Objectives. To investigate the add-on effect of solifenacin for Japanese men with remaining overactive bladder (OAB) symptoms after tamsulosin monotherapy for lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) in real-life clinical practice. Methods. Patients aged ≥ 50 having remaining OAB symptoms (≥ 3 of OAB symptom score (OABSS) with ≥2 of urgency score) after at least 4 weeks treatment by 0.2 mg of tamsulosin for BPO/LUTS received 2.5 or 5.0 mg of solifenacin for 12 weeks. The International Prostate Symptom Score (IPSS), QOL index and OABSS, maximum flow rate (Qmax) and postvoid residual urine volume (PVR) were determined. Results. A total of 48 patients (mean age 72.5 years) completed the study. There were significant improvement in IPSS (15.1 to 11.2) and QOL index (4.2 to 3.0) by add-on of solifenacin. Although the IPSS storage symptom score was significantly improved, there were no changes observed in the IPSS voiding symptom score. The OABSS showed significant improvement (8.0 to 4.8). No changes were observed in Qmax and PVR. Conclusions. Under the supervision of an experienced urologist, the additional administration of solifenacin to patients with BPO/LUTS treated with tamsulosin, is effective in controlling remaining OAB symptoms.
Overactive bladder (OAB) is subtyped into OAB-wet and OAB-dry, based on the presence or absence, respectively, of urgency incontinence. In order to better understand patient and physician perspectives on symptoms among women with OAB-wet and OAB-dry, we conducted patient focus groups and interviews with experts in urinary incontinence.
Materials and Methods
Five focus groups totaling 33 patients with OAB symptoms, including three groups of OAB-wet and 2 groups of OAB-dry patients, were conducted. Topics addressed patients’ perceptions of OAB symptoms, treatments, and outcomes. Twelve expert interviews were then conducted in which experts were asked to describe their views on OAB-wet and OAB-dry. Focus groups and expert interviews were transcribed verbatim. Qualitative data analysis was performed using Grounded Theory methodology, as described by Charmaz.
During the focus groups sessions, women screened as OAB-dry shared the knowledge that they would probably leak if no toilet is available. This knowledge was based on a history of leakage episodes in the past. Those few patients with no history of leakage had a clinical picture more consistent with painful bladder syndrome than OAB. Physician expert interviews revealed the belief that many patients labeled as OAB–dry may actually be mild OAB-wet.
Qualitative data from focus groups and interviews with experts suggest that a spectrum exists between very mild OAB-wet and severe OAB-wet. Scientific investigations are needed to determine if urgency without fear of leakage constitutes a unique clinical entity.
focus groups; qualitative research; urge urinary incontinence; grounded theory; overactive bladder
Lower urinary tract symptoms (LUTS) can have multiple causes in men. Overactive bladder (OAB) is an empirical diagnosis used as the basis for initial management after assessing symptoms, physical findings, urinalysis and other indicated evaluations. In men, the diagnosis is complicated by the potential of benign prostatic hyperplasia (BPH), which is a histological diagnosis. Although storage symptoms (i.e., those associated with OAB) are the most bothersome group of LUTS in men with BPH, these patients are usually treated with BPH rather than OAB drugs. The standard pharmacologic treatment of patients with bothersome voiding and storage LUTS at low risk of progression should be an α1-AR antagonist. The combination α1-AR antagonist + antimuscarinic agent is an appropriate and valid option for male patients with voiding symptoms and persistent storage symptoms.
Antagonists of α1-adrenergic receptors (α1ARs) relax prostate smooth muscle and relieve voiding and storage symptoms. Recently, increased expression of α1ARs with change of its subtype expression has been proved in bladder outlet obstruction (BOO). To search for the evidence of changes in α1ARs subtype expression and activity in the peripheral and spinal routes, the effects of spinal and peripheral administration of tamsulosin (an α1A/D-selective AR), naftopidil (an α1A/D-selective AR), and doxazosin (non-selective AR) on bladder activity were investigated in a rat model with or without BOO.
A total of 65 female Sprague-Dawley rats were divided into the BOO surgery group (n=47) and the sham surgery group (n=18). After 6 weeks, cystometry was assessed before and after intrathecal and intra-arterial administrations of tamsulosin, naftopidil, and doxazosin.
After intra-arterial administrations of all three drugs, bladder capacity (BC) was increased and maximal intravesical pressure (Pmax) was decreased in both BOO and the sham rat models (P<0.05). After intrathecal administration of all three drugs, BC was increased and Pmax was decreased in only the BOO group. The episodes of involuntary contraction in the BOO rat models were decreased by intra-arterial administration (P=0.031). The increase of BC after intrathercal and intra-arterial administrations of α1ARs was significantly greater in the BOO group than in the sham group (P=0.023, P=0.041). In the BOO group, the increase of BC and decrease in Pmax were greater by intra-arterial administration than by intrathecal administration (P=0.035). There were no significant differences of the degrees of changes in the cystometric parameters among the three different α1ARs.
Up-regulations of the α1ARs in BOO were observed by the greater increases of BC after α1AR antagonist administrations in the BOO group than in the sham group. However, there were no subtype differences of the α1ARs in functional parameters of bladder activity. In addition, α1ARs also act on the lumbosacral cord which implies that the sensitivity of α1ARs is increased in pathologic models such as BOO. Further evaluation including differential expression of α1ARs in BOO models are need.
Urinary bladder; Urinary bladder neck obstruction; Adrenergic alpha-antagonists; Rats
Overactive bladder (OAB), as defined by the International Continence Society, is characterized by a symptom complex including urinary urgency with or without urge incontinence, usually associated with frequency and nocturia. OAB syndrome has an incidence reported from six European countries ranging between 12-17%, while in the United States; a study conducted by the National Overactive Bladder Evaluation program found the incidence at 17%. In Asia, the prevalence of OAB is reported at 53.1%. In about 75%, OAB symptoms are due to idiopathic detrusor activity; neurological disease, bladder outflow obstruction (BOO) intrinsic bladder pathology and other chronic pelvic floor disorders are implicated in the others. OAB can be diagnosed easily and managed effectively with both non-pharmacological and pharmacological therapies. The first-line treatments are lifestyle interventions, bladder training, pelvic floor muscle exercises and anticholinergic drugs. Antimuscarinics are the drug class of choice for OAB symptoms; with proven efficacy, and adverse event profiles that differ somewhat.
Antimuscarinics; bladder training; overactive bladder
To evaluate the efficacy and tolerability of tamsulosin 0.4 mg once daily in Korean patients with symptomatic benign prostatic hyperplasia (BPH) and investigate whether tamsulosin 0.4 mg can improve symptoms in patients with refractory lower urinary tract symptoms (LUTS) who were previously receiving tamsulosin 0.2 mg once daily.
Materials and Methods
A total of 116 patients from 3 urology centers participated. All study subjects entered a nonblind phase consisting of 8 weeks of tamsulosin 0.2 mg monotherapy followed by an additional 8 weeks of tamsulosin 0.2 mg (0.2 mg group) or 8 weeks of tamsulosin 0.4 mg (0.4 mg group). At week 8, we chose the 0.4 mg group on the basis of International Prostate Symptom Score (IPSS), quality of life (QoL), maximal urinary flow rate (Qmax), and adverse effects. At week 16, we compared the efficacy and tolerability of tamsulosin between the 0.2 and 0.4 mg groups.
A total of 26 patients (22.4%) were escalated to tamsulosin 0.4 mg at week 8. There were significant differences in IPSS, QoL, and Qmax at week 8 in both groups. There were significant differences in improvement in IPSS, QoL, Qmax, and postvoid residual urine volume from baseline to week 16 in both groups. There were no significant differences in efficacy or tolerability between the groups at week 16.
Our trial demonstrated that tamsulosin 0.4 mg has favorable efficacy and tolerability in Korean patients with symptomatic BPH refractory to tamsulosin 0.2 mg. No patients experienced any serious adverse effects when we escalated the dose of tamsulosin to 0.4 mg.
Prostatic hyperplasia; Tamsulosin
It is well known that the use of the α-adrenergic receptor antagonists in the BPH therapy may induce ejaculatory disorder. A review of clinical literature shows a greater incidence of ejaculatory disorder during the use of tamsulosin compared with alfuzosin. Anejaculation has been until now referred to retrograde ejaculation due to relaxation of prostatic and bladder neck smooth muscle tone. In a recent researches was evaluated the effect of tamsulosin and alfuzosin on rat vas deferent "in vitro", concluding that tamsulosin may "cause ejaculatory dysfunction by altering the progression and emission of sperm". An abnormal increase of contraction would be the cause of ejaculatory disorder. The aim of our paper is to compare human and rat vas deferens contractile activity and to evaluate with a clinical study if tamsulosin causes retrograde ejaculation disorder.
We have revaluated the human and rat vas deferens contractile activity in vitro according to our experience and literature. We have also performed a clinical study on 10 patients (48–72 y) affected by anejaculation. Post-coital urine was examined to search spermatozoa.
Human and rat vas deferens activity is not comparable. Contractile activity induced by norepinephrin after tamsulosin incubation in rat prostatic vas deferens strips is similar to the contractile activity evoked by norepinephrin in human strips. Spermatozoa were found in post coital urine of 6 patients.
In our opinion the treatment with tamsulosin may induce retrograde ejaculation but not other ejaculatory disorder due to abnormal sperm progression.
The prevalence of overactive bladder (OAB) symptoms is considerable in both men and women and the impact on quality of life (QOL) is equally substantial. Ironically, despite nearly equal prevalence, OAB symptoms in men are infrequently treated, and often with medical therapies aimed at bladder outlet obstruction (BOO). In this review, we examine the pathophysiology of OAB and its evaluation in the context of benign prostatic hypertrophy and concomitant BOO. We then consider the efficacy and safety of individual therapeutic options for lower urinary tract symptoms in men, focusing on the mainstays of medical therapy: α-adrenergic blockers, 5-α reductase inhibitors, and antimuscarinic agents. Finally, we aim to comment on new therapeutic strategies and targets that may one day be available for the treatment of male OAB.
anticholinergic; benign prostatic hypertrophy; overactive bladder
In order to gain insight into the physicians' awareness of and attitude towards management of overactive bladder (OAB) in males, we performed a nationwide survey of the current strategies that urologists use to diagnose and manage OAB in male patients.
Materials and Methods
A probability sample was taken from the Korean Urological Association Registry of Physicians, and a random sample of 289 Korean urologists were mailed a structured questionnaire that explored how they manage benign prostatic hyperplasia (BPH).
A total of 185 completed questionnaires were returned. The consent rate in the survey was 64.5%. Eighty-one (44%) urologists believed that of all males with lower urinary tract symptoms (LUTS), 20% or more had OAB and 72 (39%) believed that 10-20% had OAB. Half of the urologists surveyed believed that the most bothersome symptom in male OAB patients was nocturia. Seventy-three percent of respondents reported that they prescribed alpha blockers with anticholinergics for first line management, while 19% of urologists prescribed alpha blocker monotherapy but not anticholinergics for OAB patients. Though acute urinary retention (AUR) was considered the anticholinergic adverse event of most concern, the most frequently observed adverse event was dry mouth (95%).
The present study provides insights into urologist views of male OAB. There is a discrepancy between the awareness of urologists and actual patterns of diagnosis and treatment of male OAB. This finding indicates the need to develop further practical guidelines based on solid clinical data.
Overactive bladder; physician's practice patterns; bladder outlet obstruction; benign prostatic hyperplasia; anticholinergics
The current definition of overactive bladder (OAB) is “urgency, with or without urge incontinence, usually with frequency and nocturia in the absence of an underlying metabolic or pathologic condition.” Urgency, in turn, is defined as a “sudden, compelling desire to pass urine that is difficult to defer.” While these definitions provide the framework for making a clinical diagnosis of OAB, they rely on subjective assessment of the symptoms by the patient. As well, the symptoms of OAB can be similar to those seen in other conditions, such as urinary tract infection, benign prostatic enlargement and bladder cancer. These other potential diagnoses should be ruled out in a noninvasive manner before making a diagnosis of OAB.
Overactive bladder (OAB) is a prevalent and costly condition that can affect any age group. Typical symptoms include urinary urgency, frequency, incontinence and nocturia. OAB occurs as a result of abnormal contractions of the bladder detrusor muscle caused by the stimulation of certain muscarinic receptors. Therefore, antimuscarinic agents have long been considered the mainstay of pharmacologic treatment for OAB. Currently, there are five such agents approved for the management of OAB in the United States: oxybutynin, tolterodine, trospium, solifenacin and darifenacin. This article summarizes the efficacy, contraindications, precautions, dosing and common side effects of these agents. All available clinical trials on trospium, solifenacin and darifenacin were reviewed to determine its place in therapy.
overactive bladder; urinary incontinence; pharmacologic management; antimuscarinic agents; anticholinergics
Overactive bladder (OAB) is a medical syndrome defined by symptoms of urgency, with or without urge urinary incontinence (any involuntary loss of urine), usually with frequency and nocturia. Although anticholinergic agents have been the first-line treatment for OAB for many years, the efficacious pharmacologic management of this condition has been compromised by concerns regarding tolerability. Flavoxate was the first anticholinergic and antispasmodic agent approved by the Food and Drug Administration (FDA) to treat symptoms of OAB but is not routinely used today since newer agents are more effective. The more recent drugs, oxybutynin and tolterodine, have appeared to be equally efficacious in treating the symptoms of OAB in clinical trials; however, tolterodine has proven to be better tolerated with fewer adverse effects. In 2004, the FDA approved the three newest agents for the class: darifenacin, solifenacin, and trospium. Compared with oxybutynin and tolterodine, these agents have a more favorable side effect profile, which can enhance tolerability and patient compliance. Side effects are reduced in part because of the drugs' greater tissue selectivity for inhibiting the bladder muscle contraction over other anticholinergic receptors in the body. In recent clinical trials, darifenacin, solifenacin, and trospium have shown superiority to placebo and efficacy comparable to that of oxybutynin and tolterodine.
To examine the effects on erectile function of concomitant treatment with an alpha-blocker (tamsulosin) and an antimuscarinic agent (solifenacin) in patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH).
Materials and Methods
Fifty-seven male patients with LUTS/BPH were assessed for the degree of LUTS and erectile function. In group 1 (tamsulosin) and group 2 (tamsulosin and solifenacin), changes in the International Prostate Symptom Score [IPSS: total scores, storage symptoms (ST), voiding symptoms (VD), and quality of life (QoL)], prostate-specific antigen, trans-rectal ultrasonography, urine flowmetry, residual urine, and a 5-item version of the International Index of Erectile Function (IIEF-5) were assessed after a 3-month treatment period. In both groups, it was determined whether treatment was associated with changes in LUTS and erectile function and whether improvement in the IPSS was correlated with the IIEF-5. Comparative analysis was also done to examine the linear relationship between improved IPSS scores and IIEF-5 scores.
A comparison of the degree of improvement in all the parameters indicated that both groups showed significant improvement in total IPSS, IPSS-ST, IPSS-VD, and IPSS-QoL (p<0.05). A comparison of the degree of improved sexual function associated with improved LUTS in each patient showed significant improvement in the IIEF-5 score associated with the degree of improvement in the IPSS-ST domain in group 1, but no significant associations were found in group 2. In cases in which tamsulosin was administered, the IIEF-5 score significantly improved as the IPSS-ST domain score improved. In the group in which tamsulosin and solifenacin were concomitantly administered, improvement of the IPSS-ST domain score had no significant effect on the IIEF-5
In patients with LUTS/BPH, tamsulosin and solifenacin combination therapy was effective for LUTS, but erectile function was not significantly improved. Therefore, although effective for improving LUTS, combination therapy with an alpha-blocker and an antimuscarinic agent was not effective for improving erectile function.
Prostatic hyperplasia; Sexual dysfunction, physiological; Solifenacin; Tamsulosin
To compare urgency symptoms in women with interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB).
Materials and Methods
Women with diagnoses of IC/BPS (n = 194) and OAB (n = 85) were recruited from the clinical practices of Urologists (n = 8) and Gynecologists (n = 16) with recognized expertise in the diagnosis and management of these conditions. Subjects completed a comprehensive telephone survey about their current symptoms. The questionnaire included 11 questions about urinary urgency. Responses were compared between the two groups.
Urgency was commonly reported as a symptom by women with both conditions (81% IC/BPS and 91% OAB). Compared with IC/BPS, urgency in OAB more often resulted in leakage, and was perceived to be more of a problem. In IC/BPS, the urgency was primarily reported as due to pain, pressure, or discomfort, while in OAB the urgency was more commonly due to fear of leakage. However, approximately 40% of women with OAB also report urgency due to pain, pressure, or discomfort. Similar proportions of both groups (~60%) indicated that the urgency occurred “suddenly” instead of more gradually over a period of minutes or hours.
Urgency symptoms differed in women diagnosed with IC/BPS versus those diagnosed with OAB, but there was significant overlap. This suggests that “urgency” is not a well-defined and commonly understood symptom that can be utilized to clearly discriminate between IC/BPS and OAB. These findings reinforce the clinical observation that it is often challenging to differentiate between these two conditions.
sensations; specificity; symptoms
Naftopidil, approved only in Japan, is an α1-adrenergic receptor antagonist (α1-blocker) used to treat lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Different from tamsulosin hydrochloride and silodosin, in that it has higher and extremely higher affinity respectively, for the α1A-adrenergic receptor subtype than for the α1D type, naftopidil has distinct characteristics because it has a three times greater affinity for the α1D-adrenergic receptor subtype than for the α1A subtype. Although well-designed large-scale randomized controlled studies are lacking and the optimal dosage of naftopidil is not always completely determined, previous reports from Japan have shown that naftopidil has superior efficacy to a placebo and comparable efficacy to other α1-blockers such as tamsulosin. On the other hand, the incidences of ejaculatory disorders and intraoperative floppy iris syndrome induced by naftopidil may be lower than for tamsulosin and silodosin having high affinity for the α1A-adrenergic receptor subtype. However, it remains unknown if the efficacy and safety of naftopidil in Japanese is applicable to white, black and Hispanic men having LUTS/BPH in western countries.
benign prostatic hyperplasia; lower urinary tract symptoms; α1-blocker; naftopidil
Chronic pelvic pain syndrome (CPPS) is treated by use of various protocols. We compared tamsulosin monotherapy with tamsulosin in combination with antibiotics or anti-inflammatory agents and evaluated the efficacy of these treatments in patients with CPPS.
Patients (n=107) who were younger than 55 years and diagnosed with CPPS were randomly assigned to treatment with tamsulosin at 0.2 mg (group A), tamsulosin at 0.2 mg plus anti-inflammatory drugs (group B) or tamsulosin at 0.2 mg plus antibiotics (group C) daily. We applied the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (IPSS) to evaluate 100 patients who were treated for 12 weeks (7 withdrew). Scores of the three groups were compared by analysis of variance and we also evaluated subscores, which included pain, voiding and quality of life (QoL).
All three groups showed statistically significant decreases in NIH-CPSI score, IPSS and subscore scores (P<0.05). There were no statistically significant differences between the groups except for the QoL domain of the IPSS (group A vs. C; P<0.01).
Tamsulosin monotherapy for 12 weeks was effective for treating patients with CPPS, compared with combination therapy with antibiotics or anti-inflammatory drugs.
Chronic Prostatitis with Chronic Pelvic Pain Syndrome; Tamsulosin
To evaluate the relationship between urodynamic detrusor overactivity (DO) and overactive bladder (OAB) symptoms in men and women.
We reviewed the records of adult males and females who attended a tertiary referral center for urodynamic evaluation of OAB syndrome symptoms with the presence or absence of DO. DO was calculated for symptoms alone or in combination.
The overall incidence of DO was 76.1% and 58.7% in male and female OAB patients, respectively. Of men 63% and 61% of women with urgency (OAB dry) had DO, while 93% of men and 69.8% of women with urgency and urgency urinary incontinence (OAB wet) had DO. Of women, 58% who were OAB wet had stress urinary incontinence symptoms with 26.4% having urodynamic stress incontinence. 6% of men and 6.5% of women with OAB symptoms had urodynamic diagnosis of voiding difficulties with postvoid residual greater than 100 mL. Combination of symptoms is more accurate in predicting DO in OAB patients. The multivariate disease model for males included urge urinary incontinence (UUI) and urgency while for females it included UUI and nocturia.
There was a better correlation in results between OAB symptoms and the urodynamic diagnosis of DO in men than in women, more so in OAB wet than in OAB dry. Combination of symptoms of the OAB syndrome seems to have a better correlation with objective parameters from the bladder diary, filling cystometry, and with the occurrence of DO.
Overactive bladder; Urodynamic investigation; Urinary incontinence; Detrusor overactivity
Overactive bladder (OAB) syndrome is the term used to describe the symptom complex of urinary urgency with or without urge incontinence, usually with frequency and nocturia. Drug treatment continues to have an important role in the management of women with OAB. Other treatment options include conservative management with lifestyle interventions, modification of fluid intake, and physiotherapy including bladder retraining. Surgery remains the last resort in the treatment and is usually reserved for intractable detrusor overactivity, as it is associated with significant morbidity. This article reviews the management of the overactive bladder with specific focus on newer developments in the medical treatment of OAB in women.
Prospective randomized study to compare the efficacy and safety of alfuzosin and tamsulosin in patients suffering from acute urinary retention caused by benign prostatic hyperplasia (BPH).
Patients with acute urinary retention (AUR) due to BPH (total 150) were catheterized and randomized into three groups: Group A: alfuzosin 10 mg (50 patients), Group B: tamsulosin 0.4 mg (50 patients), Group C: placebo (50 patients). After three days, catheter was removed, and patients were put on trial without catheter (TWOC). Patients with successful TWOC were followed up for three months, taking into account the prostate symptom score (AUA Score), post-void residual urine volume (PVRV), and peak flow rate (PFR). ANOVA was used for statistical analysis.
Both group A (alfuzosin) and group B (tamsulosin) had similar results of TWOC (group A – 66%, group B – 70%), which were significantly superior than group C (placebo) – 36%. In follow up, three (9.1%) patients in group A, three (8.6%) patients in group B and eight (44.4%) patients in group C had retention of urine, requiring recatheterization. These patients were withdrawn from the study. After three months, alfuzosin- or tamsulosin-treated patients showed a significant decrease in AUA score and PVRV; and a significant increase in PFR as compared to placebo.
TWOC was more successful in men treated with either alfuzosin or tamsulosin and the subsequent need for recatheterization was also reduced. Tamsulosin was comparable to alfuzosin in all respects, except a small but significant side effect of retrograde ejaculation.
Acute urinary retention; alfuzosin; BPH; trial without catheter; tamsulosin
To analyze the effectiveness of tamsulosin 0.2 mg once daily for 3 months according to the degree of intravesical prostatic protrusion (IPP) in patients with benign prostatic hyperplasia (BPH).
Materials and Methods
A total of 134 BPH patients over 40 years of age treated with tamsulosin 0.2 mg between January 2007 and January 2009 were enrolled retrospectively. The patients were classified into three groups according to the degree of IPP: below 5 mm (group A), between 5 and 10 mm (group B), and over 10 mm (group C). Prostate volume, prostate-specific antigen (PSA), prostatic urethral length (PUL), and prostatic adenoma urethral length (PAUL) were evaluated before treatment. International Prostate Symptom Score and Quality of Life (IPSS/QoL), maximal urine flow rate (Qmax), and postvoid residual (PVR) volume were measured before treatment, and improvement in the three groups was compared after 3 months.
The mean age of the patients was 65.01±7.38 years. Mean IPPs were 0.90±1.39 mm (group A, n=90), 6.92±1.10 mm (group B, n=24), and 16.60±4.06 mm (group C, n=20). Prostate volume, PUL, PAUL, PSA, Qmax, and PVR showed significant correlations with IPP (p<0.05), but not with IPSS/QoL score (p>0.05). Comparison of parameters before and after 3 months showed that medication improved total IPSS and subscores (p<0.001), QoL (p<0.001), Qmax (p<0.001), and PVR (p=0.030) in group A. In group B, it improved total IPSS (p=0.01), irritative subscore (p<0.001), and obstructive subscore (p=0.03). In group C, only total IPSS (p=0.01) and irritative score (p<0.001) were significantly improved.
Tamsulosin may be more effective in improving symptom scores and Qmax in patients with mild IPP than in those with moderate or severe IPP.
Prostate; Prostatic hyperplasia; Ultrasonography
Bladder outlet obstruction (BOO) causes storage and voiding dysfunction in the lower urinary tract. We investigated the expression of transient receptor potential cation channel subfamily M member 8 (TRPM8) to evaluate the relationship between TRPM8 expression and overactive bladder (OAB) in a rat model of BOO.
Fifty female Sprague-Dawley rats were divided into 4 groups; normal (n=10), normal-menthol (n=10), BOO (n=15), BOO-menthol (n=15). After 3 weeks, cystometry was performed by infusing physiological saline and menthol (3 mM) into the bladder at a slow infusion rate. The histological changes and expression of TRPM8 in the bladder were investigated by Masson's trichrome staining, immunofluorescence and reverse transcription-polymerase chain reaction.
Cystometry showed that the intercontraction interval (ICI; 428.2±23.4 vs. 880.4±51.2, P<0.001), micturition pressure (MP; 25.7±1.01 vs. 71.80±3.01, P<0.001), and threshold pressure (2.9±0.25 vs. 9.2±1.58, P<0.01) were significantly increased in BOO rats. The bladder wall was significantly dilated compared with the control. Detrusor muscle hypertrophy and a thick mucosa layer were observed in BOO bladder. After menthol treatment, ICIs were decreased and MPs were increased in the menthol treatment groups. TRPM8-positive cells and mRNA were predominantly increased in the bladder and dorsal root ganglia of all groups compared with the normal group.
Increased bladder wall thickness and proportion of collagen probably affect voiding dysfunction. Furthermore, an increase of TRPM8 expression in BOO may induce entry of Ca2+ from the extracellular space or stores. The increase of Ca2+ probably causes contraction of smooth muscle in BOO. However, OAB symptoms were not observed after menthol treatment although the expression of TRPM8 was abundant in the bladder epithelium after menthol treatment. Although OAB in BOO models may be caused by complex pathways, regulation of TRPM8 presents possibilities for OAB treatment.
TRPM8; Menthol; Cold receptor; Bladder outlet obstruction
Brazilian patients with benign prostatic hyperplasia were randomised in a 12-week, double-blind, double-dummy study to receive doxazosin gastrointestinal therapeutic system (GITS) 4 mg q.i.d. (n = 82) or tamsulosin 0.4 q.i.d. (n = 83). Primary endpoints were the absolute and percentage change from baseline in symptoms measured by International Prostate Symptom Score (IPSS). Secondary endpoints included IPSS, quality-of-life (QOL) question from the IPSS, and questions 6 and 7 of the Sexual Function Abbreviated Questionnaire (SFAQ) at weeks 4 and 12. Doxazosin GITS and tamsulosin improved IPSS with no significant differences between groups at week 12. During weeks 4–8, tamsulosin-treated patients demonstrated a slower improvement (p < 0.001) in IPSS than doxazosin GITS-treated patients. The proportion of satisfied patients was observed earlier with doxazosin GITS (p = 0.006) vs. tamsulosin. At week 12, the proportion of patients with little or no difficulty at ejaculation (Q6 of SFAQ) was higher in the doxazosin GITS group (p = 0.019). Both treatments were well tolerated.
Doxazosin; tamsulosin; benign prostatic hyperplasia; international prostate symptom score; prostate; ejaculation; gastrointestinal therapeutic system
To investigate the tolerability of tolterodine extended release (ER) in older subjects with overactive bladder (OAB).
This was a retrospective analysis of pooled data from five large, randomised, double-blind, placebo-controlled trials. Subjects with OAB symptoms, including urinary frequency and urgency (and nocturia in two studies) with or without urgency urinary incontinence, received qd treatment with tolterodine ER (4 mg) or placebo for 8–12 weeks. Data were stratified post hoc by age group: < 65 (n = 2531), 65–74 (n = 1059) and ≥ 75 years (n = 573). Tolerability was assessed by evaluating the occurrence of adverse events (AEs). AE occurrences from each study were mapped to the MedDRA coding dictionary of preferred terms.
Discontinuation rates were slightly higher among subjects ≥ 75 years of age vs. those < 65 years of age; however, this was observed in subjects treated with placebo as well as tolterodine ER. Overall, there were no significant differences in the occurrence of dry mouth, headache, constipation, nausea, urinary tract infection, blurred vision, dry eye, dizziness and micturition disorder in older (65–74 or ≥ 75 years) vs. younger (< 65 years) subjects treated with tolterodine ER relative to placebo (treatment × age; all p > 0.1). Dry mouth was the only AE consistently associated with tolterodine ER treatment (< 65 years, 17%; 65–74 years, 16%; ≥ 75 years, 15%). The occurrence of all other AEs was ≤ 5% in most age and treatment cohorts. Most AEs were mild or moderate in all age and treatment cohorts.
The nature and frequency of AEs associated with tolterodine ER treatment were similar across age groups in subjects with OAB, suggesting that tolterodine ER was not associated with an increased risk of AEs in older vs. younger subjects and, thus, is a suitable first-line pharmacotherapy treatment for OAB in this population.
To investigate the type of nocturia and concomitant voiding dysfunction (VD) and the effect of desmopressin treatment on nocturia in women.
Materials and Methods
We reviewed 84 women who experienced more than 2 nocturia episodes as recorded on a pretreatment frequency volume chart and who were treated with desmopressin. All patients underwent history taking, physical examination, urinalysis, International Prostate Symptom Score assessment, completion of a urinary sensation scale, and completion of a 3 day frequency volume chart. Nocturia was divided into nocturnal polyuria (NP), reduced nocturnal bladder capacity (RNBC), and mixed type. After treatment with desmopressin, a reduction in nocturia of over 50% compared with baseline was regarded as effective.
Among 84 women, the most common concomitant VD was overactive bladder (OAB, 60.7%). NP was observed in 70.2% (59/84) of the women, RNBC in 7.1% (6/84), and mixed type in 22.6% (19/84). After medication with desmopressin, 73 women (86.9%) showed a significantly reduced number of nocturia episodes (1.4±1.5) compared with baseline (3.7±1.3, p<0.05). Eleven women (13.1%) did not show improvement. Of the 73 women who showed improvement, 41 women showed a reduction of more than 50% over baseline, and these women had a lower baseline urgency grade.
In the majority of women, nocturia coexisted with other VD such as OAB. Treatment with desmopressin effectively reduced the nocturia. However, other lower urinary tract symptoms (LUTS) such as urgency may reduce the effect of desmopressin. Therefore, consideration of concomitant LUTS seems to be necessary to increase the treatment effect of desmopressin on nocturia in women.
Deamino arginine vasopressin; Lower urinary tract symptoms; Nocturia; Women
Overactive bladder (OAB) is a chronic syndrome defined by symptoms of urinary urgency with no underlying medical causes. First-line treatment of OAB comprises fluid intake advice and bladder training, supplemented by anticholinergic drugs if necessary. Owing to the chronic nature of OAB, the ideal anticholinergic treatment should have good long-term efficacy and tolerability. There are many anticholinergics available, although some of these are not specific for the bladder and can cause adverse effects such as dry mouth, constipation, blurred vision or cognitive impairment. Imidafenacin (a newer anticholinergic which has been marketed in Japan since 2007) was developed to improve the tolerability of anticholinergic therapy. This article summarizes the pharmacological properties, pharmacokinetics, clinical efficacy and tolerability of imidafenacin in the treatment of OAB. Data from key clinical studies of imidafenacin show that it has a fast onset of action and is effective for the treatment of OAB. It selectively binds to muscarinic receptors in the bladder and is associated with a good safety profile compared with other anticholinergics. The clinical efficacy, superior tolerability and adjustable dosing of imidafenacin make it a good anticholinergic for the treatment of OAB.
bladder selectivity; efficacy; imidafenacin; overactive bladder; pharmacokinetics; tolerability