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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
16
the primary care physician can follow a treatment
algorithm developed by the Canadian Urological
Association, Figure 1.
16
The treatment algorithm is
based on prostate size, BPH symptoms, and “bother.”
For a patient with a small prostate and minimal
bother from symptoms, the recommended treatment
consists of “watchful waiting” and patient education
about lifestyle modification. Examples of lifestyle
modification include managing fluid intake during
the day and after dinner (decreasing consumption
of tea, coffee and alcohol), stopping smoking,
decreasing consumption of spicy foods, decreasing
use of drugs that affect the bladder (eg, decongestants
and antihistamines), avoiding or treating constipation,
and performing “bladder training” or pelvic-floor
exercises. These suggested lifestyle modifications
may decrease symptoms, but they do not reduce the
size of the prostate or prevent prostate growth or the
progression of BPH.
Medical management of BPH
If conservative treatment such as watchful waiting
and lifestyle management of BPH is unsuccessful,
then two main classes of drugs may be used to treat
patients with symptomatic BPH: alpha blockers and
5-alpha reductase inhibitors (5-ARIs).
Alpha blockers
The use of alpha blockers to manage BPH symptoms
began in the 80s with the use of the nonselective
antihypertensive agent phenoxybenzamine, which
was discovered to have a side effect of increasing
urine flow. It also caused significant orthostatic
hypotension.
The rationale for using an alpha blocker to treat
BPH is based on the knowledge that stimulation of
alpha receptors in the smooth muscle fibers in the
bladder neck, prostatic urethra, and the prostate
can increase the smooth muscle tone (tightness) and
thereby cause functional obstruction of the bladder
with symptoms of decreased urine flow, increased
frequency, nocturia, and urgency (due to decreased
bladder emptying).
The three main alpha receptor subtypes are alpha
1A, alpha 1B, and alpha 1D. Alpha 1A receptors are
found in the smooth muscle of the bladder neck and
prostate, alpha 1B receptors are found mainly in the
smooth muscle of the peripheral vasculature, and
alpha 1D receptors are found mainly in the spinal
cord.
17
Nonselective alpha blockers can block receptors
found in places in the body other than the prostate.
Recently, “uroselective alpha blockers” that act
specifically on alpha-1 receptors became available.
These drugs relieve LUTS through three proposed
mechanisms: relaxation of the smooth muscle tone
in prostate stroma and the bladder neck, relaxation
of bladder smooth muscle, and action on the central
nervous system.
18-21
In most men, treatment with alpha blockers
provides a fairly fast (within 48 hours to 1 week),
30% to 50% improvement in symptoms compared
to placebo. However, patients who receive alpha
blockers are only likely to maintain this response
for up to 4 years, and alpha blockers do not prevent
BPH progression, shrink the prostate, or affect PSA
levels.
13,22
Alpha blockers, including more uroselective
preparations, have very similar efficacies.
23
They also
have similar rates of potential side effects, including
postural hypotension (5%), dizziness (15%), nasal
congestion (5%), headache (5%-10%), and asthenia
(5%-10%). Tamsulosin is associated with a 3%-10%
rate of abnormal ejaculation, and the alpha blockers
may cause or improve erectile dysfunction (ED).
19,20,24
5-alpha reductase inhibitors
Testosterone is broken down to its metabolite
dihydrotestosterone (DHT) by the action of the
enzyme 5-alpha reductase. DHT is the active chemical
that is absorbed into the prostate cells and stimulates
prostate cellular and glandular (stromal) growth.
The 5-alpha reductase enzyme has two isoenzymes:
type 1 and type 2, which are present in different
concentrations within the different types of prostate
tissue (eg, cancer versus benign disease).
25,26
If the breakdown of testosterone to DHT is
inhibited by a 5-ARI, DHT absorption into the prostate
is reduced, and as a result, the prostate shrinks and
symptoms caused by the BPH will decrease.
27
Two 5-ARIs -- finasteride (Proscar) and dutasteride
(Avodart) -- are currently available. Dutasteride
inhibits both types of 5-alpha reductase isoenzymes,
whereas finasteride only inhibits the type 2 isoenzyme.
As a result, finasteride reduces DHT production by
about 70%, whereas dutasteride reduces it by more
than 92%.
28
In recent monotherapy trials comparing the
5-ARIs to placebo, both finasteride and dutasteride
demonstrated significant positive effects.
27,29
The
trials enrolled men with symptomatic BPH. In these
monotherapy trials, men who received finasteride
or dutasteride had greater improvements in clinical
symptoms after 6 to 12 months and their IPSS scores
were 15% to 30% lower after 2 to 4 years, compared
BARKIN