similar urologic improvements for ThuLEP

compared with
TURP and similar perioperative benefits as HoLEP [74].

Transurethral needle ablation In a randomized trial comparing radiofrequency

ablation with TURP in 121 men with BPH, patients treated with TURP had a greater
improvement in symptom scores for the first four years of the study, though
symptom scores were similar in the fifth year [75]. Peak urinary flow was higher
with TURP, and postvoid residual volume was lower. However, patients treated with
radiofrequency ablation had fewer adverse events, including lower rates of
retrograde ejaculation (0 versus 41 percent), erectile dysfunction (3 versus 21
percent), urinary incontinence (3 versus 21 percent), and urethral stricture (2
versus 7 percent). More patients treated with radiofrequency ablation required
retreatment (14 versus 2 percent). Similar outcomes were reported in a systematic
review that included both randomized and nonrandomized studies [76]. In a study
of long-term outcomes (five years of follow-up) in 188 patients who underwent
radiofrequency ablation, clinical improvement was maintained in most patients, but
approximately 25 percent required additional treatment (medical or surgical) [77].
Microwave thermotherapy TURP provides greater improvements in urinary
symptom scores and flow improvements, and reduces the need for subsequent
BPH treatments compared with microwave thermotherapy. A systematic review
identified 15 studies involving 1585 patients who underwent microwave
thermotherapy [78]. Six studies compared microwave thermotherapy with TURP and
eight were comparisons with sham thermotherapy. The pooled mean urinary
symptom scores decreased by 77 percent with TURP and by 65 percent with
microwave thermotherapy. The pooled mean peak urinary flow increased by 119
percent with TURP, and by 70 percent for microwave thermotherapy. The weighted
mean differences for the International Prostate Symptom Score (IPSS) and peak
urinary flow were significantly greater for TURP. However, compared with TURP,
microwave thermotherapy was associated with decreased rates of retrograde
ejaculation, urethral stricture, hematuria, blood transfusion, and the transurethral
resection syndrome, but increased an incidence of dysuria, urinary retention, and
retreatment for BPH symptoms.

Transurethral incision Transurethral incision (TUIP) is generally considered to be

an inferior treatment for BPH compared with TURP, and retreatment is common. A
systematic review identified 10 trials comparing TUIP with TURP in men with mild to
moderate BPH [51]. TUIP offered a similar level of symptomatic relief as measured
by symptom scores, but with a significantly lower risk for blood transfusion
compared with TURP (relative risk [RR] 0.06, 95% CI 0.03-0.16); reoperation rates
were significantly higher with TUIP (18.4 versus 7.2 percent).
Prostatic urethral lift Prostatic urethral lift (PUL) is a relatively new procedure
with few outcomes data. In a noninferiority trial comparing PUL with TURP, PUL was
similar to TURP with regard to relief of symptoms [79]. Although the trial suggested
that prostatic urethral lift was superior to TURP with respect to quality of recovery
and preservation of ejaculatory function, outcomes were assessed using a
questionnaire that was not yet validated, and therefore these outcomes require
further evaluation to confirm these findings.
TURP versus prostatectomy Open prostatectomy accounts for less than five
percent of operations for BPH in the United States [21,80], but it is performed more
often in other countries [81,82]. A laparoscopic/robotic technique has also been
described. Given the
emerging technologies described above (bipolar TURP, PVP, HoLEP, ThuLEP), it is
likely that the use of open prostatectomy will continue to diminish with time. At
present, it is usually generally
only offered to men who are good surgical candidates and in whom the prostate is
estimated to weigh more than 50 grams [65].
Prostatectomy can be performed through the bladder, ie, transvesically as a
suprapubic technique, or directly through the capsule of the prostate as a
retropubic technique. A study comparing laparoscopic prostatectomy with historical
controls who received open prostatectomy concluded that the procedures have
similar efficacy and that the laparoscopic procedure required longer operating
room time, but led to a shorter hospital stay and less blood loss [83].

In some studies, open prostatectomy had lower complication and mortality rates
than TURP [84], but the difference probably relates to patient selection for the
procedures [85].
In a prospective study of 902 men in Germany who underwent open prostatectomy
(mean prostate size 96 mL; baseline IPSS 20.7), the mortality rate was 0.7 percent
and the complication rate was 17 percent with 7.5 percent requiring transfusion,
5.1 percent treatment for urinary tract infection, and 3.7 percent reoperation for
severe bleeding [81]. Mean peak urine flow increased from 10.4 to 23.1 mL/sec,
and postvoid residual decreased from 145.1 to 17.5 mL
CHOICE OF PROCEDURE The choice of procedure for the treatment of BPH is
based upon patient values, medical risk, and the impact of potential complications
[86-88]. For most men who require an invasive procedure to treat BPH, we suggest
transurethral resection of the prostate (bipolar TURP), which is effective at reducing
symptoms and avoids the need for repeat treatment. At our institution, bipolar
TURP (along with plasma vaporization [ie, the button procedure]) has largely
overtaken traditional monopolar TURP, and we speculate that bipolar TURP will
completely replace monopolar TURP in the near future. Our recommendation
places a relatively higher value on reducing symptoms and avoiding repeat
treatment for benign prostatic hyperplasia (BPH)/lower urinary tract symptoms
(LUTS) and a relatively lower value
on shortening length of stay and avoiding postoperative blood transfusions.
Patients with a large prostate gland, and those with significant medical risk factors,
might reasonably choose an alternative procedure.
Options under individual circumstances may include the following:

Large prostate Monopolar or bipolar TURP, laser enucleation (HoLEP, ThuLEP),

plasma vaporization (ie, button), open prostatectomy
Anticoagulated patient Photoselective vaporization (PVP), radiofrequency
ablation (see

'Antithrombotic therapy' above)

High-risk medical patient PVP, radiofrequency ablation, transurethral incision of

the prostate
(TUIP)

Bladder outlet obstruction, small prostate TUIP

Patients with small to moderate sized prostates who seek to preserve normal
ejaculation TUIP, radiofrequency ablation, transurethral microwave thermotherapy
(TUMT), or prostatic urethral lift (PUL)
Non-TURP procedures such as transurethral enucleation (HoLEP, ThuLEP), plasma
vaporization (button) and PVP are becoming increasingly popular for the
treatment of BPH because they are associated with less blood loss compared with
TURP (monopolar), avoid hyponatremia, and can often be performed as a day
procedure [20,21,89,90]. Although there are as yet no long- term data on their
efficacy, it is anticipated that results will be comparable to standard TURP. PVP is a
particularly good option for men who are not good candidates for TURP, but less
prostatic tissue is removed with PVP. We continue to prefer TURP to PVP in good risk
patients with moderate to large prostates. (See 'Transurethral procedures' above
and 'Outcome comparisons' above.)
Microwave thermotherapy (eg, TUMT) is an effective alternative to TURP for treating
small to moderate sized prostates in men with BPH who do not have a history of
urinary retention or prior prostate procedures.
Radiofrequency ablation of the prostate is an alternative for men who are poor
candidates for surgery, particularly men who require anticoagulation, but also for
those who wish to undergo a procedure with fewer lower urinary and sexual side
effects than TURP. The improvements in urodynamic and symptom score
parameters are generally inferior to TURP or vaporization procedures; however,

radiofrequency ablation can be repeated, or a more invasive procedure can be

performed subsequently, if needed. Radiofrequency ablation should not be used in
patients on the verge of urinary retention or in patients with deteriorating renal
function caused by obstructive uropathy. (See 'Outcome comparisons' above.)
Transurethral incision of the prostate (TUIP) may be useful for men with bladder
outlet obstruction and relatively little prostate enlargement, particularly men with
medical comorbidities. Similar to transurethral needle ablation (TUNA), TURP
provides greater improvements in urinary symptom scores and flow improvements
than TUIP, and reduces the need for subsequent BPH treatments. (See 'Outcome
comparisons' above.)
Four procedures (TUIP, radiofrequency ablation, TUMT, and PUL) may be better
suited for patients who seek to preserve normal ejaculatory function [91]. These
procedures cause significantly less retrograde ejaculation than resectional
procedures such as TURP, laser enucleation, or PVP. However, patients should be
advised that these four procedures are generally used to treat a smaller prostate
volume, and that more reoperations may be required in patients who develop
recurrent LUTS symptoms. (See 'Ejaculatory dysfunction' below.)
PATIENT CARE AND FOLLOW-UP The patient should avoid straining because of
increased vulnerability to bleeding until the prostatic fossa is completely
epithelialized. Following transurethral resection or ablation of the prostate, we
suggest stool softeners.
Incidental prostate cancer Prostate cancer can be identified in the specimen in
about 5 percent of patients undergoing TURP for BPH [92,93]. Under this
circumstance, further diagnostic or therapeutic steps depend on a variety of factors
(eg, the age and comorbidities of the patient, the grade and extent of the cancer).
(See "Clinical presentation and diagnosis of prostate cancer".)
In patients with a clinically significant cancer who are candidates for active
treatment, transrectal ultrasound-guided biopsy of the prostate may be needed to

further characterize the lesion and guide treatment decisions, and if elected,
should be performed three months after
the TURP.
PERIPROCEDURAL MORBIDITY AND MORTALITY About 15 to 20 percent of
patients undergoing TURP experience significant complications, and mortality rates
ranging between
0.2 and 2.5 percent have been reported [94]. Technical modifications involving the
use of bipolar instead of monopolar electrocautery, and the use of other forms of
transurethral resection and ablation of prostate tissue have provided similar
improvement in urinary symptoms in the short term, but with generally lower
complication rates. (See 'Transurethral procedures' above and 'Outcome
comparisons' above.)
In the Veterans Administration study discussed above, there were no deaths
associated with TURP, but 9 percent of the men had perioperative (<30 days)
complications [4]. Complications related to monopolar TURP have improved over
time. In one study, a comparison of outcomes in the period from 2000 to 2005
with those from 1979 to 1994 found lower rates of transfusion (0.4 versus 7.1
percent), clot retention (2 versus 5 percent), urinary tract infection (1.7 versus
8.2 percent), urinary retention (3 versus 9 percent), and TUR syndrome (0 versus
1.1 percent) [95]. (See 'Postprostatectomy syndrome' below.)
Bleeding An increased risk of bleeding with TURP, relative to other transurethral
procedures, has been found in most [11,13,14,70,72,78,96], but not all studies
[10,97]. The risk of bleeding is increased in patients who require antithrombotic
therapy, which is needed in about 30 percent of patients undergoing TURP. (See
'Antithrombotic therapy' above.)
In the Veterans Administration study, hemorrhage requiring transfusion occurred in
1 percent of patients undergoing TURP [4]. In metaanalyses, transfusion was
required in 3 to 7 percent of TURP patients and 0 to 1 percent of patients
undergoing non-TURP resection or ablation procedures [70,72]. A systematic review
that identified 10 trials comparing transurethral

incision of the prostate (TUIP) with TURP found a significantly lower risk for blood
transfusion compared with TURP (relative risk [RR] 0.06, 95% CI 0.03-0.16) [51].
Clot retention was lower for photoselective vaporization (PVP) compared with TURP
(3 versus 29 percent) [98].
Postprostatectomy syndrome Postprostatectomy or TUR syndrome refers to
symptoms related to hyponatremia as a result of systemic absorption of hypotonic
irrigating fluid used in some transurethral prostate resection procedures.
Hyponatremia associated with TUR syndrome is discussed in detail elsewhere. (See
"Hyponatremia following transurethral resection or hysteroscopy".)
Bipolar TURP and other non-TURP procedures have the advantage of using saline
as an irrigating fluid, which is isotonic, and thus, not associated with hyponatremia.
As an example, in a systematic review that identified 15 studies involving 1585
patients, the risk for TUR syndrome was significantly reduced for patients
undergoing microwave thermotherapy compared with TURP (relative risk 0.13, 95%
CI 0.02-0.81) [78].
Sexual dysfunction The overall incidence of sexual dysfunction (eg, erectile
dysfunction, retrograde ejaculation) following surgical procedures to treat benign
prostatic hyperplasia (BPH) varies [99-101]. Although new onset erectile dysfunction
is relatively uncommon, retrograde ejaculation can occur in as many as three of
four men after certain procedures.
Ejaculatory dysfunction New onset ejaculatory dysfunction, particularly
retrograde
ejaculation, is common after surgical procedures for BPH. As an example, in a
systematic review of randomized trials, retrograde ejaculation was most prevalent
after monopolar or bipolar transurethral resection of prostate (TURP) (66 percent),
plasma vaporization (56 percent), and prostate enucleation with Holmium laser (76
to 96 percent) or Thulium laser (54 percent) [91]. Patients who had PVP were at an
intermediate risk of developing retrograde ejaculation (42 percent).

Prostate coagulation procedures, such as transurethral incision of the prostate

(TUIP) (21 percent), radiofrequency ablation (0 percent), or microwave
thermotherapy (TUMT) (21 percent), had the lowest rates of postoperative
retrograde ejaculation. Patients who underwent prostatic urethral lift (PUL) also had
a low rate of ejaculatory dysfunction, comparable to the sham control group (both
at 10 percent) [59,91].
In a separate study, the rate of ejaculatory dysfunction was similar after bipolar
versus monopolar TURP [101]. Although reduced rates of painful ejaculation after
TURP have been reported in some studies [102,103], it is not known whether this
represents true pain relief during preserved ejaculation or an inability to ejaculate.
Erectile dysfunction New onset erectile dysfunction is relatively uncommon after
surgery for BPH. In a trial comparing radiofrequency ablation with TURP in 121 men
with BPH, fewer patients treated with radiofrequency ablation had new onset
erectile dysfunction (3 versus 21 percent) [75]. In patients with pre-existing erectile
dysfunction, however, erectile function improved after TURP compared with no
surgery [102,103].
Urethral stricture Any instrumentation of the urethra carries the risk of trauma
which heals with scar formation resulting in urethral stricture [104]. (See
"Treatment of urethral stricture disease in men".)
In the Veterans Administration study discussed above [4], late postoperative
complications included contracture of the bladder neck requiring surgery (4
percent), urethral stricture requiring dilation (4 percent), and obstruction requiring
a second TURP (3 percent).
In systematic reviews, urethral stricture occurred in 2 to 4 percent of patients
undergoing plasma vaporization and other laser therapies compared with 7 to 8
percent of TURP patients [70,75,78]. In a metaanalysis of 20 randomized trials
comparing plasma vaporization (button procedure) with TURP, TURP patients had
a lower risk for urinary retention (3 versus 8 percent) and reoperation (2 versus 5
percent) compared with the button procedure [72].

Urinary incontinence In the Veterans Administration study, four men (2 percent)

undergoing TURP had persistent incontinence [4]. In a trial that compared
radiofrequency ablation with TURP, rates for urinary incontinence were higher at
21 percent for TURP, and 3 percent for radiofrequency ablation [75]. Similar rates
of urinary incontinence following TURP are reported in other studies [105,106].
INFORMATION FOR PATIENTS UpToDate offers two types of patient education
materials, "The Basics" and "Beyond the Basics." The Basics patient education
pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient
education pieces are longer, more sophisticated, and more detailed. These articles
are written at the 10th to 12th grade reading level and are best for patients who
want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also locate
patient education articles on a variety of subjects by searching on "patient info" and
the keyword(s) of interest.)
Basics topics: (see "Patient information: Benign prostatic hyperplasia (enlarged
prostate) (The
Basics)")

Beyond the Basics topics: (See "Patient information: Benign prostatic

hyperplasia (BPH) (Beyond the Basics)".)
SUMMARY AND RECOMMENDATIONS

Benign prostatic hyperplasia (BPH) becomes increasingly common as men age.

Men with
BPH who are asymptomatic or have only mild symptoms may not require
treatment. Those with more severe urinary symptoms may benefit from medical
therapy and will improve or stabilize without the need for surgical intervention.
(See 'Introduction' above and "Medical treatment of benign prostatic
hyperplasia".)
In general, men who develop upper tract injury (eg, hydronephrosis, renal
dysfunction), or lower tract injury (eg, urinary retention, recurrent infection, bladder
decompensation) require invasive therapy. (See 'Indications for Treatment' above.)
Most procedures used in the treatment of BPH are performed transurethrally.
Prostatic tissue can be removed (ie, resected), or destroyed (ie, ablated) using a
variety of techniques which include: transurethral resection of the prostate (TURP),
transurethral laser enucleation (HoLEP, ThuLEP), plasma vaporization (the button
procedure), photoselective vaporization (PVP), radiofrequency ablation, microwave
thermotherapy, and transurethral incision (TUIP). Other procedures include the
prostatic lift and injection of botulinum toxin. (See 'Transurethral procedures'
above and 'Other procedures' above.)
Most men undergoing TURP experience a marked decrease in urinary symptom
score, and a substantial increase in maximal urinary flow rates. Non-TURP
procedures that remove a sufficient quantity of prostate tissue have early results
that are comparable to TURP. The level of urinary improvement is not as good as
TURP for radiofrequency ablation and incision procedures, and retreatment is
common. Data on long-term outcomes are limited for most procedures. (See
'Outcome comparisons' above.)
For men who require an invasive procedure and are in good health, we suggest
transurethral resection of the prostate (TURP) (Grade 2B). We use bipolar
transurethral resection of the prostate (bipolar TURP), or bipolar plasma
vaporization of the prostate (button procedure), rather than traditional monopolar
TURP. Urologic symptom improvements using bipolar TURP

or vaporization are comparable to monopolar TURP, but bipolar procedures have a

better safety
profile. Where expertise and equipment are available, laser photoselective
vaporization (PVP) is an alternative that will likely produce similar outcomes.
Alternative procedures may be chosen
under selected circumstances (eg, medical comorbidities, anticoagulation,
avoidance of side effects). (See 'Choice of procedure' above.)
Complications associated with transurethral procedures include bleeding,
postprostatectomy syndrome, erectile dysfunction, retrograde ejaculation, urethral
stricture, urinary retention, and urinary incontinence. Technical modifications
involving the use of bipolar instead of monopolar electrocautery, and the use other
forms of transurethral resection and ablation of prostate tissue, have generally
lowered complication rates. (See 'Periprocedural morbidity and mortality' above.)