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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
Benign prostatic hyperplasia
Pathophysiology
Benign prostatic hyperplasia (BPH) is technically a
histologic diagnosis referring to smooth muscle and
epithelial cell proliferation in the prostatic transition
zone.
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BPH can lead to benign prostate enlargement
(BPE), further deteriorating into symptomatic
voiding difficulties, specifically lower urinary tract
symptoms (LUTS) or bladder outlet obstruction
(BOO). LUTS can be generally described as a group of
irritative or obstructive voiding symptoms including
urgency, frequency, nocturia, hesitancy, weak stream,
intermittency, or straining.
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BOO can be the result
of a constellation of findings commonly including
urinary retention, bladder calculi, increased postvoid
residuals, hematuria, recurrent urinary tract infections,
and less commonly renal failure or irreversible bladder
dysfunction. Currently, BPH, BPE, and LUTS can be
grouped together under the term symptomatic BPH
(sBPH) which is a result of increased resistance to
urinary flow from an obstructing prostate gland.
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It is
important to keep in mind, however, that symptoms
associated with sBPH can frequently overlap with
other urologic pathology or central nervous system
disorders including urethral stricture, bladder
dysfunction, Parkinson’s disease, or multiple sclerosis
to name a few. When these pathologies are suspected
further work up and different treatments may be
required in symptomatic patients.
sBPH in the aging male population can present a
significant burden to the healthcare community. The
incidence increases with age, as greater than 50% of
men over the age of 60 have sBPH, which ultimately
affects 90% of men in their 90s.
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Physicians must be
keenly aware that LUTS is not limited to the older
population as 18% of men in their 40s can begin
to experience bothersome symptoms and may be
candidates for treatment.
Pharmacologic management of sBPH is based on
the physiologic concept of decreasing both the prostatic
tone and glandular size of the prostate. This leads to
reduced resistance to urinary flow and improved
patient symptomatology. Prostate smoothmuscle tone
can be altered via alpha
1
adrenoreceptors (AR) which
are heavily concentrated in the prostatic urethra,
stroma, and bladder neck regions.
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Alpha
1
ARs are
under autonomic innervation via the neurotransmitter
norepinephrine (NE). Medications targeting these
receptors play a critical role in the management of
sBPH. Prostate glandular size is predominantly
controlled by the hormones testosterone and
dihydrotestosterone (DHT). Testosterone is converted
to DHT via two isoenzymes – 5-alpha reductase
types I and II. Type II 5-alpha reductase is more
concentrated in the prostatic stroma and epithelial
cells while type I is present in only approximately
10% of the prostate. The conversion of testosterone
to DHT mediated by type II 5-alpha reductase is the
primary moderator of prostate glandular growth and
is the target of pharmacologic therapies available for
treatment of sBPH.
When medical management in these patients fails
there are a multitude of surgical options available
for sBPH. Minimally invasive therapies including
radiofrequency needle ablation or transurethral
microwave therapy can be offered to alleviate
symptoms.
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Other surgical options includemonopolar
or bipolar transurethral resectionof theprostate (TURP),
laser therapies such as holmium laser enucleation or
ablation of the prostate (HoLEP or HoLAP), and open
or laparoscopic simple prostatectomy. All improve
urinary flow by eliminating outlet resistance from the
prostate gland.
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Pharmacology
Alpha blockers
Alpha receptor blocking medications (alpha blockers)
are one of the mainstays of medical management
of sBPH and among the first class of medications
approved for its treatment. Blocking these receptors
can lead to bladder neck and prostatic urethral
relaxation resulting in improved urine flow. As a
whole, alpha blockers are subdivided based on their
degree of selectivity for the alpha
1
AR subtype. See
Table 1.
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First generation alpha blockers (phentolamine and
phenoxybenzamine) are not recommended for use
in the management of sBPH secondary to their side
effect profile (e.g.
palpitations, dizziness, impaired
ejaculation, nasal congestion, and visual disturbances)
and lack of selectivity to the alpha
1
AR. Second
generation alpha blockers (prazosin [Minipress],
doxazosin [Cardura], terazosin [Hytrin]) are becoming
less commonly prescribed for use in sBPH as newer
medications appear on the market. Doxazosin and
terazosin require dose titration and close blood pressure
monitoring. However, they are inexpensive and can
be dosed once daily. Prazosin is not recommended by
the Canadian Urological Association or the American
UrologicalAssociation guidelines for treatment of sBPH
secondary to its side effect profile.
10,11
Cardiovascular
side effects including hypotension, dizziness, and
first dose syncope can be seen with these medications
but occur at a much lower frequency compared to
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Pharmacology for common urologic diseases: 2011 review for the primary care physician