Pharmacologic and surgical treatments of
male urinary incontinence.
L. Moy
Issues in Incontinence – Spring/Summer 2007
Urinary incontinence is the involuntary loss of urine. In the United States it may affect 13 million people,
with an economic cost of more than 20 billion dollars. 1 With the aging population, the number of
people and funds spent on managing incontinence will likely continue to grow.
The cause of urinary incontinence can be very simply viewed as an abnormaility in either bladder
function, sphincter function, or a combination of the two. Bladder abnormalities that can lead to urinary
incontinence include poor bladder compliance and detrusor overactivity. Urinary incontinence due to
sphincteric dysfunction is generally associated with previous prostate surgery, trauma, or neurologic
disease. The workup begins with good history-taking and a physical exam, including rectal and
neurologic exams. Pressure-flow studies and multichannel urodynamics with or without flouroscopy are
often useful in determining the cause of incontinence. Cystoscopy is also helpful to rule out any urethral
or bladder-neck abnormalities. Lab studies may include urinalysis and serum creatine measurement.
The most important concepts in treating male urinary incontinence are understanding the cause of the
incontinence (as the treatment options for bladder dysfunction differ significantly from the treatment
options for sphincteric incontinence) and how symptoms impact the patient's quality of life. Potential
treatments fall into the broad categories of behavioral therapy, pharmacotherapy, neuromodulation,
occlusive devices and surgical therapy (refer to table 1). It makes sense that a stepwise treatment plan
be initiated, starting with more conservative and less invasive therapies and gradually moveing to more
invasive treatments depending on the response and the desires of the patient. Although there is no one
perfect treatment, the available options, both surgical and nonsurgical, are more numerous than ever,
and our ability to treat this difficult problem continues to improve.
Behavioral therapy
The terms behavioral therapy, behavioral modification, and bladder training are often used
interchangeably in describing nonmedical, nonsurgical methods to treat various types of voiding
dysfunction. behavioral therapy includes (1) patient education about lower urinary tract function; (2)
information about lifestyle changes or dietary modification (e.g., fluid restriction, avoidance of irritants);
(3) so-called bladder training or retraining, which includes instituting intervals of timed voiding and
gradually increasing these intervals ; (4) pelvic floor physiotherapy, with or without biofeedback, both to
strengthen the pelvic floor musculature and to aid in the individual's ability to shut off an unwanted
bladder contraction; and (5) for physically or mentally challenged individuals, scheduled toileting and/or
prompted voiding.
In patients with bladder overactivity, pelvic floor physiotherapy is used primarily as an aid to patients in
suppressing unwanted bladder contractions. They are taught to do "quick flicks" of the pelvic floor
musculature in an effort to accomplish this. Putting all these things together involves establishing a
regimen for the patient and combining all of these modalities such that the patient voids according to a
timed schedule that he can initially maintain. A bladder diary is useful in following the patient's
progress. Periodically, the patient is asked to increase the intervals between micturition until an
acceptable interval is reached without the symptoms of urgency or urge incontinence interfering.
Biofeedback is a technique that provides visual and/or auditory signals to an individual with respect to
his performance of physiologic process, in this case pelvic-floor muscle contraction. Electromyography
measurements are generally used. In spite of the logic of biofeedback, most comprehensive reviews
have failed to demonstrate the superiority of pelvic-floor muscle exercise instruction with biofeedback
over pelvic-floor exercise instruction alone. It is clear however, that - whether considering stress, urge,
or mixed urinary incontinence, and using the number of incontinence, and using the number of
incontinence episodes or the amount of urine lost as primary outcome indicators - behavioral therapy is
capable of causing a significant reduction in symptoms; the quoted figures range from 40% to 80%.
We think of behavioral therapy as an overall program that can be used for treatment of urinary
incontinence of bladder overactivity without urinary incontinence. With sphincter-related incontinence,
obviously the patient should concentrate more on pelvic-floor physiotherapy for the purpose of
strengthening the pelvic-floor musculature. With the overactive bladder, with or without urge
incontinence, the patient should concentrate more on behavioral modification, using pelvic-floor
physiotherapy more as a tool to abort involuntary bladder contractions. Biofeedback is optional in
either case.
The physiologic basis for the use of anticholinergic agents is that the major portion of the neurohumoral
stimulus for physiologic and presumably involuntary bladder contraction is acetylcholine-induced
stimulation of postganglionic parasympathetic cholinergic receptor sites on bladder smooth muscle. In
patients with overactive bladder, the effects of anticholinergic agents have been described as follows;
increase in the volume to the first involuntary bladder contraction; decrease in the amplitude of
involuntary bladder contractions; and increase in total bladder capacity. The common view is that, in
cases of detrusor overactivity, the drugs act by blocking the muscarine receptors on the detrusor muscle
that are stimulated by acetylcholine, which has been released from activated cholinergic
(parasympathetic) nerves, thereby decreasing the ability of the bladder to contract. However,
antimuscarine drugs act mainly during the storage phrase, decreasing urgency and increasing bladder
capacity, and during this phase there is normally no parasympathetic input to the lower urinary tract. 3
Antimuscarinic drugs increase and anticholinesterase inhibitors decrease bladder capacity. Because
antimuscarine drugs do seem to affect the sensation of urgency during filling, this suggests ongoing
acetylcholine-mediated stimulation of detrusor tone. If this is correct, agents inhibiting
acetylcholine release or activity would be expected to contribute to bladder relaxation or maintenance
of low bladder tone during filling and storage symptoms unrelated to the occurrence of an involuntary
contraction. Outlet resistance, at least as reflected by urethral pressure measurements, does not seem
to be clinically affected. High doses of antimuscarinics can produce urinary retention in humans, but in
the dose range needed for beneficial effects in detrousor overactivity, there is little evidence for a
significant reduction of the voiding contraction.
The currently available FDA-approved antimuscarinics with the most convincing evidence of efficacy are
tolterodine, trospium, darifenacin, and solifenancin. There are many claims regarding superiority of one
agent over another in terms of efficacy, tolerability, and safety. One must be careful to separate
theoretical (marketing) "edges" from real ones.
A number of agents (most prominently oxybutynin and propiverine) are grouped under the terms
musculotropic relaxant or antispasmodic and are promoted as having more antimuscarine action. These
additional actions include smooth-muscle inhibition at a site metabolically distal to the cholinergic
receptor mechanism, and what are referred to as local anesthetic properties. The smooth-muscle
inhibition may be related to some calcium-channel blocking activity. It should be noted that both
smooth-muscle inhibition and local anesthesia can be demonstration in vitro, but it is doubtful that
when musculotrophic relaxants are administered orally either of these activities contributes to the
clinical efficacy of such agents. Clinical efficacy is most likely due simply to the fact that the effective
drugs in this category are good antimuscarinic agents.
Tricyclic antidepressants have been found by some to be useful agents for facilitating urine storage by
both decreasing bladder contractility and increasing outlet resistance.4 There is disagreement about
their effect on the latter function, but general agreement about their utility in decreasing bladder
contractility. All of these agents promote, in varying degrees, three major pharmacologic actions; (1)
they block the active transport system responsible for the reuptake of released amine neurotransmitters
serotonin and norepinephrine; (2) they have central and peripheral anticholinergic effects at some, but
not all, sites; and (3) they are sedatives, an action presumed to occur centrally but is perhaps related to
antihistaminic properties. At histamine receptors, however, tricyclic antidepressants are also
antagonistic to some extent. Imipramine has prominent systemic anticholinergic effects but only a weak
antimuscarine effect on bladder smooth muscle. This action could be mediated centrally, because an
increase in serotonin concentration in the spinal cord could cause a decrease in bladder contractility, or
it could be related to a direct inhibitory effect on bladder smooth muscle itself. In any case, the effects
of imipramine on bladder smooth muscle do not appear to mediated by an antimuscarine effect. There
is a rationale for prescribing a tricyclic antidepressant with an antimuscarinic drug before abandoning
pharmaceutical treatment in cases where antimuscarinics or agents with combined action have not
produced the desired effect.
One way of achieving a more bladder selective response is to administer a drug intravesically. This has
been easily done in the laboratory with multiple agents and has been done clinically with oxybutynin.
Most studies of intravesical oxybutynin administration are small but report definite beneficial effects
and seemingly fewer side effects that with other routes. Although the drug is absorbed into the
circulation, and effective serum levels can be measured, the first-pass metabolism through the liver is
less. It is thought that the primary liver metabolite of oxybutynin is responsible in large part for the side
effects, and thus these would be less using the mode of administration is obviously cumbersome and
requires catherization. There is no intravesical preparation of oxybutin; tablets must be dissolved in a
vehicle. It may be, however, that with intravesical administration, those drugs with a theoretical
combined action would be able to exert some direct effect of smooth muscle because of the high local
concentration, whereas with oral administration they would not.
Botulinum A toxin (BTX-A) inhibits the release of acetylcholine and other neurotransmitters at the
neuromuscular junction of autonomic nerves in smooth muscle and of somatic nerves in striated
muscle. It does this by interacting with the protein complex necessary for docking vesicles. 5 This results
in decreased muscle contractility and muscle atrophy at the injection site. The chemical denervation is
reversible, and regeneration takes place over 3-9 months. Intradetrusor injection of BTX-A has been
reported by a number of investigators to be efficacious and safe in the treatment of both neurogenic
and idiopathic detrusor overactivity. 6,7,8 Dosage schedules and sites of injection vary. The botulinum
toxin molecule cannot cross the blood-brain barrier. A potential side effect is spread to nearby muscles,
particularly when high volumes are used. Distant effects can also occur, but distant or generalized
weakness due to intravascular spread is very rare. Caution is recommended in cases of disturbed
neuromuscular transmission or for patients on treatment with aminoglyscosides. Use of BTX-B has also
been reported, but data are few and dosing is different.
One attractive modality of therapy for overactive bladder and bladder hypersensitivity, especially in an
individual who retains the ability to voluntarily initiate a detrusor contraction, is to depress sensory
neurotransmission. Capsaicin, the active ingredient of red peppers, in sufficiently high concentrations
causes desensitization of C-fiber sensory afferents by initially releasing and emptying the stores of
neuropeptides, which serve as sensory neurotransmitters, and then blocking further release. 9 C-fiber
afferents act as the primary sensory pathway in patients with voiding dysfunction secondary to spinalcord injury and some other neurologic diseases, and in response to other noxious stimuli. Due to the
inital release of neuropeptides after intravesical administration of the drug, capsaicin causes intense
local symptomatology and often requires anesthesia for administration. In addition, although beneficial
effects have been reported, these effects are not universal; positive effects, when they result, have been
reported to last for 2 to 7 months. Resinifer a-toxin is a compound with effects similar to those of
capsaicin, and it is approximately 1000 times more potent than capsaicin 10 in producing desensitization,
but only 100 to 300 times more potent in producing inflamation.11 Available information suggests that
this mode on intravesical therapy may be effective in both neurogenic and idiopathic detrusor
overactivity. At present, apparent formulation and supply problems seem to have hindered further
investigation.
The theoretical basis for pharmacologic therapy of sphincteric incontinence is the preponderance of adrenergic receptor sites in the smooth muscle of the bladder neck and proximal urethra. When
stimulated, these should produce smooth-muscle contraction. Such stimulation can alter the urethral
pressure profile by increasing maximum urethral pressure and maximum urethral closure pressure.
Current -adrenergic agonists in use (ephedrine and phenylpropanolamine) lack sensitivity for urethra
receptors and may increase blood pressure and cause sleep disturbances, headaches, tremors, and
palpitations. Although these are published reports of efficacy with these agents, the Committee of
Pharmacology of the First International Consultation on Incontinence did not recommend any of these
agents for the treatment of stress incontinence.
Sacral neuromodulation
The use of sacral neuromodulation is not uncommon, as a number of studies have shown it to be safe
and effective treatment. This therapy is FDA-approved for refractory urge incontinence, refractory
urinary urgency and frequency, and non-obstructive urinary retention. Exactly how sacral
neuromodulation works is not fully known. It is believed to modulate the local reflex control of the
lower urinary tract via stimulation of S3 afferent nerve.
Implantation of the device has evolved into a rather simple two-stage outpatient procedure. The first
stage is the percutaneous location of the S3 nerve. This can be done either in the office with a
monopolar lead, which will eventually be replaced or in the operating room with the actual quadripolar
lead that will be used if the patient has a response to therapy. The patient undergoes a testing period
of two to four weeks and, if he has greater than 50% improvement in his symptoms, he goes on to the
placement of subcutaneous generator. If he has no improvement, options include removal of the lead
or placement of another lead on the other side to determine if this is more efficious.
In a multi-center trial 12 by Schmidt and colleagues, 47% of patients (males and females) with severe
urinary incontinence due to detrusor overactivity were dry and 29% were improved with sacral
neuromodulation; the treatment remained effective at 18 months. There have been other studies with
similar findings. Sacral neuromodulation has been shown to be both effective and safe in patients with
refractory urge incontinence, though most studies include only a few men. Because of it minimally
invasive nature and the lack of significant complications, it continues to be a viable treatment for male
urge incontinence, however, more gender-specific data are needed.
Occlusive devices
There have been many patterns of external occlusive devices available for use in the male, but all seem
to take the form of a clamp that is applied across the penile urethra. The Baumrucker and Cunningham
clamps are double-sided foam cushions that squeeze the penile urethra between the two arms. The
Baumrucker clamp uses a Velcro-type fastener. Another type of compression device that is sizeadjustable encircles the penis and stops the flow of urine when it is inflated with air. Such clamps can
cause soft tissue damage by excess compression, and thus their use is extremely risky in patients with
sphincteric incontinence but, if the clamp is applied tightly enough, the patient can occlude the urethra
under any circumstances - although with distinct danger of retrograde pressure damage.
Surgical therapy
There are several surgical treatments for male urinary incontinence (table 3).
Agumentation enterocystoplasty
Creation of a low-pressure high-capacity city bladder reservoir by incorporating a detubularized bowel
segment is an important treatment modality in lower urinary tract reconstruction and in the treament of
refracttory filling and storage problems. Adequeate reservoir function can generally be achieved by
augmentation enterocystoplasty. Complications can include inadequate emptying or urinary retention,
musous accumulation and stones, electrolyte imbalavnce, recurrent infection, and rarely, malignant
change. Contradictions to aumentation enterocystoplasty include urethral disease precluding
intermittent catheterization; unwillingness or inability to perform intermittent catheterization; renal
failure; significant bowl disease; and poor medical status precluding surgery.
Autoaugmentation or detrusor myomectomy refers to the procedure whose purpose is to increase
bladder diverticulum by removing a section of the outer layer of the bladder wall down to the mucosa.
This has the obvious advantage of not requiring bowel resection and anastomosis, but opinion is divided
as to the efficacy of this procedure in increasing reservoir function in adults.
Injectable therapy
Injectable therapy for male sphincteric urinary incontinence is minimally invasive procedure that can be
effective in select men. The men for whom the treatment would be most effective are typically those
with normal bladder capacity, normal bladder compliance, and stable bladder filling with intrinsic
sphincter deficiency. Patients should be aware that multiple injections may be needed initially to reach
continence, and due to the nature of the agents, future injections will also be needed. The ideal agent is
one that can easily injected, remains at the injection site (does not migrate), and is durable (does not
break down). Although a variety of agents has been used and developed, the most popular is
gluteraldehyde cross-linked collagen. This is injected transurethrally with the aid of a cystoscope and
cystoscopic needle. The material is injected in the bladder-neck region/proximal urethra until good
urethral coaptation is visualized. Appel and McGuire reported results of transurethral collagen injection
in 134 men with post-prostatectomy incontinence and 17 men treated with radiation for prostate
cancer. 13 Of these, 16.5% regained continence and 62.2% had a significant improvement at 1 year.
Patients with significant scar/fibrotic tissue in that area may not benefit as much, and those with
previous radiation may have a higher incidence of urothelial rupture at the injection site.
Patients have also undergone injections via a suprapubic cystotomy tract. In theory, this approach lends
itself to better visualization of the bladder neck and improved tissue with less scarring in those who
have undergone radical prostatectomy. Although the overall success rates of injectable therapy are
modest. Its minimally invasive nature is appealing. There is hope that with the continued development
of alternative agents that improved outcomes will be seen.
Slings
Slings have recently gained popularity in the treatment of male urinary incontinence. The goal of the
male sling is to provide support and compression of the bulbar urethra while allowing for physiologic
voiding without causing significant obstruction. Although the idea of the male sling is not new, its
evolution into a non-mechanical, minimally invasive procedure has made it an attractive treatment
option for many men.
A gracilis muscle flap around the bulbar urethra-described by Player and Callander in 1927 - is one of the
earliest versions of the male sling. 14 In the 1970s Kaufman came up with a number of urethral
compressive procedures for male incontinence. 15,16 More recently, Schaeffer and colleagues described a
compressive bulbar urethral sling using multiple Gore-Tex vascular grafts that were placed during a
combined perineal and abdominal procedure. 17 In 36 men undergoing a single procedure, 56% became
dry and 8% were significantly improved at a median of 18 months follow-up. In 2001 Madjar and
colleagues described a procedure in which a graft was anchored to the inferior pubic rami using bone
screws, producing a fixed compression of the bulbar urethra. 18 In their small study, 12 of 14 patients
were subjectively dry using one pad or fewer per day with a mean follow-up of 12.2 months. Comiter
published results from using a bone-anchored perineal sling in 21 patients with post-prostatectomy
incontinence. 19 After a mean follow-up of 12 months, 76% of patients were totally cured, 16% were
substantially improved. Castle and colleagues did not have such impressive results; their retrospective
bone-anchored slings showed that, at 18 months, 39.5 were socially continent, and only 15.8% were
totally dry. 20
The data suggest that the modern-day sling is best suited for men with mild to moderate urinary
incontinence. There are still questions regarding what graft material should be used and how durable
the responses to initial treatment are; therefore there is a continued need to monitor the results of
male sling procedures, especially as their popularity grows.
Implantable prosthetics
Control of sphincteric urinary incontinence with implantable prosthetics has evolved rapidly over the
last 30 years. Clearly the most significant contribution was the introduction, by Scott and coworkers, of a
totally implantable artificial sphincter that could be used in adults and children of both genders.21 This
was originally introduced in the early 1970s. The end result of the biomechanical evolution of this
device is that it is not only considered the gold standard for treating post-prostatectomy incontinence,
but its use has been championed by various clinicians for refractory sphincteric incontinence of virtually
every etiology, assuming that bladder storage is or can be converted to normal. This sphincter consists
of an inflatable cuff that generally fits around the urethra or bladder neck, a reservoir that is usually
placed under the rectus muscle, and an inflate/deflate pump or bulb that transfers the fluid from the
cuff to the reservoir, allowing refilling of the cuff over 3 to 4 minutes. The pump is placed in a
dependent portion of the scrotum. High success rates have need achieved by experienced surgeons.
This incidence of mechanical malfunction and infection, though initially high, is now quite low.
The AMS-800 is the currently used model of the artificial urinary sphincter. The device includes a
deactivation button in the control pump that allows for easy external control of cuff activation, and a
narrow-backed cuff pressure to the underlying tissue, this decreasing tissue atrophy and erosion.
Although used by many patients with urinary incontinence, it is contraindicated for patients with poor
bladder compliance, low-volume neurogenic detrusor overactivity, detrusor sphincter dyssynergia, or
unstable urethral urologic procedures that require frequent instrumentation, which may damage the
cuff or cause cuff erosion.
There have been numerous studies showing the success of artificial urinary sphincter placement. The
percentage dry may range anywhere from 44% to 91%, with most series having results greater than 75%
dry. 22,23 Other variations to improve results have included transcorporeal placement of the cuff 24 as
well as using tandem cuffs to produce resistance over a greater length of urethra. 25 Both of these
modifications can be done safely with very good results.
Summary
Urinary incontinence is a major health and social problem that affects millions of men. Presently there
are more treatment options that ever that can significantly improve or "cure" this problem.
Understanding the cause (s) of a patient's incontinence is paramount in assuring that the correct
therapy is initiated so that the best results may be obtained. Continued research in the
pathophysicalogy of incontinence and treatment will lead to improved treatment outcomes and quality
of life.
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