Implications of recent epidemiology studies for the clinical management of lower urinary tract symptoms

Authors


Steven A. Kaplan, Department of Urology, Weill Cornell Medical College, 1300 York Ave, New York, NY 10021, USA.
e-mail: kaplans@med.cornell.edu

Abstract

Lower urinary tract symptoms (LUTS) include storage, voiding, and postmicturition symptoms, and occur commonly in both men and women. Findings from two recent epidemiological studies, the Epidemiology of LUTS study and the Boston Area Community Health survey, further extend the understanding of the prevalence of individual LUTS, the overlap of LUTS in men and women, the associations of LUTS with other comorbid conditions, the impact of LUTS on health-related quality of life (HRQL), and the relationships between frequency and bother of LUTS and treatment-seeking behaviour. Examining the clinical implications of these findings might provide directions to physicians for managing their patients with LUTS. For example, common findings of separate patient groups spanning a spectrum from those with typically one urinary symptom of mild to moderate severity to those with multiple more severe LUTS and frequent comorbidities might further encourage the diagnosis and treatment of comorbid conditions as a standard part of the management of patients with LUTS. Likewise, understanding that the impact of LUTS on HRQL and the degree of bother, rather than the frequency of LUTS, are significant drivers for treatment seeking might aid in assisting patients to make decisions about treatment.

Abbreviations
OAB

overactive bladder

BMI

body mass index

EpiLUTS

Epidemiology of LUTS

BACH

Boston Area Community Health (survey)

HRQL

health-related quality of life

SI

Symptom Index

SF-12

Medical Outcomes Study 12-item Short Form Survey

CRP

C-reactive protein

ED

erectile dysfunction

PCS-12

physical health component score

MCS-12

mental health component score.

INTRODUCTION

The prevalence of LUTS is known to increase with age in both men and women [1–8]. LUTS in men, whilst often attributed solely to histological BPH, are now recognized to occur with increasing frequency with age, with a reported prevalence of 50% in men aged 51–60 years, increasing to up to 90% in men aged ≥80 years [9]. Several studies have attempted, in our view erroneously, to estimate the prevalence of the clinical consequences of histological BPH by determining the presence of LUTS suggestive of BOO associated with BPH. In 2000, ≈6.5 million of 27 million white men aged 50–79-years in the USA met the criteria for discussion of potential treatment for BPH [10]. In outpatients aged ≥40 years who were users of Department of Veteran Affairs healthcare services, the prevalence of BPH/LUTS was 4.8%[11]. Using the criteria of an IPSS of >7, 42% of men aged ≥50 years and visiting their primary-care physician for routine care had LUTS suggestive of BPH [12]. The prevalence of BPH in a slightly older population of 33 077 men in France aged 55–70 years consulting their GP was 57.5%[13]. Studies of BPH prevalence conducted in Tunisia [14], Iran [15], Turkey [16] and Italy [17] have reported prevalence rates of LUTS attributed to BPH of 16.1%, 22.4%, 24.9% and 19%, respectively.

Although the prevalence might be higher in men, LUTS typically attributed to BPH in men are also reported by women [1,18], suggesting a more expansive underlying pathophysiology than the prostate alone. Studies conducted in different populations and geographical regions showed that LUTS, i.e. all urinary symptoms, including storage, voiding, and postmicturition symptoms, occur commonly with similar prevalence for both men and women, although there are gender differences in the distribution of individual symptoms (Fig. 1) [1–3]. For example, incontinence, particularly stress urinary incontinence, is more common in women, with stress urinary incontinence reported by half of women aged 30–49 years in a Swedish population [19] and accounting for 35% of incontinence in a study of European women [20]. Incontinence in men is commonly related to previous prostatic surgery [21,22]. However, pivotal studies from the ICS [23] showed that although voiding symptoms were most prevalent in male patients being referred to secondary-care centres for surgery, storage symptoms (i.e. overactive bladder, OAB) were the most bothersome [24].

Figure 1.


The prevalence of LUTS (A) storage (B) voiding, and (C) postmicturition symptoms by country and gender, from the EPIC study. Reproduced from [1] with permission from Elsevier. Nocturia is defined as one or more episode per night.

OAB has also been typically thought to be more prevalent in women. However, population-based prevalence surveys conducted in Europe [2] and the USA [3] reported that OAB symptoms affect up to 17% of the population, with age-related increases in both men and women. When OAB was defined as the presence of any of the storage symptoms (urgency, frequency, incontinence, or nocturia), the prevalence of OAB was 9.8% in men and 11.9% in women aged 50–54 years, rising to 41.9% for the men and 31.3% for the women aged ≥75 years [2]. Later studies using the current ICS definition for OAB, which specifies that urgency must be present, have reported a slightly lower prevalence of OAB [25]. In the EPIC study [1], which was conducted in five countries in >19 000 men and women aged ≥18 years, using the ICS definitions for LUTS and OAB, the overall prevalence of OAB was 10.8% in men and 12.8% in women, and its prevalence increased with age. The prevalence was also similar for men and women for storage (51.3% and 59.2%, respectively), voiding (25.7% and 19.5%), and postmicturition symptoms (16.9% and 14.2%).

These findings support a more expansive view of LUTS that looks beyond an organ-specific focus to the interaction of the whole urinary system, as well as relationships with other conditions such as obesity, hypertension and the metabolic syndrome [26]. In addition to age, several studies have reported associations between body mass index (BMI), waist-hip ratio, alcohol consumption, smoking, and cardiovascular, metabolic and endocrine factors with LUTS [27,28]. In this supplement, findings from two recent epidemiological studies, the Epidemiology of LUTS (EpiLUTS) study [29] and the Boston Area Community Health (BACH) survey [30], are presented, which further extend the understanding of the prevalence of individual LUTS, the overlap between LUTS in men and women, the associations of LUTS with other comorbid conditions, the impact of LUTS on health-related quality of life (HRQL), and the relationships between frequency and bother of LUTS and treatment seeking. The clinical implications of these findings in providing directions to physicians for managing their patients with LUTS will be explored in this review.

EpiLUTS: MAIN STUDY FINDINGS

EpiLUTS is a cross-sectional, population-representative, Internet-based survey conducted in the USA, the UK and Sweden in 30 000 (USA 20 000; UK 7500; Sweden 2500) men and women aged 40–99 years (mean 56.6) to assess the prevalence and associated bother of LUTS (Table 1) [29,30–33]. When LUTS were reported at least sometimes, 72.3% of men and 76.3% of women respondents reported at least one LUTS. When LUTS were reported often or more frequently, 47.9% of male and 52.5% of female respondents reported at least one LUTS. At least half the participants were bothered somewhat or more by most LUTS that occurred at least sometimes, whereas a similar level of bother was reported by at least 70% of participants for LUTS experienced often or more, except for terminal dribble in men and split stream in women (Fig. 2) [29]. Although voiding symptoms occurred more frequently in men, the prevalence of storage symptoms was generally higher than voiding symptoms for both men and women. The prevalence of all LUTS increased with age in men, but only urgency, urgency with fear of leaking, weak stream, urgency incontinence, and nocturnal enuresis increased with age in women.

Table 1.  Overview of the EpiLUTS and BACH studies
EpiLUTS [29,31,33]BACH [30,32]
Description
Cross-sectional, population-representative, Internet-based survey conducted in the USA, the UK and Sweden in 30 000 (USA 20 000; UK 7500; Sweden 2500) men and women aged 40–99 years (mean age, 56.6 years)Population-based epidemiological survey among 5503 randomly selected adults residing in Boston aged 30–79 years in three race/ethnic groups (2301 men, 3202 women; 1767 black, 1877 Hispanic, 1859 white respondents)
LUTS prevalence
1 LUTS at least sometimes: 72.3% (men), 76.3% (women) 1 LUTS at least often: 47.9% (men), 52.5% (women)LUTS (AUA-SI ≥ 8): 18.7% (men), 18.6% (women); increased with age (10.5% for 30–39 years to 25.5% for 70–79 years), no difference by race/ethnicity (16.2%−19.3%)
Bother
Rates of bother were lower for LUTS classified as at least ‘sometimes’ than those classified as at least ‘often’.Mean bother scores were higher in those with LUTS (vs no LUTS) and for women vs men
However, leaking urine during sexual activity, which was reported infrequently, was highly bothersome (82.1% men; 87.2% women), whereas terminal dribble, which was reported frequently, was less bothersome (40.6% men; 40.2% women) 
Treatment seeking
Treatment seeking was low, but most common in those in the voiding + storage + postmicturition subgroup: 29.1% men, 27.5% women; prescription medication use was also highest in this subgroup (17.6% and 10.4%, respectively)Prescription medication use for urinary symptoms was low even among those with AUA-SI ≥ 8, at 9.8% men, and 2.1% (women)
Comorbidities
Comorbid conditions were most common in the voiding + storage + postmicturition subgroup with significant associations for LUTS with arthritis, asthma, chronic anxiety, depression, diabetes (men only), heart disease, irritable bowel syndrome, neurological conditions, recurrent UTI, and sleep disorders; childhood nocturnal enuresis was significantly associated with most LUTS subgroupsLUTS (AUA-SI ≥ 8) was associated with heart disease, diabetes (men only), and depression
Figure 2.

The prevalence of individual LUTS from the EpiLUTS study for (A) men and (B) women [29]. The prevalence of individual LUTS over a 4-week recall period was assessed with five Likert responses in two ways: (1) ‘never’ and ‘rarely’ vs ‘sometimes’ or more (at least sometimes); and (2) ‘never’, ‘rarely’, and ‘sometimes’ vs ‘often’ or more (at least often). The ‘at least sometimes’ and ‘at least often’ data are presented in this figure. Nocturia is reported as two or more episodes per night and perceived frequency as the percentage of ‘yes’ responders to the question, ‘Do you feel that you urinate too often during the day?’). (Reproduced with permission from Blackwell Publishers.)

BACH SURVEY MAIN FINDINGS

The BACH survey is a population-based epidemiological survey of a broad range of urological symptoms and risk factors among randomly selected adults aged 30–79 years in three race/ethnic groups, recruited from April 2002 to June 2005 in the city of Boston (Table 1) [30]. The community-dwelling population-representative sample included 5503 adults (2301 men, 3202 women; 1767 black, 1877 Hispanic, 1859 white respondents). The BACH survey is unique among LUTS prevalence studies in the controls provided for effects of gender, race/ethnicity, and socio-economic status in a random, population-representative sample. The overall prevalence of LUTS (AUA Symptom Index, SI, of ≥8) was 18.7% and increased with age (10.5% for 30–39 years to 25.5% for 70–79 years), but did not differ by gender or race/ethnicity. As had been observed in the EpiLUTS study, voiding symptoms occurred more frequently in men, but the prevalence of storage symptoms was generally higher than voiding symptoms for both men and women. Respondents with LUTS had significantly reduced HRQL (assessed by Medical Outcomes Study 12-item Short Form Survey, SF-12). The use of prescription medications for urinary symptoms was low even among those with AUA-SI of ≥8 (<10%).

CO-OCCURRENCE OF SYMPTOMS

Historically, the first cluster analysis of urological symptoms was conducted by Norman et al. in 1994 [34]. Data from men with severe to moderate LUTS (Canadian Symptom Index ≥8, of a maximum of 35) associated with BPH who had participated in a telephone survey of 508 Canadian men aged ≥50 years were analysed, and five clusters were identified. Symptom scores in the first cluster (40% of respondents) were lower (mean score 10.3) and were evenly distributed across all seven symptoms. The remaining four clusters were moderate irritative (now known as storage rather than ‘irritative’, 31%), severe irritative (6%), moderate obstructive (18%), and severe obstructive (5%). The severe clusters had higher symptom scores (mean scores 20.4–24.3 vs 13.1–13.2 for moderate) and a clearer dominance of their respective symptom category. Although urgency and hesitancy were the primary distinguishing symptoms for storage and obstructive clusters, respectively, it was found that storage and obstructive symptoms occurred together, especially in men with more severe symptom scores.

Using EPIC study data, Coyne et al.[35] conducted separate cluster analyses among men and women reporting at least one LUTS. Six distinct symptom cluster groups were identified; the largest cluster (56% of men and 57% of women) consisted of respondents reporting minimal symptoms. The remaining five clusters differed somewhat for men and women. For men, the clusters were defined by a predominant symptom and were nocturia at least twice per night (12%), terminal dribble (11%), urgency (10%), multiple symptoms (9%), and postvoid incontinence (5%). For women, clusters were defined as nocturia at least twice per night (12%), terminal dribble (10%), urgency (8%), stress incontinence (8%), and multiple symptoms (5%). The multiple-symptom clusters for both men and women included subjects who had numerous and varied LUTS, were older, and had more comorbid conditions.

Separate cluster analyses were performed on the male [36] and female [37] data from the BACH survey. Five clusters were identified among symptomatic men (Table 2) [36,37]; the largest cluster (half of symptomatic men) had a low prevalence and frequency of urological symptoms and a low level of interference with activities of daily living. Men in the second, third, and fourth clusters had mixed patterns of voiding, storage, and postmicturition symptoms, with intermediate levels of symptom frequency and prevalence. The remaining cluster included predominantly older men (mean age 58.9 years) with a high prevalence and frequency of urological symptoms (mean 9.9, sd 2.1) and higher frequency of comorbid conditions (e.g. cardiovascular disease, kidney and bladder infections, previous urological surgery). Men with a more sedentary lifestyle and a larger waist circumference were over-represented in the more symptomatic clusters.

Table 2.  Cluster analysis from the BACH survey [36,37]
Symptom subgroupn (%); predominant symptoms (% prevalence)
Men Women 
Asymptomatic684 (30.1)  764 (24.1) 
Cluster 1: minimal symptoms801 (35.2)Nocturia (30.1)1296 (40.9)Nocturia (37.1)
Frequency (25.5) Frequency (23.8)Urinary incontinence (19.2)
Cluster 2:282 (12.4)Perceived frequency (100) 577 (18.2)Perceived frequency (94.5)
Frequency (45.7) Frequency (85.4)
Nocturia (33.7) Nocturia (54.2)
Cluster 3:184 (8.1)Frequency (99.5) 330 (10.4)Urinary incontinence (97.9)
Perceived frequency (88.6) Frequency (66.1)
Nocturia (67.9) Stress urinary incontinence (62.4)Urge urinary incontinence (62.4)
Cluster 4:195 (8.6)Dribbling (77.9)  
Frequency (61.5)
Urinary incontinence (55.4)  
Cluster 4/5: multiple symptoms130 (5.7)Perceived frequency (96.9) 200 (6.3)Frequency (98.0)
Frequency (92.3) Perceived frequency (94.5)
Nocturia (85.4) Urinary incontinence (94.5)

Four clusters were identified among symptomatic women (Table 2); 54% of symptomatic women were assigned to the first cluster, which was characterized by nocturia and urinary frequency with a low prevalence of other urological symptoms (mean of 1.4 symptoms). The second cluster, representing 24.0% of women with symptoms, had a mean of 3.9 symptoms with perceived frequency (95%) and frequency (85%) reported predominantly. The third (13.7%) and fourth (8.3%) clusters were characterized by a high prevalence and frequency of incontinence, which was associated with more symptoms overall than with the other two clusters (mean number of symptoms was 6.0 for cluster 3 and 10.6 for cluster 4). The mean age was also highest for these two clusters (52.4 and 54.9 years for cluster 3 and 4, respectively). Compared with other cluster groups or asymptomatic women, BMI and waist circumference were higher and rates of diabetes, hypertension and cardiovascular disease were higher for the women in the fourth cluster.

The overlap of LUTS and assessments of the relationships among urinary symptoms were examined using data from the EpiLUTS study. To examine the overlap of LUTS, eight LUTS subgroups from the EpiLUTS study data were evaluated [31], including no/minimal LUTS, voiding only, storage only, postmicturition only, voiding + storage, voiding + postmicturition, storage + postmicturition, and voiding + storage + postmicturition groups. Overlap was common, with 47% of men and 46% of women reporting LUTS from more than one symptom group (Table 3) [31]. The largest symptomatic subgroup for both men and women was those with voiding, storage and postmicturition symptoms (men, 24.3%; women, 26%), whereas the smallest subgroup was storage + postmicturition symptoms in men (2%) and postmicturition only in women (0.9%). For men, those without LUTS were younger (mean age 53.9 years), and those in the voiding + storage group were oldest (mean age 60.3 years). Age differences were less marked among women, with mean ages of 55.0–57.8 years. The prevalence of individual LUTS was highest in the multiple symptom groups, particularly the voiding + storage + postmicturition group. Common symptoms for both men and women in this subgroup included terminal dribble, nocturia, urgency, and postmicturition dribble. Women in the storage groups reported high rates of urgency with a fear of leaking, urgency incontinence, and stress incontinence. Among postmicturition symptoms, postmicturition dribble was more common among men than incomplete emptying, whereas the opposite was true for women.

Table 3.  The overlap of symptoms, from the EpiLUTS study [31]
Symptom subgroupMen, n (%)Women, n (%)
No/minimal LUTS4097 (29.0)4006 (25.3)
Voiding only1704 (12.1) 822 (5.2)
Storage only1280 (9.1)3545 (22.4)
Post-micturition only 427 (3.0) 143 (0.9)
Voiding + storage1449 (10.3)2340 (14.8)
Voiding + postmicturition1463 (10.4)  311 (2.0)
Storage + postmicturition 288 (2.0) 574 (3.6)
Voiding + storage + postmicturition3433 (24.3)4120 (26.0)

COMORBIDITIES AND FACTORS ASSOCIATED WITH LUTS

Several studies have reported associations between other medical conditions and factors with LUTS. For example, the HUNT cross-sectional study conducted in Norway reported that BMI, waist-hip ratio, alcohol consumption, smoking, diabetes, a history of stroke, muscle complaints, and osteoarthritis were positively associated with increased moderate and severe LUTS [38]. Links between cardiovascular, metabolic, and endocrine factors with the development of LUTS have been reported [27,28]. Men aged ≥40 years and with diabetes were 10 times more likely to have LUTS than men without diabetes, in a cross-sectional population-based survey in Malaysia [27]. Patients with type 2 diabetes or elevated fasting glucose levels were also two and three times more likely to have enlarged prostates than those without those conditions in the Baltimore Longitudinal Study of Aging [39]. Associations between low testosterone levels and BPH and the metabolic syndrome have been reported [40]. Related findings that testosterone therapy improved several of the components of the metabolic syndrome in hypogonadal men with type 2 diabetes further support these associations [41].

Adding to this research, data from the BACH survey were analysed to examine the association of LUTS (AUA-SI ≥ 8) with heart disease, type 2 diabetes, hypertension, and depression [32]. The occurrence of LUTS was associated with heart disease and depression among both men and women, whereas there was an association with diabetes only among men. The associations between LUTS and these chronic diseases were influenced by the severity and duration of the symptoms. Apart from depression, the association of individual LUTS and chronic illnesses varied by gender. For men, increased severity and duration of nocturia were associated with increased odds of heart disease. Men reporting more severe intermittency had a similar increased risk of heart disease, whereas increased severity of urgency was associated with increased risk of diabetes in men. Among women, increased severity and duration of nocturia were associated with increased odds of diabetes. There was an increased risk of hypertension only among women reporting more severe urgency for >1 year.

A subsequent analysis from the BACH survey assessed the relationship between LUTS defined by AUA-SI and the metabolic syndrome defined as the presence of three or more of the following criteria: (i) waist circumference >102 cm; (ii) systolic blood ≥130 mmHg or diastolic blood pressure ≥85 mmHg, or antihypertensive medication use; (iii) high-density lipid cholesterol <40 mg/dL or lipid medication use; (iv) self-reported type 2 diabetes or elevated blood glucose or diabetes medication use; (v) triglycerides >150 mg/dL [42]. Compared with men with an AUA-SI score of 0 or 1, there was an increased likelihood of metabolic syndrome in men with mild (AUA-SI 2–7) and moderate/severe symptoms (AUA-SI 8–35). Metabolic syndrome was significantly associated with the voiding score but not with the storage score. Interestingly, there was an increased odds of metabolic syndrome with mild symptoms of incomplete emptying, intermittency and nocturia.

A potential role of chronic inflammation (C-reactive protein, CRP) as a possible pathogenetic factor in the development of LUTS (AUA-SI ≥ 8) was supported by findings from a recent analysis of the BACH survey sample [43]. There was an increase in the prevalence of LUTS (overall and individual symptoms) with CRP level, and the association between CRP levels and overall LUTS among both men and women was statistically significant. For individual symptoms, nocturia and straining were associated with elevated CRP levels among men, whereas incomplete emptying and weak stream were associated with higher CRP levels among women.

LUTS comorbidities and associated factors were also examined using EpiLUTS study data [33]. The highest rates of comorbid conditions for both men and women were in the voiding + storage + postmicturition symptoms subgroup, whereas the no/minimal LUTS or postmicturition-only subgroups had the lowest rates of comorbid conditions. Compared with having no/minimal LUTS, increasing age was associated with voiding only, storage only, voiding + storage, and voiding + storage + postmicturition symptoms in men, but was not significantly associated with any of the LUTS subgroups in women. The greatest number of significant associations for comorbid conditions and factors was for voiding + storage (women) and voiding + storage + postmicturition symptoms (men). Among men, depression and heart disease were linked to all subgroups containing voiding symptoms, depression was linked with storage + postmicturition symptoms, hypertension was linked to storage symptom subgroups and to voiding + postmicturition symptoms, and enlarged prostate/prostatitis was associated with all symptom subgroups, except postmicturition only. Among women, there were associations for recurrent UTIs with all LUTS subgroups except voiding + postmicturition; irritable bowel syndrome with all subgroups except postmicturition only; arthritis, depression and hypertension with all storage symptom subgroups; and neurological conditions with voiding + storage, voiding + postmicturition, and voiding + storage + postmicturition. A history of childhood nocturnal enuresis was linked to all symptom combinations, except voiding + storage + postmicturition in men and voiding only and postmicturition only in women. For women, a similar pattern of association was found for BMI. Vigorous activity was protective for voiding + storage + postmicturition symptoms in men, and voiding + storage symptoms in women.

LUTS AND SEXUAL DYSFUNCTION

Rosen et al.[44] reported a strong association between LUTS and sexual dysfunction, i.e. erectile dysfunction (ED) and ejaculatory dysfunction, independent of age and comorbidities, in the Multinational Survey of the Aging Male. Bivariate and multivariate analyses of the BACH survey data revealed that urological symptoms were associated with a significant decrease in sexual activity and function in both men and women [45]. In multivariate logistic regression models for sexual activity with a partner, there were significant associations of sexual inactivity with LUTS (IPSS ≥ 8; men), prostatitis (men), OAB with urine leakage (women), depression (both men and women), and decreased alcohol use (both men and women). There were significant associations of decreased sexual desire with prostatitis (men), depression (both men and women), and alcohol use (i.e. increased alcohol consumption was associated with less reporting of low desire; women) in the multivariate analysis. Prostatitis and nocturia were associated with ED in men; depression was associated with ED in men and sexual dysfunction in women; and decreased alcohol use was associated with sexual dysfunction for women, but not for men, in the multivariate analysis.

In a subanalysis of data from 11 384 men participating in the EpiLUTS study, the occurrence of LUTS was associated with ED, ejaculatory dysfunction, and premature ejaculation in men [46]. Mild to severe ED (Erectile Function domain of the International Index of Erectile Function score <26 of 30) was reported in 26% of men, with the incidence of severe ED increasing with age, and LUTS severity as assessed with the IPSS. Compared with men with no/minimal LUTS or LUTS from one ICS category (storage, voiding and postmicturition), men with overlapping ICS categories of LUTS tended to have more severe ED. Individual LUTS associated with ED included urgency with fear of leaking, weak stream, splitting or spraying of stream, leaking for no reason, and leaking during sexual activity. Increasing age was also associated with ejaculatory dysfunction. Other significant predictors of ejaculatory dysfunction (defined as an inability to ejaculate at least half the time or more) included prostate cancer and depression, and several individual LUTS, with the most robust being ‘leaking during sex’, stress urinary incontinence, pain during sex, and urgency with fear of leaking. Ejaculation earlier than desired was reported to occur at least half the time in 22.5% of the men. Younger age, hypertension and the absence of prostatitis were significantly associated with premature ejaculation, as were the presence of terminal dribble, incomplete emptying, split stream, and absence of nocturnal enuresis.

IMPACT OF LUTS ON HRQL

The prevalence of LUTS in the USA is predicted to exceed 42 million persons in 2025 [47]. The impact of LUTS, urine leakage, painful bladder syndrome and prostatitis on physical health is reported to be equivalent to that of other chronic conditions, such as high blood pressure and diabetes, and the impact of these symptoms on mental health might be greater than that of these chronic conditions [47]. A nested case-control analysis of EPIC study data confirmed the substantial impact of OAB alone and OAB with additional LUTS on work productivity, sexuality and overall health [48]. Significantly greater bother, worse HRQL and higher rates of depression and decreased sexual enjoyment were reported by those in the OAB + voiding + postmicturition symptoms subgroup than in other subgroups.

Multivariate linear regression models (adjusted for age group, race/ethnicity, and comorbidity) were used to assess the impact of LUTS on the SF-12 physical health component (PCS-12) and mental health component (MCS-12) scores in previously identified urinary cluster groups from the BACH survey [49]. Compared with the asymptomatic group, there were significant associations for lower PCS-12 scores in men in the most symptomatic cluster, and for lower MCS-12 scores for all clusters, except for the least symptomatic cluster. For women, all clusters were significantly associated with a lower PCS-12 score and the most symptomatic clusters (clusters 3 and 4) were significantly associated with lower MCS-12 scores.

The impact of LUTS on HRQL was also assessed in the EpiLUTS study, in which participants were asked about condition-specific HRQL, generic health status, anxiety, and depression [50]. Men and women in the storage + voiding + postmicturition subgroup reported the lowest levels of urinary-specific HRQL and generic health, and the highest rates of clinical anxiety and depression. In both men and women, storage symptoms were significantly associated with more bladder problems, but voiding symptoms were not. Individual LUTS associated with anxiety were limited to nocturia, urgency, stress urinary incontinence and split stream in women, and to nocturia and incomplete emptying in men. Similarly, significant associations with depression were limited to urgency and stress urinary incontinence for women, and perceived frequency and incomplete emptying in men.

LUTS BOTHER AND TREATMENT SEEKING

A greater understanding of the relationship between prevalence, bother and treatment seeking is developing. Assessment of the level of bother and intensity and bother of symptoms is increasingly included in prevalence studies of LUTS [1,30]. For example, a nested case-control analysis of EPIC study data found that 54% of participants (54% men, 53% women) with OAB had symptom bother [51]. More men and women with OAB and urinary incontinence reported bother (77% men, 67% women) than did those with OAB without urinary incontinence (44% men, 36% women). Participants reporting bother were significantly more likely to use coping strategies and seek healthcare advice than those without bother.

In the EpiLUTS study, rates of bother were greatest among men and women who reported multiple storage, voiding and postmicturition symptoms [31]. For this LUTS subgroup, 83.4% of men and 89.4% of women reported that they experienced bother somewhat or more with one or more of their LUTS. About half of men in each of the dual-symptom groups, but ≤15% in the postmicturition only and voiding only groups, reported this degree of bother. Among women, the proportion experiencing bother ranged was 68–76% in the dual-symptom groups that included storage symptoms, but was lowest for voiding only and postmicturition only (≤16%).

Participants in the voiding + storage + postmicturition subgroup were the most likely to have sought treatment for their LUTS, but even in this group, less than a third of men and women reported seeking treatment. Increasing age (postmicturition only, voiding + postmicturition, and storage + postmicturition subgroups for women), more healthcare provider visits for any reason, and more comorbid conditions were related to treatment seeking across all LUTS subgroups. Overall, there were more symptom-specific bother variables associated with treatment seeking than symptom frequency variables, but the frequency of some symptoms, especially incontinence and urgency symptoms, was also strongly related to treatment seeking in men and women.

CLINICAL IMPLICATIONS

LUTS are prevalent in both men and women, with differences in distribution of storage and voiding symptoms representing underlying pathophysiological factors between the genders. As noted above, the prevalence of LUTS is expected to increase as the overall population ages, with the prevalence of LUTS expected to exceed 42 million persons in the USA by 2025 [47]. The worldwide prevalence of LUTS is predicted to reach 2.3 billion adults (≥20 years) within the next 10 years, based on data from the EPIC study and United States Census Bureau International Database [52]. Although the prevalence of LUTS is known to be age-related, the natural history of LUTS in both genders is poorly understood. A recent 6.5-year study in women participating in a health-screening survey in Austria showed that LUTS in women without urinary incontinence has a mean annual incidence of 5.3% and a mean annual remission rate of 4.6%, with storage symptoms the most likely to improve [18,53]. By comparison with the natural history of LUTS in men assessed over 5 years in two separate studies [54,55], LUTS in women appear to be more of a dynamic rather than strictly progressive disease.

The LUTS cluster analysis studies reported common findings of separate patient groups spanning a spectrum from those with typically one symptom of mild to moderate severity to those with multiple more severe LUTS and frequent comorbidities. These findings might help the clinician in creating individualized treatment plans for patients who present with LUTS. Although currently the common treatments used in clinical practice do not affect individual symptoms in a differentiated manner, clearly in clinical practice patients present with particular predominating symptoms, e.g. storage or voiding symptoms. In addition, because there are many metabolic and cardiovascular factors affecting the urogenital system, physicians must take these factors and their relationship to each other into account when considering a treatment strategy for men and women with LUTS. A more holistic clinical management approach is needed, looking beyond the bladder and the prostate, to evaluate other possible associated comorbid conditions, such as type 2 diabetes, hypertension, and metabolic syndrome, which might be expressed via the final common pathway of the urinary tract.

A diagnostic and treatment algorithm for patients should be designed based on the patient profiles identified as a result of these epidemiological studies. This will help clinicians to understand these conditions and commonly associated comorbidities, and will facilitate better patient management through improved history taking, clinical examination and diagnosis. As an example, similar to the National Cholesterol Education Program criteria for monitoring of coronary artery disease and hyperlipidaemia risk factors [56], clinicians treating patients with LUTS need to look for potential associated comorbidities, such as depression and metabolic syndrome, through a proper history, clinical examination, and appropriate laboratory evaluation, and institute optimal medical, behavioural and dietary therapy and follow-up as appropriate. Realization of relationships between LUTS and sexual dysfunction, obesity/increased BMI, and metabolic syndrome should prompt healthcare providers caring for men with LUTS to investigate these possible contributing factors. Although there is no direct proof that treatment of metabolic syndrome, reduction in weight, and other lifestyle changes will affect LUTS, these factors should be investigated and be part of counselling sessions with patients.

Additional longitudinal studies and validation of the findings from symptom cluster analysis in the clinical setting might help physicians to identify and characterize these patients phenotypically, and individualize patient management, involving an evaluation of comorbid conditions. Further research is also needed to understand the role of chronic inflammation (CRP), the possible common pathophysiology of LUTS and associated comorbidities, and to determine a temporal sequence. Investigation of this association with treatment impact will provide additional guidance to the clinicians in managing these patients.

LUTS occur commonly, but as noted in the findings from these recent epidemiological studies, the frequency of symptoms does not always translate into treatment-seeking behaviour. Many men and women might not be sufficiently bothered by the LUTS they experience or might be too embarrassed to seek treatment, might not have healthcare access, or not know that treatment is available. However, the impact of LUTS on HRQL and the level of bother are significant drivers for seeking treatment. This suggests a need to assess both the frequency and related bother of symptoms in helping patients to make decisions about treatment. The shame and stigma associated with LUTS, especially incontinence, is a significant barrier to seeking treatment [57]. Additional public education and improved clinical detection might lessen this stigma.

In addition to focusing on improved diagnoses and managing LUTS and their associated conditions in both men and women, physicians should also start examining preventive/prophylactic measures based on patient characteristics or the phenotype of the clusters identified from these epidemiological studies. Longitudinal analysis of some of the epidemiological studies, focusing on the impact of treatment, including prophylaxis, and additional studies in controlled clinical populations should be targeted to validate these observations.

ACKNOWLEDGEMENTS AND POTENTIAL CONFLICTS OF INTEREST

Steven Kaplan is a consultant and lecturer with Pfizer. Claus Roehrborn is a consultant with Aeterna Zentaris, AMS, GlaxoSmithKline, Eli Lilly, Pfizer, Sanofi Aventis, and Spectrum, and a scientific advisor with Aeterna Zentaris, AMS, and the NIH/NIDDK. Christopher Chapple is a scientific consultant and researcher with Allergan, Astellas, Novartis, and Pfizer. Raymond Rosen is a scientific consultant and advisor with Sanofi Aventis, Eli Lilly, and Bayer Schering. Debra Irwin is a scientific consultant for Pfizer. Zoe Kopp, Patrick Mollon, and Lalitha Aiyer are employees of Pfizer.

This study was funded by Pfizer Inc. Editorial support was provided by Janet E. Matsuura, PhD, at Complete Healthcare Communications, Inc., and was funded by Pfizer Inc.

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