The exposure to volatile organic compounds associate positively with overactive bladder risk in U.S. adults: a cross-sectional study of 2007-2020 NHANES.

Objective: The aim of this study was to comprehensively investigate the potential relationship between blood volatile organic compounds (VOCs) and overactive bladder (OAB) risk. Methods: A total of 11,183 participants from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) were included in this cross-sectional study. We used multivariate logistic regression models to investigate the relationship between nine blood VOCs and OAB risk. Restricted cubic spline (RCS) analysis was used to investigate the dose-response relationship between blood VOCs and OAB. In addition, the overall association of blood VOCs with OAB risk was assessed by weighted quantile sum (WQS) regression model. Finally, we conducted subgroup analyses to explore the findings in different high-risk populations. Results: After adjusting for potential confounders, logistic regression analysis revealed that blood 2,5-dimethylfuran (aOR = 2.940, 95% CI: 1.096-7.890, P = 0.032), benzene (aOR = 1.460, 95% CI: 1.044-2.043, P = 0.027) and furan (aOR = 9.426, 95% CI: 1.421-62.500, P = 0.020) were positively independent associated with the risk of OAB. And dose-response risk curves indicated that 2,5-dimethylfuran, benzene and furan in the blood were linearly positive associated with OAB risk. WQS regression analysis showed that exposure to mixed blood VOCs increased the risk of OAB (OR = 1.29, 95% CI: 1.11-1.49), with furans having the greatest weight. In subgroup analyses, we found that OAB was more susceptible to blood VOCs in young and middle-aged, male, non-hypertensive, and alcohol-drinking populations. Conclusions: The results of this study indicate that high exposure to VOCs is independently and positively associated with OAB risk in U.S. adults, particularly 2,5-dimethylfuran, benzene, and furan. In addition, age, gender, hypertension and alcohol consumption may influence the association. Our study provided novel epidemiologic evidence to explore the potential role of environmental pollutants in OAB.

Diabetes mellitus, systemic inflammation and overactive bladder.

Background: Increasing evidence emphasizes the potential relationship between diabetes and OAB (overactive bladder). However, large population epidemiology is still lacking. Methods: This cross-sectional study included six cycle NHANES surveys, with a total of 23863 participants. Logistic regression models were constructed to analyze the association between diabetes mellitus, diabetes-related markers, and inflammatory biomarkers with OAB. Restricted cubic splines were used to analyze the non-linear associations. Mediating analysis was performed to test the effect of inflammatory biomarkers on the relationship between diabetes-related markers and OAB. Finally, machine learning models were applied to predict the relative importance and construct the best-fit model. Results: Diabetes mellitus participants' OAB prevalence increased by 77% compared with non-diabetes. As the quartiles of diabetes-related markers increased, the odds of OAB monotonically increased in three models (all p for trend < 0.001). Glycohemoglobin exhibited a linear association with OAB (p for nonlinearity > 0.05). White blood cells significantly mediated the associations between diabetes-related markers (glycohemoglobin, fasting glucose, and insulin) with OAB, and the proportions were 7.23%, 8.08%, and 17.74%, respectively (all p < 0.0001). Neutrophils partly mediated the correlation between (glycohemoglobin, fasting glucose, and insulin) and OAB at 6.58%, 9.64%, and 17.93%, respectively (all p < 0.0001). Machine learning of the XGBoost model constructs the best fit model, and XGBoost predicts glycohemoglobin is the most important indicator on OAB. Conclusion: Our research revealed diabetes mellitus and diabetes-related markers were remarkably associated with OAB, and systemic inflammation was an important mediator of this association.

Efficacy and safety of onabotulinumtoxinA in patients with overactive bladder: subgroup analyses by sex and by serum prostate-specific antigen levels in men from a randomized controlled trial.

PURPOSE: We aimed to assess onabotulinumtoxinA treatment outcomes by sex in patients with overactive bladder (OAB) and then explore the impact of serum prostate-specific antigen (PSA) levels in men. METHODS: Patients inadequately managed with OAB medications were randomized to receive single-dose onabotulinumtoxinA (100 U) or placebo intravesical injection in a phase III trial in Japan. We performed subgroup analyses by sex and post-hoc subgroup analyses using male PSA categories. RESULTS: In women (n = 186), onabotulinumtoxinA demonstrated statistically significant and clinically relevant improvements in all urinary symptoms at Week 12. In men with lower PSA (< 1.5 ng/mL, n = 40), onabotulinumtoxinA also showed numerically greater reductions in urinary symptom frequency than placebo; the between-group differences (onabotulinumtoxinA minus placebo) in change from baseline in the average daily number at Week 12 for urinary incontinence (UI), urgency UI, micturition, urgency, and nocturia were - 1.43, - 1.79, - 2.81, - 2.45, and - 0.32 episodes, respectively. In men with higher PSA (≥ 1.5 ng/mL, n = 22), onabotulinumtoxinA did not reduce urinary symptom frequency. Some patients treated with onabotulinumtoxinA showed elevated post-void residual urine volume at Week 2 (≥ 200 mL): 4 of 91 women, none of the men with lower PSA and 3 of 11 men with higher PSA. CONCLUSIONS: OnabotulinumtoxinA was efficacious and well tolerated in women and in men with lower PSA levels. Given our post-hoc subgroup analyses which suggested that onabotulinumtoxinA treatment is a good treatment option for OAB males with lower PSA levels, future studies having prostate volume data with larger sample size are warranted to verify our findings. CLINICALTRIALS. GOV IDENTIFIER: NCT02820844 (first posted July 1, 2016). https://clinicaltrials.gov/ct2/show/NCT02820844 .

The association between serum serotonin levels and overactive bladder: results from a community-based cross-sectional study in Japan.

PURPOSE: To investigate the association between serum serotonin (5-HT) levels and overactive bladder (OAB) in a community-dwelling population. METHODS: This cross-sectional study analyzed 1024 subjects who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. OAB was assessed using the Overactive Bladder Symptom Score (OABSS). OAB was defined as an occurrence of urinary urgency at least once a week and an OABSS of ≥ 3. We assessed serum 5-HT levels, laboratory data, and comorbidities of each participants. Participants' mental health status was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale. The association of serum 5-HT levels and OAB was analyzed by multivariable logistic regression analysis. RESULTS: This study included 394 men and 630 women. Of those, 118 (44 male and 74 female) were OAB sufferers. There were significant group differences in age, history of cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus, and CES-D score. Participants' serum 5-HT levels in the OAB group were significantly lower than those in the non-OAB group (100 vs. 127 ng/mL, P < 0.001). Multivariable analysis showed that age (odds ratio [OR]; 1.06, 95% confidence interval [CI]; 1.04-1.08, P < 0.001) and log serum 5-HT level (OR; 0.25, 95% CI; 0.10-0.68, P = 0.006) were independently associated with OAB. CONCLUSIONS: Lower serum 5-HT levels could independently be associated with the presence of OAB. Further study is necessary to elucidate a possible causal relationship between serum 5-HT levels and OAB.

The Effect of a Sharp Increase in Estrogen Levels on Overactive Bladder Symptoms in Women Undergoing Ovulation Induction.

OBJECTIVE: To assess the effect of a sharp increase in estrogen levels on overactive bladder (OAB) symptoms among women undergoing ovulation induction. METHODS: 100 consecutive women (mean age 36.9 ± 5.2 years) who underwent IVF treatments, were prospectively enrolled. Three validated questionnaires on urinary urgency, urinary incontinence, and lower urinary tract symptoms were used to evaluate patient's OAB symptoms before ovulation induction (low estradiol level) and prior to ovum pickup (peak estradiol level). RESULTS: Of the 100 women, 49 reported OAB symptoms prior to ovulation induction (mean USIQ severity score 33) and 51 women were asymptomatic. Of the 49 symptomatic women, 44 (90%) remained symptomatic (mean USIQ severity score 34) and 5 women became asymptomatic through ovulation induction. Of the 51 asymptomatic women, 24 (47%) developed de novo OAB symptoms, while 27 women (53%) remained asymptomatic through ovulation induction. The mean peak estradiol level was significantly higher among women who remained asymptomatic in comparison to women with de novo OAB symptoms (2069 versus 1372 pg/ml; respectively). Moreover, in most (63%) women who remained asymptomatic, peak estradiol levels were higher than 1500 pg/ml, whereas in most (67%) women who became symptomatic, peak estradiol levels were lower than 1500 pg/ml. CONCLUSION: A higher estradiol level appears to have a protective effect against the development of OAB symptoms during ovulation induction. Further, in most (63%) women who remained asymptomatic, peak estradiol levels were higher than 1500 pg/ml. This finding may suggest a threshold for estradiol activity in the lower urinary tract.

Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity.

BACKGROUNDMirabegron is a ß3-adrenergic receptor (ß3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that ß3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSIONThese findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of ß3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATIONClinicaltrials.gov NCT03049462.FUNDINGThis work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).

Metabolism of fatty acids and bile acids in plasma is associated with overactive bladder in males: potential biomarkers and targets for novel treatments in a metabolomics analysis.

OBJECTIVES: The present study was conducted to identify metabolites using a metabolomics approach and investigate the relationship between these metabolites and urgency as a major symptom of overactive bladder (OAB). PATIENTS AND METHODS: In 47 male participants without any apparent neurological disease, OAB was defined as an urgency score on the International Prostate Symptom Score of 2 and higher (OAB group, n = 26), while patients with a score of 1 or 0 were placed in a control group (n = 21). A comprehensive study on plasma metabolites was conducted, and metabolites were compared between the OAB and control groups. RESULTS: Age was significantly higher in the OAB group, while prostate volume did not differ between the groups. A 24-h bladder diary revealed that nocturnal urine volume, 24-h micturition frequency, nocturnal micturition frequency, and the nocturnal index were significantly higher in the OAB group, whereas maximum voided volume was significantly lower in this group. The metabolomics analysis identified 79 metabolites from the plasma of participants. The multivariate analysis showed that increases in the fatty acids (22:1), erucic acid and palmitoleic acid, and a decrease in cholic acid correlated with incidence of male OAB. A decrease in acylcarnitine (18:2)-3 and an increase in cis-11-eicosenoic acid also appeared to be associated with OAB in males. CONCLUSIONS: OAB in males may occur through the abnormal metabolism of fatty acids and bile acids. Further studies on these pathways will contribute to the detection of new biomarkers and development of potential targets for novel treatments.

Evaluation of Choline and Acetylcholine Levels in Responders and Nonresponders to Anticholinergic Therapy for Overactive Bladder Syndrome.

OBJECTIVE: This study aimed to determine whether levels of choline (Ch) and acetylcholine (Ach) differ between responders and nonresponders to anticholinergic therapy. METHODS: Patients prescribed an anticholinergic were evaluated using the Overactive Bladder Symptom Score; Medical, Epidemiologic and Social Aspects of Aging and Incontinence Questionnaire; and Incontinence Impact Questionnaire-7. A 1-day voiding diary and a urine sample were collected. After treatment for 12 weeks, the questionnaires were administered and 1-day voiding diary was completed. Levels of Ach and Ch were measured by liquid chromatography with tandem mass spectrometry. Subjects were divided into responders and nonresponders. Wilcoxon rank sum test and Fisher exact test were used to express differences between groups. Spearman ρ correlation coefficient was used to determine the relationship between Ach and Ch and symptom severity, patient demographics, and questionnaire scores. RESULTS: Thirty-one women were included in the analysis. The treatment response rate was 48.8%. The median age was 67 years (interquartile range, 50-76 years), and median body mass index was 32.3 kg/m2 (27.5-40.6 kg/m2), with 41.2% having an additional complaint of stress incontinence. There were no significant differences in symptom severity or questionnaire scores between groups.The median Ch and Ach levels were higher in responders (28.6 vs 9.2 µL, P = 0.04) and (83.1 vs 18.7 nL, P = 0.02), respectively. Levels of both Ch and Ach had moderate positive correlations with the Medical, Epidemiologic and Social Aspects of Aging and Incontinence Questionnaire urgency urinary incontinence score (ρ = 0.533 [P = 0.002] and ρ = 0.453 [P = 0.01], respectively). CONCLUSION: In women with overactive bladder, urinary Ach and Ch levels are higher in responders to anticholinergic therapy compared with nonresponders.

Overactive bladder and associated psychological symptoms: A possible link to vitamin D and calcium.

INTRODUCTION: Overactive bladder (OAB) is a prevalent syndrome that is associated with multiple urinary tract symptoms and could affect the patient's quality of life and well-being. Vitamin D is shown to be linked to OAB syndrome, which exacerbated by stress conditions. This study evaluated the relationship between vitamin D status, daily calcium intake and OAB, and the associated psychological symptoms. METHODS: The study included 55 patients with OAB and 129 healthy controls. Psychological symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Serum vitamin D was measured. Patients with OAB with low vitamin D level received orally vitamin D supplementation. Urinary symptoms, psychological symptoms, and quality of life were evaluated before and after vitamin D supplementation plus dairy products. RESULTS: Vitamin D deficiency was more prevalent in cases (80%) vs controls (34.9%). Depression (43.7% vs 20.2%) and anxiety (52.8% vs 10.9%) scores (HADS, ≥8) were also more frequent in cases vs controls, respectively. Some 85.5% of the patients' group had musculoskeletal pain vs 0.0% for the control. Depression was negatively correlated with daily calcium intake and positively with anxiety. Logistic regression analysis revealed that age, vitamin D, and anxiety scores were significant predictors of OAB. Vitamin D supplements with increased calcium intake had significant improvement in urinary symptoms, psychological distress, and quality of life. CONCLUSIONS: Vitamin D supplements and improved calcium intake may improve urinary and psychological symptoms and quality of life among patients with OAB syndrome. Assessment for vitamin D status in patients with OAB may be warranted.

[Sensitivity and specificity of urinary and serum neurotrophins in the diagnosis of neurogenic detrusor overactivity in multiple sclerosis].

Lower urinary tract dysfunction is common among neurological patients. Traditionally, the basic method of diagnosis is a complex urodynamic study. In recent years, many studies have focused on the search for new non-invasive diagnostic modalities. In particular, neurotrophins are considered as potential biological markers of a neurogenic bladder. AIM: To estimate the sensitivity and specificity of the serum and urinary nerve growth factor (NGF) and brain neurotrophic factor (BDNF) in MS patients as markers of detrusor overactivity. MATERIALS AND METHODS: The study comprised 20 patients with multiple sclerosis, who complained of voiding problems. The control group consisted of 20 people without neurological diseases, lower urinary tract symptoms and detrusor overactivity estimated by filling cystometry. Apart from standard laboratory tests, diagnostic evaluation included a complex urodynamic study, ultrasound of the urinary tract, cystoscopy, testing serum and urinary NGF and BDNF using the enzyme immunoassay. The diagnostic significance of neurotrophins was evaluated using ROC analysis. RESULTS: According to the ROC analysis, the diagnostic sensitivity and specificity of serum NGF as a marker of detrusor hyperactivity was 57% and 93%, respectively (for serum NGF more or equal 26 pg/ml). The quality of the test according to the expert scale of AUC values was "very good" (AUC=0.806). Detecting NGF in patients urine was less effective. The sensitivity and specificity were 52% and 40%, respectively (for NGF more or equal 6 pg/ml). The quality of the test according to the expert scale of AUC values was "average" (AUC=0.64). The serum BDNF demonstrated high sensitivity (90%) and low specificity (23%), AUC=0.56. The urinary BDNF was more informative, (AUC=0.65). The combination of all four markers provides a sensitivity of 85.7% and a specificity of 66.7% (AUC=0.824). CONCLUSIONS: Testing serum and urinary neurotrophins in patients with multiple sclerosis can be used to diagnose detrusor overactivity. The NGF is a highly specific biomarker, while the BDNF is highly sensitive. Combined testing for serum NGF and BDNF is most informative.

Impact of serum 25-OH vitamin D level on lower urinary tract symptoms in men: a step towards reducing overactive bladder.

OBJECTIVES: To evaluate the impact of serum vitamin D level on male lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Men with LUTS who visited the outpatient clinic of the urology department at one of two hospitals between March 2014 and April 2017 were eligible for inclusion in the study. The impact of vitamin D on LUTS was evaluated using multivariate analysis to adjust for age, body mass index, prostate-specific antigen, testosterone, glycated haemoglobin, physical activity and prostate volume. To exclude the effect of seasons, we also analysed the impact during each season. RESULTS: Vitamin D level was lowest in winter. According to the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS), the severity of LUTS peaked in winter. There were no seasonal differences between prostate volume, maximum urinary flow rate (Qmax ) and post-void residual urine volume (PVR). For all patients, multivariate analysis showed that lower vitamin D level was significantly associated with higher total OABSS, whereas it was not associated with prostate volume, Qmax , PVR or total IPSS. In winter, lower vitamin D level was significantly associated with higher total OABSS based on multivariate analysis, whereas it was not during other seasons. In patients with vitamin D deficiency, the total OABSS significantly decreased after vitamin D replacement. The greatest improvement in total OABSS was associated with lower pre-treatment total OABSS and higher post-treatment vitamin D level. CONCLUSIONS: Vitamin D deficiency in men with LUTS may play a role in aggravated overactive bladder (OAB) symptoms, especially in winter. Increasing vitamin D level in patients with vitamin D deficiency appears to alleviate OAB symptoms.

Metabolomic Analysis of Overactive Bladder in Male Patients: Identification of Potential Metabolite Biomarkers.

OBJECTIVES: To identify metabolites that are associated with an overactive bladder (OAB) using metabolomics. MATERIALS AND METHODS: A total of 58 male patients without apparent neurologic disease completed 24-hour bladder diaries of their micturition behavior and International Prostate Symptom Score (IPSS) for the assessment of micturition behavior and lower urinary tract symptoms. Urgency was defined as an IPSS urgency score of ≥2 (OAB group), and patients with IPSS urgency scores of ≤1 belonged to the control group. A comprehensive study of plasma metabolites was also conducted using capillary electrophoresis time-of-flight mass spectrometry. Metabolite levels were compared between the control and OAB groups using the Mann-Whitney U test. Potential metabolite biomarkers were selected using multivariate logistic regression analysis. RESULTS: Of the 58 subjects, the control and OAB groups consisted of 32 and 26 male patients, respectively. Nocturnal urinary volume, 24-hour micturition frequency, nocturnal micturition frequency, and the nocturia index were significantly higher in the OAB group. Metabolomic analysis revealed 60 metabolites in the subjects' plasma. The levels of 11 metabolites differed between the control and OAB groups. Multivariate analysis showed that an increased glutamate level and reduced arginine, glutamine, and inosine monophosphate levels are significantly associated with OAB in male patients. Reduced levels of asparagine and hydroxyproline could also be associated with OAB. CONCLUSIONS: Urgency is associated with abnormal metabolism. Analyses of amino acid profiles might aid the search for new treatment targets for OAB.

Association between Metabolic Syndrome and Serum Nerve Growth Factor Levels in Women with Overactive Bladder.

OBJECTIVE: This study aimed to determine the association between overactive bladder (OAB), metabolic syndrome (MetS) and serum nerve growth factors (NGF). STUDY DESIGN: Serum samples from a group of 90 women that included patients with OAB (group 1), patients with both OAB and MetS (group 2) and healthy women without OAB and MetS (group 3). Each group included 30 patients. Serum levels of NGF were compared among the groups. RESULTS: When the groups were compared with respect to NGF levels, group 2 was found to have significantly higher NGF levels (p = 0.001). A NGF threshold of >380 ng/mL had a sensitivity of 81.7% and a specificity of 100% to discriminate between groups 2 and 3. CONCLUSION: Our findings support the theory that possible sympathetic overactivity, proinflammatory status, oxidative stress and other pathological conditions associated with MetS and potentially involved in the development of OAB lead to increased serum NGF levels. These findings may help to shed light on the complicated pathogenesis of OAB.

Assessment of lower urinary symptom flare with overactive bladder symptom score and International Prostate Symptom Score in patients treated with iodine-125 implant brachytherapy: long-term follow-up experience at a single institute.

BACKGROUND: The aim of this study was to evaluate the combined use of the overactive bladder symptom score (OABSS) and International Prostate Symptom Score (IPSS) as an assessment tool for urinary symptom flare after iodine-125 (125I) implant brachytherapy. The association between urinary symptom flare and prostate-specific antigen (PSA) bounce was investigated. METHODS: Changes in the IPSS and OABSS were prospectively recorded in 355 patients who underwent seed implantation. The percentage distribution of patients according to the difference between the flare peak and post-implant nadir was plotted to define significant increases in the scores. The clinicopathologic characteristics, treatment parameters, and post-implant dosimetric parameters were compared between the non-flare and flare groups. PSA bounce was defined as an elevation of ≥0.1 ng/mL or ≥0.4 ng/mL compared to the previous lowest value, followed by a decrease to a level at or below the pre-bounce value. RESULTS: A clinically significant increase required an IPSS increase of at least 12 points and an OABSS increase of at least 6 points based on a time-course analysis of total scores and the QOL index. Assessment only by IPSS failed to detect 40 patients (11%) who had urinary symptom flare according to the OABSS. Univariate and multivariate analyses revealed that patients treated with higher biologically effective doses and those without diabetes mellitus had higher risks of urinary flare. There was no statistical correlation between the incidence and time of urinary symptom flare onset and that of a PSA bounce. CONCLUSIONS: To our knowledge, this is the first report to prove the clinical potential of the OABSS as an assessment tool for urinary symptom flare after seed implantation. Our findings showed that persistent lower urinary tract symptoms after seed implantation were attributed to storage rather than to voiding issues. We believe that assessment with the OABSS combined with the IPSS would aid in decision-making in terms of timing, selection of a treatment intervention, and assessment of the outcome.

Urinary Excretion Contributes to Long-Lasting Blockade of Bladder Muscarinic Receptors by Imidafenacin: Effect of Bilateral Ureteral Ligation.

Imidafenacin is a potent and selective antagonist of M1 and M3 muscarinic receptors that is safe, efficacious, and well tolerated for controlling the symptoms of overactive bladder (OAB). However, the precise mechanisms responsible for the bladder-selective pharmacological effects of this agent remain unclear. The in vivo pharmacologic effects of imidafenacin result from receptor occupancy. Therefore, the present study was performed to characterize in vivo muscarinic receptor binding by tritium-labeled imidafenacin with high specific activity ([3H]imidafenacin) in the bladder and other tissues of mice, and to clarify the mechanisms underlying selective binding of imidafenacin to bladder muscarinic receptors. After intravenous injection of [3H]imidafenacin, its binding to muscarinic receptors in the bladder and other tissues of mice was assessed by a radioligand binding assay. [3H]Imidafenacin showed a significantly longer duration of binding to muscarinic receptors in the bladder than in other tissues, and muscarinic receptor binding of [3H]imidafenacin was markedly suppressed in the bladder alone after bilateral ligation of the ureters. After intravenous injection, the [3H]imidafenacin concentration was markedly higher in the urine than in the plasma, suggesting that urinary excretion may contribute significantly to the selective and long-lasting binding of imidafenacin to bladder muscarinic receptors. These findings suggest that the intravesicular concentration of an antimuscarinic agent and its active metabolites may have a substantial influence on its pharmacological effect and duration of action in patients with OAB. In addition, factors that modulate urine production may influence the efficacy and safety of antimuscarinic agents.

Pathogenic Features of Dysuria in Young Women with Secondary Amenorrhea Caused by Body Weight Loss.

We examined 11 women aged 19-26 years (mean age 22.5±3.5 years) with secondary amenorrhea complaining frequent urination over 1.5 years and repeatedly, but unsuccessful treated for overactive bladder and chronic cystitis. The rare cause of sustained urination disorders in young female patients of reproductive age was established: development of secondary amenorrhea caused by weight loss ("cosmetic" amenorrhea) with subsequent estrogene deficit and urogenital atrophy. Morphological examination of the bladder mucosa, an important clue to the diagnosis, helps to identify the true cause of dysuria, urogenital atrophy of the bladder mucosa, in secondary ("cosmetic") amenorrhea, and determine future course of etiopathogenic treatment of sustained dysuria in young women. The treatment is often effective in case of proper and timely diagnosis and the absence of irreversible changes.

Hormonal influence on the effect of mirabegron treatment for overactive bladder.

OBJECTIVE: The aim of this study was to evaluate if levels of gonadotropic and sex steroidal hormones influence the efficacy of mirabegron in the treatment of overactive bladder. METHODS: We included 58 female participants who received treatment with mirabegron 50 mg once daily and provided a blood sample for hormone profiling before treatment was initiated. Serum hormone concentrations for estradiol, progesterone, testosterone, FSH, LH, TSH, and T4 were analyzed. Urinary Distress Inventory (UDI), (overactive bladder domain: UDIOAB), and the short form Pelvic Floor Impact Questionnaire (PFIQ-7) were used to assess subjective outcomes. RESULTS: There were significant overall improvements in UDI, UDIOAB, and the PFIQ from baseline to the 2 months of follow-up (P = 0.001, 0.001, and 0.008, respectively). The magnitude of the mean difference of improvements was similar between pre- and postmenopausal women. Estrogen levels were nonsignificantly lower in participants who experienced an improvement in UDI and UDIOAB at 2 months of follow-up as compared with those that did not (P = 0.7). There were no other clinically relevant differences in hormone levels in relation to improvements in UDI, UDIOAB, or PFIQ. In logistic regression analysis there were no associations between UDIOAB outcomes and age, previous use of anticholinergic drugs, parity, menopause, and local estrogen treatment. CONCLUSIONS: Estradiol, gonadotropic hormones, thyroid hormones, and testosterone levels did not influence the clinical effects of mirabegron in women with overactive bladder. Menopause status should not be a determinant for mirabegron treatment.

Functional and morphological alterations of the urinary bladder in type 2 diabetic FVB(db/db) mice.

AIMS: Diabetic bladder dysfunction (DBD) has been extensively studied in animal models of type 1 diabetes. We aimed to examine the functional and morphological alterations of the urinary bladder in a type 2 diabetes model, FVB(db/db) mice. METHODS: FVB(db/db) mice and age-matched FVB/NJ control mice were tested at either 12, 24 or 52weeks of age. Body weight, blood glucose and glycated hemoglobin (HbA1c) levels were measured. Bladder function was assessed by measurement of 24-h urination behavior and conscious cystometry. Bladder was harvested for Masson's Trichrome staining and morphometric analysis. RESULTS: The body weights of FVB(db/db) mice were twice as those of FVB/NJ control mice. The blood glucose and HbA1c levels were higher in FVB(db/db) mice at 12 and 24weeks, but not at 52weeks. A significant increase in the mean volume per void, but decrease in the voiding frequency, in FVB(db/db) mice was observed. Cystometry evaluation showed increased bladder capacity, voided volume, and peak micturition pressure in FVB(db/db) mice compared with FVB/NJ mice. Morphometric analysis revealed a significant increase in the areas of detrusor muscle and urothelium in FVB(db/db) mice. In addition, some FVB(db/db) mice, especially males at 12 and 24weeks, showed small-volume voiding during 24-h urination behavior measurement, and detrusor overactivity in the cystometry measurement. CONCLUSIONS: The FVB(db/db) mouse, displaying DBD characterized by not only increased bladder capacity, void volume, and micturition pressure, but also bladder overactivity, is a useful model to further investigate the mechanisms of type 2 diabetes-related bladder dysfunction.

Hypovitaminosis D is an independent associated factor of overactive bladder in older adults.

AIM OF THE STUDY: Urinary incontinence and vitamin D deficiency are common problems encountered in geriatric population. We aimed to investigate if there is a relationship between these conditions. SUBJECTS AND METHOD: Among 2281 patients who were admitted to our geriatric medicine outpatient clinic spanning the last three years, 705 patients with known vitamin D status, urinary incontinence and subtype, and calcium plus vitamin D therapy data were included in statistical analysis. Patients who are using calcium plus vitamin D therapy were excluded. SPSS (Statistical Package for Social Sciences) version 15.0 for Windows was used for statistical analysis and p<0.05 was considered as statistically significant. RESULTS: Mean age of the study population was 72.3±6.4years and 62.8% were female. Plasma vitamin D level (OR: 0.968, 95%CI: 0.943-0.993, p=0.013), MMSE (Mini Mental State Examination) score (OR: 0.944, 95%CI: 0.902-0.989, p=0.014), and serum ALP (Alkaline Phosphatase) level (OR: 0.995, 95%CI: 0.992-0.998, p=0.001) were found to be inversely correlated factors, and serum calcium level (OR: 1.772, 95%CI: 1.008-2.888, p=0.022) was found to be a positively correlated factor of overactive bladder. Considering the different clinical subtypes of urinary incontinence, only urgency incontinence was associated with lower plasma vitamin D level (p=0.013). CONCLUSIONS: Vitamin D deficiency and insufficiency are independent associated factors for overactive bladder in older adults. This is explicable by effects of vitamin D on muscle growth and function.

[DISTINCTIVE FEATURES OF VEGETATIVE AND HORMONAL REGULATION IN WOMEN WITH OVERACTIVE BLADDER SYNDROME].

Using indices of heart rate variability the authors identified patterns in alterations of vegetative status in women with overactive bladder syndrome in different periods of the reproductive function. They established predominant role of sympathetic influences in the development of the OAB syndrome in reproductive period, during menopause and in postmenopause. The study results verified the role of hormonal levels in women with OAB syndrome in different periods of the reproductive function, having a different initial tone of the autonomic nervous system.