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1.  Influence of Type of Nocturia and Lower Urinary Tract Symptoms on Therapeutic Outcome in Women Treated With Desmopressin 
Korean Journal of Urology  2013;54(2):95-99.
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.
PMCID: PMC3580312  PMID: 23549374
Deamino arginine vasopressin; Lower urinary tract symptoms; Nocturia; Women
2.  Association of overactive bladder and C-reactive protein levels. Results from the Boston Area Community Health (BACH) Survey 
Bju International  2011;110(3):401-407.
To investigate the association between overactive bladder (OAB) and C-reactive protein (CRP) in a population-based sample of men and women.
Epidemiological survey of urological symptoms among men and women aged 30–79 years. A multi-stage stratified cluster design was used to randomly sample 5503 adults from the city of Boston. Analyses were conducted on 1898 men and 1854 women with available CRP levels.
The International Continence Society defines OAB as ‘Urgency with or without urge incontinence, usually with frequency and nocturia.’ OAB was defined as: (1) urgency, (2) urgency with frequency, and (3) urgency with frequency and nocturia.
Odds ratios (OR) and 95% confidence intervals (95% CI) of the CRP and OAB association were estimated using logistic regression.
Prevalence of OAB increased with CRP levels in both men and women.
In men, adjusted ORs (95% CI) per log10(CRP) levels were 1.90 (1.26–2.86) with OAB defined as urgency, 1.65 (1.06–2.58) with OAB defined as urgency and frequency, and 1.92 (1.13–3.28) with OAB defined as urgency, frequency and nocturia.
The association was more modest in women with ORs (95% CI) of 1.53 (1.07–2.18) for OAB as defined urgency, 1.51 (1.02–2.23) for OAB defined as urgency and frequency, and 1.34 (0.85–2.12) for OAB defined as urgency, frequency and nocturia.
Results show a consistent association of increasing CRP levels and OAB among both men and women.
These results support our hypothesis for the role of inflammation in the development of OAB and a possible role for anti-inflammatory agents in its treatment.
PMCID: PMC3325364  PMID: 22176817
C-reactive protein; epidemiology; inflammation; overactive bladder
3.  Dietary Macronutrient Intake and Lower Urinary Tract Symptoms in Women 
Annals of epidemiology  2011;21(6):421-429.
To examine associations between macronutrient and total energy intakes with lower urinary tract symptoms (LUTS) in women.
Cross-sectional analysis of 2,060 women aged 30–79 years in the population-based Boston Area Community Health Survey (2002–2005). Data were collected by validated food frequency questionnaire and in-person interviews. Outcomes for multivariate logistic regression were moderate-to-severe total LUTS, storage, voiding, and post-micturition symptoms.
Greater total energy intake was positively associated with LUTS, specifically among women with lower waist circumferences (<76 cm, P=0.005, pinteraction=0.01). Increased saturated fat intake was associated with post-micturition symptoms (Quintile 5 vs. 1, OR 3.94, 95% CI 1.57, 9.89, ptrend =0.04). High protein intake was positively associated with storage symptoms (ptrend =0.03), particularly nocturia. No consistent associations were observed for carbohydrate, monounsaturated or polyunsaturated fat intakes.
Among women with low waist circumferences, high total daily calorie intake was associated with moderate-to-severe LUTS. While greater saturated fat intake was linked to post-micturition symptoms, the possibility that post-micturition symptoms in women represent more extensive or severe conditions should be explored in future research. These novel results indicate that dietary contributors to LUTS in women are distinct from those in men and may depend on symptom subtype and body size.
PMCID: PMC3090524  PMID: 21421330
Diet; Energy intake; Nutrition; Urination disorders; Lower urinary tract symptoms; Urinary tract; Fatty acids; saturated; Dietary fats; Dietary proteins
4.  Prostatic hyperplasia is highly associated with nocturia and excessive sleepiness: a cross-sectional study 
BMJ Open  2012;2(3):e000505.
The objective of this study is to assess the impact of nocturia on sleep in patients with lower urinary tract symptoms (LUTS)/benign prostatic enlargement (BPE) (nocturia≥2).
Cross-sectional survey.
798 urologists and general practitioners randomly selected from the overall population of urologists and general practitioners of every French region.
A total of 2179 LUTS/BPE men (aged 67.5±7.5 years old) were recruited.
Primary and secondary outcome measures
Validated patients' self-administered questionnaires were used to assess the severity of LUTS/BPE (the International Prostate Symptom Score), sleep characteristics (sleep log) and sleep disorders (the International Classification of Sleep Disorders (ICSD-2) and the DSM-IV). Sleepiness was assessed with the Epworth Sleepiness Scale (ESS). The volume of 24 h diuresis (1500 ml) was measured.
Participants had on average 2.9±0.9 nocturia episodes (three or more episodes in 67%) and the International Prostate Symptom Score of 15.8±5.7; 60.9% complained of insomnia according to the ICSD-2, 7.9% of restless leg syndrome and 6.4% of obstructive sleep apnoea. 32.3% had excessive sleepiness (ESS >10) and 3.1% severe excessive sleepiness (ESS >16). Insomnia was mainly nocturnal awakenings with an average wake after sleep onset of 89±47 min. The number of episodes of nocturia per night correlated significantly with wake after sleep onset and ESS but not with total sleep time and sleep latency.
Nocturia is significantly associated with sleep maintenance insomnia and sleepiness in men with BPE.
Article summary
Article focus
Complaint of nocturia and its links with excessive sleepiness.
Assessment of the impact of nocturia on sleep.
Key messages
By being disruptive to sleep, the nocturia episodes affected sleep efficiency and quality.
The number of nocturia episodes was associated with an increased sleepiness in men with benign prostatic hyperplasia.
Strengths and limitations of this study
This is a cross-sectional study. It would have been more convincing to compare our subjects to a similar group of older people with no benign prostatic hyperplasia. However, our study focused on the frequency of insomnia and on the correlates between benign prostatic hyperplasia and insomnia.
PMCID: PMC3367152  PMID: 22649170
5.  A Survey on Lower Urinary Tract Symptoms (LUTS) Among patients with Benign Prostatic Hyperplasia (BPH) in Hospital Universiti Sains Malaysia (HUSM) 
Patients with Benign Prostatic Hyperplasia (BPH) commonly presents with lower urinary tract symptoms (LUTS), which can be of obstructive symptoms such as hesitancy, incomplete voiding, post void dribbling or of irritative symptoms such as urgency, frequency and nocturia. Various recent studies indicate that nocturia is a very important and bothersome lower urinary tract symptom especially among patients with Benign Prostatic Hyperplasia (BPH). The aims of the study was to determine the frequency of common urinary symptoms among patients with BPH in HUSM as well as to evaluate the extent of bothersomeness of each and every symptom to these patients. This study too was aimed at evaluating the success of TURP in resolving pre operative LUTS. This was a questionnaire-based survey using a validated ICSBPH model whereby patients with BPH were selected and quizzed personally by an investigator. A subset of patients who had undergone TURP were further questioned regarding their satisfaction with the procedure. When nocturia is defined as waking up at night once or more to pass urine, the prevalence of nocturia was about 90%, but only 1 in 6 patients considered this is a very serious symptom. Even if the definition was changed to waking up twice or more, the prevalence is still quite high at over 80%. Urgency were noted in half of the patients, but only a quarter of them consider it a serious problem. 1 in 5 patients experienced significant leak and almost all consider it serious. About one third of the studied population had to be catheterized due to urinary obstruction and interestingly only about half of them considered it as a very serious event. Overall, a great majority of these patients considered suffering from these urinary symptoms for the rest of their life as very devastating. This study conclude that although the prevalence of nocturia was high among BPH patients, but it was not considered serious by majority of them. In fact, LUTS in our BPH patients did not differ much from BPH patients elsewhere. On the whole, TURP resolved most of the LUTS effectively.
PMCID: PMC3442630  PMID: 22993495
Survey; lower urinary tract symptoms; benign prostatic hyperplasia; nocturia; bothersomeness
6.  What Is the Most Bothersome Lower Urinary Tract Symptom? Individual- and Population-level Perspectives for Both Men and Women 
European Urology  2014;65(6):1211-1217.
No study has compared the bothersomeness of all lower urinary tract symptoms (LUTS) using a population-based sample of adults. Despite this lack of evidence, investigators have often cited their LUTS of interest as the “most bothersome” or “one of the most bothersome.”
To compare the population- and individual-level burden of LUTS in men and women.
Design, setting, and participants
In this population-based cross-sectional study, questionnaires were mailed to 6000 individuals (18–79 yr of age) randomly identified from the Finnish Population Register.
Outcome measurements and statistical analysis
The validated Danish Prostatic Symptom Score questionnaire was used for assessment of bother of 12 different LUTS. The age-standardized prevalence of at least moderate bother was calculated for each symptom (population-level burden). Among symptomatic individuals, the proportion of affected individuals with at least moderate bother was calculated for each symptom (individual-level bother).
Results and limitations
A total of 3727 individuals (62.4%) participated (53.7% female). The LUTS with the greatest population-level burden were urgency (7.9% with at least moderate bother), stress urinary incontinence (SUI) (6.5%), nocturia (6.0%), postmicturition dribble (5.8%), and urgency urinary incontinence (UUI) (5.0%). Burden from incontinence symptoms was higher in women than men, and the opposite was true for voiding and postmicturition symptoms. At the individual level, UUI was the most bothersome for both genders. Although the response proportion was high, approximately a third did not participate.
Both men and women with UUI report moderate or major bother more frequently than individuals with other LUTS. At the population level, the most prevalent bothersome symptoms are urgency, SUI, and nocturia.
Patient summary
Urinary urgency was the most common troubling symptom in a large population-based study; however, for individuals, urgency incontinence was the most likely to be rated as bothersome.
Take Home Message
Population-based study assessing bother of individual lower urinary tract symptoms (LUTS) found the highest age-standardized prevalence for bothersome urgency. However, among individuals affected by LUTS, urgency incontinence was the most likely to cause significant bother. LUTS were generally well tolerated across ages and genders.
PMCID: PMC4018666  PMID: 24486308
Age factors; Bothersomeness; Definition; Lower urinary tract symptoms; Overactive bladder; Prevalence; Sex; Urinary incontinence; Urination disorders; Voiding dysfunction
7.  Characterization of overactive bladder in women in a primary care setting 
Overactive bladder (OAB) represents a disorder with overall increasing prevalence in the American population. However, gender-specific characteristics of OAB and how it relates to the general practitioner are not well described. We sought to determine the distribution and characteristics of OAB in women in a primary care setting.
Self-administered questionnaires were distributed to patients visiting a family medicine outpatient center. The modified questionnaire included eight questions on evidence of lower urinary tract symptoms (LUTS, OAB-validated 8-question screener [OAB-V8]), two questions on stress urinary incontinence, and one question on incomplete emptying. The questionnaire included demographic characteristics and relevant medical and surgical history. Body mass index was calculated based on weight and height. Chi-square test and risk ratio analysis were used to analyze the relationship between OAB and other independent variables.
Of 1025 questionnaires administered, 386 were completed. Patients ranged from 16 to 97 years, the majority were African American (78.2%), and 49.7% were premenopausal while 50.3% were postmenopausal. OAB was present in 46.4% of premenopausal women and 41.7% of postmenopausal women. OAB was significantly associated with overweight status (body mass index 25.0–29.9, P = 0.042) and obesity (body mass index ≥30, P < 0.001). Overall, obese women were twice as likely to have OAB (relative risk = 1.99, 1.31–3.04) than women with normal weight. OAB was not shown to correlate with race, cigarette use, history of hysterectomy, or parity.
OAB was evident in 44% of all female patients surveyed, which is much higher than previously reported estimates. In addition, overweight women were more likely to have OAB. Increased awareness of OAB in the primary care setting should be considered for women’s general health.
PMCID: PMC3818934  PMID: 24198633
overactive bladder; incontinence; women; primary care
8.  The Urologist's View of Male Overactive Bladder: Discrepancy between Reality and Belief in Practical Setting 
Yonsei Medical Journal  2010;51(3):432-437.
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.
PMCID: PMC2852801  PMID: 20376898
Overactive bladder; physician's practice patterns; bladder outlet obstruction; benign prostatic hyperplasia; anticholinergics
9.  Men's Lower Urinary Tract Symptoms Are Also Mental and Physical Sufferings for Their Spouses 
Journal of Korean Medical Science  2009;24(2):320-325.
Lower urinary tract symptoms (LUTS) in men may have an adverse effect on spouse health-related quality of life (HRQL), and these effects are probably influenced by cultural and perceptional differences. This study was conducted to explore the impact of LUTS in Korean men on their spousal HRQL in relation to symptom severities and other demographic parameters. A total of 130 spouses, whose husbands had a nocturia, frequency of greater than once per night, who shared a bed with their husbands, and accompanied husbands at consultation, were subsequently enrolled and asked to complete a structured questionnaire. Almost all spouses (98%) suffered one or more inconveniences that affected HRQL to some degree. Sleep disturbance was rated to be most inconvenient. The sleep disturbances were significantly correlated with nocturia frequency and husband co-morbidity. Husband's LUTS caused partners to feel fatigued (62%), embarrassed (79%), concerned about the possibilities of cancer (69%) and surgery (81%), sexual life deteriorated (58%), and dissatisfied, unhappy, or terrible (36%). Spouse's perception on HRQL was found to be well correlated with husband's quality of life. Men with LUTS need to understand that their LUTS is also mental and physical sufferings for their spouses.
PMCID: PMC2672136  PMID: 19399278
Lower Urinary Tract Symptom; Prostate; Spouse, Quality of Life
10.  Ramelteon combined with an α1-blocker decreases nocturia in men with benign prostatic hyperplasia 
BMC Urology  2013;13:30.
Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study.
Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon.
The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events.
Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH.
PMCID: PMC3687682  PMID: 23758651
Ramelteon; Melatonin; Nocturia; Benign prostate hyperplasia; α1-blocker
11.  Current role of treatment in men with lower urinary tract symptoms combined with overactive bladder 
Prostate International  2014;2(2):43-49.
Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) are highly prevalent in older men. The storage subcategory of LUTS is synonymous with overactive bladder (OAB) syndrome, which is an empirical diagnosis. Traditionally, alpha-blockers are widely prescribed to manage the LUTS of BPH, although storage symptoms may persist in many men despite treatment. Therefore, because therapies that target the prostate often fail to alleviate storage symptoms, they may not be the appropriate therapy for OAB. In past years, most physicians appeared to give more weight in elderly men to voiding symptoms than to storage symptoms and to be more concerned with initial treatment with anticholinergics for males with storage symptoms. Considering the recent increase in data on the efficacy and safety of combination treatment with alpha receptor antagonists and antimuscarinic agents, the standard pharmacologic treatment of patients with LUTS combined with OAB should be an alpha receptor antagonist and an antimuscarinic agent. Beta-3 adrenoreceptor agonists may also potentially be useful for the treatment of male LUTS combined with OAB.
PMCID: PMC4099395  PMID: 25032191
Prostatic hyperplasia; Overactive urinary bladder; Pharmacology
12.  Commonly-used antihypertensives and lower urinary tract symptoms: Results from the Boston Area Community Health (BACH) Survey 
Bju International  2011;109(11):1676-1684.
To examine differences in the prevalence of lower urinary tract symptom (LUTS) among users of five common antihypertensive (AHT) classes compared to non-users, adjusted for LUTS risk factors in a large, representative sample.
Subjects and Methods
Data were from the Boston Area Community Health Survey, a population-based study of community-dwelling male and female (30–79y) residents of Boston, MA for whom prescription drug information was collected (2002–2005). The urologic symptoms of storage, voiding, and nocturia were assessed using interviewer-administered questionnaires and the American Urologic Association Symptom Index. This analysis was conducted among 1,865 participants with an AHT indication. Associations of angiotensin-converting enzyme inhibitors, beta blockers, calcium channel blockers (CCBs), loop and thiazide diuretics with the three groups of LUTS were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) from multivariate logistic regression (referent group=untreated hypertension). Overlap in use was accounted for using monotherapy and combination therapy exposure categories.
Among women, monotherapy with CCBs was associated with increased prevalence of nocturia (OR=2.65, 95% CI: 1.04–6.74) and voiding symptoms (OR=3.84, 95% CI: 1.24–11.87); these results were confined to women aged <55. Among men of all ages, positive associations were observed for thiazides and voiding symptoms (monotherapy OR=2.90, 95% CI: 1.17–7.19), and loop diuretics and nocturia (combination therapy OR=2.55, 95% CI: 1.26–5.14).
Results are consistent with the hypothesis that certain AHTs may aggravate LUTS. The presence of new or worsening LUTS among AHT users suggests review of medications and consideration of a change in AHT class.
PMCID: PMC3249016  PMID: 21951754
urination disorders; antihypertensive agents; epidemiology
13.  Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 
BJU international  2012;110(7):1050-1059.
To investigate the relationship between non-steroidal anti-inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)-related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development.
Patients and methods
At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate-specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n = 4771).
During follow-up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006–2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia.
Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self-reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥ 30 mL on any follow-up DRE) and elevation in PSA level (> 1.4 ng/mL on any follow-up PSA test).
Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92–1.21, P = 0.043–0.91) and frequency of use (risk ratio for one category increase in NSAID use = 0.98–1.11, P-trends = 0.10–0.99) with incident BPH/LUTS.
The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development.
PMCID: PMC3382045  PMID: 22429766
aspirin; benign prostatic hyperplasia; ibuprofen; lower urinary tract symptoms; non-steroidal anti-inflammatory drugs
14.  Serenoa repens monotherapy for benign prostatic hyperplasia (BPH): an updated Cochrane systematic review 
BJU international  2012;109(12):1756-1761.
To estimate the effectiveness and harms of Serenoa repens monotherapy in the treatment of lower urinary tract symptoms (LUTS) consistent with benign prostatic hyperplasia (BPH).
Materials and methods
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and other sources through to January 2012 to identify randomised trials.
Trials were eligible if they randomised men with symptomatic BPH to receive Serenoa repens extract monotherapy for at least 4 weeks in comparison with placebo, and assessed clinical outcomes and urodynamic measurements.
Our primary outcome was improvement in LUTS, based on change in urological symptom-scale scores.
In all, 17 randomised controlled trials (N = 2008) assessing Serenoa repens monotherapy (typically 320 mg/day) vs placebo met inclusion criteria, although only five reported American Urological Association Symptom Index (AUASI) or International Prostate Symptom Scores (IPSS). Trial lengths ranged from 4 to 72 weeks. The mean age of all enrolees was 64.3 years and most participants were of White race. The mean baseline total score was 14 points, indicating moderately severe symptoms. In all, 16 trials were double blinded and adequate treatment allocation concealment was reported in six trials.
In a meta-analysis of three high quality long-to-moderate term trials (n = 661), Serenoa repens therapy was no better than placebo in reducing LUTS based on the AUASI/IPSS (weighted mean difference [WMD] −0.16 points, 95% confidence interval [CI] −1.45 to 1.14) or maximum urinary flow rate (Qmax; WMD 0.40 mL/s, 95% CI −0.30 to 1.09). Based on mostly short-term studies, Qmax measured at study endpoint were also not significantly different between treatment groups (WMD 1.15 mL/s, 95% CI −0.23 to 2.53) with evidence of substantial heterogeneity (I2 58%).
One long-term dose escalation trial (72 weeks) found double and triple doses of Serenoa repens extract did not improve AUASI compared with placebo and the proportions of clinical responders (≥ 3 point decrease in the AUASI) were nearly identical (43% vs 44% for Serenoa repens and placebo, respectively) with a corresponding risk ratio of 0.96 (95% CI 0.76–1.22).
Long-term, Serenoa repens therapy was no better than placebo in improving nocturia in one high-quality study (P = 0.19). Pooled analysis of nine short-term Permixon® trials showed a reduction in the frequency of nocturia (WMD −0.79 times/night, 95% CI−1.28 to −0.29), although there was evidence of heterogeneity (I2 76%)
Adverse events of Serenoa repens extracts were few and mild, and incidences were not statistically significantly different vs placebo. Study withdrawals occurred in ≈10% and did not differ between Serenoa repens and placebo.
Serenoa repens therapy does not improve LUTS or Qmax compared with placebo in men with BPH, even at double and triple the usual dose.
Adverse events were generally mild and comparable to placebo.
PMCID: PMC3513282  PMID: 22551330
Serenoa repens; benign prostatic hyperplasia; phytotherapy; systematic review
15.  Are commonly-used psychoactive medications associated with lower urinary tract symptoms? 
Lower urinary tract symptoms (LUTS) such as urinary frequency and urgency are bothersome and associated with reduced quality-of-life. Atypical antipsychotics (AAPs) have been implicated in increasing the risk of urinary incontinence. In a large community-based sample of men and women, we examined the associations of AAP use and selective serotonin reuptake inhibitor (SSRIs) use with LUTS.
Data were collected (2002–2005) from a generalizable sample of Boston, MA, USA residents aged 30–79 (N=5503). LUTS were assessed using the American Urologic Association Symptom Index (AUA-SI). The prevalence of clinically-significant LUTS was estimated using a cutoff AUA-SI score of 8+ to indicate moderate-to-severe symptoms. Confounder-adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated from multivariate logistic regression to estimate the associations for psychoactive drugs used in the previous month (SSRIs, AAPs, both) and LUTS.
Among women, AAP users had a higher prevalence of LUTS (46.2%) compared to SSRI users (23.5%) and those with depressive symptoms not using SSRIs or AAPs (26.3%). Corresponding prevalence estimates among men were 32.7%, 29.8%, and 33.3%. In multivariate models, AAP use was significantly associated with LUTS among women when used either with SSRIs (OR=2.72, 95%CI:1.45–5.10), or without SSRIs (OR=3.05, 95%CI:1.30–7.16) but SSRI use without AAP use was not associated with LUTS, compared to non-users without depressive symptoms. No associations were observed among men.
In our study, AAPs but not SSRIs were associated with increased prevalence of LUTS among women only. Further prospective research is needed to determine time sequence and cause-and-effect.
PMCID: PMC3538827  PMID: 22138718
antipsychotic agents; antidepressive agents; urination disorders; pharmacoepidemiology; epidemiology
16.  The Effect of Benign Lower Urinary Tract Symptoms on Subsequent Prostate Cancer Testing and Diagnosis 
European urology  2013;63(6):1021-1027.
Lower urinary tract symptoms (LUTS) are common and have been associated with the subsequent diagnosis of prostate cancer (PCa) in population cohorts.
To determine whether the association between LUTS and PCa is due to the intensity of PCa testing after LUTS diagnosis.
Design, setting, and participants
We prospectively followed a representative, population-based cohort of 1922 men, aged 40–79 yr, from 1990 until 2010 with interviews, questionnaires, and abstracting of medical records for prostate outcomes. Men were excluded if they had a previous prostate biopsy or PCa diagnosis. Self-reported LUTS was defined as an American Urological Association symptom index score >7 (n = 621). Men treated for LUTS (n = 168) were identified from review of medical records and/or self report. Median follow-up was 11.8 yr (interquartile range: 10.7–12.3).
Outcome measurements and statistical analysis
Associations between self-reported LUTS, or treatment for LUTS, and risk of subsequent prostate biopsy and PCa were estimated using Cox proportional hazard models.
Results and limitations
Fifty-five percent of eligible men enrolled in the study. Men treated for LUTS were more likely to undergo a prostate biopsy (hazard ratio [HR]: 2.4; 95% confidence interval [CI], 1.7–3.3). Men younger than 65 yr who were treated for LUTS were more likely to be diagnosed with PCa (HR: 2.3, 95% CI, 1.5–3.5), while men aged >65 yr were not (HR: 0.89, 95% CI, 0.35–1.9). Men with self-reported LUTS were not more likely to be biopsied or diagnosed with PCa. Neither definition of LUTS was associated with subsequent intermediate to high-risk cancer. The study is limited by lack of histologic or prostate-specific antigen level data for the cohort.
These results indicate that a possible cause of the association between LUTS and PCa is increased diagnostic intensity among men whose LUTS come to the attention of physicians. Increased symptoms themselves were not associated with intensity of testing or diagnosis.
PMCID: PMC3637922  PMID: 23313032
17.  Prevalence of post-micturition symptoms in association with lower urinary tract symptoms and health-related quality of life in men and women 
BJU international  2011;108(9):1452-1458.
To estimate the prevalence of post-micturition symptoms (a feeling of incomplete emptying following urination and post-micturition dribble) in a population-based sample of men and women, and to examine overlap with storage and voiding LUTS and associations with health-related quality of life (HRQL).
Patients and methods
Data were obtained by in-person interview in the Boston Area Community Health survey, a population-based random sample of 2301 men and 3202 women aged 30–79 years in the USA.
Lower urinary tract symptoms (LUTS) were defined using the International Prostate Symptom Score and standardized terminology.
Multivariate linear regression was used to evaluate associations between urological symptoms and validated HRQL measures (SF-12 and activities interference) cross-sectionally.
The overall prevalence of post-micturition symptoms was 11.8% in men and 8.5% in women.
The prevalence increased with age in men but not women.
In men, post-void dribbling contributed to much of the post-micturition symptoms, whereas, in women, incomplete emptying was more common.
For both genders, over 50% with voiding symptoms also had post-micturition symptoms, compared to less than 50% of respondents who reported storage symptoms.
The presence of post-micturition symptoms, particularly incomplete emptying, was indicative of mildly impaired physical HRQL and activities interference in men and women, and mental HRQL in men (P < 0.01).
Post-micturition symptoms were more prevalent than any individual voiding symptom and commonly overlapped with other LUTS.
Over half of men and women with a voiding symptom also had a post-micturition symptom.
The presence of post-micturition symptoms was indicative of impaired HRQL.
PMCID: PMC3135743  PMID: 21223471
urological diseases; urination disorders; urinary incontinence; urinary retention; prevalence; post-micturition symptoms; health-related quality of life
18.  Correlation between Nocturia and Sleep: A Questionnaire Based Analysis 
Korean Journal of Urology  2010;51(11):757-762.
This study evaluated the effectiveness and quality of sleep (QoS) in adult patients with nocturnal lower urinary tract symptoms (LUTS) including nocturia and nocturnal polyuria.
Materials and Methods
A total of 102 patients with nocturia and daytime LUTS were enrolled in this study. All patients completed a questionnaire that included the International Prostate Symptom Score (IPSS), quality of life score (QoL), overactive bladder questionnaire (OABq), and a sleepiness index. The sleepiness index was measured with the Korean Beck Depression Inventory (K-BDI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Berlin Questionnaire (BQ), and the International Restless Legs Syndrome Study Group (IRLSSG). Statistical analyses included the Student's t-test and chi-square test. Differences were considered significant at a p-value of less than 0.05.
Nocturia during sleep was experienced by 68 (66.7%) out of 102 patients. There was no significant association between the nocturia- and the sleep-related scales, but with multiple regression analysis for sex and age, the K-BDI score (p=0.05), IPSS score (p=0.05), and OABq (p=0.02) were significantly higher in patients who woke up to void during sleep. A total of 57 (55.9%) patients diagnosed with overactive bladder with nocturia had severe daytime sleepiness on the ESS questionnaire (p=0.019) and more urgency symptoms on the IPSS questionnaire (p=0.007).
Patients with nocturia had a greater risk of being depressive and felt sleepier during the daytime. LUTS including nocturia and sleep quality closely affected each other. Therefore, clinicians should consider patients' LUTS and sleep problems or QoS as well to provide more satisfying outcomes.
PMCID: PMC2991572  PMID: 21165195
Nocturia; Quality of life; Sleep disorders
19.  Strong Impact of Nocturia on Sleep Quality in Patients with Lower Urinary Tract Symptoms 
The World Journal of Men's Health  2012;30(2):123-130.
Nocturia is a bothersome symptom that impacts sleep quality in patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). This study was performed to evaluate the impact of nocturia on sleep quality.
Materials and Methods
A total of 58 male patients with LUTS/BPH were enrolled. LUTS/BPH patients without nocturia were included in the control group. The inclusion criteria were eight or more points on the International Prostate System Score (IPSS) including more than one episode of nocturia and a prostate volume larger than 20 ml. IPSS, prostate volume, uroflowmetry, and the Pittsburgh Sleep Quality Index (PSQI) from each patient were recorded.
Patients with nocturia showed a higher mean global PSQI (8.5±0.4) than patients without nocturia (4.82±0.4) (p<0.01). Patients with nocturia showed a higher percentage of severe sleep disorders (74.1%) than patients without nocturia (35.3%) (p<0.01). The regression coefficient between the number of episodes of nocturia and mean global PSQI was 0.42 (p<0.01).
Patients with nocturia showed poor sleep quality, and this was related to the number of episodes of nocturia. This suggests that nocturia has a strong impact on sleep quality in patients with LUTS/BPH.
PMCID: PMC3623520  PMID: 23596599
Nocturia; Sleep; Prostatic hyperplasia
20.  A Prospective Study of Lower Urinary Tract Symptoms and Erectile Dysfunction 
The Journal of urology  2008;179(6):2321-2326.
Several studies have reported that men with lower urinary tract symptoms (LUTS) are more likely to experience erectile dysfunction (ED). All but one of these studies was cross-sectional, limiting inferences about whether LUTS precipitate ED.
Materials and Methods
The association between LUTS and incident ED was examined prospectively in the Health Professionals Follow-up Study. LUTS were assessed biennially by the American Urological Association Symptom Index, which captures symptoms of frequency, urgency and force of urinary stream. Severe LUTS was defined as a symptom score of ≥ 20 points and no LUTS was defined as a score of ≤ 7 points, both among men not treated for LUTS. In 2000, the men were asked to rate their erectile function for several time periods. ED was defined as “poor” or “very poor” function or use of ED medications and no ED was defined as “very good” or “good” function and no use of ED medications. We estimated risk ratios using Poisson regression adjusting for age and other potentially confounding factors.
We observed 3,953 incident ED cases among 17,086 men. Men with severe LUTS in 1994 or earlier had a statistically significant 40% higher risk of ED subsequently than men without LUTS. The risk of ED increased with increasing LUTS severity (p trend < 0.0001). The positive association between LUTS and ED was stronger among younger than older men (p interaction = 0.03).
This study provides evidence that men with LUTS are more likely to develop ED subsequently.
PMCID: PMC3217213  PMID: 18423761
erectile dysfunction; prostatic hyperplasia; urination disorders; prospective studies
21.  Nonsteroidal Antiinflammatory Drug Use and Lower Urinary Tract Symptoms: Results From the Boston Area Community Health Survey 
American Journal of Epidemiology  2011;173(9):1022-1031.
There is evidence for a role of inflammation in the etiology of lower urinary tract symptoms (LUTS), raising the possibility that use of nonsteroidal antiinflammatory drugs (NSAIDs) may inhibit the development or progression of LUTS. The authors examined the association between use of prescription and over-the-counter NSAIDs and LUTS among 1,974 men and 2,661 women in the Boston Area Community Health Survey (2002–2005). Multivariable-adjusted logistic regression was used to estimate odds ratios and 95% confidence intervals for LUTS, voiding symptoms, storage symptoms, and nocturia. There was no clear association between use of prescription or over-the-counter NSAIDs (compared with no NSAID use) and overall LUTS, voiding symptoms, or nocturia in men or women. However, over-the-counter NSAID use was positively associated with storage symptoms in women (odds ratio = 1.37, 95% confidence interval: 1.03, 1.83), and there was a positive association between over-the-counter NSAID use and overall LUTS among women with a history of arthritis (odds ratio = 2.09, 95% confidence interval: 1.20, 3.64). These results do not provide strong support for an association between NSAIDs and LUTS. However, the associations between over-the-counter NSAID use and certain urologic symptoms, particularly among women with arthritis, and the potential mechanisms involved should be evaluated in future studies.
PMCID: PMC3121220  PMID: 21357657
analgesics; anti-inflammatory agents; non-steroidal; cyclooxygenase 2 inhibitors; nocturia; urination disorders
22.  Estimating EQ-5D and OAB-5D health state utilities for patients with overactive bladder 
Limited utility data on patients suffering from overactive bladder (OAB) are available in the literature. The objectives of this study were to estimate utility values in patients with OAB using the generic EQ-5D questionnaire and the OAB-5D disease specific questionnaire, to investigate the relationship between utilities and symptoms, and to evaluate the sensitivity of the two instruments to changes in symptom severity.
Analyses were based on pooled data from three large multicenter randomized 12-week placebo-controlled trials (SCORPIO, ARIES, CAPRICORN). Patients completed a micturition diary, EQ-5D and OAB-q (a quality of life questionnaire from which OAB-5D is derived) at baseline and at weeks 4, 8 and 12. Time trade-off tariffs elicited from UK population were applied to obtain utilities from both instruments. Repeated measures regressions were used to estimate EQ-5D and OAB-5D utilities by micturition frequency and incontinence severity level. As a test of sensitivity of the instruments, utility changes from baseline to week 12 were estimated by symptomatic response (improvement, stable or worsening).
The sample included 4427 patients. Mean utilities (± standard deviation) across all visits were 0.82 (±0.21) for EQ-5D and 0.86 (±0.09) for OAB-5D. Correlation between EQ-5D and OAB-5D was 0.34 (p < 0.0001). Both OAB-5D and EQ-5D utilities increased as OAB symptoms improved. Utility values were similar for severe levels of symptoms, but higher with OAB-5D than with EQ-5D for mild cases. Micturitions and incontinence had similar impact on EQ-5D utilities, but micturitions had greater impact on OAB-5D utilities than incontinence. Changes from baseline in OAB-5D utilities differed significantly according to symptomatic response. Changes in EQ-5D utilities were not significantly associated with changes in micturition frequency and weakly associated with changes in incontinence severity among patients with mild symptoms at baseline.
This study showed that both EQ-5D and OAB-5D can detect changes in severity of OAB, especially in severe cases. However, OAB-5D is more sensitive than EQ-5D in measuring differences between treatments in milder cases. Both OAB-5D and EQ-5D–although leading to different results–may be useful to derive utilities from clinical trial data and perform cost-effectiveness analyses.
Trial registration
Clinical Trials NCT00689104, NCT00662909, NCT00912964.
PMCID: PMC3842710  PMID: 24246044
Health-related quality of life; Overactive bladder; EQ-5D; OAB-5D; Quality-adjusted life-years; Utility assessment
23.  The Add-On Effect of Solifenacin for Patients with Remaining Overactive Bladder after Treatment with Tamsulosin for Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Obstruction 
Advances in Urology  2010;2010:205251.
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.
PMCID: PMC2964005  PMID: 20981257
24.  Risk of Hospitalization for Acute Cardiovascular Events among Subjects with Lower Urinary Tract Symptoms: A Nationwide Population-Based Study 
PLoS ONE  2013;8(6):e66661.
Background and Purpose
Lower urinary tract symptoms (LUTS) have been reported to be associated with metabolic syndrome and may predispose subjects to cardiovascular disease. The magnitude of the impact on the medical care remains to be elucidated. Based on a population-based claims dataset in Taiwan, we explored the association between LUTS and the risk of subsequent hospitalization for acute cardiovascular events.
Materials and Methods
Among a representative sample of one million subjects from nationwide health insurance enrollees, subjects with codes of LUTS in service claims and without previous cardiovascular diseases including stroke were compared with age- and sex-matched non-LUTS subjects in subsequent hospitalization for acute coronary syndrome or stroke from the recruited date (between 2001–2004) to 2009. The risk of outcomes was assessed with Kaplan-Meier curves and the impact of LUTS was estimated with Poison regression analysis and Cox proportional hazards models.
We included 4,553 LUTS subjects and 22,765 matched non-LUTS subjects, with a mean age of 47 years and 43% of men. Hypertension, diabetes, and hyperlipidemia were more prevalent in the LUTS group. The incidence rate of the composite endpoint was significantly higher in the LUTS group than in the non-LUTS group (5.4/1000 vs. 4.0/1000 person-years). The difference mainly derived from stroke rather than acute coronary syndrome. After adjusting for age, sex, diabetes, hypertension, and hyperlipidemia in multivariable analysis, LUTS remained a significant predictor (hazard ratio, 1.29; 95% confidence incidence, 1.06–1.50).
Subjects free of cardiovascular disease and presenting with LUTS are at risk of subsequent hospitalization for acute cardiovascular events, mainly stroke. The information might prompt practitioners encountering such patients to undergo appropriate diagnostic and preventive measures.
PMCID: PMC3680437  PMID: 23776691
25.  Current Evaluation and Treatment of Nocturia 
Korean Journal of Urology  2013;54(8):492-498.
Nocturia is usually considered to be just one of the symptoms included with lower urinary tract symptoms (LUTS) and is treated with therapy based on LUTS. Recent research suggests, however, that nocturia is not merely a simple symptom of LUTS but is a multifactorial condition with many contributing etiological factors. The causes of nocturia can be classified into bladder storage problems, increased urine output, sleep disturbance problems, and other potential diseases. The frequency-volume chart (FVC) is very important in evaluating and diagnosing nocturia. Patients usually record the volume and timing of voids for a period of 1 to 3 days on the FVC. The FVC data can provide information on voiding patterns and clues about the etiology and treatment of nocturia. It is doubtful that alpha-blockers will have clinical significance for treatment because the difference in nocturia episodes between treatment with alpha-blockers and placebo is too small. Antimuscarinics also exert no effect on nocturnal polyuria, and the evidence supporting the efficacy of antimuscarinics for the treatment of nocturia is limited. However, several randomized placebo-controlled trials have shown the efficacy of oral desmopressin in the treatment of adults with nocturia. Short-acting hypnotics may be helpful for patients with sleep disturbances. Although surgical or interventional therapy is not indicated for nocturia, transurethral resection of the prostate appears to confer a greater improvement in benign prostatic hyperplasia symptoms including nocturia. The management of nocturia may require a team approach by making optimal use of multidisciplinary expertise.
PMCID: PMC3742899  PMID: 23956822
Epidemiology; Evaluation; Nocturia; Pathophysiology; Treatment

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