Prostate Hyperplasia, Benign

Author: Raymond J Leveillee, MD, FRCS(Glasg), Professor of Clinical Urology, Radiology

and Biomedical Engineering, Department of Urology, University of Miami Miller School of
Medicine; Chief, Division of Endourology/Laparoscopy and Minimally Invasive Surgery,
Department of Urology, Jackson Memorial Hospital
Coauthor(s): Vipul R Patel, MD, Consulting Surgeon, Global Robotics Institute, Florida
Hospital Celebration Health; Vincent G Bird, MD, Assistant Professor of Clinical Urology,
University of Miami, Miller School of Medicine; Consulting Staff, Department of Urology,
Division of Endourology/Laparoscopy and Minimally Invasive Surgery, University of Miami
Miller School of Medicine/Jackson Memorial Hospital; Charles R Moore, MD,, Endourology
Fellow, Department of Urology, University of Miami School of Medicine
Contributor Information and Disclosures

Updated: Jun 18, 2010

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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.

Benign prostatic hyperplasia (BPH) diagnosis and treatment algorithm.

[ CLOSE WINDOW ]
Benign prostatic hyperplasia (BPH) diagnosis and treatment algorithm.

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.

[ CLOSE WINDOW ]
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

United States

As many as 14 million men in the United States have symptoms of BPH.

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:

• Urinary frequency - The need to urinate frequently during the day or night (nocturia),
usually voiding only small amounts of urine with each episode
• Urinary urgency - The sudden urgent need to urinate quickly owing to the sensation of
imminent loss of urine without control
• Hesitancy
o Difficulty initiating the urinary stream
o Interrupted, weak stream
• Incomplete bladder emptying - The feeling of persistent residual urine, regardless of the
frequency of urination
• Straining - The need strain or push (Valsalva maneuver) to initiate and maintain urination
in order to more fully evacuate the bladder
• Decreased force of stream - The subjective loss of force of the urinary stream over time
• 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.

• 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.
• A more precise volumetric determination can be made using transrectal ultrasonography
(TRUS) of the prostate.
• Anal sphincter tone or lack of it may indicate an underlying neurological disorder.
• 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.
• 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.
• 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
Neurogenic Bladder
Prostatitis, Bacterial

Other Problems to Be Considered

The differential diagnoses of benign prostatic hyperplasia (BPH), in which bladder outlet
obstruction (BOO) must be differentiated from lower urinary tract symptoms (LUTS), include
the following:

• Cystitis
• Prostatitis
• Prostatodynia
• Prostatic abscess
• Overactive bladder (OAB)
• Carcinoma of the bladder
 • Foreign bodies in the bladder (stones or retained stents)
• Urethral stricture due to trauma or a sexually transmitted disease
• Prostate cancer
• Neurogenic bladder
• Pelvic floor dysfunction

Excluding these entities based on findings from a thorough history and appropriately directed
diagnostic studies is essential.

Workup
Laboratory Studies

• 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.
• 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.
• Prostate-specific antigen
o 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
 Starting at age 50 years in men who are expected to live at least 10 more
years
 Starting at age 45 years in men at high risk for prostate cancer (African-
Americans and men with a close relative with prostate cancer)
 Starting at age 40 years in men with multiple close relatives with prostate
cancer
o A physician should discuss the risks and benefits of PSA screening with the
patient.
o Notably, men with larger prostates may have slightly higher PSA levels.
• 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

• 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.
• 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.
 o In patients with elevated PSA levels, TRUS-guided biopsy may be indicated.
o 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.
• 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

• Medical history: A medical history should be taken to qualify and quantify voiding
dysfunction. Identification of other causes of voiding dysfunction and medical
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 lower-extremity 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
o 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.
o 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).
 o 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):
1. 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)
2. 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)
3. 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)
4. 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)
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)
6. 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)
7. 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)
o Bother score: The IPSS uses the same 7 questions as the AUA-SI, with the
addition of the following disease-specific 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

• Flow rate
o 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.
 o 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.
o 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.
• Postvoid residual urine
o Obtain this value after the patient voids in order to gauge the severity of bladder
decompensation.
o It can be obtained invasively with a catheter or noninvasively with a
transabdominal ultrasonic scanner.
o A high PVR (ie, 350 mL) may indicate bladder dysfunction and may predict a
negative response to treatment.
• Pressure flow studies
o 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.
o Urodynamic studies are the only way to help distinguish poor bladder contraction
ability (detrusor underactivity) from outlet obstruction.
o BOO is characterized by high intravesical voiding pressures (>60 cm water)
accompanied by low urine flow rates (Qmax <15 mL/s).
• 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.
• 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)

• 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.
• 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-alpha-reductase 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-1-adrenergic 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

• Alpha-adrenergic receptor blockers

o The alpha-blocking agents administered in BPH studies can be
subgrouped according to receptor subtype selectivity and the duration
of serum elimination half-lives.
o Nonselective alpha-blockers include phenoxybenzamine.
o Selective short-acting alpha-1 blockers include prazosin, alfuzosin, and
indoramin.
o Selective long-acting alpha-1 blockers include terazosin, doxazosin and
slow-release (SR) alfuzosin.
o Partially subtype (alpha-1a)–selective agents include tamsulosin and
silodosin.
• Nonselective alpha-blockers
o 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.
o Because of the availability of more alpha-1-receptor–specific agents,
phenoxybenzamine is currently not often used for the treatment of
BPH.
• Intraoperative floppy iris syndrome
o 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
o 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 5-year 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 alpha-blockers.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

o 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.
o 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.
o 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.
o Adverse effects are primarily sexual in nature (decreased libido,
erectile dysfunction, ejaculation disorder).
o 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.
o 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.
o In patients with LUTS and enlarged prostates, 5-alpha-reductase
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

• 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
• The Symptom Management After Reducing Therapy (SMART-1) trial
demonstrated that, after 6 months of combination therapy, discontinuation of
the alpha-1-blocker 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.

• The Proscar Long-Term Efficacy and Safety Study (PLESS) evaluated clinical
data of randomized controlled trials using alpha-adrenergic receptor blockers
and/or 5-alpha-reductase 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
• 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
• 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
• 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 BPH-related 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
• The Combination of Avodart and Tamsulosin (CombAT) is an ongoing 4-year,
multicenter, randomized, double-blind, 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
adverse-effect profile of combination therapy was similar to that of
monotherapy (with either drug), although drug-related adverse events were
more common with combination therapy.13

Phytotherapeutic agents and dietary supplements

• 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.
• 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.
• 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.
• 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.
• 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
• The origins of phytotherapeutic agents are as follows:
o Saw palmetto, ie, American dwarf palm (Serenoa repens, Sabal
serrulata) fruit
o South African star grass (Hypoxis rooperi) roots
o African plum tree (Pygeum africanum) bark
o Stinging nettle (Urtica dioica) roots
o Rye (Secale cereale) pollen
o Pumpkin (Cucurbita pepo) seeds
• The mechanisms of action of some selected phytotherapeutic agents are as
follows:
o 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, 5-alpha-
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.
o 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.
o 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

• 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.
• Patients with symptomatic OAB not relieved with alpha-1-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

• 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
• 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

• Transurethral resection of the prostate

o 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%).
o 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 device is usually attached to a
video camera to provide vision for the surgeon.
o 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
o 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.
o 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.
o 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
o 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.
o 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.
o 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.
o 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.
o 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.
o 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 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.
o 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 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.
o 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.
o 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.
o 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.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

10 mg PO bid

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Used concurrently, alpha-adrenergic agonists decrease effects; beta-blockers increase toxicity

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; patients in whom a fall in blood pressure would be undesirable

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus
Precautions

Caution in cerebral or coronary arteriosclerosis and renal impairment; can worsen symptoms of
respiratory tract infections; fatigue, dizziness, impaired ejaculation, nasal stuffiness, and
difficulty with visual accommodation may occur

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.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

2 mg PO bid

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Acute postural hypotensive reaction from beta-blockers may worsen; indomethacin may decrease
antihypertensive activity; verapamil may increase serum levels and may increase patients'
sensitivity to prazosin-induced postural hypotension; may decrease antihypertensive effects of
clonidine

• Dosing
• Interactions
• Contraindications
• Precautions
Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

Precautions

Caution in renal insufficiency; adverse effects include dizziness, asthenia, peripheral edema,
hypotension, reflex tachycardia, miosis, sedation, nasal stuffiness, and erectile dysfunction

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.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

2.5 mg PO tid or ER (extended release) 10 mg PO qd

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Effects may increase with coadministration of diuretics and antihypertensive medications

• Dosing
• Interactions
 • Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Dizziness, fatigue, and headache may occur; patients should avoid situations in which injury
could result if syncope occurs; exclude presence of carcinoma of prostate before beginning
therapy

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.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

20 mg PO bid

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
 • Precautions

Acute postural hypotensive reaction from beta-blockers may worsen; indomethacin may decrease
antihypertensive activity; verapamil may increase serum levels and may increase patients'
sensitivity to indoramin-induced postural hypotension; may decrease antihypertensive effects of
clonidine

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

Precautions

Caution in renal insufficiency; adverse effects include dizziness, asthenia, peripheral edema,
hypotension, reflex tachycardia, miosis, sedation, nasal stuffiness, and erectile dysfunction

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.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

1-5 mg PO qhs; may titrate to maximal dose of 10 mg based on tolerability and symptomatic
improvement
Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Effects decrease with coadministration of NSAIDs; effects increase with coadministration of

diuretics and antihypertensive medications

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal impairment; may cause marked hypotension following first dose and
coadministration with beta-blockers; adverse effects include dizziness, headache, asthenia,
peripheral edema, hypotension, reflex tachycardia, miosis, sedation, nasal stuffiness, and erectile
dysfunction; incidence of erectile dysfunction is lower compared to other antihypertensive agents

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.

• Dosing
• Interactions
• Contraindications
• Precautions
Adult

1 mg PO qhs; may titrate to maximal dose of 8 mg based on tolerability and symptomatic

improvement

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Effects decrease with coadministration of NSAIDs; effects increase with coadministration of

diuretics and antihypertensive medications

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal impairment; may cause marked hypotension following first dose and with
coadministration of beta-blockers; adverse effects include dizziness, headache, asthenia,
peripheral edema, hypotension, reflex tachycardia, miosis, sedation, nasal stuffiness, and erectile
dysfunction; incidence of erectile dysfunction is lower compared to other antihypertensive agents

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.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

0.4 mg PO qd initially; may increase to 0.8 mg PO qd; no dose titration needed

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Cimetidine may significantly increase plasma concentrations; may increase toxicity of warfarin

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Not for use as antihypertensive drug; may cause orthostasis; avoid situations that may result in
injuries if syncope occurs; exclude presence of carcinoma or cancer before initiating treatment;
adverse effects include increased rate of retrograde ejaculation and rhinitis
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.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

8 mg PO qd with food
CrCl 30-50 mL/min: 4 mg PO qd

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

Coadministration with strong CYP3A4 inhibitors (eg, itraconazole, clarithromycin, ritonavir) or

P-glycoprotein inhibitors (eg, cyclosporine) increases serum levels; concurrent use with other
alpha-blockers may increase effect; coadministration with antihypertensive agents may increase
incidence of dizziness and orthostatic hypotension

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; severe renal impairment (ie, CrCl <30 mL/min); severe hepatic
impairment (ie, Child-Pugh score >10); coadministration with strong CYP3A4 inhibitors

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions

Risk of postural hypotension and resulting symptoms (eg, dizziness, syncope); caution with
moderate renal impairment; may cause intraoperative floppy iris syndrome during cataract
surgery; may cause retrograde ejaculation

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.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

5 mg PO qd; minimum of 6 mo treatment necessary to determine response

Pediatric

Not established

• Dosing
• Interactions
• Contraindications
• Precautions

None reported

• Dosing
• Interactions
• Contraindications
• Precautions

Documented hypersensitivity; lactation, children

• Dosing
 • Interactions
• Contraindications
• Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in liver function abnormalities; monitor patients with severely diminished urinary flow
for obstructive uropathy (may not be candidates for this therapy); generally well tolerated with
few adverse effects; rare headache, loss of libido, and impotence may occur; lowers serum PSA
level by 50% after 6 mo of therapy

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 5alpha-reductase
isoenzymes types I and II. Suppresses >95% conversion of testosterone to DHT, causing serum
DHT levels to decrease.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

0.5 mg PO qd

Pediatric

Contraindicated

• Dosing
• Interactions
• Contraindications
• Precautions

CYP450 3A4 substrate; data limited, caution with potent CYP450 3A4 inhibitors (eg,
ketoconazole, ritonavir, erythromycin) or inducers (eg, rifampin, phenytoin)

• Dosing
• Interactions
 • Contraindications
• Precautions

Documented hypersensitivity; pregnancy or lactation; women or children

• Dosing
• Interactions
• Contraindications
• Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Unknown whether excreted in breast milk; caution with hepatic disease; establish new baseline
PSA level 3 mo after therapy initiation

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.

• Dosing
• Interactions
• Contraindications
• Precautions

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) secondary to BPH

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)

Patient Education

• For excellent patient education resources, visit eMedicine's Prostate Health Center and
Kidneys and Urinary System Center. Also, see eMedicine's patient education articles
Enlarged Prostate, Bladder Control Problems, and Inability to Urinate.

Miscellaneous
Medicolegal Pitfalls

• 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.
• 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.