1.

Clinical manifestations and diagnostic evaluation of benign prostatic

hyperplasia
Authors
Glenn R Cunningham, MD
Dov Kadmon, MD
Section Editor
Michael P O'Leary, MD, MPH
Deputy Editor
Lee Park, MD
Disclosures: Glenn R Cunningham, MD Nothing to disclose. Dov Kadmon, MD
Nothing to disclose. Michael P O'Leary, MD, MPH Nothing to disclose. Lee
Park, MD Employee of UpToDate, Inc. Employment (Spouse): Novartis. Equity
Ownership/Stock Options (Spouse): Novartis. Contributor disclosures are
reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through
requirements for references to be provided to support the content.
Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence. Conflict of interest policy
All topics are updated as new evidence becomes available and our peer
review process is complete.
Literature review current through: Sep 2014. | This topic last updated: Mar
18, 2013.
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
"Epidemiology and pathogenesis of benign prostatic hyperplasia" and
"Medical treatment of benign prostatic hyperplasia" and "Transurethral
procedures for treating benign prostatic hyperplasia" and "Lower urinary
tract symptoms in men" and "Acute urinary retention".)

CLINICAL MANIFESTATIONS The clinical manifestations of BPH are lower

urinary tract symptoms (LUTS) that include increased frequency of urination,
nocturia, hesitancy, urgency, and weak urinary stream. These symptoms
typically appear slowly and progress gradually over a period of years.
However, they are not specific for BPH. Furthermore, 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

[1] that occur with aging and from enlargement of the transitional zone of
the prostate that is not always evident on rectal examination.

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 "Etiology and evaluation of
hematuria in adults".)

NATURAL HISTORY The natural history of BPH is becoming better

understood [2]. In population-based studies, 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. Longitudinal studies have
shown only modest increases in the American Urologic Association (AUA)
Symptom Index scores. These surrogate measures of BPH suggest a
continuum of disease severity and not a threshold effect.

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.

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 [3]. 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 [4].

Population based studies include:

The community-based Olmstead County, Minnesota, study evaluated a

random sample of 477 white men aged 40 to 79 years with no previous
prostate surgery or prostate cancer [5]. Men with prostate volumes above
50 mL were more likely to have moderate to severe symptoms of BPH,
adjusted for age (OR 3.5, 95% CI 1.6-7.5). Based upon the clinician's
diagnosis in the medical record, the annual incidence of new diagnoses of
BPH in Olmsted County increased from 727 per 100,000 men in 1987 to
1212 in 1992 and then decreased to 546 in 1997 [6]. The rise in incidence

prior to 1992 is attributed to widespread introduction of PSA determinations

and prostate screening in the United States, and part of the fall since then
may be related to individuals being diagnosed at an earlier stage in the
previous years. Although the Olmsted County study was a population-based
prospective study, most of the men were white. It is unclear whether the
results translate to other racial and ethnic groups.
The Massachusetts Male Aging Study evaluated men 40 to 70 years of age
in communities surrounding Boston and assessed them for the prevalence of
BPH for the periods between 1987 and 1989 and 1995 and 1997 [7]. This
study primarily involved white men. Patients were considered to have BPH if
they had frequent or difficult urination and had been told by a health
professional that they had an enlarged prostate, or if they had undergone
surgery for BPH. The overall prevalence of BPH was 19.4 percent in men
over age 38.
A study from the Nationwide Inpatient Sample, which samples community
hospitals in the United States, found that the age-adjusted prevalence of
BPH as a primary diagnosis decreased from 0.88 to 0.48 percent from 1998
to 2008 [8]. Discharges for BPH surgery decreased 51 percent and
discharges for primary BPH with acute renal failure increased more than 400
percent. There were no significant changes in discharges for primary BPH
with urinary retention, bladder stones, or urinary infection.
Symptoms need not be progressive. In one study, for example, about onethird 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 [9]. On the other hand, many men have progressive disease
that eventually requires treatment. In the Olmstead County Study there was
a one-point increase in the AUA symptom score over five years [10]. Peak
flow rates decreased approximately 2.1 percent per year [11], and prostate
volume increased about 1.6 percent per year [12]. In a 30-year prospective
study of 1057 men that was reported in 1991, 527 (50 percent) were given a
diagnosis of BPH and 110 (10 percent) underwent prostatectomy [13].

As mentioned, the natural history of BPH has also been studied in the
placebo arms of clinical trials, although there are concerns that such results
may not accurately reflect outcomes in the general population. 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 (AUR) ranged from 0.4 to
6.0 percent [14]. 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.

Age, symptoms, urinary flow rate and prostate volume are risk factors for
acute urinary retention at least in population-based studies, though not in
all clinical trials [15]. Men with symptomatic BPH who are not treated have
about a 2.5 percent per year risk of developing acute urinary retention

[16,17]. Serum PSA is a stronger predictor of prostate growth than age or

baseline prostate volume [18], and therefore PSA should be a good predictor
of risk for acute urinary retention. (See "Acute urinary retention".)

A population-based study followed 1688 men 50 to 75 years of age and

found that prostate volume was associated with age and prior prostate
volume over a period of 4.2 years [19]. This allowed prediction of 'normal'
prostate volume using age and prostate volume history. The authors suggest
that it may be possible to use a model to identify men who should be
treated and those who can be followed without treatment.

Prostate cancer BPH is not believed to be a risk factor for prostate cancer,
although studies have come to conflicting results [20]. 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 [21].

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 [22]. The American Urologic Association (AUA) updated these
guidelines in 2010 [23], 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
[24,25].

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 [26,27]
Symptoms of neurologic disease that would suggest a neurogenic bladder
Sexual dysfunction, which is correlated with LUTS [28-30]
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 [24].

Lower urinary tract symptoms in men are discussed in detail separately.

(See "Lower urinary tract symptoms in men".)

American Urologic Association symptom score The AUA symptom score

was developed to measure outcomes in studies of different treatments for
BPH (table 1) [31]. 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 [31]. 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

[32]. However, it correlates poorly with prostate size and peak urinary flow
rates [33-35].

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?" [35].

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 [36].

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 [37]) and consistency and to detect nodules,
induration, and asymmetry, all of which raise suspicion for malignancy. (See
"Clinical presentation and diagnosis of prostate cancer".) Rectal sphincter
tone should be determined, and a neurological examination performed.

RECOMMENDED TESTS The American Urologic Association (AUA)

recommends an urinalysis and a serum PSA for the routine management of
patients with LUTS [23]. 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 age-matched controls [38,39]. 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 "Etiology and evaluation of hematuria in
adults".)

Among those with gross hematuria in whom no cause other than BPH can be
identified, finasteride often suppresses the hematuria [40,41].

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 [24]. 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 'Ultrasonography and plain abdominal x-rays'
below.)

Serum prostate specific antigen Prostate cancer can cause obstructive

symptoms, although the presence of symptoms is not predictive of prostate
cancer [32]. 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 [24]. The following points
should be kept in mind when serum PSA determinations are ordered and the
results interpreted (see "Measurement of prostate specific antigen"):

The specificity of the serum PSA assay is lower in men with obstructive
symptoms than in asymptomatic men [42]. In men with prostate
enlargement, the serum PSA value and prostate volume have a log-linear
relationship [43,44], but there are conflicting data on its utility for predicting
development of LUTS [45,46]. 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 [47].
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 "Screening for prostate
cancer", section on 'Effect of lowering PSA cutoffs'.)
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 [48].
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 [24].

Post-void residual urine volume Residual urine volume can be determined

by in-out 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
[49]. 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 [24].

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
[50].

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 "Epidemiology and etiology
of urothelial (transitional cell) carcinoma of the bladder", section on
'Cigarette smoke'.)

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 [51]. 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 [52].
Hematuria, a history of renal stones, urinary tract infection, or previous
urinary tract surgery are indications for intravenous urography.

Ultrasonography and plain abdominal x-rays Ultrasonography is useful in

men who have a high serum creatinine concentration or a urinary tract
infection. It can be coupled with plain x-rays 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 [53].

Total prostate volume can be measured by ultrasonography to assess

disease progression, and it is useful when considering medical treatment
with a 5-alpha-reductase inhibitor or when considering surgery [45,54].

When prostate volume was compared with enucleated prostate weight in

men with BPH undergoing open prostatectomy, transurethral 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) [55]. 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
glandular-ductal versus stromal-low ductal tissues [56]. 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
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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
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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

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 'Clinical
manifestations' above.)
The natural history of BPH is becoming more clearly understood. Age,
LUTS, PSA, prostate volume, and peak flow rates can help predict
progression of BPH. (See 'Natural history' 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 'Diagnostic approach' above and 'Recommended tests'
above.)
The American Urologic Association symptom score (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 'American
Urologic Association symptom 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 x-rays) should be reserved for

unusual patients and for those being considered for invasive treatments.
(See 'Optional tests' above.)

2.
Epidemiology and pathogenesis of benign prostatic hyperplasia
Authors
Glenn R Cunningham, MD
Dov Kadmon, MD
Section Editor
Michael P O'Leary, MD, MPH
Deputy Editor
Lee Park, MD
Disclosures: Glenn R Cunningham, MD Nothing to disclose. Dov Kadmon, MD Nothing to disclose. Michael
P O'Leary, MD, MPH Nothing to disclose. Lee Park, MD Employee of UpToDate, Inc. Employment (Spouse):
Novartis. Equity Ownership/Stock Options (Spouse): Novartis.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Sep 2014. | This topic last updated: Sep 10, 2013.
INTRODUCTION Benign prostatic hyperplasia (BPH) is a common problem among older
men, and is responsible for considerable disability; however, it is an infrequent cause of death.
According to the World Health Organization database, the mortality rates for most developed
countries in the 1980s were 0.5 to1.5/100,000 [1]; death from BPH is rare in the United States
[2]. A cohort study of 4,708 men who underwent transurethral resection of the prostate between
1976 and 1984 at the Kaiser Permanente Medical Center in Oakland revealed no excess
mortality when compared with mortality of age-matched men who did not undergo the surgery
[3].
The large number of men with the symptoms of this disorder, the easy access to diagnostic
tests, and the availability of drug therapy make it appropriate for the primary care provider to
participate in the management of men with this disorder. To do so requires an appreciation for
what is known regarding the epidemiology and etiology of BPH, which will be reviewed here.
The diagnosis and management of this disorder are discussed elsewhere. (See "Clinical
manifestations and diagnostic evaluation of benign prostatic hyperplasia" and "Medical
treatment of benign prostatic hyperplasia" and "Transurethral procedures for treating benign
prostatic hyperplasia".)
EPIDEMIOLOGY The prostate on average weighs 20 grams in normal 21- to 30-year-old
men, and the weight changes little thereafter unless the man develops BPH [4]. However,
because of the prevalence of this disorder, the mean prostate weight at autopsy increases after
age 50 years (figure 1).
Prevalence The prevalence of histologically diagnosed prostatic hyperplasia increases from
8 percent in men aged 31 to 40, to 40 to 50 percent in men aged 51 to 60, to over 80 percent in
men older than age 80 (figure 2). The Baltimore Longitudinal Study of Aging compared the age-

specific prevalence of pathologically defined BPH at autopsy with the clinical prevalence based
upon history and the results of digital rectal examination [5]. There was good agreement
between the clinical prevalence and autopsy incidence in men of all ages.
A major difficulty in comparing the prevalence of clinical BPH among different groups has been
the lack of a common definition. The Olmsted County study found the prevalence of moderate
or severe lower urinary tract symptoms (LUTS) for men in the fifth, sixth, seventh, and eighth
decades of life to be 26, 33, 41, and 46 percent, respectively [6]. In a community-based group of
502 men aged 55 to 74 years without prostate cancer, the prevalence of BPH was 19 percent
using the criteria of a prostate volume above 30 mL and a high International Prostate Symptom
Score (IPSS) [7]. However, the prevalence was only 4 percent if the criteria were a prostate
volume above 30 mL, a high score, a maximal urinary flow rate below 10 mL/sec, and a postvoid residual urine volume greater than 50 mL.
Risk factors Race has some influence on the risk for BPH severe enough to require surgery.
While the age-adjusted relative risk (RR) of BPH necessitating surgery is similar in black and
white men, black men less than 65 years old may need treatment more often than white men
[8]. In a study of 34,624 men, compared with whites, Asians had a lower risk for nocturia (RR
0.7, 95% CI 0.5-0.9), physician diagnosed BPH (RR 0.7, CI 0.2-0.5), and transurethral prostate
surgery (RR 0.2, CI 0.1-0.6), while risks for blacks and whites were similar [9]. In the American
Male Health Professional Study, men of Asian ancestry were less likely (relative risk 0.4, 95% CI
0.2-0.8) to undergo surgery for BPH as compared with white men [10]. Black men had similar
risk to white men in this study. In a community sample of 2480 men in the United States,
moderate to severe LUTS were more common in blacks than in whites (41 versus 34 percent)
[11], and blacks had greater total and transitional zone prostate volume [12,13]. However, there
is evidence that differences in risk of LUTS is more related to socioeconomic factors such as
income and insurance than to race [14].
One study applied the American Urological Association symptom score to 289 Japanese men
ranging in age from 40 to 79 years: the Japanese men had somewhat higher symptom scores
than American men [15]. However, the American men had an approximately
6 mL/decade increase in prostate size, as compared with 3 mL/decade for the Japanese men.
This correlates with the lower age-specific prevalence of BPH in Japan. An autopsy study of
men who lived in Beijing and Shanghai found that the frequency of BPH was similar to that in
Western countries, although prostate cancer was much less common [16]. There have been
inconsistent results across studies about the effects of various dietary components and
supplements on the risk of symptomatic BPH [17-19].
In the Massachusetts Male Aging Study, increased risk of BPH was associated with higher free
PSA levels, heart disease, and use of beta-blockers [20]. Decreased risk of BPH was
associated with cigarette smoking (1 to 20 per day) and higher levels of physical activity. Risk
was not altered by total fat caloric intake, sexual activity, alcohol intake, body mass index, waisthip-ratio, waist circumference, diastolic BP, diabetes, or serum levels of androgens or
estrogens. In other studies, diastolic BP has been found to be associated with LUTS [21,22].
Obesity, fasting glucose, diabetes, and adiponectin levels are associated with BPH [23,24], and
alcohol consumption and exercise associated with a decreased risk of LUTS [21]. One study
found an increased risk of BPH in men with a family history of bladder cancer, but not prostate
cancer [25]. The amount of inflammatory infiltrate within the prostate may correlate with
components of the metabolic syndrome [26].
Other studies have suggested a relationship between BPH and hormone levels. Higher serum
levels of testosterone and estradiol were associated with increased risk of future development of

symptomatic BPH in the Prostate Cancer Prevention Trial [27]. There appears to be a weak
inverse relationship between autopsy findings of BPH and cirrhosis. Men with advanced
cirrhosis have lower urinary symptom scores, smaller prostate volumes and higher ratios of
serum estradiol to serum testosterone [28].
Most men with cirrhosis have chronic alcoholism. Alcohol consumption, particularly consumption
of excessive amounts of alcohol (three or more drinks per day), which can reduce androgen
levels, may reduce the risk of BPH [29].
Aging men and women have similar urinary symptom scores even though they differ greatly in
bladder outlet obstruction [30]. There is no relationship between vasectomy and BPH. In a
longitudinal, population-based study, prostatitis was associated with an increased risk of
subsequent prostatism, enlarged prostate, or BPH [31]. An observational study found an inverse
association between use of nonsteroidal antiinflammatory drugs (NSAIDs) and risk of BPH [32];
this may be related to actual improvements in BPH when men take NSAIDs [33].
Erectile dysfunction is common in men with LUTS [34]. A study of 500 urology offices in
Germany evaluated 10,000 consecutive patients with LUTS and found that 62 percent of
patients had symptoms of erectile dysfunction [35].
HISTOLOGY BPH develops primarily in the periurethral or transitional zone of the prostate.
The hyperplastic nodules comprise primarily stromal components and to a lesser degree
epithelial cells; stereologic measurements have revealed a four-fold increase in stroma and a
two-fold increase in glandular components [36]. In one immunohistochemical study, stroma
comprised 62 percent of the volume, epithelium 15 percent, and glandular lumens 23 percent;
the stroma-to-epithelium ratio was 4.6 [37]. Some studies have found inflammation to be a
common finding in BPH tissue. Inflammation was assessed by cytological and
immunohistochemical parameters in 282 surgical specimens [38]. The investigators found a
high correlation between inflammation, International Prostate Symptom Score (IPSS), and
prostate volume. Similarly, an analysis from the placebo arm of the Prostate Cancer Prevention
Trial found that low-soluble tumor necrosis factor receptor II and elevated interleukin 6
concentrations were associated with increased BPH risk [39].
PATHOGENESIS Older age and the presence of functioning Leydig cells of the testes are
essential for the development of BPH. Thus, BPH is very rare in men with hypogonadism with
onset before age 40 years who are not treated with androgen. Studies have examined the
molecular and cellular changes associated with BPH [40]. It is likely that multiple factors are
causally related to the development of BPH [41].
The pathogenesis of BPH remains incompletely understood. Population-based observational
studies, disease registries, in vitro studies of human tissue, and clinical trials continue to
contribute to our understanding of the pathogenesis of this common disorder.
Androgen The necessity for androgen, in particular dihydrotestosterone, during prostate
development is best illustrated by observations in men with congenital deficiency of 5-alphareductase activity (type 2), the enzyme that converts testosterone to dihydrotestosterone in the
prostate and other androgen-sensitive tissues [42]. Men with this disorder have a rudimentary
prostate throughout life despite normal serum testosterone concentrations and normal androgen
receptors (see "Steroid 5-alpha-reductase 2 deficiency"). The importance of androgen in the
development of BPH is seen in androgen's ability to induce BPH in dogs [43,44], as well as the
regression of BPH in men when serum testosterone concentrations are lowered with
medications. (See "Medical treatment of benign prostatic hyperplasia".)

In general, the concentrations of dihydrotestosterone in prostatic tissue are not higher in men
with BPH than in those without BPH. Thus, excess intraprostatic conversion of testosterone to
dihydrotestosterone is not responsible for the development of BPH [45]. There are, however,
changes in androgen receptors in the prostate. These receptors are primarily located in
epithelial cells in normal prostatic tissue, as compared with a more heterogeneous distribution
(epithelial and stromal cells) in hyperplastic prostatic tissue [46]. A segment of DNA for the AR
encodes for a variable number of glutamine repeats. Results of one study suggest that risk of
surgery for BPH is increased with decreased CAG repeats [47]; however, analysis of 416 BPH
cases and 527 controls from the Prostate Cancer Prevention Trial failed to find an association
between CAG repeat length and BPH risk [48]. One study reported an increase in coactivators
and another noted a decrease in corepressors of the androgen receptor in BPH tissue [49,50].
Serum testosterone or dihydrotestosterone concentrations do not appear to be higher in men in
whom the prostate ultimately becomes hyperplastic than in men in whom it does not. The
Physicians' Health Study found similar serum testosterone concentrations at the initial
examination in 320 men who had BPH treated surgically up to nine years later and 320 men
who did not develop prostatic disease [51]. A nested case-control study of steroid
concentrations and risk of BPH found that the lowest quartiles of testosterone, estradiol, and
testosterone:17beta-diol-glucoronide ratio were associated with the highest risk of BPH [27].
In summary, the available evidence indicates that testosterone and dihydrotestosterone are
necessary but not sufficient to cause BPH.
Estrogen The most compelling evidence for a role of estrogen in the pathogenesis of BPH is
that induction of the disorder in dogs is potentiated by the addition of estrogen [43,44]. This
relationship has been partially explained by estrogen induction of androgen receptors. In
addition, the finding of an increase in the ratio of estrogen to androgen in the serum in older
men suggests a role for estrogen in the maintenance, but not necessarily the causation, of BPH.
The age-related increase in the serum estrogen/androgen ratio is associated with an increase in
the estrogen/androgen ratio in prostatic tissue, especially in the stroma [52]. The prostate also
contains the enzymes needed to convert DHEA and testosterone to estradiol [53].
The results of other studies relating estrogen with BPH are conflicting [51,54-57]. The following
observations, for example, are compatible with a role for estrogen:

In a study of 86 men between 52 and 82 years of age who had a family history of
prostatic cancer, transition zone and total prostate volume correlated with serum
estrone concentrations [54]. There was no correlation with serum total or free
testosterone or estradiol concentrations.

In 64 men aged 42 to 71 years with small prostate cancers who underwent radical
prostatectomy, the volume of hyperplastic prostatic tissue (excluding the tumor)
correlated with the serum free testosterone, estradiol, and estrone concentrations [56].

The Physicians' Health Study demonstrated a strong trend for increasing risk of BPH
across quintiles for serum estradiol concentrations and a weak inverse trend for serum
estrone concentrations in the 320 men who developed BPH necessitating surgery up to
nine years later [51].

On the other hand, there are also findings arguing against an important role for estrogen:

Prostatic stromal cells contain estrogen receptors, and the concentrations are lower in
hyperplastic than in normal prostatic tissue [58]. The concentrations of progesterone
receptors in the two types of tissue are similar.

Treatment of men with BPH with atamestane, an aromatase inhibitor, reduced serum
estrogen concentrations but did not relieve symptoms, increase the urine flow rate, or
reduce prostatic size [57]. However, mepartricin, an antifungal agent that also reduces
serum estrogen concentrations, has been reported to improve symptoms and peak flow
rates without changing prostate volume or serum PSA concentrations [59].

Dysregulation of stromal growth factors Since BPH is primarily a disease of the stroma,
the stroma might have intrinsic properties that enable it to proliferate and also to induce
hyperplasia of the epithelium. In the presence of androgen, mesenchymal tissue derived from
the urogenital sinus can induce differentiation of prostate epithelium [60]. In contrast, stroma
lacking functional androgen receptors cannot induce differentiation of normal epithelium. These
observations emphasize the importance of the stroma in development of the prostate.
It has been suggested that BPH occurs because prostatic tissue reverts to an embryonic-like
state in which it is unusually sensitive to various growth factors. Tissue concentrations of several
growth factors are increased in hyperplastic prostatic tissue as compared with normal prostatic
tissue. The most consistent increases are in several fibroblast growth factors, insulin-like growth
factor-II, and transforming growth factor-beta and the mRNAs for these substances [60-65]. In
vitro, epidermal growth factor, transforming growth factor-alpha, several fibroblast growth
factors, and insulin-like growth factors-I and-II stimulate and transforming growth factor-beta
inhibits prostatic epithelial cell growth. Most of these factors stimulate stromal cell growth. A
nested case control study found that serum Insulin-like growth factor binding protein-3 (IGFBP3)
was inversely associated with BPH risk among men with severe symptoms, while the IGF1:IGFBP3 ratio was positively associated with BPH risk [66]. T lymphocytes and macrophages
appear to play an important role in the induction of cell proliferation [67].
Inflammation Inflammatory infiltrates are common in the prostates of patients with BPH. The
cause for the inflammation has not been identified with certainty; however, BPH is more
common in obese patients and obesity is associated with increased inflammatory cytokines.
Dietary fats have been implicated, and lipopolysaccharides can induce prostatic inflammation in
experimental animals. It has been hypothesized that macrophages secrete cytokines that
stimulate stromal and epithelial hyperplasia. Investigators have found increased concentrations
of hypoxia-inducible factor-1 alpha (HIF-1 alpha), which can be secreted by epithelial cells, is
known to be induced by proinflammatory cytokines, and is involved in testosterone-medicated
hyperplasia [68]. HIF-1 alpha enhances epithelial-mesenchymal transition in experimental
models. These investigators proposed that developing agents that block the effects of HIF-1
alpha could provide a new approach to treatment of BPH. If inflammation is a causal
mechanism for BPH, it also could provide an explanation for improvement with nonsteroidal
antiinflammatory drugs [33]. There is also some evidence that phosphodiesterase-5 inhibitors
decrease fibroblast to myofibroblast transdifferentiation, which could be a mechanism by which
they decrease symptoms [69].
Decreased cell death The average life span of stromal cells exceeds 30 years, while the
average life span of epithelial cells exceeds two years. These observations are consistent with
the infrequency with which mitoses or apoptotic bodies are seen in hyperplastic prostatic tissue,
and indicate that decreased cell death may be a major contributor to prostatic hyperplasia and
enlargement [70]. Increased immunoreactivity for interleukin-2 and its receptors and for bcl-2

are consistent with a lower apoptotic rate in BPH [71,72]. These observations also attest to the
difficulty in causing regression of established BPH in the absence of increasing cell death.
Furthermore, androgen deprivation does not alter Bcl-2 expression, which has been found to be
increased in hyperplastic tissue [73].
Increased stem cells The size of the prostate in rats is defined by the absolute number of
potential stem cells and their subsequent recruitment and maturation [51,74]. An increase in
stem cells that reside in the basal epithelial compartment is hypothesized to cause BPH [75].
The relevance of these observations to prostatic growth in humans is not known.
Genetic susceptibility In a survey of men in Olmsted County, Minnesota, 21 percent of
2,119 men between 40 and 70 years of age had a family history of an enlarged prostate [76].
The odds ratio of a man with a positive family history of BPH having moderate to severe lower
urinary tract symptoms was 1.3 (95% CI, 1.1-1.7). Twin studies suggest that heritability is a
more important determinant of lower urinary tract symptoms than age, transition zone volume or
total prostate volume [77].
The possible role of genetic factors was evaluated in a case-control study of men under 64
years of age who had undergone prostatectomy for BPH and in whom more than 37 grams of
tissue was resected [78]. The first-degree relatives of these men had a four-fold increased risk
of developing BPH that required surgical therapy as compared with the relatives of normal men.
Segregation analysis suggested an autosomal dominant mode of disease transmission (with an
estimated penetrance of 0.89) and an allele frequency of 3.4 percent in the population.
Hereditary BPH could account for 9 percent of all cases requiring surgery, and more than 50
percent in men under 60 years of age. Finally, men with three or more affected family members
have large prostate glands, above-normal serum androgen concentrations and a normal
response to 5-alpha-reductase inhibition [75]. BPH may have an autosomal dominant mode of
inheritance [79].
One study evaluated genes expressed in prostates that were <60 mL and compared them with
glands >60 mL in men undergoing surgery [80]. Analyses of microarrays revealed 227 genes
that were differentially expressed between the two groups. This included growth factor genes,
cell cycle genes, apoptosis genes, inflammation genes and androgen-regulated genes.
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(The Basics)")

Beyond the Basics topics (see "Patient information: Benign prostatic hyperplasia (BPH)
(Beyond the Basics)")

SUMMARY

The prevalence of histologically diagnosed prostatic hyperplasia increases from 8

percent in men aged 31 to 40, to 40 to 50 percent in men aged 51 to 60, to over 80
percent in men older than age 80. (See 'Prevalence' above.)

Black men are more likely than white men to have larger prostate volume and more
moderate to severe LUTS. Asian men are less likely than white and black men to have
BPH. Increased risk of BPH was associated with higher free PSA levels, heart disease,
use of beta-blockers, and lack of physical exercise. (See 'Risk factors' above.)

BPH develops primarily in the periurethral or transitional zone of the prostate, with a
fourfold increase in stromal tissue and a twofold increase in glandular components.
(See 'Histology' above.)

Although testosterone, dihydrotestosterone, and estrogen may be involved in the

development of BPH, these hormones alone are not sufficient to cause BPH.
(See 'Androgen' above and 'Estrogen' above.)

It has been suggested that BPH occurs because prostatic tissue reverts to an
embryonic-like state in which it is unusually sensitive to various growth factors.
(See 'Dysregulation of stromal growth factors' above.)

Twin studies suggest that heritability is a more important determinant of lower urinary
tract symptoms than age, transition zone volume, or total prostate volume.
(See 'Genetic susceptibility' above.)

The pathogenesis of BPH remains incompletely understood. Population-based

observational studies, disease registries, in vitro studies of human tissue, and clinical
trials continue to contribute to our understanding of the pathogenesis of this common
disorder. (See 'Pathogenesis' above.)

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REFERENCES

3.
Medical treatment of benign prostatic hyperplasia
Authors
Glenn R Cunningham, MD
Dov Kadmon, MD
Section Editor
Michael P O'Leary, MD, MPH
Deputy Editor
Lee Park, MD
Disclosures: Glenn R Cunningham, MD Nothing to disclose. Dov Kadmon, MD Nothing to disclose. Michael
P O'Leary, MD, MPH Nothing to disclose. Lee Park, MD Employee of UpToDate, Inc. Employment (Spouse):
Novartis. Equity Ownership/Stock Options (Spouse): Novartis.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Sep 2014. | This topic last updated: Jul 17, 2014.
INTRODUCTION Benign prostatic hyperplasia (BPH) becomes increasingly common as men
age (figure 1). BPH can lead to urinary symptoms that may benefit from medical or surgical
treatment. However, many men with BPH are asymptomatic or have only mild symptoms and
may not require therapy.
The medical therapy of BPH will be reviewed here. Surgical and other invasive therapies, the
clinical manifestations, natural history, diagnosis of BPH, and the epidemiology and
pathogenesis of BPH are all discussed separately. (See "Transurethral procedures for treating
benign prostatic hyperplasia" and "Clinical manifestations and diagnostic evaluation of benign
prostatic hyperplasia" and "Epidemiology and pathogenesis of benign prostatic hyperplasia".)
Lower urinary tract symptoms (LUTS) in men of uncertain etiology, or from etiologies other than
BPH, also are discussed separately. (See "Lower urinary tract symptoms in men".)
DEFINITIONS A number of different terms and abbreviations are used when discussing
symptomatic BPH. These include:
Lower urinary tract symptoms (LUTS)
Benign prostatic enlargement (BPE)
Benign prostatic obstruction (BPO)
Bladder outlet obstruction (BOO)

BPE is the physical enlargement of the prostate that occurs as the result of the histologic
changes of BPH. BPO is BOO in the setting of BPE.
BPE and BOO secondary to BPH are frequently diagnosed clinically on the basis of LUTS. We
will use the abbreviation BPH/LUTS for LUTS presumed to be secondary to BPH, sometimes
called symptomatic BPH.
INDICATIONS FOR THERAPY The common symptoms of BPH are increased frequency of
urination, nocturia, hesitancy, urgency, and weak urinary stream. These symptoms typically
appear slowly and progress gradually over a period of years. (See "Clinical manifestations and
diagnostic evaluation of benign prostatic hyperplasia", section on 'Natural history'.)
In general, these symptoms only require therapy if they have a significant impact on a patient's
quality of life [1]. Even without therapy, many men will experience stabilization or improvement
in symptoms over time [2]. One review found that over a follow-up period of 2.6 to 5 years, 16
percent of men had stable symptoms and 38 percent improved [3]. Thus, the decision to
treat BPH/LUTS involves balancing the severity of the patient's symptoms with potential side
effects of therapy.
BPH may also require therapy if BOO is creating a risk for 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; post-void
residuals of >25 percent of total bladder volume) [4]. In general, patients who develop these
symptoms will require invasive therapy [2]. (See "Transurethral procedures for treating benign
prostatic hyperplasia".)
The decision to treat is usually based on the severity of symptoms and the patient's tolerance
for these symptoms. Use of the AUA symptom score (also known as the International Prostate
Symptom Score [IPSS]) (table 1) permits quantitation of symptom severity and monitoring of
symptom progression over time. Additionally, the IPSS adds a question about "bother" to the
AUA score. These questionnaires are easy and quick to complete; however, not all clinicians
use them to assess symptoms.
Urine flow rate during voiding can also be easily measured. This is a noninvasive test that is
readily available to urologists, but usually is not available to primary care clinicians. Thus,
medical treatment usually is initiated on the basis of symptoms in the primary care setting.
When symptoms occur in the setting of autonomic or severe peripheral neuropathy or following
invasive treatment of the urethra or prostate, patients should be referred for urologic evaluation
rather than started on treatment by a primary care clinician.
AGENTS The bladder outlet obstruction of BPH has two components:
A dynamic (physiologic, reversible) component related to the tension of prostatic smooth
muscle in the prostate, prostate capsule, and bladder neck
A fixed (structural) component related to the bulk of the enlarged prostate impinging upon
the urethra
Two classes of drugs, alpha-adrenergic antagonists and 5-alpha-reductase inhibitors, act upon
the dynamic and fixed components of bladder outlet obstruction, respectively.
Alpha-adrenergic antagonists appear to be more effective than 5-alpha-reductase inhibitors for
short-term and long-term treatment of BPH/LUTS [5]. However, only 5-alpha-reductase
inhibitors have demonstrated the potential for long-term reduction in prostate volume and need

for prostate surgery. The use of agents from both classes in combination may be superior to
using either class alone.
Antiandrogens and gonadotropin-releasing hormone (GnRH) agonists also have been used.
GnRH agonists may be somewhat more effective for BPH/LUTSthan the above medications, but
the resulting androgen deficiency generally makes their use unacceptable to patients.
Studies, using surveys and claims data, have examined which therapies are most commonly
chosen for patients [6-8]. In the United States, many patients are initially managed with watchful
waiting [6]; those who are prescribed a medication are most likely prescribed an alphaadrenergic antagonist [6,8]. Initial management with watchful waiting appears to be somewhat
less common in Europe; initial therapy with an alpha-adrenergic antagonist appears to be most
common [7].
Alpha-1-adrenergic antagonists Five long-acting alpha-1antagonists, terazosin, doxazosin, tamsulosin, alfuzosin, and silodosin have been approved by
the Food and Drug Administration in the United States for treatment of the symptoms of BPH
[9]. Prazosin, a short-acting alpha-1-antagonist, is generally not used for BPH, due to need for
frequent dosing and the potential for more cardiovascular side effects.
Mechanism Alpha-1-adrenergic antagonists such as terazosin act against the dynamic
component of bladder outlet obstruction by relaxing smooth muscle in the bladder neck,
prostate capsule, and prostatic urethra.
Alpha-1 receptors are abundant in the prostate and base of the bladder, and sparse in the body
of the bladder [10,11]. The density of these receptors is increased in hyperplastic prostatic
tissue [12].
Three alpha-1 adrenoreceptor sub-types have been characterized: 1A, 1B, and
1D. Terazosin, doxazosin, and alfuzosin antagonize all three receptor subtypes with similar
affinity, whereas tamsulosin demonstrates relative selectivity for alpha-1A and -1D receptors
[13]. Silodosin is a relatively selective alpha-1A receptor antagonist [14].
Alpha-1A subtype receptors comprise approximately 70 percent of adrenoreceptors in prostate
tissue whereas alpha-1B receptors are more prevalent in smooth muscle of the vasculature
[15,16]. The alpha-1D subtype receptors comprise less than 30 percent of prostatic
adrenoreceptors and are located in prostatic stromal elements [16]. Alpha-1D receptors are also
found in the detrusor muscle of the bladder, bladder neck, and the sacral region of the spinal
cord [16].
In one report, there was a direct relationship between the smooth muscle content of prostatic
tissue and the increase in maximal urinary flow rate in men with BPH treated with terazosin [17].
In vitro studies showed that terazosin and doxazosin, but not tamsulosin, caused prostatic
apoptosis [18,19]. In a randomized trial of over 500 men with LUTS treated for three months
with alfuzosin, there was no reduction in prostate volume [20]. Changes in prostate volume have
not been shown to correlate with clinical efficacy.
Efficacy The approved alpha-1-adrenergic antagonists appear to have similar efficacy
[21,22], although there have been few direct comparisons. A meta-analysis of trials
with alfuzosin, terazosin, doxazosin, or tamsulosin published prior to October 1998 provides an
overview of the efficacy and side effects of these drugs [23]. There were 6333 men in placebocontrolled trials and 507 men in comparative studies. The results indicated that the drugs were
more effective than placebo and that the efficacy of the drugs was similar. In the drug-treated

men, the symptom scores (table 1) decreased 30 to 40 percent, and urinary flow rates
increased 16 to 25 percent.
The selective alpha-1D antagonist, naftopidil, may also be effective although long term
randomized controlled trials are needed prior to recommendation for use [24].
In a meta-analysis comparing alpha-adrenergic antagonist monotherapy versus finasteride (a 5alpha-reductase inhibitor), doxazosin and terazosin were more effective in improving urinary
symptoms compared to finasteride [5]. Tamsulosin and finasteride were equally
effective. Alfuzosin, silodosin, and naftopidil were not studied in this meta-analysis. (See '5alpha-reductase inhibitors' below.)
Dosing Initiation and dose titration is shown in a table (table 2).
Medication therapy for BPH/LUTS is generally ongoing. Patients who remain symptomatic on a
submaximal dose of an alpha-adrenergic antagonist, and are not experiencing adverse effects,
should have the dose increased.
Side effects and interactions In the above meta-analysis, the drugs differed in their sideeffect profiles [23]. 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.
The most important side effects were orthostatic hypotension and
dizziness. 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. If there is a hiatus in drug administration, retitration is usually required.
The hypotensive action can be useful in older men who have hypertension, but they require
careful monitoring. 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: Recommendations", section on 'Alpha blockers'.)
Tamsulosin, alfuzosin, and silodosin have lower potential to cause hypotension and syncope
than either terazosin or doxazosin [15,25-27], and tamsulosin may further have slightly less
effect on blood pressure than alfuzosin [23]. These differential effects on blood pressure by
different alpha-1-antagonists may be due to their differential blocking of alpha-1A receptor
subtype [28]. (See 'Mechanism' above.)
The hypotensive effects of terazosin and doxazosin can be potentiated by concomitant use of
the phosphodiesterase-5 (PDE-5) inhibitors sildenafil orvardenafil. The risks with tadalafil are
less clear. We feel that men who are on lower doses of terazosin or doxazosin and are not
experiencing orthostatic blood pressure changes can be treated with PDE-5 inhibitors as long
as dosing is separated by at least four hours. Tamsulosin at a dose of 0.4 mg/day does not
appear to significantly potentiate the hypotensive effects of sildenafil [29].
Other common side effects of alpha-1-antagonists include asthenia and nasal
congestion. Tamsulosin and silodosin, in particular, can affect ejaculation. 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 [30]. Silodosin
produces retrograde ejaculation in approximately 28 percent of patients [27].
5-alpha-reductase inhibitors There are two 5-alpha-reductase inhibitors approved in the
United States, finasteride and dutasteride.

Mechanism These drugs act by reducing the size of the prostate gland. Treatment for 6 to
12 months is generally needed before prostate size is sufficiently reduced to improve
symptoms. 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. Its
clinical importance is suggested by the observation that men with inactivating mutations of the
gene for the enzyme have very small prostate glands and do not develop BPH [31]. The type 1
form of the enzyme is present in liver, non-genital skin, and some areas of the brain [32].
Efficacy In a multicenter trial 895 men with BPH were treated with placebo or 1 or
5 mg/day of finasteride for 12 months [33]. The following benefits were noted in the men treated
with finasteride:
Serum dihydrotestosterone concentrations decreased by about 70 percent and serum
testosterone concentrations increased by 10 percent in bothfinasteride treatment groups.
A reduction in obstructive and non-obstructive symptom scores by 23 and 18 percent,
respectively, in the men given 5 mg daily but less in the men given 1 mg daily and none in
the men given placebo.
An increase in maximal urinary flow rate of 1.6 mL/sec in the men given 5 mg/day versus
1.4. mL/sec with 1 mg/day, and 0.2 mL/sec with placebo. The baseline value was
approximately 7.3 mL/sec; values above 15 mL/sec are usually associated with no
obstructive symptoms.
A reduction in mean prostatic volume by 19 and 18 percent in the two treatment groups
versus 3 percent in the placebo group.
The efficacy of finasteride appears to persist with long-term treatment. As an example, 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 [34]. The most important findings were that 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 2). Patients
who remained on finasteride for six years in an open-label extension of the study had sustained
benefits [35].
The efficacy of finasteride is greater in men with larger prostate volumes than in men with
smaller prostate volumes. (See 'Short-term efficacy' below.)
Finasteride increases the apoptotic index of epithelial and stromal cells [36] and decreases the
volume of epithelium [37]. After 12 months of treatment finasteride also decreases detrusor
pressure at maximum flow rates in men with larger prostate glands (>40 mL) [38].
Finasteride also may suppress gross hematuria in those in whom other causes (particularly
prostate and bladder cancer) have been ruled out [39,40]. In a randomized trial, 57 men with
BPH, evidence of bleeding from friable prostatic tissue on flexible cystoscopy, and chronic
intermittent gross hematuria with no other identifiable cause were assigned to finasteride or a
control arm [39]. Finasteride was associated with a lower rate of recurrent hematuria (14 versus
63 percent) and of surgery for bleeding (0 versus 26 percent).
Dutasteride is an inhibitor of both 5-alpha reductase enzymes and may be more potent
than finasteride [41]. In a trial in 4325 men with BPH, dutasteride reduced the risk of acute
urinary retention by 57 percent and surgical intervention by 48 percent, and also reduced
prostate volume and symptoms after 24-month follow-up [42]. A subsequent trial found similar

results after 48-month follow-up in men with BPH randomly assigned to dutasteride, compared
to placebo [43].
The Enlarged Prostate International Comparator Study (EPICS), an industry-sponsored trial,
compared treatment with finasteride or dutasteride for 12 months [44]. The primary outcome
reported, reduction in prostate volume, was not significantly different for the two drugs, although
this outcome may not have clinical significance. The drugs were also not significantly different in
the secondary endpoints of urinary flow rate and urinary symptom scores, and adverse effects
were similar.
The 5-alpha-reductase inhibitors are more effective in men with larger prostates, and their
effects on acute urinary retention and reduction in need for surgery require chronic treatment for
more than a year.
Dosing Unlike with alpha antagonists, dosing with 5-alpha-reductase inhibitors do not require
titration. Finasteride can be initiated and maintained at 5 mg once daily.
Similarly, dutasteride can be initiated and maintained at 0.5 mg once daily.
Side effects The major side effects of these drugs are decreased libido and ejaculatory or
erectile dysfunction. These occurred in 4 to 6 percent of men in a randomized trial
of finasteride [33]. Rates of sexual dysfunction in a primary care trial of finasteride were
somewhat higher (13.8 percent for any sexual adverse event) [45], and this may be more
reflective of clinical practice. 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 [46].
Serum prostate-specific antigen (PSA) concentrations decrease by about 50 percent [33], a
change that must be kept in mind in interpreting the results of serum PSA measurements in men
treated with this drug [47]. Findings from the Prostate Cancer Prevention Trial suggest that PSA
values be corrected by a factor of 2 for the first 24 months of finasteride use, and by a factor of
2.5 for longer term use [48]. (See "Measurement of prostate specific antigen", section on
'Benign prostatic hyperplasia'.)
Finasteride does not cause loss of bone [49], perhaps because serum estradiol concentrations
do not change. A case-control study found no positive association between use of finasteride
and hip fracture, and actually found some evidence of lower risk of fracture with finasteride use
[50].
In randomized trials, 5-alpha-reductase inhibitors significantly decrease the incidence of
prostate cancer. However, concern has been raised about whether 5-alpha-reductase inhibitors
increase the incidence of high-grade lesions, although many believe this finding is spurious.
This is discussed in detail separately. (See "Chemoprevention strategies in prostate cancer",
section on '5-Alpha reductase inhibitors'.)
The United States Food and Drug Administration (FDA) recommends that before starting 5alpha reductase inhibitors for treatment of BPH, the patient should be assessed for other
urological conditions, including prostate cancer [51]. This advisory from the FDA emphasizes
the need to monitor these patients for prostate cancer and to recognize the effect that these
drugs have on PSA levels. (See "Clinical presentation and diagnosis of prostate
cancer" and "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia".)
Discontinuation Few studies have examined what happens when 5-alpha-reductase
inhibitor therapy is discontinued after a course of therapy in men with BPH/LUTS. Most
commonly, such therapy is continued indefinitely.

One study that examined this issue involved observational follow-up of a randomized trial that
compared one year of therapy with either finasteride ordutasteride in men on ongoing alpha
blocker therapy; prostate volume and symptoms were monitored after discontinuation of therapy
[52]. At one year after discontinuation, prostate volume had increased 19 to 21 percent, and
symptom scores had worsened.
Combination therapy Short-term therapy with combined alpha adrenergic antagonist and 5alpha-reductase inhibitor therapy appears to be superior to either agent alone in men
with BPH/LUTS and larger prostate glands [53], but not in men with only moderate BPH [54-56].
Long-term combination therapy provides some added benefit even in men with moderate BPH
[57,58].
Short-term efficacy In the Veterans Affairs Cooperative Study, 1229 men with BPH (mean
peak urinary flow rate of 10.5 mL/sec) were randomly assigned to
placebo, finasteride (5 mg/day), terazosin (10 mg/day), or both for one year [54]. Eligibility was
based upon an American Urological Association symptom score of at least eight, a maximal
urinary flow rate of no more than 15 mL/sec, and a residual urine volume of less than 300 mL;
prostate size was not a factor. The following results were noted:
Terazosin lowered the symptom score and increased the peak urinary flow rate when
compared with placebo.
Finasteride alone was no better than placebo.
The combination of finasteride and terazosin was no better than terazosin alone.
Similar findings were noted in the PREDICT trial in which 1095 men were randomly assigned
to doxazosin, finasteride, or both for one year [56]. Doxazosin was more effective than
finasteride or placebo for urinary symptoms and flow rate, but again, the combination was no
more effective than doxazosin alone.
The mean prostate volume in these studies was approximately 37 mL [54,56], lower than the
mean volume of approximately 60 mL in the Finasteride Study Group trial of finasteride alone
[33].
Long-term efficacy Randomized trials have found that long-term combination therapy is
superior to single-drug therapy for BPH symptoms [57,59].
The efficacy of long-term therapy was evaluated in the Medical Therapy of Prostatic Symptoms
(MTOPS) trial, in which 3047 men with BPH were randomly assigned to receive doxazosin, (4 to
8 mg/day), finasteride (5 mg/day), combination therapy, or placebo [57]. The mean prostate
volume was 3620 mL. The patients were evaluated for symptomatic improvement and overall
clinical disease progression, defined as an increase above baseline of at least four points in the
AUA symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or
recurrent urinary tract infection. Long-term combination therapy lowered the risk of overall
clinical progression of BPH significantly more than treatment 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.
At a mean follow-up of 4.5 years, the following results were seen (figure 3):
The risk of overall clinical progression was reduced to a similar degree
by doxazosin and finasteride (39 and 34 percent, respectively, when compared to
placebo).

Combination therapy reduced the risk of clinical progression by 66 percent, significantly

greater than with either drug alone.
Symptom scores improved with all therapies, but to a greater degree with combined
therapy.
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 forfinasteride.
Adverse effects were similar with combination therapy and monotherapy, with the
exception of abnormal ejaculation, peripheral edema, and dyspnea, which were more
common with combination therapy. Breast cancer risk was not increased in the finasterideonly or combination therapy groups.
A 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 [5].
The four year CombAT study provides additional evidence that combination therapy is effective
in men with larger prostates [59]. CombAT included men with BPH age 50 or older, an IPSS of
at least 12, a prostate volume 30 mL, a PSA 1.5 to 10 ng/mL, and a maximum urinary flow
rate >5mL and 15/second.Subjects were randomly assigned to therapy
with dutasteride, tamsulosin, or both; there was no double placebo arm. Mean prostate volume
in the 4844 men studied was approximately 55 mL. Combination therapy was superior to
tamsulosin monotherapy, but not dutasteride monotherapy, in reducing the relative risk of acute
urinary retention or BPH-related surgery. Combination therapy also was superior to either
monotherapy in reducing BPH symptoms and the relative risk of BPH clinical progression (figure
3). However, more drug-related adverse events were seen with combination therapy than with
monotherapy. Early 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 [60]. 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 in men
[61].
PDE-5 inhibitors Observational studies suggested that phosphodiesterase-5 (PDE-5)
inhibitors, primarily used as treatments for erectile dysfunction, were beneficial
for BPH/LUTS [62] and led to subsequent clinical trials. In a meta-analysis of five randomized
trials of men with LUTS secondary to BPH, PDE-5 inhibitors led to significant improvement in
IPSS after 12 weeks of therapy, compared to placebo [63]. There was no significant difference
in urodynamic parameters. However, more recent reports have found maximum urine flow rates,
as well as symptom scores (figure 4), to be improved by daily tadalafil [64]. A pooled analysis
from four randomized trials that included 1500 men assigned to tadalafil found that tadalafil
improved IPSS and BPH impact index, irrespective of LUTS severity, age, testosterone level, or
PSA-predicted prostate volume [65].
The long-term effect of PDE-5 inhibitors in patients with BPH is unclear. In the United
States, tadalafil is approved by the Food and Drug Administration for use in BPH. It seems
reasonable to discuss this option with men who have erectile dysfunction and mild or moderate
symptoms of 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-1adrenergic antagonists. (See 'Side effects and interactions' above.)

Antimuscarinics Some men with BPH/LUTS may also have frequency, urgency, and
incontinence related to an overactive bladder. Bladder contractions are stimulated by
acetylcholine effects on muscarinic receptors in smooth muscle of the bladder. A randomized
trial in patients with moderate to severe obstructive symptoms, at least a moderate bother
score, and urgency found that combination therapy with an anticholinergic agent with
antimuscarinic effects (tolterodine) plus an alpha-1-adrenergic antagonist (tamsulosin) was
reasonably safe with few episodes of urinary retention [66]. There was some suggestion that
combination therapy was more effective than tamsulosin alone. A meta-analysis found that this
combination significantly improved storage voiding parameters compared with a-blocker therapy
alone. They found minimal risk of increased post-void residual urine volume, decreased
maximal urinary flow rate, or acute urinary retention [67]. Use of antimuscarinic agents should
be restricted to men with low post-void residual volumes. (See "Lower urinary tract symptoms in
men", section on 'Anticholinergics'.)
Herbal therapies Herbal therapies for BPH are commonly used in Europe; these remedies
comprised 70 percent of spending for drug treatment of prostatism in Germany in 1997 [68].
Saw palmetto is approved by the German Commission E for stage I and II (mild to moderate)
BPH. Two herbal extracts have officially been approved for the treatment of prostatism in
France. 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.
The data concerning efficacy of these therapies are conflicting. In systematic reviews of
controlled trials, saw palmetto plant extract was as effective asfinasteride in relieving the
symptoms of prostate obstruction, although it did not decrease prostate volume [69]. A
subsequent placebo-controlled trial found no evidence that saw palmetto was superior to
placebo [70]. The evidence regarding the use of saw palmetto for BPH is discussed in detail
separately. (See"Clinical use of saw palmetto".)
There is some evidence for efficacy of other agents as well. Systematic reviews have suggested
the following:
The plant extract beta-sitosterol improved symptoms [71].
Cernilton, which is prepared from the rye grass pollen, Secale cereale, has been
evaluated in four clinical trials [72]. It improved symptoms, but did not affect urinary flow
rates or residual urine or prostate volume.
Pygeum africanum is an extract of bark from an African plum tree. In a 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 [73].
Despite these systematic reviews, questions regarding safety and efficacy remain. As has been
seen with saw palmetto (see "Clinical use of saw palmetto"), better designed trials do not
always confirm the favorable results seen in less well-designed studies. Additionally, questions
regarding standardization remain, particularly in the US. (See "Overview of herbal medicine and
dietary supplements".)
Until additional studies of herbals are performed, we suggest using alpha-adrenergic
antagonists and 5-alpha-reductase inhibitors rather than any of the above herbal therapies.
Other There is some evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) can
reduce symptoms of BPH/LUTS without improving urine flow rates [74].

MODIFICATION OF THERAPY Patients who experience side effects with either alphaadrenergic antagonists or 5-alpha-reductase inhibitors can reasonably be switched to the other
agent. Patients who have obstructive symptoms on an alpha-adrenergic antagonist may be
candidates for antimuscarinic treatment if they have low post-void residual volumes, and
patients who do not tolerate any of these therapies can be observed off therapy or can be
referred for invasive therapy.
Patients who are on combination therapy and do not experience an adequate response over 12
to 24 months may wish to consider invasive therapies as well. Patients with progression of
disease on therapy will generally require invasive therapy. (See "Transurethral procedures for
treating benign prostatic hyperplasia".)
OTHER STRATEGIES Patients with BPH/LUTS should avoid medications that can
exacerbate symptoms or induce urinary retention. These include anticholinergic medications
such as sedating antihistamines and adrenergic agents such as decongestants.
Behavioral modifications may be helpful. These 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.
A randomized trial found that, compared with men followed with watchful waiting alone, men
given an educational intervention that included teaching of behavioral modifications were
significantly less likely to experience treatment failure (mainly an increase in IPSS or
requirement for medication) [75].
ECONOMIC CONSIDERATIONS Management of BPH/LUTS is estimated to cost more than
$4 billion per year in the United States [76]. While the short-term costs of medical treatment are
less than those of invasive treatment, many have questioned whether invasive treatment might
be less expensive in the long run.
One study that examined this question in 970 privately insured men concluded that surgery was
associated with higher costs and failure rates over a five year period, and medical therapy
remained less expensive than invasive therapy over the long term [77].
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.
However, many men with BPH are asymptomatic or have only mild symptoms and may not
require therapy. Additionally, many men with symptoms will improve or stabilize without
therapy. (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 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. (See 'Other
strategies' above.)
Alpha-adrenergic antagonists provide immediate therapeutic benefits, while 5-alphareductase inhibitors require long-term treatment for efficacy. In most men with mild to
moderate symptoms of BPH where those symptoms have a sufficient effect on quality of
life that they desire therapy, we suggest initial treatment with an alpha-adrenergic
antagonist alone (Grade 2A). In men with severe symptoms, those with a large prostate
(>40 mL), and 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-alpha-reductase inhibitor (Grade 2A).
(See 'Combination therapy' above.)
The choice of alpha-adrenergic antagonist and 5-alpha-reductase inhibitor may be made
on the basis of cost and side-effect profile. Tamsulosin, alfuzosin, and silodosin have less
effect on blood pressure than either terazosin or doxazosin, and tamsulosin may further
have slightly less effect on blood pressure than alfuzosin. (See 'Alpha-1-adrenergic
antagonists' above.)
The two 5-alpha-reductase inhibitors, finasteride and dutasteride, appear to have similar
efficacy and similar adverse effects. The agents are more effective in men with larger
prostates, and their effects on acute urinary retention and reduction in need for invasive
therapies require chronic treatment for more than a year. (See '5-alpha-reductase
inhibitors' above.)
In 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
treatment with an antimuscarinic agent (Grade 2B). 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). (See 'Antimuscarinics' above and "Lower urinary tract
symptoms in men".)

Transurethral procedures for treating benign prostatic hyperplasia

Authors
Glenn R Cunningham, MD
Dov Kadmon, MD
Section Editor
Michael P O'Leary, MD, MPH
Deputy Editor
Kathryn A Collins, MD, PhD, FACS
Disclosures: Glenn R Cunningham, MD Nothing to disclose. Dov Kadmon, MD Nothing to disclose. Michael
P O'Leary, MD, MPH Nothing to disclose. Kathryn A Collins, MD, PhD, FACSEmployee of UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Sep 2014. | This topic last updated: Sep 18, 2014.
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-tosevere 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 'Initial
management' and "Acute urinary retention", section on 'Surgical therapy'.)
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 nonTURP 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 [36-38].
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) [39],
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 [40,41].
(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 [42]; 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:YttriumAluminium-Garnet (YAG) (2140 nm wavelength) laser [43-46] and Thulium:YAG (2014 nm
wavelength) [41,47-49] 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) [40,44]. 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
[50]. 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 [51-53]. 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) [53]. 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 [54].
(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)
[55].
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 [56]. 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 (eg, Urolift, Neotract, Inc.
Pleasanton, CA), appears to be well tolerated and is effective for treating BPH [57,58]. 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 [57,59,60],
longer follow-up will be needed to determine the durability of the device.
In a multicenter study, 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 [57]. 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 [59]. 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 [22,23,25,61-63]. (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 [1,4,64]. 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 [65].
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.

A systematic review compared monopolar and bipolar (TURP) for clinical effectiveness and
adverse events [63]. A total of 24 trials were included in the review. No significant differences
were found in terms of International Prostate Symptom Score (IPSS) or health-related quality of
life (HRQL) score; however, it should be noted that most of the included trials had short-term
follow-up 1 year. Compared with monopolar TURP, bipolar TURP has 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).
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 [66-68].
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 and metaanalyses 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 [69]. 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
[23,25,61,70]. 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].
Laser techniques An older systematic review that reflects the early experience with
laser techniques identified 20 trials involving 1898 patients comparing TURP primarily with
contact lasers, noncontact lasers, and other hybrid techniques [67]. The pooled
percentage improvements for mean urinary symptoms ranged from 59 to 68 percent for
laser treatments and from 63 to 77 percent for TURP. Improvements in mean peak urinary
flow ranged from 56 to 119 percent with laser treatments and from 96 to 127 percent with
TURP. Laser-treated subjects were less likely to require transfusions (less than 1 percent
versus 7 percent), or develop strictures (4 versus 8 percent), and the duration of
hospitalization was one to two days shorter. Reoperation occurred more often after laser
procedures than TURP (5 versus 1 percent). Data were too limited to come to conclusions
about the preferred laser technique or to compare laser treatment with other minimally
invasive procedures.
Photoselective vaporization An early systematic review included three trials using lower
power lasers for photoselective vaporization (PVP) [66]. A later systematic review included
higher power lasers [29]. Higher reoperation rates were reported for 60W and 80W lasers,
compared with TURP. The trial that used the KTP laser (80W) reported shorter lengths of

stay and shorter lengths of catheterization compared with TURP, and similar long-term
effectiveness [71,72]. In the later review (80W, 120W lasers), urologic symptom
improvements following TURP and PVP were similar in six trials, better for TURP in two
trials, and better for PVP in one trial [29]. Interestingly, operating time was shorter in the
TURP group by nearly 20 minutes. Later trials using higher power lasers (120W KTP [73],
180 W Greenlight [74]) found similar urine symptom scores, uroflowmetry parameters, and
complication rates compared with TURP; however, length of catheterization and length of
stay were shorter.
Laser enucleation A systematic review and meta-analysis of four small randomized
trials comparing HoLEP with TURP found significant heterogeneity across studies but
concluded that peak urine flow rates were similar with each therapy and that, although
TURP was quicker, TURP resulted in more blood loss, longer catheterization times, and
longer hospital stays [75]. A separate metaanalysis also found similar urologic
improvements for ThuLEP compared with TURP and similar perioperative benefits as
HoLEP [76].
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 [77]. 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 [78]. 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) [79].
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 [80]. 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
[50]. 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).

TURP versus prostatectomy Open prostatectomy accounts for less than five percent of
operations for BPH in the United States [21,81], but it is performed more often in other countries
[82,83]. 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 [84].
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 [85].
In some studies, open prostatectomy had lower complication and mortality rates than TURP
[86], but the difference probably relates to patient selection for the procedures [87].
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 [82]. 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 [88-90]. 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 BPH/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.
Non-TURP procedures such as transurethral enucleation (HoLEP, ThuLEP), plasma
vaporization (button) and photoselective vaporization (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
[20,21,91,92]. 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 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 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 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.)
In summary, 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 Photoselective vaporization (PVP), radiofrequency ablation,
transurethral incision of the prostate (TUIP)
Bladder outlet obstruction, small prostate Transurethral incision of the prostate (TUIP)
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 [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 [11,13,14,67,69,75,80], but not all studies [10,96]. 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 [67,69]. 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) [50]. Clot retention was lower for
photoselective vaporization (PVP) compared with TURP (3 versus 29 percent) [97].
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) [80].
Sexual dysfunction The overall incidence of sexual dysfunction (erectile dysfunction,
retrograde ejaculation) following surgical procedures to treat BPH varies [98-100]. Although new
onset erectile dysfunction is uncommon (<10 percent), retrograde ejaculation is common at
about 65 percent.
In the VA study described above, sexual function was similar after TURP or watchful waiting
[65]. However, in a second study in which men with BPH were randomly assigned to TURP,
laser therapy, or watchful waiting, reduced ejaculation was common in the surgery and laser
groups [101]. On the other hand, erectile function and pain on ejaculation were both improved in
the surgery group compared with the other two groups. Similarly, a prospective study found
worsening ejaculatory function after TURP, but trends toward improved erectile function and
pain on ejaculation [102].
No differences in new onset sexual dysfunction were seen in a trial that compared monopolar
TURP with bipolar TURP [100]. Microwave thermotherapy had a significantly decreased risk for
retrograde ejaculation compared with TURP (relative risk, 0.39, 95% CI 0.21-0.75) in a
systematic review [80]. In a trial comparing radiofrequency ablation with TURP in 121 men with
BPH, patients treated with radiofrequency ablation had fewer adverse events, including
retrograde ejaculation (0 versus 41 percent), and erectile dysfunction (3 versus 21 percent) [77].
Urethral stricture Any instrumentation of the urethra carries the risk of trauma which heals
with scar formation resulting in urethral stricture [103]. (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
[67,77,80]. 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 [69].
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 [77]. Similar rates of urinary continence following TURP are reported in
other studies [104,105].
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). (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.)