© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
The PDE5i class is relatively new as a treatment for
BPH-LUTS. In the United States, Canada, Europe and
some Asian countries only tadalafil is approved for this
indication, although others have been studied.
29-33
The
exact mechanism of action is unknown, it is believed
that the PDE5i increase the signaling of the NO/cGMP
pathway, which, in turn, reduces smooth muscle tone
in the lower urinary tract.
34
In a study published in
2012, Oekle et al compared tadalafil and tamsulosin
in a placebo controlled study. They noted statistically
significant, yet similar, improvements versus placebo in
BPH-LUTS as early as 1 week which was sustained for
the 12week studyperiod. PDE5i differentiate themselves
fromalpha-blockerswith the effect onsexual dysfunction.
The most significant, yet expected, difference was that
tadalafil improved erectile dysfunction.
35
Common
side effects of the PDE5i include headache, back pain,
dizziness and dyspepsia. These side effects are less in
the once daily dosing used for BPH as opposed to the
on-demand dosing used for erectile dysfunction.
36,37
They are contraindicated in patients who use nitrates,
and should be used with caution in patients treated
with alpha-blockers, since the combination may lead to
hypotension. Tadalafil should not be used in patients
with a history of non-arteritic anterior ischemic optic
neuropathy (NAION).
20
Cardiac statusmust be assessed
for patient risk before taking these medications.
38
Patients with a large prostate (> 30 mL) may find
that treating the dynamic component of BPH-LUTS
with only an alpha-blocker or a PDE5i is not sufficient,
and neither of thosemedications will halt the growth of
the prostate. This enlargement may result inworsening
symptoms as well as the risk of acute urinary retention
andpossibly the need for surgical intervention. The goal
of therapy then becomes preventing the progression
by reducing the static component or the bulk of this
enlarged gland. Prostate growth is stimulated by
dihydrotestosterone (DHT) with is converted from
testosterone by the 5-alpha reductase inhibitor (5ARI).
Decreases in DHT have been shown to induce prostatic
epithelial apoptosis, reducing prostate size and
decreasing PSA up to 50% after 6-12 months.
39-41
There are two 5ARIs available, finasteride and
dutasteride.
20
Both medications showed significant
improvement over placebo in reducing prostate size and
reducing the risks of symptomprogression, acuteurinary
tract retention and surgical intervention.
41
Quick relief
will not occur with the 5ARI alone as eithermedications
generally require 3-6 months before the effect is noted.
For this reason combination with an alpha-blocker or a
PDE5iwith the 5ARI is recommended. Studies have also
shown that early and continued combination therapy
results in significant improvement in symptom and
bother scores as compared to monotherapy with either
medication.
42-44
In regards to stopping combination
therapy in favor of monotherapy, the studies are
inconclusive and expert opinion favors continuing
combination therapy in the at-risk patient.
10,45
The most commonly reported adverse reactions
of the 5ARIs include decreased libido, ejaculatory
disorders, erectile dysfunction and gynecomastia.
20
The
clinician should be aware that the PSA level will reduce
approximately50%within thefirst year andshouldnever
increase as long as the 5ARI is still beused. Any elevation
should therefore be investigated.
1
Two crucial trials on
prostate cancer chemoprevention found a slightlyhigher
incidence of high-grade cancers in the 5ARI patients as
compared to those taking placebo.
46,47
Although experts
havedebated the relationship thepatient shouldbemade
aware of the risk and monitored appropriately.
Follow up
There is no set rule on the interval for follow up after
initiating treatment for OAB. Some PCPs find a
2 week interval is adequate while others recommend
4week. What is important is that there is a conversation
between the patient and the PCPoutlining expectations.
The PCP should address these expectations and
encourage the patient not to give up if these expectations
are not met immediately.
48
Each followup appointment
should reinforce behavioral modifications as well
as medication compliance. If the initial medication
dose does not provide the desired effect then a simple
drug change or titration may help. There are many
medication choices and no one treatment is right for
every patient, therefore, failing with one drug or class
allows an opportunity to try another. Historically, there
has been a high discontinuation ratewithOAB therapy.
Having multiple medications within a class, as well as
more than one class may assist in reversing this trend.
If a PVR was performed as part of the initial
evaluation, it may be prudent to check it again during
the follow up period. Studies have shown that if
retention is to occur when on medication therapy, it is
likely to happen within the first 30 days.
26
When to call in the specialist
As emphasized throughout this paper, the diagnosis
of OAB can be made empirically without the use of
specialized equipment or testing, and thus, treatment
can be initiated comfortably by the PCP. However, it
can be expected that in some cases treatment will fail to
alleviate the problem even after switching medications
or titrating them. In that situation it is appropriate to
9
A practical primary care approach to overactive bladder
