CME

Benign prostatic hyperplasia: A clinical review

Danielle Skinder, PA-C; Ilana Zacharia, PA-C; Jillian Studin, PA-C; Jean Covino, DHSc, MPA, PA-C

ABSTRACT
Benign prostatic hyperplasia (BPH) is an increasingly com-
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mon diagnosis seen in men over age 50 years. Primary care

providers must be aware of patient presentation, diagnostic
tests, appropriate lifestyle modifications, treatment options,
and potential complications in order to properly manage
and educate patients with BPH. If left untreated, BPH can
significantly decrease a man’s quality of life; however, many
pharmacologic and surgical treatments are available to
control the symptoms.
Keywords: benign prostatic hyperplasia, alpha-adrenergic
antagonists, 5-alpha-reductase inhibitors, transurethral
resection of the prostate, TURP, urinary retention

Learning objectives
Discuss the cause, pathophysiology, and risk factors
for developing BPH.
Explain the clinical presentation of BPH and the
screening methods and diagnostic tests used in its
evaluation.
Discuss management options for patients with BPH.

B
enign prostatic hyperplasia (BPH) is one of the lead-
ing diagnoses affecting men of increasing age. By age

© ISM / PHOTOTAKE
50 years, about 50% of men are diagnosed with
BPH; by 80 years, 90% of men are diagnosed, and the
greatest prevalence occurs among men ages 70 to 79 years.1,2
In BPH, a proliferation of prostatic cells leads to an increase
in prostate size, urethral obstruction, and lower urinary
tract symptoms.2,3 Men with BPH can experience great diagnoses, and must be able to recognize and treat the
discomfort with urination and may develop complications disorder.
including recurrent urinary tract infections (UTIs) and
renal failure.2 Given the aging population, healthcare PATHOPHYSIOLOGY
providers can expect an overall increase in the rates of BPH BPH occurs in the prostate’s transitional zone, where stro-
mal and epithelial cells interact. The growth of these cells
At New York-Presbyterian/Columbia University Medical Center in is affected by sex hormones and cytokine responses.2
New York City, Danielle Skinder practices interventional cardiology, Dihydrotestosterone (DHT) Within the prostate, testos-
Ilana Zacharia practices oncology, and Jillian Studin practices in the
cardiothoracic ICU. Jean Covino is a clinical professor and director of
terone is converted to DHT, the androgen thought to be
didactic education at Pace University-Lenox Hill Hospital and practices the main mediator of prostatic hyperplasia. The clinical
at Medemerge Family Practice in Green Brook, N.J. The authors have importance of DHT became clear when patients treated
disclosed no potential conflicts of interest, financial or otherwise. with orchiectomy and 5-alpha-reductase inhibitors (which
DOI: 10.1097/01.JAA.0000488689.58176.0a stop conversion of testosterone to DHT) showed decreases
Copyright © 2016 American Academy of Physician Assistants in BPH symptomatology. The role of DHT was further

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Copyright © 2016 American Academy of Physician Assistants

CME

RISK FACTORS
Key points
Common risk factors for BPH include increasing age,
BPH is a common diagnosis in men age 50 years and older. functioning testicles, metabolic syndrome, family history
Men with BPH suffer from storage and voiding symptoms. of BPH, obesity, history of diabetes, and black race.2,5
IPSS is used to assess severity of BPH and guide treat- A patient’s diet, smoking, and exercise can influence BPH
ment decisions. progression.2,6,7 Patients who consume a diet rich in vege-
Alpha-adrenergic antagonists and 5-alpha-reductase tables appear to have less severe BPH symptoms than those
inhibitors are first-line medications for patients suffering who do not, although the consumption of fruit has not
from BPH. been shown to have a similar significant relationship to
TURP is the gold-standard surgical treatment. BPH severity. A diet high in starches and meat has been
linked to an increased risk of developing BPH. Studies have
also shown that excessive alcohol intake can increase BPH
demonstrated when men with BPH were found to have risk and progression.2 Although smoking may be a risk
significantly higher DHT levels within prostate tissue com- factor for BPH, conflicting evidence precludes the establish-
pared with men whose prostates were of normal size.4 ment of such a relationship.7
Age Because plasma androgen levels decrease with age, Studies demonstrate that a sedentary lifestyle can increase
more data are needed to specify why BPH occurs as men the risk of developing BPH or intensify the severity of lower
get older. Estrogens may play a role in BPH, targeting urinary tract symptoms in patients who already have the
stromal cells through an estrogen receptor mechanism. The condition.6 Incorporating exercise and physical activity into
ratio of estrogens to androgens increases with age, and this the daily routine are important, because activity can help
may explain why BPH occurs among men as they get older; prevent BPH as well as metabolic syndrome, which is
however, more evidence is needed to reach a definitive strongly linked to BPH. Being physically active is also more
conclusion.4 cost-effective than using pharmacologic or surgical inter-
Cytokines Cytokines contribute to prostate enlargement ventions for treating BPH.6
by inciting an inflammatory response and by inducing epi- Once a patient is diagnosed with BPH, clinicians and
thelial growth factors. As the prostate enlarges due to patients must be aware of factors associated with worsen-
hyperplasia, the portion of the urethra that passes through ing disease progression, including increased age, severe
the prostate is compressed, ultimately compromising urinary lower urinary tract symptoms, increased prostate size, and
outflow and leading to obstructive symptoms. The patient high prostate-specific antigen (PSA) levels.5
develops bladder hyperactivity, inflammation, and distension
as bladder smooth muscle cells enlarge to maintain urine CLINICAL MANIFESTATIONS
flow in response to resistance from prostatic obstruction. The symptoms of BPH can be grouped into two main cat-
These changes cause oxidative stress and free radical forma- egories: storage and voiding (Table 1). Men may have few
tion, as well as alterations to the alpha-adrenergic nerves of of these symptoms initially, but with increasing age and
the bladder, resulting in storage symptoms (Table 1). When disease progression, symptoms can become more prevalent.3
bladder smooth muscle cells can no longer grow and thereby Patients with BPH often report that the symptoms are dis-
counteract this resistance, smooth muscle contractions tressing and bothersome, and impair their quality of life.8
become impaired and voiding symptoms dominate.2
DIAGNOSIS
TABLE 1. Symptoms of BPH5 Practically speaking, BPH is a diagnosis of exclusion. When
Storage symptoms men over age 50 years complain of lower urinary tract
• Urinary frequency symptoms, the following tests can be used to rule out all
• Urinary urgency other possible causes before arriving at a BPH diagnosis.1
• Urinary incontinence History Healthcare providers must ask specific questions
• Nocturia about storage and voiding symptoms, and should be aware
• Dysuria of excessive water consumption or diuretic use that may
account for a patient’s symptoms.5 The American Urologi-
Voiding symptoms
cal Association Symptom Index (AUASI) and the Interna-
• Difficulty initiating urinary stream
tional Prostate Symptom Score (IPSS) are subjective
• Urinary hesitancy
questionnaires that can be used to help evaluate lower
• Straining to void
urinary tract symptoms and their effect on patients suffering
• Decreased urinary flow
from BPH.3,5 These questionnaires have patients rate symp-
• Intermittency
toms of incomplete bladder emptying, frequency, intermit-
• Dribbling
tency, urgency, weak stream, straining, and nocturia on
• Incomplete bladder emptying
scales from 0 (not at all) to 5 (almost always). The scores

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 Benign prostatic hyperplasia: A clinical review

TABLE 2. BPH medications and adverse reactions5,8

Drug Recommendation Adverse reactions
Alpha-adrenergic antagonists First-line Fatigue, headache, dizziness, hypotension,
(terazosin, alfuzosin, doxazosin, syncope, dry eyes, dry mouth, nasal congestion,
silodosin, tamsulosin) erectile dysfunction, ejaculatory dysfunction
5-alpha-reductase inhibitors First-line or adjunct Erectile dysfunction, ejaculatory dysfunction,
(finasteride, dutasteride) loss of libido, gynecomastia
PDE-5 inhibitor (tadalafil) First-line for concomitant BPH Headache, flushing, nasal congestion,
and erectile dysfunction; shown indigestion, back pain
efficacious as BPH monotherapy
Anticholinergics (darifenacin, Adjunct therapy Headache, dry eyes, dry mouth, dyspepsia,
solifenacin, trospium chloride, constipation
oxybutynin, tolterodine, fesoterodine)

are then tallied, and classified as mild (0-7), moderate (8-19), score of 8 or greater.11 Symptoms of BPH can be associated
or severe (20-35).9 These rankings help to guide treatment with urinary retention, and a large residual volume in
decisions and responses.3 The IPSS contains identical ques- combination with other tests may indicate BPH.5
tions to that of AUASI, but includes an additional quality Prostatic ultrasound Transabdominal or transrectal pros-
of life measure, asking patients to classify their feelings if tatic ultrasound also may be considered to accurately
they had to live with their urinary symptoms for the rest of evaluate the size, shape, anatomy, and potential pathology
their lives on a scale of 0 (delighted) to 6 (terrible).9,10 of the prostate in a minimally invasive, cost-effective, and
Digital rectal examination (DRE) Perform a DRE to assess reproducible way.2,12 A transabdominal ultrasound also can
the size, shape, and consistency of the prostate gland.3 An assess the bladder and postvoid residual urine, which may
enlarged prostate often presents on examination as soft, be contributing to a patient’s symptoms.2
smooth, boggy, mobile, and with an obscured sulcus. Note any Blood urea nitrogen (BUN) and creatinine Serum BUN
nodules or indurations, which may suggest prostate cancer. and creatinine levels may be used in diagnosing and mon-
Prostate-specific antigen (PSA) level Given the challenges itoring BPH, although the use of these levels in initial BPH
of evaluating true prostate size in primary care offices by assessment is controversial. The European Association of
DRE, obtaining a PSA level makes it easier to diagnose BPH. Urology (EAU) recommends obtaining baseline BUN and
PSA levels often correlate with prostate size; therefore, a PSA creatinine measurements and watching for potential renal
level of 1.5 ng/mL is often indicative of BPH.1 However, this failure complications associated with BPH.2 The American
value is highly variable and may fluctuate based on the patient’s Urological Association (AUA) does not suggest obtaining
age, race, medications, or comorbid urinary conditions. Due these baseline levels because preliminary renal insufficiency
to the nonspecific nature of PSA, a diagnosis of BPH cannot tends to be equal among men of similar ages regardless of
be made from PSA levels alone. Yet in the presence of other whether they have BPH.11 However, measuring the patient’s
positive diagnostic outcomes, an elevated PSA level can help BUN and creatinine levels may help evaluate progressive
a primary care provider arrive at a BPH diagnosis.1 obstruction and impaired renal function.
Urinalysis Ordering a urinalysis is recommended as a Refer the patient to a urologist if his symptoms are too
primary step in order to exclude UTI, prostatitis, cystoli- severe or complicated to evaluate and treat in a primary
thiasis, nephrolithiasis, renal cancer, and prostate cancer care setting.5 Increasing PSA levels, persistent hematuria,
as causes of lower urinary tract symptoms.5 urinary retention, recurrent urinary tract infections, pos-
Voiding diaries Documenting the time voided, volume sible prostate cancer, renal failure, or inadequate pharma-
voided, and associated activities (such as fluid intake) in a cologic treatment are indications for a urology consult.3
voiding diary may help in BPH diagnosis, especially in
patients with urinary frequency. The primary care provider TREATMENT
can differentiate if symptoms are BPH-related or due to Many pharmacologic (Table 3) and surgical interventions
polyuria, overactive bladder, or behavioral causes. Patients have been approved for treating BPH, with the goals of
should keep a voiding diary for at least 24 hours, although improving patient symptoms and quality of life while slow-
many primary care providers suggest keeping it for 3 to 7 ing disease progression and reducing complications.9 Treat-
days so that they can evaluate trends.2,11 Voiding diaries ment decisions are based on the severity of the condition.
also can be used to evaluate treatment efficacy. Watchful waiting For men with mild BPH symptoms (IPSS
Measuring postvoid residual volume A postvoid residual less than 8), watchful waiting is recommended. This includes
volume measurement is recommended for patients with yearly follow-up appointments with history and physical
moderate or severe symptoms, defined by an AUASI/IPSS examination to determine the progression of the disorder and

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CME

reevaluate treatment options.5 During this time period, vari- Tadalafil This drug, mainly used to treat erectile dysfunc-
ous behavioral modifications, such as avoiding antihistamines, tion, is the phosphodiesterase-5 inhibitor approved for BPH
reducing fluid intake in the evening, and decreasing alcohol treatment. Tadalafil causes smooth muscle relaxation of the
and caffeine consumption can provide symptom relief.11 detrusor muscle, prostate, and vascular cells of the urinary
Men suffering from moderate to severe symptoms (IPSS of tract, and decreases prostatic and bladder hyperplasia.5 After
8 and greater) may consider lifestyle changes, but will likely 4 weeks of use, tadalafil improves lower urinary tract symp-
require pharmacologic treatment or surgery if pharmacologic toms and quality of life, and is an option for men suffering
treatment fails.2,11 Patients on medication should be evaluated from concomitant BPH and erectile dysfunction.5,8
at least twice a year in the office to discuss the efficacy of the Anticholinergic agents This class of medication has been
medication and potential dose adjustment. They also should approved as add-on therapy when alpha-adrenergic antago-
undergo DRE and PSA screening at least annually. nists fail to control BPH symptoms. Anticholinergics block
Alpha-adrenergic receptor antagonists The mainstay of muscarinic receptors on the detrusor muscle and improve
BPH treatment, these medications inhibit sympathetic adren- storage symptoms after fewer than 12 weeks of therapy.5
ergic receptors, causing prostatic and bladder smooth muscle However, anticholinergics may exacerbate constipation,
cell relaxation.5 The resultant reduced urethral constriction cognitive impairment, and dementia in older adults, and
and improved urinary flow lessen obstructive BPH symptoms.3 should be avoided or closely monitored if used in these
Alpha-adrenergic receptor antagonists are further subclas- patients.13
sified according to their extent of selectivity for certain alpha-1 Saw palmetto This herb has been used to reduce lower
receptors. Doxazosin, terazosin, and alfuzosin are considered urinary tract symptoms; however, recent data propose that
nonselective, blocking all alpha-1 receptors equally; silodo- symptom improvement may be solely a placebo effect.14
sin and tamsulosin are selective for alpha-1A receptors that Surgery Surgical treatment for BPH is indicated when
are mainly located in the urogenital tract.5 Selective agents medical treatment fails to elicit a sufficient response, when
are associated with fewer systemic adverse reactions (such symptoms are severe, if there is concern for complications,
as hypotension, dizziness, and fatigue) than nonselective or if the patient has renal failure, refractory gross hematu-
agents.3,9 Clinicians should avoid prescribing nonselective ria, recurrent UTIs, or bladder stones.11 Recommended
alpha-blockers to older adults because these drugs can cause options include open surgery, transurethral resection of the
orthostatic hypotension and syncope.13 However, a patient prostate (TURP), and transurethral holmium laser enucle-
with BPH and hypertension may be a candidate for a non- ation of the prostate (HoLEP).2
selective agent because it would treat both conditions. Open surgery involves removing the prostatic adenoma
Both types of alpha-adrenergic receptor antagonists cause from the adjacent prostate tissue. With the enlarged pros-
clinically significant decreases in BPH symptoms after 1 tate no longer compressing the urethra, voiding symptoms
week of therapy, as reflected by AUASI score decreases; improve postoperatively. This procedure carries the risk of
however, 2 to 4 weeks of treatment is recommended to several complications including wound infection, hemor-
achieve the full effect of the medication. rhage, UTI, and sepsis.
Alpha-adrenergic receptor antagonists should not be TURP is the gold standard for BPH treatment and is the
prescribed to patients planning to have cataract surgery most commonly performed procedure for men suffering
due to the risk of floppy iris syndrome.5 Because this class from BPH.1,2 During TURP, an endoscope is inserted through
of medications does not reduce prostate size, patients are the urethra and the prostatic adenoma is removed via loop
still at risk for urinary retention, associated complications, electrode. TURP is effective for improving BPH symptoms
and disease progression.3 but may cause complications such as hemorrhage, hypo-
5-alpha-reductase inhibitors Another first-line drug option natremia, and retrograde ejaculation.
is a 5-alpha-reductase inhibitor, which blocks the conver- Bipolar TURP uses bipolar current and is a minimally
sion of testosterone to DHT, inhibiting prostatic hyperpla- invasive procedure associated with fewer complications
sia, reducing prostate size, and slowing disease progression. and a shorter hospital stay. Because 0.9% sodium chloride
Treatment with a 5-alpha-reductase inhibitor reduces urinary solution can be used for irrigation instead of nonconduct-
retention and the need for future BPH surgeries, and should be ing glycine as in monopolar TURP, the procedure can be
started in patients with PSA levels greater than 1.5 ng/mL, longer and complications are reduced.
as long as patients have no contraindications. Within 2 to HoLEP, another minimally invasive procedure, involves
6 months, men taking 5-alpha-reductase inhibitors for BPH removal of the prostate adenoma by laser irradiation, and
treatment should experience a 25% decrease in prostate can be considered in men who do not qualify for TURP
size and an improvement in BPH symptoms.5 These drugs due to prostate size. Although HoLEP is a longer surgical
can be used as monotherapy or adjunct therapy to alpha- procedure than TURP, it is less commonly associated with
adrenergic receptor antagonists. Combination therapy is complications and requires a shorter hospital stay.2,9
more successful than monotherapy but is associated with Temporary and permanent urethral stents are also used
more adverse reactions.5 to treat BPH in high-risk patients who are unable to undergo

22 www.JAAPA.com Volume 29 • Number 8 • August 2016

Copyright © 2016 American Academy of Physician Assistants

 Benign prostatic hyperplasia: A clinical review

invasive surgery. The minimally invasive procedure involves CONCLUSION

endoscopic stent placement into the prostatic urethra, As the US population ages, the prevalence of BPH is bound
improving BPH symptoms and minimizing complications to increase. Primary care providers must be well-versed on
because of the smaller incision and reduced trauma to the the definition, pathophysiology, associated risk factors,
surrounding tissue.2 evaluation, diagnosis, treatment, prevention, and complica-
Botulinum toxin is another potential treatment option that tions of BPH. Providers must ask patients about lower
has been explored but is not approved. Injecting the toxin urinary tract symptoms when taking a health history of
into the prostate inhibits acetylcholine release, resulting in older men, so they can manage patients optimally and refer
smooth muscle paralysis and tissue atrophy.2 Acute inflam- them to a specialist when indicated. JAAPA
mation is followed by scarring and shrinkage of the prostate.
Earn Category I CME Credit by reading both CME articles in this issue,
COMPLICATIONS reviewing the post-test, then taking the online test at http://cme.aapa.org.
Successful completion is defined as a cumulative score of at least 70%
Recurring urinary retention is a common complication of correct. This material has been reviewed and is approved for 1 hour of
BPH. Men at greater risk for urinary retention are those clinical Category I (Preapproved) CME credit by the AAPA. The term of
with PSA levels above 1.6 ng/mL or prostate volumes over approval is for 1 year from the publication date of August 2016.
31 mL. Other complications include bladder calculi as a
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