214 Benign Prostatic Hyperplasia ALG

• There is poor correlation between size of pros- LABORATORY TESTS

BASIC INFORMATION tate and symptoms (BPH may be asymptomatic
• 
Prostate-specific antigen (PSA): protease
if it does not encroach on the urethral lumen). secreted by epithelial cells of the prostate;
DEFINITION
• Most patients with BPH report difficulty in ini- elevated in 30% to 50% of patients with BPH.
Benign prostatic hyperplasia (BPH) is the benign tiating urination (hesitancy), decrease in cali- Testing for PSA increases detection rate for
growth of the prostate, generally originating ber and force of stream, incomplete emptying prostate cancer and tends to detect cancer at
in the periureteral and transition zones, with of bladder often resulting in double voiding an earlier stage. However, the PSA test does
subsequent obstructive and irritative voiding (need to urinate again a few minutes after not discriminate well between patients with
symptoms. voiding), postvoid “dribbling,” and nocturia. symptomatic BPH and those with prostate
SYNONYMS cancer, particularly if the cancer is pathologi-
ETIOLOGY cally localized and curable. The test may also
BPH Multifactorial; a functioning testicle is necessary trigger additional evaluation, including ultra-
Prostatic hypertrophy for development of BPH (as evidenced by the sound biopsy of the prostate. Asymptomatic
absence in males who were castrated before men with PSA levels >2 ng/ml do not need
ICD-9CM CODES
puberty). annual testing. According to the AUA, PSA
600 Benign prostatic hyperplasia
ICD-10CM CODES testing and DRE should be offered to any
N40  Hyperplasia of prostate DIAGNOSIS asymptomatic man <50 yr with a life expec-
N40.0 Enlarged prostate without lower tancy of 10 yr. PSA testing can also be offered
urinary tract symptoms DIFFERENTIAL DIAGNOSIS at an earlier age in men at higher risk of
• Prostatitis. prostatic cancer (e.g., first-degree relatives
• Prostate cancer. with prostate cancer; African American race).
EPIDEMIOLOGY & • Strictures (urethral).
• 
Measurement of “free” PSA is useful to
DEMOGRAPHICS • Medications interfering with the muscle assess the probability of prostate cancer
• 80% of men have evidence of BPH by age 80 fibers in the prostate and also with bladder in patients with normal DRE and total PSA
yr. function. between 4 and 10 ng/ml. In these patients
• Medical and surgical intervention for prob- 1. Opiates: impaired autonomic function. the global risk of prostate cancer is 25%.
lems caused by BPH is required in <20% of 2. Decongestants: increased sphincter tone. However, if the free PSA is >25%, the risk of
males by age 75 yr. 3.  Antihistamines: decreased parasympa- prostate cancer decreases to 8%, whereas
• Transurethral resection of the prostate (TURP) thetic tone. if the free PSA is <10%, the risk of cancer
is the tenth most common operative proce- 4.  Tricyclic antidepressants: anticholinergic increases to 56%. Free PSA is also useful
dure (~400,000/yr in the United States). effects. to evaluate the aggressiveness of prostate
• 10% to 30% of men with BPH have occult • Neurogenic bladder. cancer. A low free PSA percentage generally
prostate cancer. • Bladder cancer. indicates a high-grade cancer, whereas a
high free PSA percentage is generally associ-
PHYSICAL FINDINGS & CLINICAL WORKUP ated with a slower growing tumor.
PRESENTATION Symptom assessment (use of American
• 
Elevated measurement of prostate cancer

• 
Digital rectal examination (DRE) reveals Urological Association [AUA] Symptom Index for gene 3 (PCA3) in urine specimens collected
enlargement of the prostate. BPH [Table B1-4]), laboratory tests, and imag- after digital exam is helpful in deciding about

• 
Focal enlargement may be indicative of ing studies Fig. B1-24 describes a diagnostic prostate biopsy in men with elevated PSA
malignancy. approach to patients with BPH. (increased PCA3 = increased likelihood of
prostate cancer).

TABLE B1-4  American Urological Association (AUA) Symptom Score*

SCORE
Less Than ≤50% of ± 50% of ≥50% of Almost Total
Symptom Not at All 1 Time in 5 the Time the Time the Time Always Score
Incomplete emptying: Over the past month, how often have you had a 0 1 2 3 4 5
sensation of not emptying your bladder completely after you finished
urinating?
Frequency: Over the past month, how often have you had to urinate 0 1 2 3 4 5
again <2 hr after you finished urinating?
Intermittency: Over the past month, how often have you found you 0 1 2 3 4 5
stopped and started again several times when you urinated?
Urgency: Over the past month, how often have you found it difficult to 0 1 2 3 4 5
postpone urination?
Weak stream: Over the past month, how often have you had a weak 0 1 2 3 4 5
urinary stream?
Straining: Over the past month, how often have you had to push or 0 1 2 3 4 5
strain to begin urination?
5 or More
None 1 Time 2 Times 3 Times 4 Times Times
Nocturia: Over the past month, how many times did you most typically 0 1 2 3 4 5
get up to urinate from the time you went to bed at night until the
time you got up in the morning?
Total AUA symptom score =

*Interpretation: 0-7 mild symptoms; 8-19 moderate symptoms; 20-35 severe symptoms.
 ALG Benign Prostatic Hyperplasia 215

Patient presenting with voiding symptoms

B
AUA symptom score (AUASS) (completed
before history and physical examination)
History (see text)

Indications for immediate * Medications (diuretic, anticholinergic,

urologic intervention: α-adrenergic: side effects)
Urinary retention, renal failure, * Previous instrumentation or transurethral
gross hematuria, recurrent urinary procedure; prior pelvic surgery

and Disorders
Diseases
tract infections, bladder stones * Neurologic disease/diabetes

PHYSICAL EXAMINATION • Focused GU examination:

back, abdomen, external genitalia
• Focused neurologic examination
• DRE I
PERTINENT • Renal function
DIAGNOSTIC STUDIES • Urinalysis
• Serum PSA
• Urine cytology, if urinary symptoms
are mostly irritative

Mild symptoms Moderate symptoms Severe symptoms

(mild bothersomeness) (moderate bothersomeness) (severe bothersomeness)
AUASS 7 AUASS 13 AUASS 19

TREATMENT OPTIONS*

OBSERVATION MEDICAL TREATMENT SURGERY

or low-dose α-blocker, • Initiate α-blocker with or
particularly if symptoms without 5-α reductase
are mild to moderate specific inhibitor for
moderate symptoms and
moderate prostate size
* Treatment options in the absence
(30 g)
• Initiate 5-α reductase
of (1) indications for immediate specific inhibitor with or
urologic consultation/intervention without α-blocker for severe
and/or (2) abnormal DRE or PSA. symptoms and large
prostate size (40 g)
Symptoms associated with
indication(s) for immediate
urologic consultation/
Failures intervention:
TUIP vs. TURP vs. OPEN
PROSTATECTOMY vs.
MINIMALLY INVASIVE
(i.e., laser, VaporTrode,
hyperthermia, microwave)

FIGURE B1-24  Critical pathway for patients with benign prostatic hypertrophy.  AUA, American
Urological Association; DRE, digital rectal examination; GU, genitourinary; PSA, prostate-specific antigen;
TUIP, transurethral incision of the prostate; TURP, transurethral resection of the prostate. (From Nseyo UO [ed]:
Urology for primary care physicians, Philadelphia, 1999, Saunders.)
216 Benign Prostatic Hyperplasia
• Urinalysis, urine culture, and sensitivity to
rule out infection (if suspected).
• Blood urea nitrogen and creatinine to rule out
postrenal insufficiency.
IMAGING STUDIES
• Transrectal ultrasound may be indicated in
patients with palpable nodules or significant
elevation of PSA. It is also useful to estimate
prostate size. BPH may also be evident in
suprapubic ultrasound and MRI.
• Uroflowmetry may be used to determine rela-
tive impact of obstruction on urine flow. Urethral
pressure profile is useful to predict prostatic
hypertrophy within the urethral lumen.
• Pressure flow studies, although invasive, are
particularly helpful in patients whose history
and/or examination suggests primary blad-
der dysfunction as a cause of symptoms of
prostatism. They are also useful in patients
for whom a distinction between prostatic
obstruction and impaired detrusor contractil-
ity may affect the choice of therapy. However,
pressure flow studies may not be useful in
the workup of the usual patient with symp-
toms of prostatism.
• Postvoid residual urine measurement has not
been proved useful in predicting the need for
or response to treatment; it may be useful
in monitoring the course of the disease in
patients who elect nonsurgical treatment.
• Urethral cystoscopy is an option during later
evaluation if invasive treatment is being
planned.
TREATMENT
NONPHARMACOLOGIC THERAPY
• Avoidance of caffeine or any other foods that
may exacerbate symptoms.
• Avoidance of medications that may exacer-
bate symptoms (e.g., most cold and allergy
remedies).
GENERAL Rx
• Asymptomatic patients with prostate enlarge-
ment caused by BPH generally do not require
treatment. Patients with mild to moderate
symptoms are candidates for pharmacologic
treatment (see below). For patients who have
specific complications from BPH, prostate
surgery is usually the most appropriate form
of treatment. However, surgery may result in
significant complications (e.g., incontinence,
infection).
• Alpha-blockers (e.g., tamsulosin, alfuzosin,
doxazosin, prazosin, terazosin) relax smooth
muscle of the bladder neck and prostate and
can increase peak urinary flow rate. They have
no effect on the size of the prostate. Alpha-1
ALG
blockers are useful in symptomatic patients
to relieve symptoms of obstruction by caus-
ing relaxation of smooth muscle tone in the
prostatic capsule, urethra, and bladder neck.
• Hormonal manipulation with finasteride, a
5-alpha-reductase inhibitor that blocks con-
version of testosterone to dihydrotestos-
terone, can reduce the size of the prostate.
Usual dose is 5 mg qd. Treatment requires ≥6
mo for maximal effect.
• Dutasteride is also a 5-alpha-reductase inhibi-
tor useful to decrease prostate size and improve
urinary flow. In addition to inhibiting the isoform
of 5-alpha-reductase located in the prostate,
the medication inhibits a second isoform and
reduces dihydrotestosterone formation in the
skin and liver. Usual dose is 0.5 mg qd.
• Combined drug therapy for BPH with an
alpha-blocker and a 5-alpha-reductase
inhibitor is superior to monotherapy with
either agent.
• Tadalafil 5 mg qd has been FDA-approved
to treat patients with signs and symptoms
of BPH and patients with both ED and signs
and symptoms of BPH. Tadalafil can potenti-
ate the hypotensive effect of alpha-blockers
and should not be used in combination with
alpha-blockers.
• The dietary supplement saw palmetto is
commonly used for relief of symptoms of
BPH. Recent trials using 160 mg of saw
palmetto bid did not improve symptoms of
BPH. This contrasts with the positive findings
of many previous studies. Trials with high-
er dose-ranging protocols are currently in
progress.
• TURP is the most commonly used surgi-
cal procedure for BPH. It is recommended
for patients unresponsive to medical ther-
apy who have renal insufficiency, recurrent
UTIs, bladder stones, or gross hematuria.
Transurethral incision of the prostate (TUIP),
a procedure almost equivalent in efficacy, is
limited to patients whose estimated resection
tissue weight would be 30 g or less. TUIP
can be performed in an ambulatory setting
or during a 1-day hospitalization. Open pros-
tatectomy is typically performed on patients
with very large prostates. A prostatic ure-
thral lift implant (Urolift) is now available
for BPH. It is placed transurethrally at the
site of obstruction to open the urethra by
compressing the obstructing prostatic lobes
and holding them permanently retracted with
suture-based implants.
• Laser therapy for BPH is a less invasive alter-
native to TURP; YAG laser enucleation has
minimal effect on potency, libido, or patient
satisfaction with his sex life and is associ-
ated with retrograde ejaculation. However,
recent studies indicate that at least in the
initial 7 mo after surgery, TURP is moderately
more effective than laser therapy in relieving
symptoms of BPH.
• Transurethral needle ablation with radio-
frequency to remove periurethral prostate
tissue is being increasingly used in patients
with prostate volume >60 mL and moderate
symptoms. It has a low morbidity rate, but
treatment failure is approximately 25% at 5
yr and >80% at 10 yr.
• Balloon dilation of the prostatic urethra is less
effective than surgery for relieving symptoms
but is associated with fewer complications. It
is a reasonable treatment option for patients
with smaller prostates and no middle lobe
enlargement.
• Surgery need not be the treatment of last
resort for most patients; that is, patients
need not undergo other treatments for BPH
before they can have surgery. However, rec-
ommending surgery on the grounds that a
patient’s surgical risk will “only increase with
age” is generally inappropriate.
DISPOSITION
With appropriate therapy, symptoms improve or
stabilize in >70% of patients with BPH.
REFERRAL
Urology referral for patients with severe or intol-
erable symptoms and for any patient suspected
of having prostate cancer (10% to 30% of men
with BPH).
PEARLS &
CONSIDERATIONS
COMMENTS
• 
Emerging technologies for treating BPH,
including transurethral holmium laser enu-
cleation, transurethral electrovaporization,
and transurethral microwave thermotherapy
of the prostate, appear promising; however,
long-term effectiveness has not yet been
demonstrated.
• The increase in the use of pharmacologic
management has resulted in >30% reduction
in the total number of TURP procedures.
EVIDENCE
Available at www.expertconsult.com
SUGGESTED READINGS
Available at www.expertconsult.com
RELATED CONTENT
Enlarged Prostate (Patient Information)
AUTHOR: FRED F. FERRI, M.D.
Benign Prostatic Hyperplasia
EVIDENCE
Abstract[1]
Purpose:
We evaluated the long-term efficacy and safety of low-dose oral desmo-
pressin in elderly patients with benign prostatic hyperplasia with more
than two nocturnal voids and nocturnal polyuria (more than 30% of total
daily urine volume).
Materials and Methods:
Eligible patients with benign prostatic hyperplasia older than 65 years
with nocturia, nocturnal polyuria, and International Prostate Symptom
Score 14 or greater were included in the study. All patients received pla-
cebo or 0.1 mg desmopressin orally at bedtime. Patients were required
to visit the outpatient clinic from the first visit, and after 1, 3, 6, and 12
months of treatment. Patients maintained flow volume charts and used
diaries to record voiding data throughout the study. During follow-up
urinalysis, urine sodium, urine osmolality, serum electrolytes, prostate
specific antigen, International Prostate Symptom Score, quality of life,
transrectal ultrasonography of prostate, uroflowmetry, and post-void re-
sidual urine volume were performed at each visit.
Results:
A total of 115 patients were enrolled in the study and randomized as 58
in the placebo group and 57 in the desmopressin group. Desmopressin
significantly decreased nocturnal urine output and the number of noctu-
ria episodes and prolonged the first sleep period (p <0.01). Compared
with before treatment, desmopressin gradually decreased serum sodium
and induced statistically but not clinically significant hyponatremia after
12 months of treatment. No serious systemic complications were found
during medication.
Conclusions:
Low-dose oral desmopressin is an effective and well-tolerated treatment
for nocturnal polyuria in the lower urinary tract symptoms of patients
with benign prostatic hyperplasia. Long-term desmopressin therapy
gradually decreases serum sodium and it might induce hyponatremia
even in patients without initial hyponatremia. For long-term desmopres-
sin administration serum sodium should be assessed carefully, at least
at 1 week after treatment.
Abstract[2]
Purpose:
To evaluate whether prostatic arterial embolization (PAE) might be a fea-
sible procedure to treat lower urinary tract symptoms associated with
benign prostatic hyperplasia (BPH).
Materials and Methods:
Fifteen patients (age range, 62 to 82 yr; mean age, 74.1 yr) with symp-
tomatic BPH after failure of medical treatment were selected for PAE with
nonspherical 200-μm polyvinyl alcohol particles. The procedure was per-
formed by a single femoral approach. Technical success was considered
when selective prostatic arterial catheterization and embolization was
achieved on at least one pelvic side.
Results:
PAE was technically successful in 14 of the 15 patients (93.3%). There
was a mean follow-up of 7.9 months (range, 3 to 12 months). Inter-
national Prostate Symptom Score decreased a mean of 6.5 points (P
= 0.005), quality of life improved 1.14 points (P = 0.065), International
Index of Erectile Function increased 1.7 points (P = 0.063), and peak
urinary flow increased 3.85 mL/sec (P = 0.015). There was a mean pros-
tate-specific antigen reduction of 2.27 ng/mL (P = 0.072) and a mean
prostate volume decrease of 26.5 mL (P = 0.0001) by ultrasound and
28.9 mL (P = 0.008) by magnetic resonance imaging. There was one
major complication (a 1.5-cm2 ischemic area of the bladder wall) and
four clinical failures (28.6%).
Conclusions:
In this small group of patients, PAE was a feasible procedure, with pre-
liminary results and short-term follow-up suggesting good symptom
control without sexual dysfunction in suitable candidates, associated
with a reduction in prostate volume.
216.e1
Abstract[3]
Medical Treatment
Purpose:
Tadalafil has regulatory approval for the treatment of men with signs/
symptoms of benign prostatic hyperplasia with and without erectile dys-
function. We assessed whether the effects of treatment with tadalafil for
lower urinary tract symptoms/benign prostatic hyperplasia are indepen-
dent of improvements in erectile dysfunction.
Materials and Methods:
Four separate analyses used integrated data from 4 randomized, double-
blind, placebo controlled studies in men with lower urinary tract symp-
toms/benign prostatic hyperplasia with and without erectile dysfunction to
test whether total I-PSS (International Prostate Symptom Score) improve-
ment was due to improvement in IIEFEF (International Index of Erectile
Function-Erectile Function domain score). Unidirectional and bidirectional
path analysis models determined direct and indirect treatment effects
mediated by improvements in lower urinary tract symptoms/benign pros-
tatic hyperplasia and erectile dysfunction symptoms.
Results:
A total of 1,496 men, of whom 77% had erectile dysfunction, received at
least 1 dose of tadalafil 5 mg once daily or placebo. The placebo adjusted
treatment effect for men with erectile dysfunction was represented by
a mean decrease of ‒2.3 (p < 0.0001) in total I-PSS versus_2.2 (p =
0.0007) for men without erectile dysfunction. The correlation between
change from baseline in total I-PSS and IIEF-EF was weak (r(2) = 0.08, p
<0.0001). The unidirectional path analysis model suggested that the to-
tal treatment effect on total I-PSS score improvement (2.25) was derived
from a direct treatment effect of 1.57 (70%, p <0.001) and an indirect
treatment effect of 0.67 (30% via IIEF-EF improvement, p <0.001). Bidi-
rectional path analysis showed that total I-PSS improvement was largely
attributed to direct (92.5%, p <0.001) versus indirect (7.5%, p = 0.32)
treatment effects via IIEF-EF improvement.
Conclusions:
Regardless of the analytical approach, self-reported erectile dysfunc-
tion status did not appreciably influence tadalafil treatment response
in men with lower urinary tract symptoms/benign prostatic hyperplasia,
supporting the dual action of tadalafil on lower urinary tract symptoms/
benign prostatic hyperplasia and erectile dysfunction.
Evidence-Based References
Wang CJ et al.: Low-dose oral desmopressin for nocturnal polyuria in patients
with benign prostatic hyperplasia: a double-blind, placebo controlled, random-
ized study, J Urol 185:219–223, 2011.
Pisco JM: Prostatic arterial embolization to treat benign prostatic hyperplasia,
J Vasc Interv Radiol 22:11–19, 2011.
Brock GB, McVary KT, Roehrborn C, et al.: Direct effects of tadalafil on lower
urinary tract symptoms versus indirect effects mediated through erectile
dysfunction symptom improvement: integrated data analyses from 4 placebo
controlled clinical studies, J Urol 191:405–411, 2014.
SUGGESTED READINGS
AUA Practice Guidelines Committee: AUA guideline on management of benign
prostatic hyperplasia, J Urol 170, 2003.
Barry MJ et al.: Effect of increasing saw palmetto extract on lower urinary tract
symptoms: a randomized trial, JAMA 306(12):1344–1351, 2012.
Crawford ED et al.: Diagnostic performance of PCA3 to detect prostate cancer in
men with increased prostate specific antigen: a prospective study of 1,962
cases, J Urol 188:1726–1731, 2012.
Edwards JL: Diagnosis and management of benign prostatic hyperplasia, Am Fam
Physician 77(10):1403–1410, 2008.
Fullhase J: Systematic review of combination drug therapy for non-neurogenic
male lower urinary tract symptoms, Eur Urol 64:228–243, 2013.
Larcher A et al.: Urethral lift for benign prostatic hyperplasia: a comprehensive
review of the literature, Curr Urol Rep 14:620, 2013.
Lepor H: Insights into the natural history and treatment of benign prostatic hyper-
plasia, J Urol 175:815, 2006.
Sarma AV, Wei JT: Benign prostatic hyperplasia and lower urinary tract symptoms,
N Engl J Med 367:248–257, 2012.