Official reprint from UpToDate

www.uptodate.com 2014 UpToDate

Authors
Glenn R Cunningham, MD
Dov Kadmon, MD
Section Editor
Michael P OLeary, MD, MPH
Deputy Editor
Lee Park, MD
Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 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 clinicians 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.

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Symptoms need not be progressive. In one study, for example, about one-third of men had a 50 percent reduction in the severity of
their symptoms of urinary obstruction when followed with no treatment for 2.5 to 5 years after symptom onset [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 mans 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:
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:
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
Urethral stricture
Bladder neck contracture
Carcinoma of the prostate
Carcinoma of the bladder
Bladder calculi
Urinary tract infection and prostatitis
Neurogenic bladder
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)

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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"):
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
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.)

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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 5 to 6 grade reading level, and they answer the four or five
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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 10 to 12 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.)
SUMMARY AND RECOMMENDATIONS
th th
th th
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)")
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
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Topic 6889 Version 14.0
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 patients 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.)

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GRAPHICS
Prevalence of benign prostatic hyperplasia
pathology with age
Age-associated increase in pathologic evidence of benign prostatic
hyperplasia in 1075 men at autopsy. The percentage with benign
prostatic hyperplasia was determined during 10-year intervals from five
different studies; the mean values are shown.
Data from Berry, SJ, Coffey, DS, Walsh, PC, et al. The development of
human benign prostatic hyperplasia with age. J Urol 1984;132:474.
Graphic 55614 Version 1.0
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International Prostate Symptom Score (IPSS)
Questions
to be
answered
Not at all
Less
than 1
time in
5
Less
than
half the
time
About half
the time
More than
half the
time
Almost
always
Your
score
1. Over the
past month,
how often
have you had
a sensation of
not emptying
your bladder
completely
after you
finished
urinating?
0 1 2 3 4 5
2. Over the
past month,
how often
have you had
to urinate
again less
than 2 hours
after you
finished
urinating?
0 1 2 3 4 5
3. Over the
past month,
how often
have you
found you
stopped and
started again
several times
when you
urinated?
0 1 2 3 4 5
4. Over the
past month,
how often
have you
found it
difficult to
postpone
urination?
0 1 2 3 4 5
5. Over the
past month,
how often
have you had
a weak
urinary
stream?
0 1 2 3 4 5
6. Over the
past month,
how often
have you had
to push or
strain to begin
urination?
0 1 2 3 4 5
7. Over the
past month,
how many
0 (none) 1 (1 time) 2 (2 times) 3 (3 times) 4 (4 times) 5 (5 or
more times)
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times did you
most typically
get up to
urinate from
the time you
went to bed
at night until
the time you
got up in the
morning?
Sum of numbers (AUA symptom score):
Total score:
0 to 7: Mild symptoms
8 to 19: Moderate symptoms
20 to 35: Severe symptoms
Quality of
life due
to urinary
symptoms
Delighted Pleased
Mostly
satisfied
Mixed -
about
equally
satisfied
and
unsatisfied
Mostly
dissatisfied
Unhappy Terrible
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?
0 1 2 3 4 5 6
Modified with permission from: Barry, MJ, Fowler, FJ Jr, O'Leary, MP, et al. The American Urological Association Symptom
Index for Benign Prostatic Hyperplasia. J Urol 1992; 148:1549. Copyright 1992 Lippincott Williams & Wilkins.
Graphic 57680 Version 8.0
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