NATIONAL MEDICAL STUDENT CURRICULUM

This document was amended in February 2021 to reflect

literature that was released since the last update in April 2020.
This document will continue to be periodically updated to reflect
the growing body of literature related to this topic.

BENIGN PROSTATIC HYPERPLASIA

KEYWORDS: Prostatic hypertrophy, prostatic hyperplasia, PSA, voiding dysfunction, lower urinary
tract symptoms (LUTS).
At the end this unit, the medical student will be able to:

1. Identify and name the major anatomic and histologic features of the prostate gland
2. Identify the predominant location in the prostate where BPH develops and describe how
this fact relates to the symptoms and signs of BPH
3. Define BPH
4. Describe the distinctive epidemiological features and natural history of BPH
5. List the symptoms and signs of BPH
6. List the important components of the history when interviewing a patient with BPH
7. List the important components of the physical exam of a patient with BPH
8. Summarize the laboratory, radiologic, or urodynamic tests, if any, that should be ordered in
a patient with BPH
9. List the indications for treatment of BPH
10. List the medical and surgical treatment options for BPH.
11. Describe when a patient with BPH should be referred to a urologist

PROSTATE ANATOMY

There are 4 basic anatomic zones of the prostate, as illustrated in Figure 1: the anterior zone,
the peripheral zone, the central zone, and the transition zone. The anterior zone is entirely
fibromuscular and non-glandular, and it appears to have little significance in prostatic function
or pathology. This area comprises approximately 20% of the bulk of prostatic tissue. The
peripheral zone is composed entirely of acinar tissue. It comprises the posterior surface of the
prostate, including the apical, lateral, posterolateral and anterolateral portions of the prostate.
The peripheral zone and anterior zone, together, represent approximately 70% of glandular
volume in the normal adult prostate. The vast majority of prostatic carcinomas arise in the
peripheral zone of the prostate. The central gland is composed of the proximal urethra, the
prostate tissue around the posterior urethra and the smooth muscle of the internal urethral
sphincter. It forms the central portion of the prostate and extends from the base of the prostate to
the verumontanum. The transition zone surrounds the urethra, and although this region accounts
for only 10% of prostate glandular tissue in young men, it exhibits significant growth with age.
Indeed, it is in the transition zone is where benign prostatic hyperplasia (BPH) develops.
 Figure 1. The zones of the normal prostate.

BENIGN PROSTATIC HYPERPLASIA-DEFINITION

Benign prostatic hyperplasia (BPH) refers to the proliferation of epithelial and smooth
muscle cells within the transition zone of the prostate (Figure 2). Other terms for BPH
include benign prostatic hypertrophy and benign prostatic enlargement (BPE). The term has
been used to describe a constellation of voiding symptoms that occurs in men with aging.
These symptoms are generally referred to as obstructive in nature, as the hyperplastic tissue
leads to a narrowing of the prostatic urethra. Such symptoms include decreased force of
stream, hesitancy, straining, incomplete bladder emptying, and nocturia. Irritative symptoms
are also associated with BPH and include urinary frequency, urgency, and occasionally
dysuria.

Figure 2. Diagram of a normal and enlarged prostate.

BPH has been used synonymously with “prostatism” and “bladder outlet obstruction”,
implying that obstruction to urinary outflow, secondary to prostatic enlargement, is the cause
of such symptoms. More recently, it has been recognized that prostatic enlargement is not
necessary for such symptoms. Furthermore, women may experience similar symptoms with
age. Thus, “lower urinary tract symptoms” (LUTS) is currently the preferred term to describe
this complex of obstructive and irritative urinary symptoms that occur in both sexes with age.

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 Voiding dysfunction in the aging male may be due to a variety of factors including changes in the
bladder, prostate and/or urethra. Intrinsic changes in the bladder, such as bladder instability,
decreased bladder compliance and decreased bladder capacity may all lead to LUTS. However, in
many men these symptoms are due to BPH. With age, the prostate exhibits glandular enlargement,
increased smooth muscle tone and decreased compliance secondary to altered collagen deposition;
these changes can lead to altered urinary symptoms due to outlet obstruction. Urethral stricture and
bladder neck contracture are other forms of obstruction or blockage that can present with similar
symptoms.

BPH is one of the most frequent diagnoses leading to urology referral. It begins to develop before
age 30 with almost 10% of men having histologic evidence of BPH by 40 years of age, and 50% of
men showing evidence by age 60. Overall, nearly 80% of men will develop BPH, and as many as
30% will receive treatment for it. In studies that examine the natural history of BPH, the incidence
of acute urinary retention or the development of a significant post-void residual urinary volume is
2% per year. Although BPH is seldom life-threatening, it significantly impacts patient quality of life.
Thus, the burden of BPH on the healthcare system is substantial.

BENIGN PROSTATIC HYPERPLASIA-DIAGNOSIS

In the initial evaluation of LUTS possible due to BPH, clinicians should obtain a medical
history, conduct a physical exam, and collect a urinalysis. After excluding other causes of
LUTS, both objective and subjective parameters are used to decide whether or not treatment is
indicated. Objective parameters include determination of prostate size, measurement of urinary
flow rate and determination of the post-void residual urine volume. Although several subjective
instruments are available to quantify the severity of LUTS, the American Urological Association
Symptom Index (AUA-SI) is widely used. When a quality-of-life score is added to the AUA-SI,
it is the International Prostatic Symptom Score (IPSS) (Figure 3). This questionnaire consists of
7 items that determines the severity of irritative and obstructive voiding symptoms.

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 Figure 3. Validated objective survey instrument for voiding symptoms.

Symptom severity related to urinary frequency, nocturia, weak urinary stream, hesitancy,
intermittency, incomplete bladder emptying and urinary urgency is assessed, as well as its effect on
quality of life. On a scale of 0-35, mild symptoms exist with scores of 0-7, moderate symptoms
with scores of 7-15 and severe symptoms with a score of >15. This index demonstrates predictive
validity, reliability and internal consistency. There is some correlation between the objective and
subjective measures in that the lower the peak urinary flow rate, the more severe the urinary
symptoms and the larger the prostate. Using the AUA-SI and the information from the clinical
evaluation, treatment options can be reviewed, as outlined in Figure 4.

Importantly, there are several signs or symptoms that may coexist with voiding symptoms that can
alter the treatment algorithm. If the patient has urinary retention, an acute condition in which urine
is unable to be voluntarily voided, then immediate treatment is indicated, and may include surgical
intervention. A trial of Foley catheter or clean intermittent catheterization (CIC) and alpha blocker
medication may avoid surgical treatment in the future in about 80% of cases in which urinary
retention coexists with LUTS. Recurrent urinary tract infections, persistent or recurrent gross
hematuria, and bladder stones are also coexisting conditions that may necessitate surgical rather
than medical treatment.

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 Figure 4. Diagnostic and treatment algorithm of BPH.

BENIGN PROSTATIC HYPERTROPHY-TREATMENT

Watchful waiting

Before initiating medical or surgical treatments, conservative options can help curtail mild LUTS.
Avoiding decongestants or antihistamines, decreasing fluid intake at bedtime and decreasing
caffeine and alcohol intake can all reduce and often delay the need for other treatments.

Drug Therapy

Medical therapy for BPH attempts to shrink or stop the growth of the prostate or open the urethral
channel within the prostate, without using surgery. The FDA has currently approved multiple
drugs to relieve the symptoms associated with an enlarged prostate.

Medications in the class known as 5-alpha-reductase inhibitors (5-ARIs) result in decreased

production of the hormone dihydrotestoterone (DHT), which is responsible for growth of the
acinar glands of the prostate. These include Finasteride, FDA-approved in 1992, and dutasteride,
FDA-approved in 2001. The 5-ARIs may either prevent progression of growth of the prostate or
actually shrink the prostate in some men.

Another class of drugs used for treating BPH is the alpha-1-adrenergic receptor blockers (alpha
blockers), which act by relaxing the smooth muscle of the prostate and bladder neck to improve
urine flow and reduce bladder outlet obstruction.. This class includes terazosin, doxazosin,
tamsulosin, and alfuzosin. . Terazosin and doxazosin were developed as blood pressure pills, but
tamsulosin and alfuzosin were developed specifically to treat BPH. There is excellent clinical

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trial data that shows that combination therapy with a 5-ARI and an alpha blocker (finasteride and
doxazosin) together is more effective than using either drug alone to relieve symptoms and
prevent BPH progression. The dual-drug regimen reduced the risk of BPH progression by 67
percent, compared with 39 percent for doxazosin alone and 34 percent for finasteride alone.

Conventional Surgical Therapy

When selecting the best surgical treatment, the optimal option is often based on the size of the
prostate and surgeon preference (Figure 5).

Figure 5. Surgical Management of Lower Urinary

Tract Symptoms Attributed to Benign Prostatic
Hyperplasia Algorithm.

Transurethral resection of the prostate (TURP). Surgical therapy with transurethral resection of
the prostate (TURP) has traditionally been the “gold standard” treatment for men with BPH. In
1986, it was estimated that TURP accounted for 24% of the professional workload for practicing
urologists in the U.S. In this type of surgery, no external incision is needed. After giving
anesthesia, the surgeon reaches the prostate by inserting an instrument called a resectoscope
through the urethra (Figure 6). The resectoscope is about 12 inches long and 1/2 inch in
diameter, contains a light, valves for controlling irrigating fluid, and an electrical loop that cuts
tissue and seals blood vessels. During the 60-90-minute operation, the surgeon uses the scope's
wire loop to remove the obstructing tissue one piece at a time. The pieces of tissue are carried by
the fluid into the bladder and then flushed out at the end of the operation. A TURP is used for
approximately 90% of all prostate surgeries for BPH. In most patients, before TURP is
performed, consideration has already been given to medical therapy. In general, TURP is
reserved for very symptomatic men or those who develop complications including urinary tract
infection, bladder stones, or gross hematuria as mentioned above.

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A variation of the TURP procedure is called transurethral incision of the prostate (TUIP). Instead
of removing tissue, as with TURP, this procedure widens the urethra by making a few small cuts
in the bladder neck, where the urethra joins the bladder, and in the prostate gland itself. Although
some people believe that TUIP gives the same relief as TURP with less risk of side effects such
as retrograde ejaculation, its advantages and long-term side effects have not been clearly
established.

Figure 6. Diagram of Transurethral Resection (TURP).

Surgical “open” prostatectomy. In the few cases when a transurethral procedure is not able to be
done, because the prostate is too large, the bladder has been damaged or contains bladder stones,
or important identifying landmarks not visible for TURP, open prostatic surgery in indicated.
With all open surgical procedures, anesthesia is given and an incision is made. Once the surgeon
reaches the prostate capsule, he or she scoops out the enlarged tissue from inside the gland.
Importantly, as with other types of surgery and procedures for BPH, the part of the prostate at
risk for prostate cancer development is not removed and therefore men who have procedures for
BPH are still at risk for developing prostate cancer.

Transurethral laser surgery. Surgical procedures that employ side-firing laser fibers and Nd: YAG
lasers to vaporize obstructing prostate tissue are also used to treat BPH. A laser fiber is passed
into the urethra near the prostate using a cystoscope and then several bursts of energy lasting 30
to 60 seconds are delivered through the laser fiber. The laser energy destroys prostate tissue and
causes shrinkage. As with TURP, laser surgery requires anesthesia and a hospital stay. One
advantage of laser surgery over TURP is that laser surgery causes less blood loss and allows for a
quicker recovery. But laser surgery may not be effective on larger prostates and the long-term
effectiveness of laser surgery is unclear. There are two variations of laser surgery for BPH:
Photoselective Vaporization of the Prostate (PVP) uses a high-energy laser to destroy prostate
tissue and seal the treated area, and Interstitial Laser Coagulation involves placing the tip of the
fiberoptic probe directly into the prostate tissue to destroy it.

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Laser enucleation. Holmium laser enucleation of the prostate (HoLEP) or thulium laser
enucleation of the prostate (ThuLEP) is a minimally invasive technique that can be offered to
patients with larger prostate glands. The main benefits of this procedure is that it can be used for
virtually any size prostate including very large (>100 gm) glands.

Although these approaches are often successful, some adverse effects may occur. The cutting of
prostatic tissue may result in significant bleeding and the absorption of irrigation fluid into veins
that are cut open may result in a life-threatening syndrome of fluid overload and dilutional
hyponatremia known as “TUR syndrome”. In addition, electrical energy may damage important
surrounding structures. Damage to the internal urethral sphincter may cause retrograde
ejaculation and possible incontinence, whereas damage to the nerves responsible for erection
(which run along the outer rim of the prostate) may result in impotence.

Minimally Invasive Therapy

A number of minimally invasive procedures have been developed to relieve BPH symptoms,
while avoiding general anesthesia and the potential adverse effects listed above. In general,
these procedures are less invasive than conventional surgery for BPH.

Prostatic urethral lift. Prostatic urethra lift is a transurethral procedure that can be office-based
whereby implants are delivered to retract the obstructing prostatic lobes. Symptoms reduction
and flow rates for this procedure are less significant as compared to TURP, but this procedure
can be offered to patients who are concerned with preservation of ejaculatory and erectile
function.

Transurethral microwave procedures. This device uses microwaves to heat and destroy excess
prostate tissue. In the procedure called transurethral microwave thermotherapy (TUMT), the
device sends microwaves through a catheter to heat selected portions of the prostate to at least
111 degrees Fahrenheit. A cooling system protects the urinary tract during the procedure. The
procedure is performed on an outpatient basis in an hour without general anesthesia. TUMT has
not been reported to lead to erectile dysfunction or incontinence. Although microwave therapy
does not cure BPH, it reduces urinary frequency, urgency, straining, and intermittent flow. It does
not correct the problem of incomplete emptying of the bladder. The long-term effects of
microwave therapy are still not clear however.

Water vapor thermal therapy. This therapy uses heated water to destroy excess tissue in the
prostate. A catheter containing multiple shafts is positioned in the urethra so that a treatment
balloon rests in the middle of the prostate. A computer controls the temperature of the water,
which flows into the balloon and heats the surrounding prostate tissue. The system focuses the
heat in precise regions of the prostate, while surrounding tissues in the urethra and bladder are
protected. Destroyed tissue either escapes with urine through the urethra or is reabsorbed by
the body. This therapy may be offered to patients who are desirous of preserving erectile and
ejaculatory function.

Transurethral needle ablation (TUNA). The TUNA system delivers low-level

radiofrequency energy through twin needles to burn away selected regions of the enlarged
prostate. Shields protect the urethra from heat damage. AUA Guidelines no longer
recommend this therapy for the treatment of LUTS attributed to BPH.
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 High-intensity focused ultrasound (HIFU). The use of low frequency ultrasound waves to
destroy prostate tissue is the youngest of the minimally invasive therapies developed for BPH. It
appears as safe as other minimally invasive methods but long-term outcome data is not available
as of yet.

BENIGN PROSTATIC HYPERPLASIA AND PSA

Prostate Specific Antigen (PSA) is a serine protease produced by benign and malignant prostate
tissue. Functionally, PSA is the enzyme responsible for liquefaction of the seminal fluid after
ejaculation. Although produced in small amounts in other tissues, it should be considered to be
prostate specific. PSA circulates in the serum in both free (unbound) and complexed (bound)
forms. In addition to being elevated by BPH and prostate cancer, PSA may also be transiently
elevated in cases of prostatic inflammation (prostatitis) or infarction, and after prostatic
manipulation by biopsy. However, routine digital rectal examination (DRE) usually has little
effect on serum PSA levels. The half-life of serum PSA is 2.2 to 3.2 days. Therefore, one should
wait 4 to 8 weeks after prostate manipulation and inflammation (cystoscopy, prostate biopsy, and
prostatitis) before obtaining a PSA.

A flawless and standardized interpretation of elevated PSA values has yet to be

determined. Although it has been well demonstrated that patients with elevated serum PSA levels
are more likely to be harboring aggressive disease serum PSA screening interpreted outside the
context of important patient-specific variables carries with it a significant risk of what has been
called over diagnosis: the identification and treatment of patients who might otherwise have lived
out the rest of their lives without experiencing any of the terrible symptoms associated with
advanced prostate cancer. Since the treatment of prostate cancer is associated with a significant
level of patient morbidity (including bowel dysfunction, urinary dysfunction, and impotence), the
use of serum PSA as a screening tool has been a topic of significant controversy. In May of 2012,
the United States Preventative Services Task Force (USPSTF), released their recommendation
against routine PSA screening, stating they have found "fair evidence that [PSA screening] is
ineffective or that harms outweigh the benefits." Nevertheless, the AUA recognizes that the
interpretation of an asymptomatic patient’s PSA level is a nuanced exercise that must be tailored
to the patient in question.

Potential screening should be preceded by an informed discussion of the risks and benefits
of screening, early diagnosis and treatment. Given the added cost and anxiety associated
with PSA screening, in combination with a lack of randomized trials showing that
screening decreases morbidity and mortality, such screening is not recommended for
everyone. With such information, the patient can make an individual decision regarding
PSA screening.

SUMMARY

1. The prostate is composed of several regions and zones: two zones of interest are the peripheral
zone, where most cancers arise, and the transition zone, where BPH arises.
2. The diagnosis of voiding dysfunction due to BPH is made based on both subjective and
objective findings on clinical evaluation.
3. Medical treatment of BPH involves treatment that relaxes the muscular stromal tissue of the
bladder neck and prostatic urethra (alpha-blockers) and reduction in the acinar-glandular volume
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 of the prostate through reduced DHT production (5-alpha-reductase inhibitors).
4. Indications for surgical intervention with BPH includes urinary retention, gross hematuria,
bladder stones, and urinary tract infection.
5. Serum PSA, a serine protease that liquefies the ejaculate, increases over time with both BPH and
prostate cancer, which makes it a difficult diagnostic marker for cancer alone.

REFERENCES

AUA Clinical Guideline: Surgical Management of Benign Prostatic Hyperplasia/Lower

Urinary Tract Symptoms (2018, amended 2019, 2020).
https://www.auanet.org/guidelines/benign-prostatic-hyperplasia-(bph)-guideline

Harkaway RC, Issa MM. Medical and minimally invasive therapies for the treatment of
benign prostatic hyperplasia. Prostate Cancer Prostatic Dis. 2006;9(3):204-14. Epub
2006 J

2021 AUTHORS
Adam B. Weiner, MD
Chicago, IL
Disclosures: Nothing to disclose

Seth A. Cohen, MD
Glendora, CA
Disclosures: Nothing to disclose

2020 AUTHORS
Gina Badalato, MD
New York, NY
Disclosures: Nothing to disclose

2016 AUTHORS
Gilad Amiel, MD
Houston, TX
Disclosures: Nothing to disclose

Michael Hollis, MD
Brighton, MA
Disclosures: Nothing to disclose

Ranjith Ramasamy, MD
Miami, FL
Disclosures: Nothing to disclose
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© 2013, 2016, 2020, 2021 American Urological Association Education and Research, Inc.® All Rights Reserved

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