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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
hormone-releasing hormone (LHRH) deficiency or
pituitary-hypothalamic injury from trauma, tumors,
or radiation. These men have low serum testosterone
levels but have gonadotropins levels in the normal or
low range. The expertise of an endocrinologist may
be necessary when the diagnosis of hypogonadism is
suspected.
Pharmacology
Primary therapy in patients with hypogonadism
includes testosterone replacement therapy (TRT).
Treatment with TRT may improve sexual function
and have other effects on bone density and improved
mood/libido.
34-36
General side effects of TRT include
gynecomastia, erythrocytosis, and testicular atrophy.
Several methods of testosterone delivery are available
for use: oral, intramuscular (IM) injection, and topical
formulations, Table 6. Oral alkylated androgens
(e.g., fluoxymesterone, methyltestosterone) are
administered daily and undergo hepatic elimination
making it difficult to achieve consistent therapeutic
levels in serum. This can result in unwanted mood
swings and sexual side effects. Due to this method
of metabolism, liver toxicity including hepatocellular
adenomas, hemorrhagic cysts, and cholestatic jaundice
have been reported.
37
Oral administration of alkylated
androgens has lost its popularity in the United
States secondary to its pharmacokinetics and list of
side effects. In contrast, testosterone undecanoate
[Andriol] is the only oral form available in Canada.
This formulation avoids the first pass effect in the
liver all but eliminating liver toxicity from its side
effect profile.
38
IM injections (testosterone cypionate
[Depo-Testosterone] and testosterone enanthate
[Delatestryl]) can be dosed every 2-4 weeks but can be
associated with supraphysiologic levels of hormone
and low nadirs resulting in alterations in mood and
infertility through negative feedback suppression of
FSH and LH.
32
Transdermal patches [Androderm]
and gels [AndroGel, Testim] can be directly applied
to the skin and have been found to more closely
follow physiologic cycles of serum hormone levels.
32
Fortesta™ (testosterone gel) was approved by the US
FDA in December 2010 (not approved in Canada)
and indicated for testosterone replacement in
hypogonadal men and is approved for application
to the inner thigh region. Axiron, a testosterone
topical solution, is another formulation in this class
approved in November 2010 by the US FDA also for
TRT in hypogonadal men. Skin irritation or rash is a
common side effect of the patch and less seen in the gel
formulation.
39
Patients should wash their hands after
any topical application of gels to prevent transmission
of drug to others and should also be cautioned to
allow the gel to dry completely before smoking as this
formulation can be flammable.
Newer long acting testosterone derivatives
have been released onto the US market in the last 2
years. Testosterone undecanoate [Nebido] IM can be
administered at 6-12 week intervals.
40
Implantable
pellets [Testopel] can be placed in the upper buttock
under local anesthesia every 6 months. These
modalities are safe, efficacious, and present convenient
dosing intervals for TRT in the hypogonadal male.
32
Buccal preparations [Striant] have also demonstrated
favorable results with a low side effect profile (mainly
buccal irritation and bitter taste) but are not yet
available in Canada.
41
TRT in patients with a history of prostate cancer
should be avoided. Its use for hypogonadal men
after treatment of prostate cancer with radical
prostatectomy has drawn interest.
42
However, primary
care physicians should seek urologic consultation in
this patient population prior to initiating treatment.
Overactive bladder
Pathophysiology
Physiologic bladder filling, storage, and emptying
of urine is a complex neuromuscular interaction
between the brain, spinal cord, and autonomic
nervous system. The filling and storage phase is
moderated by a sympathetic norepinephrine pathway
and is normally characterized by low intravesical
pressures protecting against vesico-ureteral reflux,
incontinence, and bladder dysfunction.
43,44
Voiding is
mediated by parasympathetic stimulation of detrusor
smooth muscle leading to bladder contraction with
a concomitant decrease in urethral resistance and
relaxation of the external striated sphincter (inhibition
of sympathetic tone to somatic nerves controlling
the external sphincter).
45
The neurotransmitter
acetylcholine interacts with muscarinic (M) receptors
foundwithin the bladder (mainlyM2 andM3 receptors)
resulting in bladder smoothmuscle contraction during
normal voiding.
45
The International Continence Society (ICS) defines
overactive bladder (OAB) as a syndrome characterized
by urgency, with or without urgency incontinence,
usually with frequency and nocturia.
46
Depending on
surveymethods and OAB definition, the prevalence of
symptoms vary in population-based studies. However,
OAB is estimated to affect 1 in 5 Canadian adults and
increases in prevalence with aging.
47-49
The cost of
OAB diagnosis and treatment has been estimated
to approach $12 billion USD per year. The causes of
31
Pharmacology for common urologic diseases: 2011 review for the primary care physician