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Male Lower Urinary Tract Symptoms – Epidemiology, Terminology and Pathophysiology
The majority of the larger clinical studies evaluating the efficacy of the
Table 1: Antimuscarinic Therapy for Overactive Bladder
various antimuscarinics in treating OAB included patient populations that
contained many more women than men. However, enough clinical data
Generic Trade Name Approval Year
have been obtained to demonstrate that antimuscarinics are effective in
Trospium Sanctura
®
2004
Darifenacin Enablex
®
/Emselex
®
2004
treating OAB in the male population. There is substantial clinical
Solifenacin Vesicare™/Vesikur
®
2004
experience with the older drugs – particularly tolterodine, which has
Tolterodine Detrol
®
/Detrusitol
®
1998
provided significant insights into the science of OAB. This drug has been
Oxybutynin Ditropan XL
®
1998
the subject of multiple clinical trials that have resulted in more than 350
One possible reason why antimuscarinic therapy does not precipitate
AUR is that during voiding there is a massive release of acetylcholine from
There is substantial clinical experience
the parasympathetic nervous system. This binds well to the
acetylcholinesterase receptors, thus displacing the antimuscarinic drug,
with the older drugs – particularly
with the result that normal voiding is achieved. At therapeutic doses of
tolterodine, which has provided
antimuscarinics there is no affect on normal voiding and no increased
incidence of AUR. This hypothesis is supported by clinical evidence on the
significant insights into the science of
urinary safety of antimuscarinics at recommended doses.
16
overactive bladder.
Correct Diagnosis Is Essential
However, as BPH and detrusor overactivity result in similar symptoms, and
are often found together, it is very difficult to differentiate the true cause
publications in peer-reviewed journals. In total, more than 12 million OAB and to know what to treat. The fact that there is a positive correlation
patients, including two million men, have received tolterodine. In the
LUTS setting, the TIMES study demonstrated that male patients with
bothersome LUTS that included documented OAB symptoms reported
The fact that there is a positive
significant treatment benefit with extended-release tolterodine in
correlation between age and
combination with the α-1 blocker tamsulosin.
12
Extended-release
oxybutynin in combination with tamsulosin has also been shown to be
overactive bladder symptoms in
effective in reducing storage LUTS in men.
13
both men and women suggests that
bladder outlet obstruction is unlikely
Antimuscarinics pose a theoretical risk of instigating AUR, among other
side effects. However, various trials have found the actual incidence of AUR to be the culprit for all cases of male
in men with LUTS who take tolterodine to be low.
12
The most common side
lower urinary tract symptoms.
effects are dry mouth, constipation, dyspepsia, dizziness and somnolence.
14
Lipophilic anticholinergics that can cross the blood–brain barrier could
potentially compromise cognitive functions, especially in those geriatric between age and OAB symptoms in both men and women suggests that
patients who are already taking cholinesterase inhibitors for memory BOO is unlikely to be the culprit for all cases of male LUTS. Moreover,
problems. However, tolterodine does not affect cognitive performance.
15
detrusor dysfunction could be at least partially responsible for OAB in
both sexes. It is less clear whether detrusor dysfunction can be caused by
BOO. This uncertainty makes many physicians hesitant to prescribe
Antimuscarinics pose a theoretical risk
antimuscarinic agents to men.
of instigating acute urinary retention
While there is little observable difference in the incidence of OAB between
(AUR), among other side effects.
men and women, a 12-month longitudinal study carried out in 2004
However, various trials have found the revealed that women are four times more likely to receive antimuscarinic
therapy than men.
17
actual incidence of AUR in men with
Men with LUTS are predominantly treated with BPH
agents rather than with OAB agents. One study reported at the ICS
lower urinary tract symptoms who take
conference in 2005 found that of 4,806 men diagnosed with OAB and
tolterodine to be low.
BPH, 47% received no treatment, while 36% received treatment for BPH
only. Fewer than 18% received OAB treatment either with or without BPH
medication. For the 12,192 men in the study with OAB only, the situation
Overall, tolterodine has proven efficacy. It improves OAB symptoms of was even worse: 61% received no treatment at all and 22% received
incontinence, urgency and frequency; reduces the most bothersome treatment for nonexistent BPH. Only 17% of men received OAB
symptoms of patients; improves HRQoL; has fast onset with sustained treatment, including 6% who received medication for both conditions.
18
long-term efficacy; has excellent tolerability and safety; and is safe and
effective across different patient types, including those with severe For those men with confirmed BPH, response to treatment will vary. In
symptoms, those with mixed urinary incontinence (UI), elderly patients order to evaluate this difference, Lee et al. undertook a study to assess
and men. the efficacy of combined treatment with α-blocker doxazosin and
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