Review – IncontinencePharmacologic Treatment of Male Stress Urinary Incontinence: Systematic Review of the Literature and Levels of Evidence
Introduction
Urinary incontinence (UI) is a common symptom that affects both men and women. Even though it is not life-threatening, it has a significant impact on patients’ psychosocial well-being [1], [2] and quality of life (QoL) [3]. Compared to continent people, men and women with UI have a higher level of anxiety, lower QoL, and poorer life satisfaction [3]. The majority of epidemiologic studies have been conducted in women, confirming the highly prevalent nature of UI, impact on QoL, and frequency of medical consultations [4]. Therefore, UI might appear a problem predominantly of women. However, a review of prevalence studies estimated UI rates of 11–34% for older men and 3–5% for middle aged or younger men [5]. The male prevalence data have recently been confirmed in large surveys conducted mainly in the United States, where the overall prevalence of male UI was reported to be 12.7–17%, of whom 24.5% had stress UI (SUI) [6], [7].
The International Continence Society defines SUI as the complaint of involuntary leakage on effort, exertion, sneezing, or coughing [8]. SUI is a symptom mainly caused by sphincteric incompetence and usually occurs in women after delivery or pelvic surgery, whereas most cases of male UI occur after prostatectomy. UI after radical prostatectomy is related to intrinsic sphincter deficiency in most patients [9], [10], [11], [12], although detrusor overactivity or compliance abnormalities may also exist [13]. One of the largest studies that evaluated incontinent patients after prostatectomy was published in 2005 and included a total of 146 patients [14]. After video-urodynamic investigation, 139 men (95%) were classified as having SUI and had leakage of contrast media through the bladder neck and urethra during the Valsalva manoeuvre or coughing. Of these patients, 24 (17%) also had detrusor overactivity defined as involuntary detrusor contractions with amplitude of > 15 cm H2O, and 11 patients (8%) had reduced bladder compliance (compliance < 12.5 ml/cm H2O).
In general, sphincter deficiency might be caused by damage of smooth muscle cells of the bladder neck or proximal urethra, striated muscle cells of the urethral sphincter, or nerves innervating these anatomic structures. To identify possible drugs that could have a therapeutic effect on male SUI, it is crucial to understand the mechanisms maintaining continence. The urinary continence mechanism is complex, involving the integration of the central and peripheral nervous systems as well as skeletal and smooth muscles. The storage phase of the micturition cycle requires relaxation of the detrusor to allow accommodation of increasing urine volumes at low vesical pressure in conjunction with increased bladder outlet resistance, that is, enhanced tone of the bladder neck, urethra, and pelvic floor [15]. Detrusor relaxation is mainly mediated by β3-adrenoceptor stimulation via noradrenaline release in the hypogastricus nerve. Increased bladder outlet resistance is provided by (1) smooth muscle cell contraction in the bladder neck and proximal urethra mediated by noradrenaline and α1-adrenoceptor stimulation and (2) striated muscle cell contraction in the external sphincter and pelvic floor mediated by acetylcholine and nicotine receptor stimulation. The rhabdomyosphincter activity is controlled by the Onuf nucleus in the sacral spinal cord and neurons releasing serotonin and noradrenaline modulate this activity.
Surgical procedures have been the standard treatment of SUI for decades and implantation of the artificial urinary sphincter has been the standard treatment for male SUI after prostatectomy SUI [16]. Recently, duloxetine was introduced for the treatment of female SUI [17]. Drug treatment for SUI aims to increase outflow resistance. Because SUI is a symptom that is commonly considered to occur mainly in women, studies investigating the effects of pharmacotherapy in men are sparse. Additionally, anatomic differences of the lower urinary tract between men and women are believed to be responsible for the different underlying pathophysiologic mechanisms of SUI. Even though drugs act on the same structures of the lower urinary tract in both men and women, gender differences might be relevant. Therefore, treatment data from female populations cannot simply be extrapolated to men. This systematic literature review aims to clarify the drug classes suitable for treatment of male SUI, summarise the results of the individual drug trials, and judge the level of evidence of the available studies.
Section snippets
Methods
A Medline search was conducted for articles published between 1966 and June 2007 using the MeSH terms “drug therapy” and “stress urinary incontinence.” In addition, a PubMed and ISI of Knowledge Web of Science database literature search was performed with the search terms “medical treatment,” “pharmacotherapy,” and “post-prostatectomy incontinence.” The reference list of the retrieved articles was additionally studied to identify any articles published before 1966. Articles were also identified
Results
The literature search revealed studies with potentially beneficial effects for symptoms of male SUI using α-adrenoceptor agonists, β2-adrenoceptor agonists, or serotonin and noradrenaline reuptake inhibitors. Nine trials were identified using drugs of these three distinct classes and the trials of these drugs formed the basis of this article (Table 1). Only one of these studies included a comparison arm. Studies without a comparison arm make the judgement of placebo effects on and spontaneous
Conclusions
Even though medical treatment of SUI has been investigated mainly in women, some studies do exist for male SUI, especially in patients after radical prostatectomy. Most of these studies do not have the most appropriate design for evaluating the effects of treatment and have a low evidence level (level 4 according to the Oxford classification). The newer drug duloxetine with proven efficacy in female SUI seems to be effective in male SUI as well. Although studies with this compound are limited,
Conflicts of interest
The authors have nothing to disclose.
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