Download Patients with benign prostatic hyperplasia (BPH - Dis Lair

Prostate Hyperplasia, Benign
Introduction
Background
Benign prostatic hyperplasia (BPH), also known as benign
prostatic hypertrophy, is a histologic diagnosis characterized
by proliferation of the cellular elements of the prostate.
Cellular accumulation and gland enlargement may result
from epithelial and stromal proliferation, impaired
preprogrammed cell death (apoptosis), or both. BPH involves
the stromal and epithelial elements of the prostate arising in
the periurethral and transition zones of the gland. The
hyperplasia presumably results in enlargement of the
prostate that may restrict the flow of urine from the bladder.
BPH is considered a normal part of the aging process in men
and is hormonally dependent on testosterone and
dihydrotestosterone (DHT) production. An estimated 50% of
men demonstrate histopathologic BPH by age 60 years. This
number increases to 90% by age 85 years; thus, increasing
gland size is considered a normal part of the aging process.
The voiding dysfunction that results from prostate gland
enlargement and bladder outlet obstruction (BOO) is termed
lower urinary tract symptoms (LUTS). It has also been
commonly referred to as prostatism, although this term has
decreased in popularity. These entities overlap; not all men
with BPH have LUTS, and, likewise, not all men with LUTS
have BPH. Approximately half of men diagnosed with
histopathologic BPH demonstrate moderate-to-severe LUTS.
Clinical manifestations of LUTS include urinary frequency,
urgency, nocturia (getting up at night during sleep to
urinate), decreased or intermittent force of stream, or a
sensation of incomplete emptying. Complications occur less
commonly but may include acute urinary retention (AUR),
impaired bladder emptying, or the need for corrective
surgery.
Prostate volume may increase over time in men with BPH. In
addition, peak urinary flow, voided volume, and symptoms
may worsen over time in men with untreated BPH. The risk of
AUR and the need for corrective surgery increases with age.
Pathophysiology
The prostate is a walnut-sized gland that forms part of the
male reproductive system. It is located in front of the rectum
and just below the urinary bladder. It is in continuum with
the urinary tract and connects directly with the penile
urethra. It is therefore a conduit between the bladder and
the urethra. The gland is composed of several zones or lobes
that are enclosed by an outer layer of tissue (capsule). These
include the peripheral, central, anterior fibromuscular
stroma, and transition zones. BPH originates in the transition
zone, which surrounds the urethra. Microscopically, BPH is
characterized as a hyperplastic process. The hyperplasia
results in enlargement of the prostate that may restrict the
flow of urine from the bladder, resulting in clinical
manifestations of BPH. The prostate enlarges with age in a
hormonally dependent manner. Notably, castrated males (ie,
who are unable to make testosterone) do not develop BPH.
Benign prostatic hyperplasia. The
prostate is located at the apex of
the bladder and surrounds the
proximal urethra.
The traditional theory behind BPH is that, as the prostate
enlarges, the surrounding capsule prevents it from radially
expanding, potentially resulting in urethral compression.
However,
obstruction-induced
bladder
dysfunction
contributes significantly to LUTS. The bladder wall becomes
thickened, trabeculated, and irritable when it is forced to
hypertrophy and increase its own contractile force. This
increased sensitivity (detrusor instability), even with small
volumes of urine in the bladder, is believed to contribute to
urinary frequency and LUTS. The bladder may gradually
weaken and lose the ability to empty completely, leading to
increased residual urine volume and, possibly, acute or
chronic urinary retention.
The main function of the prostate gland is primarily
secretory; it produces alkaline fluid that comprises
approximately 70% of the seminal volume. The secretions
produce lubrication and nutrition for the sperm. The alkaline
fluid in the ejaculate results in liquefaction and helps to
neutralize the acidic vaginal environment. The prostatic
urethra is a conduit for semen and prevents retrograde
ejaculation (ie, ejaculation resulting in semen being forced
backwards into the bladder) by closing off the bladder neck
during sexual climax. Ejaculation involves a coordinated
contraction of many different components, including the
smooth muscles of the seminal vesicles, vasa deferentia,
ejaculatory ducts, and the ischiocavernosus and
bulbocavernosus muscles.
Frequency
International
Worldwide, approximately 30 million men have symptoms
related to BPH.
Mortality/Morbidity
In the past, chronic end-stage BOO often led to renal failure
and uremia. Although this complication is much less common
now, chronic BOO secondary to BPH may lead to urinary
retention, renal insufficiency, recurrent urinary tract
infections, gross hematuria, and bladder calculi.
Race
The prevalence of BPH in white and African-American men is
similar. However, BPH tends to be more severe and
progressive in African-American men, possibly because of
higher testosterone levels, 5-alpha-reducatase activity,
androgen receptor expression, and growth factor activity in
this population. The increased activity leads to an increased
rate of prostatic hyperplasia and subsequent enlargement
and its sequelae.
Sex
BPH occurs only in males. Women do not have prostate
glands.
Age
BPH is a common problem that affects the quality of life
(QOL) in approximately one third of men older than 50 years.
BPH is histologically evident in up to 90% of men by age 85
years.
Clinical
History
The diagnosis of benign prostatic hyperplasia (BPH) can often
be suggested based on history alone. Special attention to the
onset and duration of symptoms, general health issues
(including sexual history), fitness for any possible surgical
intervention, severity of symptoms and how they are
affecting QOL, medications, and previously attempted
treatments is essential to making the correct diagnosis.
Symptoms often attributed to BPH can be caused by other
disease processes, and a history and physical examination are
essential in ruling out other etiologies of LUTS (See Other
Problems to be Considered).
When the prostate enlarges, it may act similar to a "clamp on
a hose," constricting the flow of urine. Nerves within the
prostate and bladder may also play a role in causing the
following common symptoms:
1. Urinary frequency - The need to urinate frequently
during the day or night (nocturia), usually voiding only
small amounts of urine with each episode
2. Urinary urgency - The sudden urgent need to urinate
quickly owing to the sensation of imminent loss of urine
without control
3. Hesitancy
o Difficulty initiating the urinary stream
o Interrupted, weak stream
4. Incomplete bladder emptying - The feeling of persistent
residual urine, regardless of the frequency of urination
5. Straining - The need strain or push (Valsalva maneuver)
to initiate and maintain urination in order to more fully
evacuate the bladder
6. Decreased force of stream - The subjective loss of force
of the urinary stream over time
7. Dribbling - The loss of small amounts of urine due to a
poor urinary stream
Epidemiologic studies have identified LUTS as an
independent risk factor for erectile dysfunction and
ejaculatory dysfunction.1
Physical
Conduct a focused physical examination to assess the
suprapubic area for signs of bladder distention and a
neurological examination for sensory and motor deficits.
The digital rectal examination (DRE) is an integral part of the
evaluation in men with presumed BPH.
1.
During this portion of the examination, prostate size and
contour can be assessed, nodules can be evaluated, and
areas suggestive of malignancy can be detected. The
normal prostate volume in a young adult male is
approximately 20 g.
2. A more precise volumetric determination can be made
using transrectal ultrasonography (TRUS) of the prostate.
3. Anal sphincter tone or lack of it may indicate an
underlying neurological disorder.
4. In general, an estimation of the number of index finger
pads that one can sweep over the rectal surface of the
prostate during DRE is a useful way for nonurologist
examiners to communicate estimated gland size.
Anecdotally, each fingerbreadth correlates to
approximately 15-20 g of tissue. For example, one can
report the prostate size as "2-3 fingerbreadths wide"
when charting in the medical record or communicating
with a colleague. Most asymptomatic men have glands
of 2 fingerbreadths or less.
5. In addition, pelvic floor tone, the presence or absence of
fluctuance (ie, prostate abscess), and pain sensitivity of
the gland (prostatodynia/prostatitis) can be assessed.
6. The prostate is examined using the index finger of the
dominant hand. The finger is placed through the anus
after relaxation of the anal sphincter, and the prostate is
palpated circumferentially (analogous to a windshield
wiper movement).
Differential Diagnoses
Bladder Cancer
Prostatitis, Tuberculous
Bladder Stones
Radiation Cystitis
Bladder Trauma
Urethral Strictures
Chronic Pelvic Pain Urinary Tract Infection, Males
Interstitial Cystitis
Prostatitis, Bacterial
Neurogenic Bladder
Workup
Laboratory Studies
1. Urinalysis: Examine the urine using dipstick methods
and/or via centrifuged sediment evaluation to assess for
the presence of blood, leukocytes, bacteria, protein, or
glucose.
2. Urine culture: This may be useful to exclude infectious
causes of irritative voiding and is usually performed if the
initial urinalysis findings indicate an abnormality.
3. Prostate-specific antigen
 Although benign prostatic hyperplasia (BPH) does not
cause prostate cancer, men at risk for BPH are also at
risk for prostate cancer and should be screened
accordingly. The American Cancer Society recommends
that annual prostate-specific antigen (PSA) testing and
DRE for prostate cancer screening be offered at the
following ages:2
a. Starting at age 50 years in men who are expected to live
at least 10 more years
b.
Starting at age 45 years in men at high risk for prostate
cancer (African-Americans and men with a close relative
with prostate cancer)
c. Starting at age 40 years in men with multiple close
relatives with prostate cancer
 A physician should discuss the risks and benefits of PSA
screening with the patient.
 Notably, men with larger prostates may have slightly
higher PSA levels.
4. Electrolytes, BUN, and creatinine: These evaluations are
useful screening tools for chronic renal insufficiency in
patients who have high postvoid residual (PVR) urine
volumes. A routine serum creatinine measurement is not
indicated in the initial evaluation of men with lower
urinary tract symptoms (LUTS) secondary to BPH.
Imaging Studies
1. Ultrasonography (abdominal, renal, transrectal) and
intravenous urography are useful for helping determine
bladder and prostate size and the degree
of hydronephrosis (if any) in patients with urinary
retention or signs of renal insufficiency. Generally, they
are not indicated for the initial evaluation of
uncomplicated LUTS.
2. TRUS of the prostate is recommended in selected
patients. The success of certain minimally invasive
treatments (see Surgical Care) may depend on the
anatomical characteristics of the gland.
 In patients with elevated PSA levels, TRUS-guided biopsy
may be indicated.
 Imaging of the upper tracts is indicated in patients who
present with concomitant hematuria, a history of
urolithiasis, an elevated creatinine level, high PVR
volume, or history of upper urinary tract infection.
3. Other diagnostic studies, such as CT scanning and MRI,
have no role in the evaluation and treatment of
uncomplicated BPH.
Other Tests
The American Urological Association (AUA) has developed
rigorous clinical practice guidelines for BPH based on the
1994 Agency for Healthcare Research and Quality clinical
practice guidelines for BPH. In 2006, The AUA Practice
Guidelines Committee updated the 1994 evidence-based
guidelines for the diagnosis and treatment of BPH originally
created under the auspices of the United States Department
of Health and Human Services Agency for Health Care Policy
and Research.3,4 These panels have established the following
categories to classify diagnostic tests and studies. A
recommended test is one that should be performed on every
patient, whereas an optional test is of proven value in
selected patients.
Recommended tests
1. Medical history: A medical history should be taken to
qualify and quantify voiding dysfunction. Identification of
other causes of voiding dysfunction and medical
2.
3.
4.






comorbidities are essential to properly assess the
condition and to determine conditions that may
complicate treatment.
Physical examination: The physical examination consists
of a focused physical examination and a neurologic
examination. The physical examination includes a DRE to
measure prostate size and to assess for abnormalities.
The neurological examination is geared toward lowerextremity neurologic and muscular function, as well as
anal sphincter tone. Examination of the phallus and
foreskin occasionally reveals meatal stenosis,
unretractable foreskin, penile ulcers, or foreign bodies
such as warts.
PSA testing: PSA testing should be offered to any patient
with a 10-year life expectancy in whom the diagnosis of
prostate cancer would change management.
International Prostate Symptom Score (IPSS)/American
Urological Association Symptom Index (AUA-SI) for BPH
and the IPSS disease-specific QOL question
Developed to quantitate and validate responses to the
questions asked, this set of 7 questions has been
adopted worldwide and yields reproducible and
quantifiable information regarding symptoms and
response to treatment.
Each question allows the patient to choose 1 of 6
answers indicating increasing severity of symptoms on a
scale of 0-5; the total score ranges from 0-35. Questions
concern incomplete emptying, frequency, intermittency,
urgency, weak stream, straining, and nocturia. The
eighth question is known as the bother score and
pertains to the patient's perceived QOL. Scores can
range from 0 (delighted) to 6 (terrible). After calculating
the total score for all 8 eight questions, patients are
classified as 0-7 (mildly symptomatic), 8-19 (moderately
symptomatic), or 20-35 (severely symptomatic).
Specific IPSS/AUA-SI questions are as follows (adapted
from the recommendations of the International Scientific
Committee, 2000, and the AUA Guideline, 2003/updated
2006):
Incomplete emptying: Over the past month, how often
have you had the sensation of not emptying your
bladder completely after you have finished urinating?
(Not at all = 0, less than 1 time in 5 = 1, less than half the
time = 2, about half the time = 3, more than half the time
= 4, almost always = 5)
Frequency: Over the past month, how often have you
had to urinate again less than 2 hours after you finished
urinating? (Not at all = 0, less than 1 time in 5 = 1, less
than half the time = 2, about half the time = 3, more than
half the time = 4, almost always = 5)
Intermittency: Over the past month, how often have you
stopped and started again several times when urinating?
(Not at all = 0, less than 1 time in 5 = 1, less than half the
time = 2, about half the time = 3, more than half the time
= 4, almost always = 5)
 Urgency: Over the past month, how often have you
found it difficult to postpone urination? (Not at all = 0,
less than 1 time in 5 = 1, less than half the time = 2,
about half the time = 3, more than half the time = 4,
almost always = 5)
 Weak stream: Over the past month, how often have you
had a weak urinary stream? (Not at all = 0, less than 1
time in 5 = 1, less than half the time = 2, about half the
time = 3, more than half the time = 4, almost always = 5)
 Straining: Over the past month, how often have you had
to push or strain to begin urination? (Never = 0, once = 1,
twice = 2, thrice = 3, 4 times or more = 4, 5 times or
more = 5)
 Nocturia: Over the past month, how many times did you
most typically get up to urinate from the time you went
to bed until the time you got up in the morning? (Not at
all = 0, less than 1 time in 5 = 1, less than half the time =
2, about half the time = 3, more than half the time = 4,
almost always = 5)
 Bother score: The IPSS uses the same 7 questions as the
AUA-SI, with the addition of the following diseasespecific QOL question: How would you feel if you were to
spend the rest of your life with your urinary condition
just the way it is now? (Delighted = 0, pleased = 1, mostly
satisfied = 2, mixed = 3, mostly dissatisfied = 4, unhappy
= 5, terrible = 6) This helps assess perceived QOL due to
urinary symptoms, and the score ranges from 0
(delighted) to 6 (terrible).
Optional tests
1. Flow rate
 Flow rate is useful in the initial assessment and to help
determine the response to treatment. It may be
performed prior to embarking on any active treatments,
including medical treatment.
 A maximal flow rate (Qmax) is the single best
measurement, but a low Qmax does not help
differentiate between obstruction and poor bladder
contractility. For more detailed analysis, a pressure flow
study is required. A Qmax value of greater than 15 mL/s
is considered by many to be normal. A value of less than
7 mL/s is widely accepted as low.
 The results of flow rate measurements are somewhat
effort- and volume-dependent; therefore, the best plan
to make a reasonable determination of significance is to
obtain at least 2 tracings with at least 150 mL of voided
volume each time.
2. Postvoid residual urine
 Obtain this value after the patient voids in order to
gauge the severity of bladder decompensation.
 It can be obtained invasively with a catheter or
noninvasively with a transabdominal ultrasonic scanner.
 A high PVR (ie, 350 mL) may indicate bladder dysfunction
and may predict a negative response to treatment.
3. Pressure flow studies
 Although these tests are somewhat invasive, requiring
catheterization of the urethra and placement of a
transrectal pressure transducer, the findings are
invaluable for evaluating for bladder outlet obstruction
(BOO), especially prior to any invasive therapy.
 Urodynamic studies are the only way to help distinguish
poor bladder contraction ability (detrusor underactivity)
from outlet obstruction.
 BOO is characterized by high intravesical voiding
pressures (>60 cm water) accompanied by low urine flow
rates (Qmax <15 mL/s).
4. Urine cytology: Cytologic examination of the urine may
be considered in patients with predominantly irritative
voiding symptoms. Risk factors for bladder cancer
(smoking, previous bladder cancer) should alert the
physician to consider this noninvasive test.
5. Other validated assessment instruments addressing LUTS
in men with BPH
Tests that are not recommended
Routine measurement of serum creatinine is not indicated in
the initial evaluation of men with LUTS secondary to BPH.
Procedures
Endoscopy of the lower urinary tract (cystoscopy)
1. This may be indicated in patients scheduled for invasive
treatment or in whom a foreign body or malignancy is
suspected. In addition, endoscopy may be indicated in
patients with a history of sexually transmitted disease
(eg,gonococcal urethritis), prolonged catheterization, or
trauma. Findings may suggest urethral stricture as the
cause of BOO, instead of BPH.
2. Flexible cystoscopy can be easily performed in several
minutes in an office-based setting using topical gel-based
intraurethral anesthesia without sedation.
Histologic Findings
BPH is characterized by a varying combination of epithelial
and stromal hyperplasia in the prostate. Some cases
demonstrate an almost pure smooth-muscle proliferation,
although most demonstrate a fibroadenomyomatous pattern
of hyperplasia. Prostatic enlargement depends on the potent
androgen DHT. In the prostate gland, type II 5-alphareductase metabolizes circulating testosterone into DHT
(works locally, not systemically). DHT binds to androgen
receptors in the cell nuclei, potentially resulting in BPH.
In vitro studies have shown that large numbers of alpha-1adrenergic receptors are located in the smooth muscle of the
stroma and capsule of the prostate, as well as in the bladder
neck. Stimulation of these receptors causes an increase in
smooth-muscle tone, which can worsen LUTS. Conversely,
blockade of these receptors (see Treatment) can reversibly
relax these muscles, with subsequent relief of LUTS.
In the bladder, obstruction leads to smooth-muscle-cell
hypertrophy. Biopsy specimens of trabeculated bladders
demonstrate evidence of scarce smooth-muscle fibers with
an increase in collagen. The collagen fibers limit compliance,
leading to higher bladder pressures upon filling. In addition,
their presence limits shortening of adjacent smooth muscle
cells, leading to impaired emptying and the development of
residual urine.
Staging
Since BPH is a nonmalignant condition, no formal staging
systems apply.
Treatment
Medical Care
Patients with mild symptoms (IPSS/AUA-SI score <7) or
moderate-to-severe symptoms (IPSS/AUA-SI score >8) of
benign prostatic hyperplasia (BPH) who are not bothered by
their symptoms and are not experiencing complications of
BPH should be managed with a strategy of watchful waiting.
In these situations, medical therapy is not likely to improve
their symptoms and/or QOL. In addition, the risks of
treatment may outweigh any benefits. Patients managed
expectantly with watchful waiting are usually re-examined
annually.
Transurethral resection of the prostate (TURP) has long been
accepted as the criterion standard for relieving bladder outlet
obstruction (BOO) secondary to BPH. In current clinical
practice, most patients with BPH do not present with obvious
surgical indications; instead, they often have milder lower
urinary tract symptoms (LUTS) and, therefore, are initially
treated with medical therapy.
The era of medical therapy for BPH dawned in the mid 1970s
with the use of nonselective alpha-blockers such as
phenoxybenzamine. The medical therapeutic options for BPH
have evolved significantly over the last 3 decades, giving rise
to the receptor-specific alpha-blockers that comprise the first
line of therapy.
Rationale for alpha-1-receptor blockade in benign prostatic
hyperplasia
A significant component of LUTS secondary to BPH is believed
to be related to the smooth-muscle tension in the prostate
stroma, urethra, and bladder neck. The smooth-muscle
tension is mediated by the alpha-1-adrenergic receptors;
therefore, alpha-adrenergic receptor–blocking agents should
theoretically decrease resistance along the bladder neck,
prostate, and urethra by relaxing the smooth muscle and
allowing passage of urine. BPH is predominantly a stromal
proliferative process, and a significant component of
prostatic enlargement results from smooth-muscle
proliferation. The stromal-to-epithelial ratio is significantly
greater in men with symptomatic BPH than in those with
asymptomatic BPH.
The 3 subtypes of the alpha-1 receptor include 1a, 1b, and 1c.
Of these, the alpha-1a receptor is most specifically
concentrated in the bladder neck and prostate. Provided that
the alpha-1a subtype is predominant in the prostate, bladder
neck, and urethra, but not in other tissues, drugs that are
selective for this receptor (ie, tamsulosin) may have a
potential therapeutic advantage.
Tamsulosin is considered the most pharmacologically
uroselective of the commercially available agents because of
its highest relative affinity for the alpha-1a receptor subtype.
Recently, a new alpha-1a receptor selective blocker, silodosin
(Rapaflo) was approved. It is indicated for treatment of the
signs and symptoms of BPH.
The efficacy of the titratable alpha-blockers doxazosin and
terazosin (Hytrin) is dose-dependent. Maximum tolerable
doses have not been defined for any alpha-blocker; however,
the higher the dose, the more likely the adverse events
(orthostatic hypotension, dizziness, fatigue, ejaculatory
disorder, nasal congestion).
An approximately 4- to 6-point improvement is expected in
IPSS/AUA-SI scores when alpha-blockers are used.
Interestingly, alpha-blocker therapy has not been shown to
reduce the overall long-term risk of acute urinary retention
(AUR) or BPH-related surgery.5
1. Alpha-adrenergic receptor blockers
 The alpha-blocking agents administered in BPH studies
can be subgrouped according to receptor subtype
selectivity and the duration of serum elimination halflives.
 Nonselective alpha-blockers include phenoxybenzamine.
 Selective short-acting alpha-1 blockers include prazosin,
alfuzosin, and indoramin.
 Selective long-acting alpha-1 blockers include terazosin,
doxazosin and slow-release (SR) alfuzosin.
 Partially subtype (alpha-1a)–selective agents include
tamsulosin and silodosin.
2. Nonselective alpha-blockers
 Phenoxybenzamine was the first alpha-blocker studied
for BPH. Its nonselective nature causes it to antagonize
both the alpha 1- and alpha 2-adrenergic receptors,
resulting in a higher incidence of adverse effects.
 Because of the availability of more alpha-1-receptor–
specific agents, phenoxybenzamine is currently not often
used for the treatment of BPH.
3. Intraoperative floppy iris syndrome
 Intraoperative floppy iris syndrome (IFIS) is characterized
by miosis, iris billowing, and prolapse in patients
undergoing cataract surgery who have taken or currently
take alpha-1-blockers. It is particularly prevalent among
patients taking tamsulosin. Patients on alpha-blocker
therapy must disclose this to their ophthalmologists
prior to cataract surgery so that the appropriate
preventive measures can be taken.6
 Bell et al reviewed exposure to alpha-adrenergic blockers
frequently prescribed to treat BPH and their association
with serious postoperative adverse effects following
cataract surgery. The study included more than 96,000
older men who had undergone cataract surgery over a 5year period (3.7% had recent exposure to tamsulosin and
7.7% had recent exposure to other alpha-blockers).
Exposure to tamsulosin within 14 days of cataract
surgery was significantly associated with serious
postoperative ophthalmic adverse events (7.5% vs 2.7%;
adjusted odds ratio [OR], 2.33; 95% confidence interval
[CI], 1.22-4.43), specifically IFIS and its complications (ie,
retinal detachment, lost lens or fragments,
endophthalmitis). No significant associations were noted
with exposure to other alpha-blocker medications (7.5%
vs 8%; adjusted OR, 0.91; 95% CI, 0.54-1.54) or to
previous exposure to tamsulosin or other alphablockers.7
Rationale for 5-alpha-reductase inhibitors in benign
prostatic hyperplasia
Hormonal medical management emerged from the discovery
of a congenital form of pseudohermaphroditism secondary to
DHT deficiency (due to a lack of 5-alpha-reductase activity).
This deficiency produced a hypoplastic prostate. The two
types of 5-alpha-reductase include type 1 (predominantly
located in extraprostatic tissues, such as skin and liver) and
type 2 (predominant prostatic reductase).
Prostatic enlargement depends on the potent androgen DHT.
In the prostate gland, type II 5-alpha-reductase metabolizes
circulating testosterone into DHT (works locally, not
systemically). DHT binds to androgen receptors in the cell
nuclei; this can result in BPH. DHT promotes growth of
prostatic tissue. Inhibition of 5-alpha-reductase type 2 blocks
the conversion of testosterone to DHT, resulting in lower
intraprostatic levels of DHT. This leads to inhibition of
prostatic growth, apoptosis, and involution. The exact role of
5-alpha-reductase type 1 in normal and abnormal prostatic
development is undefined. 5-Alpha-reductase inhibitors
improve LUTS by decreasing prostate volumes; thus, patients
with larger prostates may achieve a greater benefit. Further,
maximal reduction in prostate volume requires 6 months of
therapy.
5-Alpha reductase inhibitors
 Finasteride (Proscar), a 4-aza-steroid, has demonstrated
5-alpha type II–blocking activity, resulting in the
inhibition of DHT-receptor complex formation. This
effect causes a profound decrease in the concentration
of DHT intraprostatically, resulting in a consistent
decrease in prostate size. One third of men treated with
this agent exhibit improvements in urine flow and
symptomatology.
 Dutasteride (Avodart) has an affinity for both type 1 and
type 2 5-alpha-reductase receptors. The significance of
blockage of type 1 receptors is currently unknown.
 Both finasteride and dutasteride actively reduce DHT
levels by more than 80%, improve symptoms, reduce the
incidence of urinary retention, and decrease the
likelihood of surgery for BPH.

Adverse effects are primarily sexual in nature (decreased
libido, erectile dysfunction, ejaculation disorder).
 Both finasteride and dutasteride may reduce serum PSA
values by as much as 50%. The decrease in PSA is
typically maximally achieved when the maximal decrease
in prostatic volume is noted (6 months). Thus, one must
take this into account when using PSA to screen for
prostate cancer.
 Because these drugs interfere with the metabolism of
testosterone, they are contraindicated in children and
pregnant females. In addition, pregnant females or those
who are considering conception should not handle
crushed or broken tablets because of the potential for
absorption and subsequent potential risk to a male fetus.
 In patients with LUTS and enlarged prostates, 5-alphareductase inhibitors are believed to be appropriate and
effective treatment.
Rationale for combination therapy with alpha-1-receptor
blockade and 5-alpha-reductase inhibitors in benign
prostatic hyperplasia
1. The alpha-1-receptor blockers provide rapid relief, while
the 5-alpha-reductase inhibitors target the underlying
disease process.5 The Medical Therapy of Prostatic
Symptoms (MTOPS) trial demonstrated that combination
therapy reduced the risk of progression and showed a
greater improvement in IPSS with combination therapy
than with finasteride or doxazosin alone. The risks of
AUR and BPH-related surgery were reduced with
combination therapy or finasteride in comparison to
doxazosin monotherapy.8
2. The Symptom Management After Reducing Therapy
(SMART-1) trial demonstrated that, after 6 months of
combination therapy, discontinuation of the alpha-1blocker is possible in men with moderate LUTS.
However, those with severe LUTS may require longer
combination therapy.8
Landmark clinical trials
Numerous phase II and phase III trials of drugs used in the
treatment of BPH have been conducted. A few landmark
studies are selected below.
1. The Proscar Long-Term Efficacy and Safety Study (PLESS)
evaluated clinical data of randomized controlled trials
using alpha-adrenergic receptor blockers and/or 5-alphareductase inhibitors. This was a multicenter, 4-year,
double-blind, placebo-controlled study of 3,040 men.
Men with PSA levels of more than 10 ng/mL and those
with prostate cancer were excluded. In the PLESS study,
patients were randomized to receive placebo versus
finasteride (5 mg/d) for 4 years. Results showed that
patients treated with finasteride were at a significantly
lower risk of developing AUR or needing surgery.9
2. The Medical Therapy of Prostatic Symptoms (MTOPS)
trial was a multicenter, 4- to 6-year, double-blind,
randomized, placebo-controlled trial of 3,047 men with
symptomatic BPH. The men were separated into 4
treatment groups to receive placebo, doxazosin,
finasteride, or a combination of doxazosin and
finasteride. Combination therapy was superior to
placebo and monotherapy in reducing the risk of primary
endpoints of the study (reduction in AUA-SI score, AUR,
recurrent infections, renal insufficiency, incontinence,
changes in flow, and PSA level and a lower rate of
invasive treatments) and was well tolerated.10
3. The Alfuzosin Long-Term Efficacy and Safety Study
(ALTESS) was a double-blind, placebo-controlled study
conducted to assess the impact of the alpha-1-blocker
alfuzosin 10 mg daily on the risk of BPH/LUTS
progression. This was a 2-year study of 1,522 men.
Notably, this cohort of study patients consisted of men
with greater risk factors for BPH progression (older age,
higher IPSS scores, larger prostate size, lower Qmax, and
higher PVR) than those in the MTOPS trial. Alfuzosin
decreased the risk of LUTS deterioration and significantly
improved QOL and peak flow urinary flow rate. Alfuzosin
did not reduce the risk of AUR but tended to reduce the
risk of surgery.11
4. The international real-life practice study of alfuzosin
once daily (ALF-ONE) was a 3-year study conducted to
assess the efficacy and safety of alfuzosin 10 mg once
daily in 689 European men with a mean age of 67.6
years. The IPSS decreased by one third. There were
significant improvements in nocturia and bother score.
Clinical progression of worsening of IPSS (>4 points) was
seen in 12.4%, AUR in 2.6%, and requirement of BPHrelated surgery in 5.7%. Alfuzosin was well tolerated,
with dizziness the most common adverse effect (4.5%).
Notably, symptom worsening during treatment and high
PSA levels appeared to be the best predictors of clinical
progression.12
5. The Combination of Avodart and Tamsulosin (CombAT) is
an ongoing 4-year, multicenter, randomized, doubleblind, parallel group study evaluating the safety and
efficacy of dutasteride (dual 5-alpha-reductase inhibitor)
and tamsulosin (alpha-1-blocker) separately and in
combination. The cohort consists of 4,844 men aged 50
years or older with moderate-to-severe BPH symptoms
(IPSS >12), prostate volume of 30 mL or greater, and a
PSA level of 1.5-10 ng/mL. The two-year results revealed
that combination therapy improved symptoms, urinary
flow, and QOL better than monotherapy. The adverseeffect profile of combination therapy was similar to that
of monotherapy (with either drug), although drugrelated adverse events were more common with
combination therapy.13
Phytotherapeutic agents and dietary supplements
1. Phytotherapeutic agents and dietary supplements are
considered emerging therapy by the AUA Guidelines
panel and are not recommended for the treatment of
BPH because of the lack of evidence at this time.
2. Pharmaceuticals derived from plant extracts are widely
used throughout the world for the treatment of various
medical ailments. In 1998, Americans spent a total of
$3.65 billion on all herbal remedies. In France and
Germany, plant extracts have a market share of up to
50% of all drugs prescribed for symptomatic BPH. In the
United States, these agents are also popular and readily
available.
3. The attraction to phytotherapeutic agents appears to be
related to the perception of therapeutic healing powers
of natural herbs, the ready availability, and the lack of
adverse effects.
4. Most of the phytotherapeutic agents used in the
treatment of LUTS secondary to BPH are extracted from
the roots, seeds, bark, or fruits of plants listed below.
Some
suggested
active
components
include
phytosterols, fatty acids, lectins, flavonoids, plant oils,
and polysaccharides. Some preparations derive from a
single plant; others contain extracts from 2 or more
sources.
5. Each agent has one or more proposed modes of action.
The following modes of action are suggested:
o Antiandrogenic effect
o Antiestrogenic effect
o Inhibition of 5-alpha-reductase
o Blockage of alpha receptors
o Antiedematous effect
o Anti-inflammatory effect
o Inhibition of prostatic cell proliferation
o Interference with prostaglandin metabolism
o Protection and strengthening of detrusor
6. The origins of phytotherapeutic agents are as follows:
a. Saw palmetto, ie, American dwarf palm (Serenoa repens,
Sabal serrulata) fruit
b. South African star grass (Hypoxis rooperi) roots
c. African plum tree (Pygeum africanum) bark
d. Stinging nettle (Urtica dioica) roots
e. Rye (Secale cereale) pollen
f. Pumpkin (Cucurbita pepo) seeds
7. The mechanisms of action of some selected
phytotherapeutic agents are as follows:
 Saw palmetto (American dwarf palm): Extracts of the
berries are the most popular botanical products for BPH.
The active components are believed to be a mixture of
fatty acids, phytosterols, and alcohols. The proposed
mechanisms of action are antiandrogenic effects, 5alpha-reductase inhibition, and anti-inflammatory
effects. The recommended dosage is 160 mg orally twice
daily. Studies show significant subjective improvement in
symptomatology without objective improvements in
urodynamic parameters. Minimal adverse effects include
occasional GI discomfort.
 African plum tree (P africanum): Suggested mechanisms
of action include inhibition of fibroblast proliferation and
anti-inflammatory and antiestrogenic effects. This
extract is not well studied.
 Rye (S cereale): This extract is made from pollen taken
from rye plants growing in southern Sweden. Suggested
mechanisms of action involve alpha-blockade, prostatic
zinc level increase, and 5-alpha-reductase activity
inhibition. Significant symptomatic improvement versus
placebo has been reported.
Treatment of concomitant overactive bladder in men
with benign prostatic hyperplasia
1. Historically, anticholinergics were discouraged in men
with BPH because of concerns of inducing urinary
retention. Trials have demonstrated a slight increase in
PVR; however, AUR rates were low. Importantly, these
trials consisted of patients with low baseline PVR.
2. Patients with symptomatic OAB not relieved with alpha1-blockers may benefit from anticholinergic therapy. It is
prudent to record the baseline PVR prior to initiation of
anticholinergic therapy to assess for urinary retention.14
Treatment of concomitant erectile dysfunction in men with
lower urinary tract symptoms/ benign prostatic hyperplasia
1. It is recommended to first establish the alpha-1 blocker
dose before treating the erectile dysfunction. The
medication used to treat erectile dysfunction should be
titrated to the lowest effective dose. Furthermore,
sildenafil doses of greater than 25 mg should not be
taken within 4 hours of any alpha-blocker.15,16,17
2. In addition, data suggest that sildenafil may improve
mild-to-moderate LUTS. Nitric oxide may mediate
relaxation of the prostatic urethra and/or bladder neck.
The utility of phosphodiesterase inhibitors in the
treatment of LUTS has yet to be defined.18
Surgical Care
1. Transurethral resection of the prostate
I.
TURP is considered the criterion standard for relieving
BOO secondary to BPH. The indications for surgical
intervention include AUR, failed voiding trials, recurrent
gross hematuria, urinary tract infection, and renal
insufficiency secondary to obstruction. Additional
indications to proceed with a surgical intervention
include failure of medical therapy, a desire to terminate
medical therapy, and/or financial constraints associated
with medical therapy. However, TURP carries a
significant risk of morbidity (18%) and mortality risk
(0.23%).
II.
TURP is performed with regional or general anesthesia
and involves the placement of a working sheath in the
urethra through which a hand-held device with an
attached wire loop is placed. High-energy electrical
cutting current is run through the loop so that the loop
can be used to shave away prostatic tissue. The entire
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device is usually attached to a video camera to provide
vision for the surgeon.
Although TURP is often successful, it has significant
drawbacks.
When prostatic tissue is cut away, significant bleeding
may occur, possibly resulting in termination of the
procedure, blood transfusion, and a prolonged hospital
stay.
Irrigating fluid may also be absorbed in significant
quantities through veins that are cut open, with possible
serious sequelae termed transurethral resection
syndrome (TUR syndrome). A urinary catheter must be
left in place until the bleeding has mostly cleared.
The large working sheath combined with the use of
electrical energy may also result in stricturing of the
urethra.
The cutting of the prostate may also result in a partial
resection of the urinary sphincteric mechanism, causing
the muscle along the bladder outlet to become weak or
incompetent. As a result, when the individual ejaculates,
this sphincteric mechanism cannot keep the bladder
adequately closed. The ejaculate consequently goes
backwards into the bladder (ie, retrograde ejaculation),
rather than from the end of the penis. Additionally, if the
urinary sphincter is damaged, urinary incontinence may
result.
TURP usually requires hospitalization.
The nerves associated with erection run along the outer
rim of the prostate, and the high-energy current and/or
heat generated by such may damage these nerves,
resulting in impotence.
Open prostatectomy
This procedure is now reserved for patients with very
large prostates (>75 g), patients with concomitant
bladder stones or bladder diverticula, and patients who
cannot be positioned for transurethral surgery.
Open prostatectomy requires hospitalization and
involves the use of general/regional anesthesia and a
lower abdominal incision. The inner core of the prostate
(adenoma), which represents the transition zone, is
shelled out, thus leaving the peripheral zone behind. It
may involve significant blood loss, resulting in
transfusion. Open prostatectomy usually has an excellent
outcome in terms of improvement of urinary flow and
urinary symptoms.
More recently, laparoscopic simple prostatectomy has
been performed at a number of institutions and appears
to be feasible. However, prostatectomy performed in
this fashion still appears to be associated with risk for
significant blood loss. Experience to date with this
procedure is limited.19
Minimally invasive treatment for benign prostatic
hyperplasia
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There is considerable interest in the development of
other therapies to decrease the amount of obstructing
prostate tissue while avoiding the above-mentioned
adverse effects associated with TURP. These therapies
are collectively called minimally invasive therapies.
Most minimally invasive therapies rely on heat to
destroy prostatic tissue; however, this heat is delivered
in a limited and controlled fashion with the hope that
the complications associated with TURP may be avoided.
They also allow for the use of milder forms of anesthesia,
which translates into less anesthetic risk for the patient.
Heat may be delivered in the form of laser energy,
microwaves, radiofrequency energy, high-intensity
ultrasound waves, and high-voltage electrical energy.
Delivery devices are usually similarly passed through a
working sheath placed in the urethra, although they are
usually of a smaller size than that needed for TURP.
Devices may also simply be attached or incorporated
into a urinary catheter or passed through the rectum,
from which the prostate may also be accessed.
Keep in mind that many of these minimally invasive
therapies are undergoing constant improvements and
refinements, resulting in increased efficacy and safety.
Ask urologists about the specifics of the minimally
invasive therapies that they use and what results they
have experienced.
Transurethral incision of the prostate (TUIP) has been in
use for many years and, for a long time, was the only
alternative to TURP. It may be performed with local
anesthesia and sedation.
TUIP is suitable for patients with small prostates and for
patients unlikely to tolerate TURP well because of other
medical conditions.
TUIP is associated with less bleeding and fluid absorption
than TURP. It is also associated with a lower incidence of
retrograde ejaculation and impotence than TURP.
Lasers deliver heat to the prostate in various ways.
Lasers heat prostate tissue, causing tissue death by
coagulative necrosis, with subsequent tissue contraction;
however, laser coagulation of the prostate in this specific
sense has met with limited results. Lasers have also been
used to directly evaporate, or to melt away, prostate
tissue, which is more effective than laser coagulation.
Photoselective vaporization of the prostate produces a
beam that does not directly come into contact with the
prostate; rather, it delivers heat energy into the
prostate, resulting in destruction/ablation of the
prostate tissue. Potassium-titanyl-phosphate (KTP) and
holmium lasers are used to cut and/or enucleate the
prostate, similar to the TURP technique. These are
widely used laser techniques.
Transurethral vaporization/ablation with the KTP or
holmium laser can be performed with general or spinal
anesthesia and can be performed in an outpatient
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setting. Catheter time usually lasts less than 24 hours.
Recent studies suggest that photoselective vaporization
of the prostate can significantly improve and sustain
symptomatic and urodynamic outcomes. This procedure
has been quite useful in patients who require
anticoagulation (blood thinning) for various medical
conditions, since anticoagulation does not need to be
interrupted for this procedure, thus further decreasing
patient risk.20,21
Lasers may be used in a knifelike fashion to directly cut
away prostate tissue (ie, holmium laser enucleation of
the prostate), similar to a TURP procedure. The holmium
laser allows for simultaneous cutting and coagulation,
making it quite useful for prostate resection. Recent
studies demonstrate that laser enucleation of the
prostate is a safe and effective procedure for treatment
of symptomatic BPH, regardless of prostate size, with
low morbidity and short hospital stay. TUR syndrome is
not seen with this technique, because iso-osmotic saline
is used for irrigation. Additionally, removed prostatic
tissue is available for histologic evaluation, whereas
vaporization/ablation technique does not provide tissue
for evaluation. Holmium laser enucleation of the
prostate may prove to be the new criterion standard for
surgical management of BPH.21,22
Laser treatment usually results in decreased bleeding,
fluid absorption, length of hospital stay, and decreased
incidence of impotence and retrograde ejaculation when
compared with standard TURP. Additionally, because
treating tissue with a laser involves a time interval during
which dead cells slough and healing follows, patients
may experience urinary urgency or irritation, resulting in
frequent or uncomfortable urination for a few weeks.
The results of laser therapy vary from one another
because not all wavelengths yield the same tissue
effects. For example, interstitial lasers (eg, indigo lasers)
are designed to heat tissue within the confines of the
prostate gland and spread radiant energy at relatively
low energy levels. They do not directly involve the
urethral portion; thus, irritative symptoms following the
procedure are potentially reduced. Contact lasers such
as KTP or holmium, on the other hand, are designed to
cut and vaporize at extremely high temperatures They
usually bring about more relief of urinary symptoms than
treatment with medicines, but not always as much as is
provided with TURP. However, KTP laser vaporization
and holmium laser enucleation yield results that rival
those of TURP.
The use of microwave energy, termed transurethral
microwave therapy (TUMT), delivers heat to the prostate
via a urethral catheter or a transrectal route.
The surface closest to the probe (the rectal or urethral
surface) is cooled to prevent injury. The heat causes cell
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death, with subsequent tissue contraction, thereby
decreasing prostatic volume.
TUMT can be performed in the outpatient setting with
local anesthesia.
Microwave treatment appears to be associated with
significant prostatic swelling; a considerable number of
patients require replacement of a urinary catheter until
the swelling subsides. In terms of efficacy, TUMT places
between medical therapy and TURP.
Transurethral needle ablation of the prostate (TUNA)
involves using high-frequency radio waves to produce
heat, resulting in a similar process of thermal injury to
the prostate as previously described. A specially
designed transurethral device with needles is used to
deliver the energy.
TUNA can be performed under local anesthesia, allowing
the patient to go home the same day.
Similar to microwave treatment, radiofrequency
treatment is quite popular, and a number of urologists
have experience with its use.
Radiofrequency treatment appears to reliably result in
significant relief of symptoms and better urine flow,
although not quite to the extent achieved with TURP.
High-intensity ultrasound energy therapy delivers heat to
prostate tissue, with the subsequent process of thermal
injury.
High-intensity ultrasound waves may be delivered
rectally or extracorporeally and can be used with the
patient on intravenous sedation.
Urinary retention appears to be common with its use.
High-intensity ultrasound energy also produces
moderate results in terms of improvement of the urinary
flow rate and urinary symptoms, although its use is now
relatively limited compared to the more popular TUNA
and TUMT.
High-intensity ultrasound is considered investigational at
this time and should not be offered outside of clinical
trials.
Mechanical approaches are used less commonly and are
usually reserved for patients who cannot have a formal
surgical procedure. Mechanical approaches do not
involve the use of energy to treat the prostate.
Prostatic stents are flexible devices that can expand
when put in place to improve the flow of urine past the
prostate. Their use has been associated with
encrustation, pain, incontinence, and overgrowth of
tissue through the stent, possibly making their removal
quite difficult. To date, their full role and long-term
effects are not fully known.
Balloon dilation involves transurethral placement of a
balloon, which is then inflated with the intent of
expanding the prostatic urethra by "cracking" the
prostatic capsule. Balloon dilation has largely been
abandoned. Efficacy has not been demonstrated with
this procedure.
Diet
Data from the Prostate Cancer Prevention Trial was
evaluated for dietary risk factors for BPH. The data revealed
that a diet low in fat and red meat and high in protein and
vegetables may reduce the risk of symptomatic BPH.
Additionally, regular alcohol consumption was associated
with a reduced risk of symptomatic BPH, but this is to be
interpreted cautiously given the untoward effects of
excessive alcohol consumption.23
Medication
The goals of pharmacotherapy are to reduce morbidity and
to prevent complications.
Alpha-adrenergic blockers
These agents block effects of postganglionic synapses at the
smooth muscle and exocrine glands.
Phenoxybenzamine (Dibenzyline)
Nonselective alpha-adrenergic receptor blocker that
antagonizes both alpha-1 and alpha-2 receptors. The
nonselectivity leads to higher incidence of adverse effects,
causing a decrease in use in clinical settings. Induces
subjective improvement in urinary flow rates when
compared to placebo. May improve daytime and nighttime
urinary frequency. Improves symptoms in 75% of patients.
Adult: 10 mg PO bid
Prazosin (Minipress)
Treats prostatic hypertrophy. Improves urine flow rates by
relaxing smooth muscle. Relaxation is produced by blocking
alpha-1 adrenoreceptors in the bladder neck and prostate.
Advantage over nonselective alpha-adrenergic blockers
includes lower incidence of adverse effects. Because of
availability of longer-acting, once-daily selective agents,
clinical utility for BPH has been reduced. Improves urinary
flow rate and frequency of micturition. Subjective
improvement observed in 82% of patients treated. When
increasing dosages, administer first dose of each increment
at bedtime to reduce syncopal episodes. Although doses >20
mg/d do not usually increase efficacy, some patients may
benefit from up to 40 mg/d.
Adult: 2 mg PO bid
Alfuzosin (UroXatral)
Alpha-1 blocker of adrenoreceptors in prostate. Blockade of
adrenoreceptors may cause smooth muscles in bladder neck
and prostate to relax, resulting in improvement in urine flow
rate and reduction in symptoms of BPH.
Adult: 2.5 mg PO tid or ER (extended release) 10 mg PO qd
Indoramin
Not available in the United States. Helps treat prostatic
hypertrophy. Improves urine flow rates by relaxing smooth
muscle. Relaxation produced by blocking alpha-1
adrenoreceptors in the bladder neck and prostate.
Advantage over nonselective alpha-adrenergic blockers
includes lower incidence of adverse effects. Because of
availability of longer-acting, once-daily selective agents,
clinical utility for BPH has been reduced. Improves urinary
flow rate and frequency of micturition.
Adult: 20 mg PO bid
Terazosin (Hytrin)
Quinazoline compound that counteracts alpha1-induced
adrenergic contractions of bladder neck, facilitating urinary
flow in presence of BPH. Effect on voiding symptoms and
flow rates is dose-dependent. Improves irritative and
obstructive voiding symptoms. Improvement in flow rate is
objective. Hytrin starter pack available for easy dosing
progression to 5 mg.
Adult: 1-5 mg PO qhs; may titrate to maximal dose of 10 mg
based on tolerability and symptomatic improvement
Doxazosin (Cardura)
Inhibits postsynaptic alpha-adrenergic receptors, resulting in
vasodilation of veins and arterioles and decrease in total
peripheral resistance and blood pressure. Long-acting
alpha1-blocking agent with similar profile to terazosin.
Improves irritative and obstructive voiding symptoms.
Adult: 1 mg PO qhs; may titrate to maximal dose of 8 mg
based on tolerability and symptomatic improvement
Tamsulosin (Flomax)
Alpha-adrenergic blocker specifically targeted to alpha-1
receptors. Has advantage of relatively less orthostatic
hypotension and requires no gradual up-titration from initial
introductory dosage. Inhibits postsynaptic alpha-adrenergic
receptors, resulting in vasodilation of veins and arterioles and
decrease in total peripheral resistance and blood pressure.
Improves irritative and obstructive voiding symptoms.
Adult: 0.4 mg PO qd initially; may increase to 0.8 mg PO qd;
no dose titration needed
Silodosin (Rapaflo)
Selectively antagonizes postsynaptic alpha1-adrenergic
receptors in prostate, bladder base, prostatic capsule, and
prostatic urethra. This action induces smooth muscle
relaxation and improves urine flow. Indicated for signs and
symptoms of BPH.
Adult: 8 mg PO qd with food CrCl 30-50 mL/min: 4 mg PO qd
5Alpha-reductase inhibitors
Inhibit the conversion of testosterone to DHT, causing DHT
levels to drop, which, in turn, may decrease prostate size.
Finasteride (Proscar)
Inhibits conversion of testosterone to DHT, causing serum
DHT levels to decrease. Beneficial in men with prostates >40
g. Improves symptoms and reduces prostatic size by 20-30%.
Reduction in prostate size sustained 5 y following treatment.
Improves urinary flow rate by 2 mL/s.
Adult: 5 mg PO qd; minimum of 6 mo treatment necessary to
determine response
Dutasteride (Avodart)
Used to treat symptomatic BPH in men with an enlarged
prostate. Improves symptoms, reduces urinary retention, and
may decrease need for BPH-related surgery. Inhibits 5alphareductase isoenzymes types I and II. Suppresses >95%
conversion of testosterone to DHT, causing serum DHT levels
to decrease.
Adult: 0.5 mg PO qd
Pediatric: Contraindicated
Combination Products
Various combination products are emerging on the market to
improve patient compliance.
Dutasteride and tamsulosin (Jalyn)
Combination of dutasteride, a 5-alpha-reductase inhibitor,
and tamsulosin, an alpha-adrenergic antagonist. Indicated for
benign prostatic hypertrophy in men with an enlarged
prostate. Each cap contains dutasteride 0.5 mg and
tamsulosin 0.4 mg.
Adult: Take 1 cap 30 min after same meal once daily
Swallow cap whole; do not chew, crush, or split
Pediatric: Contraindicated
Follow-up
Further Outpatient Care
Patients with benign prostatic hyperplasia (BPH) who have
symptoms significant enough to be placed on medication
should be evaluated during biannual (at least) office visits to
discuss the efficacy of the medication and potential dose
adjustment.
Patients should undergo DRE and PSA screening at least
annually.
Complications
Complications related to bladder outlet obstruction (BOO)
o Urinary retention
o Renal insufficiency
o Recurrent urinary tract infections
o Gross hematuria
o Bladder calculi
o Renal failure or uremia (rare in current practice)
Miscellaneous
Medicolegal Pitfalls
1. Failure to pay special attention to the onset and duration
of symptoms, general health issues (including sexual
history), fitness for any possible surgical intervention,
severity of symptoms and how they are affecting QOL,
medications, and previously attempted treatments could
lead to medicolegal liability.
2. Symptoms often attributed to benign prostatic
hyperplasia (BPH) can be caused by neurogenic
bladder, carcinoma in situ of the bladder, urethral
stricture due to trauma or a sexually transmitted disease,
cystitis, and prostatitis. Failure to exclude these entities
based on findings from a thorough history and
appropriately directed diagnostic studies could lead to
medicolegal liability.