The burden of lower urinary tract symptoms: evaluating the effect of LUTS on health-related quality of life, anxiety and depression: EpiLUTS

Authors


Karin Coyne, Senior Research Leader, United BioSource Corporation, 7101 Wisconsin Ave, Suite 600, Bethesda, MD 20814, USA.
e-mail: Karin.Coyne@unitedbiosource.com

Abstract

OBJECTIVE

To evaluate the impact of lower urinary tract symptoms (LUTS) on urinary-specific health-related quality of life (HRQL), generic health indices, depression and anxiety in a population-representative sample of men and women, as research has linked LUTS with reduced HRQL and depression, but little is known about the effects of individual LUTS on HRQL, depression and anxiety.

SUBJECTS AND METHODS

A cross-sectional population-representative survey was conducted via the Internet in the USA, the UK and Sweden. Participants rated the frequency and symptom-specific bother of individual LUTS and condition-specific HRQL, generic health status, anxiety and depression. Descriptive statistics were used to evaluate outcome differences by International Continence Society LUTS subgroups; logistic regressions were used to determine associations of LUTS and perception of bladder problems, anxiety and depression.

RESULTS

The overall survey response rate was 59.2%; 30 000 subjects (14 139 men and 15 861 women) participated. Men and women with LUTS in the all LUTS subgroup (storage, voiding and postmicturition) reported the lowest levels of HRQL and highest levels of anxiety and depression, with 35.9% of men and 53.3% of women meeting self-reported screening criteria for clinical anxiety (Hospital Anxiety and Depression Scale, HADS, Anxiety ≥8), and 29.8% of men and 37.6% of women meeting self-reported criteria for clinical depression (HADS Depression ≥8). In both men and women, storage symptoms were significantly associated with greater perceived bladder impact, whereas voiding symptoms were not. Significant predictors of anxiety included nocturia, urgency, stress urinary incontinence, leaking during sexual activity, weak stream and split stream in women; and nocturia, urgency, incomplete emptying and bladder pain in men. For depression, weak stream, urgency and stress urinary incontinence were significant for women, and perceived frequency and incomplete emptying were significant for men.

CONCLUSION

The negative effect of LUTS is apparent across several domains of HRQL and on overall perception of bladder problems, general health status and mental health. The high level of psychiatric morbidity in patients with multiple LUTS has important implications for treatment and highlights the need for further research to pinpoint specific mechanisms underlying this association.

Abbreviations
(HR)QL

(health-related) quality of life

OAB

overactive bladder

EpiLUTS

Epidemiology of LUTS

SF

Short Form

PPBC

Patient Perception of Bladder Condition

PCS

Physical Component Summary

MCS

Mental Component Summary

OAB-q SF

OAB Questionnaire Short Form

HADS (-A, -D)

, Hospital Anxiety and Depression Scale (-Anxiety, -Depression)

BMI

body mass index

SUI

stress urinary incontinence.

INTRODUCTION

The high prevalence of storage, voiding and postmicturition LUTS found in recent population-based studies [1–3] is particularly troubling, given the negative impact on health-related quality of life (HRQL) of LUTS constellations, including overactive bladder (OAB), BOO and BPH. In the clinical setting, OAB is often considered to be present when storage LUTS predominate, including urgency with or without urgency incontinence, and usually with daytime frequency and nocturia [4], whereas in men, voiding symptoms tend to be considered suggestive of BOO [5]. A histological diagnosis, BPH might result in BOO with postmicturition symptoms that include incomplete emptying and postmicturition dribble [4].

Data from the EPIC study, a large population-based survey in Canada, Germany, Italy, Sweden and the UK, found the prevalence of OAB to be 12% for both men and women [1]. EPIC and other population-based studies showed that OAB diminishes overall HRQL, emotional well-being and work productivity [1,6,7]. BPH is a common condition in men, with findings from autopsy studies detecting this condition in ≈40% of men in their 50s and 70% in their 60s [8]. LUTS suggestive of BPH have also been shown be associated with lower levels of overall HRQL [9,10]. Findings from the Epidemiology of LUTS (EpiLUTS) study show that storage, voiding and postmicturition LUTS often overlap, with 47% of men and 46% of women reporting LUTS from more than one symptom group, and the largest subgroup being those with voiding, storage and postmicturition symptoms (men, 24.3%; women, 26%) [11].

Importantly, decreases in HRQL with increasing LUTS severity have been previously shown in the general population [1,9,12–14] and clinical samples [15–17], using both generic and disease-specific instruments. Frequently, generic HRQL has been evaluated in men using the single-item QL question of the IPSS instrument, with HRQL decreasing as the IPSS increases [9,12,15,18,19]. Other studies have evaluated dimensions of general physical and mental health using the Short Form 36 (SF-36) [6,20] and SF-12 [14]. Findings suggest that the impact of severe LUTS on these dimensions of health might be even greater than that of gout, hypertension, angina and diabetes [20]. Importantly, in two large epidemiological studies (Boston Area Community Health Survey and UREPIK), the robust effect of LUTS on both mental and physical health components was over and above those of comorbid illnesses [14].

As to links between LUTS and mental health indices, several studies showed associations for urinary incontinence in relation to major depression [21,22], and women with mixed urinary incontinence have been shown to have higher levels of anxiety than women with pure stress incontinence [23]. The association between depressive symptoms and LUTS has been shown to be robust even after controlling for sociodemographic factors [24–26]. Furthermore, anxiety and depression have been shown to be associated with overall HRQL in patients with LUTS [27]. Qualitative research also supports the link between LUTS and psychological well-being, with findings showing that LUTS greatly affect the daily lives and self-concept of men and women [3,17,28,29].

Understanding the burden of LUTS has important implications for public health and clinical practice. Although there is a growing body of evidence suggesting that LUTS are associated with lower levels of HRQL, rates of anxiety and depression have not been estimated in relation to ICS categories of LUTS in a large population-representative sample of men and women. In addition, the research investigating LUTS, depression and anxiety has not examined the specific impact of individual LUTS on these outcomes. In the present study, the impact of all LUTS on urinary-specific indices, as well as on general health and mental health domains, was evaluated in a population-representative sample of men and women in the USA, the UK and Sweden.

SUBJECTS AND METHODS

A population-based cross-sectional Internet survey was conducted in the USA, the UK and Sweden to examine the prevalence and symptom-specific and combined bother of LUTS, and to evaluate the impact of these symptoms on HRQL and mental health (EpiLUTS) [3]. In all, 30 000 men and women aged ≥40 years were targeted for recruitment (20 000 in the USA, 7500 in the UK and 2500 in Sweden) from three Internet-based panels in each country. The rationale for this recruitment approach, study design and Internet survey are described elsewhere [28].

The LUTS that were assessed included storage, i.e. urinary frequency, urinary urgency, nocturia, and incontinence (stress, urgency, mixed, nocturnal enuresis, leaking during sexual activity, and leaking for no reason); voiding (weak stream, terminal dribble, hesitancy, straining, intermittency, and split stream); postmicturition (incomplete emptying and postmicturition incontinence); and other (bladder pain and dysuria). The response options for most LUTS were on a five-point Likert scale (‘never’, ‘rarely’, ‘sometimes’, ‘often’, and ‘almost always’). For every LUTS frequency response of at least ‘rarely’, participants were asked how bothered they were by the particular LUTS. Similarly, bother ratings were assessed on a five- point Likert scale (‘not at all’, ‘a little bit’, ‘somewhat’, ‘quite a bit’, and ‘a great deal’).

The following outcome instruments were used:

Patient Perception of Bladder Condition (PPBC), a single item that assesses patients’ subjective perception of their current bladder problems on a six-point scale ranging from 1 (‘no problems at all’) to 6 (‘many severe problems’) which has good construct validity, responsiveness to change, and test-retest reliability among patients with OAB [30,31].

The IPSS QL question asks participants to rate their current urinary symptoms from 0 to 6 (0, ‘delighted’; 1, ‘pleased’; 2, ‘mostly satisfied’; 3, ‘mixed – about equally satisfied and dissatisfied’; 4, ‘mostly dissatisfied’; 5, ‘unhappy’; and 6, ‘terrible’). This question has been widely used as an overall assessment of urinary symptom impact [32].

The SF-12 Health Survey is a brief self-administered survey that measures generic health concepts relevant across age, disease and treatment groups, and has good psychometric properties of test-retest reliability, internal consistency and validity [33]. Results are expressed in terms of two metascores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS), with a mean of 50 and an sd of 10 in a representative sample of the USA population.

The OAB Questionnaire Short Form (OAB-q SF) was developed in long form to assess the symptom bother and impact on HRQL of OAB on patients’ lives. The OAB-q SF was derived from the original questionnaire through item-response theory analyses and consists of a six-item symptom bother scale and a 13-item HRQL scale [34]. The OAB-q SF has good internal consistency reliability, concurrent validity, discriminant validity and responsiveness.

The Hospital Anxiety and Depression Scale (HADS) was used to assess mental health, as the 14-item questionnaire includes seven items to assess anxiety and seven to assess depression [35]. The HADS has good psychometric properties in various medical settings [36]. A score of ≥8 for both the HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D) was suggested as an optimal threshold in terms of sensitivity and specificity to indicate clinically relevant levels of anxiety and depression [36].

For statistical analysis, sample matching was used to construct a population-representative sample of respondents within each country’s Internet-based panel, and poststratification weights were calculated to correct small amounts of imbalance based on differences in response rates [28]. Thus, all presented data are weighted.

Eight ICS LUTS subgroups were created: no/minimal LUTS, voiding only, storage only, postmicturition only, voiding +  storage, voiding + postmicturition, storage + postmicturition, and voiding + storage + postmicturition. Group classification was determined two ways: the proportion of participants who responded at least ‘sometimes’ (‘sometimes’, ‘often’ and ‘almost always’) for one or more of the symptoms within each LUTS subgroup and those who responded at least ‘often’ (‘often’ and ‘almost always’). Exceptions to these classification schemes were questions that did not use the 5-point Likert response, including the questions for nocturia (collected as a continuous variable but symptom presence was defined as two or more episodes of nocturia for the ‘sometimes’ group and three or more for the ‘often’ group), daytime frequency (presence was a ‘yes’ response to the question ‘Do you feel that you urinate too often during the day?’), and urinary incontinence (presence was a ‘yes’ response to one or more items in a list of situations in which people can leak urine and a response of at least ‘a few times a month’ to the follow-up frequency question). Bladder pain and dysuria were not included in the subgroup analysis because they are not classified as storage, voiding or postmicturition symptoms. Demographic variables, condition-specific HRQL outcomes, generic health, and mental health outcomes were evaluated by descriptive analyses and are presented by LUTS subgroup separately for men and women. General linear models with Scheffe post hoc subgroup comparisons were used to compare LUTS subgroups.

Logistic regressions were used to evaluate the predictors of overall perception of bladder problems and clinical levels of anxiety (HADS-A score ≥8) and depression (HADS-D score ≥8), respectively. To evaluate the effect of bladder condition, the PPBC was dichotomized with a positive PPBC response limited to those who reported moderate, severe or many severe problems, vs a report of minor problems or less. Given the relatively low prevalence of anxiety and depression in some of the LUTS subgroups, all logistic regressions were conducted on the entire sample, rather than by LUTS subgroup to maximize statistical power. For all outcomes, each regression model was conducted separately for men and women and included age, race, number of comorbid conditions, body mass index (BMI), and country as covariates, followed by the symptom-specific bother of each LUTS. Given the large sample size and multiple analyses conducted, P < 0.01 was used as the threshold for statistical significance.

RESULTS

The overall survey response rate was 59%. The sample included 30 000 participants (14 139 men and 15 861 women). The demographic information of the participants is presented separately for men and women by ICS LUTS subgroup (Table 1). Among men, those with no/minimal LUTS were youngest (mean age 53.9 years), and those in the voiding + storage group were oldest (mean age 60.3 years). Age differences were less pronounced among women, with the oldest mean age (57.8 years) in the storage-only group. Most participants were white and reflected the population demographics in each country. All data presented are weighted to ensure representative populations, which might cause slight subgroup sample size variation due to rounding estimates.

Table 1.  The demographics of the participants by LUTS occurring at least sometimes*
VariableNo LUTSV onlyS onlyPM onlyV + SV + PMS + PMV + S + PMP
  • *

    All numbers presented are weighted; subgroups might or might not equal total N because of rounding or weighted values. V, voiding; S, storage; PM, postmicturition.

Men, n409717041280427144914632883433 
Mean (sd) age, years  53.9 (9.9)  55.5 (10.3)  57.2 (11.4) 53.1 (8.6)  60.3 (11.6)  55.0 (10.2) 55.7 (10.7)  59.4 (11.2)<0.001
Race, n (%)         
 White3377 (82.4)1465 (86.0) 943 (73.7)359 (84.0)1201 (82.9)1282 (87.7)214 (74.2)2854 (83.1)<0.001
 Black 252 (6.2)  87 (5.1) 142 (11.1) 18 (4.1) 102 (7.1)  48 (3.3) 28 (9.9) 222 (6.5) 
 Asian 124 (3.0)  45 (2.7)  41 (3.2)  4 (1.0)  42 (2.9)  38 (2.6)  8 (2.8)  80 (2.3) 
 Hispanic 270 (6.6)  77 (4.5) 118 (9.2) 37 (8.7)  77 (5.3)  73 (5.0) 28 (9.8) 206 (6.0) 
 Other  73 (1.8)  30 (1.7)  35 (2.7)  9 (2.1)  26 (1.8)  22 (1.5)  9 (3.2)  71 (2.1) 
Women, n4006 82235451432340  3115744120 
Mean (sd) age, years  55.8 (10.5)  55.9 (10.4)  57.8 (10.5) 55.0 (8.9)  57.3 (10.7)  55.4 (10.5) 56.5 (10.0)  56.7 (10.6)<0.001
Race, n (%)         
 White3277 (81.8) 680 (82.7)2944 (83.0)116 (81.4)1956 (83.6) 271 (87.1)479 (83.4)3446 (83.6) 0.002
 Black 282 (7.0)  62 (7.5) 252 (7.1)  9 (6.2) 178 (7.6)  14 (4.4) 43 (7.4)  281 (6.8) 
 Asian 130 (3.2)  25 (3.0)  83 (2.3)  8 (5.7)  40 (1.7)   9 (3.1)  9 (1.6)  69 (1.7) 
 Hispanic 247 (6.2)  35 (4.3) 209 (5.9)  8 (5.4) 125 (5.3)  14 (4.5) 35 (6.1) 251 (6.1) 
 Other  69 (1.7)  20 (2.4)  58 (1.6)  2 (1.2)  41 (1.7)   3 (1.0)  8 (1.5)  74 (1.8) 

Urinary-specific HRQL differed across LUTS groups for both men and women (Table 2), with most of those in the no/minimal LUTS group reporting that their bladder condition ‘does not cause any problems at all’ (men 92.8%; women 84.2%) and that they were ‘delighted’ or ‘pleased’ by their urinary condition (men 86.4%; women 78.8%). By contrast, those who had the most burden and experienced symptoms in all categories (voiding + storage + postmicturition) more commonly reported ‘minor’ to ‘severe’ problems (men 47.9%; women 65.9%) and rated their urinary condition as ‘mostly dissatisfied’ to ‘terrible’ (men 33.9%; women 49.5%). In parallel, mean OAB-q SF scores were highest (indicating better HRQL) in the no/minimal LUTS group (men 98.5; women 97.9) and lowest in the voiding + storage + postmicturition group (men 77.7; women 69.1).

Table 2.  Condition-specific patient outcomes by LUTS occurring at least sometimes*
VariableNo LUTSV onlyS onlyPM onlyV + SV + PMS + PMV + S + PMP
  • *

    All numbers presented are weighted; subgroups might or might not equal total N because of rounding or weighted values.

  • Significant differences (P <0.001) between OABq-SF HRQL means: men; no LUTS vs S, no LUTS vs V + S, no LUTS vs V + PM, no LUTS vs S + PM, no LUTS vs V + S + PM, V vs S, V vs V + S, V vs V + PM, V vs S + PM, V vs V + S + PM, S vs PM, S vs V + S, S vs S + PM, S vs V + S + PM, PM vs V + S, PM vs V + PM, PM vs S + PM, PM vs V + S + PM, V + S vs V + PM, V + S vs V + S + PM, V + PM vs S + PM, V + PM vs V + S + PM, S + PM vs V + S + PM; women; no LUTS vs S, no LUTS vs V + S, no LUTS vs V + PM, no LUTS vs S + PM, no LUTS vs V + S + PM, V vs S, V vs V + S, V vs V + PM, V vs S + PM, V vs V + S + PM, S vs V + S, S vs S + PM, S vs V + S + PM, PM vs V + S, PM vs S + PM, PM vs V + S + PM, V + S vs V + PM, V + S vs V + S + PM, V + PM vs S + PM, V + PM vs V + S + PM, S + PM vs V + S + PM. V, voiding; S, storage; PM, postmicturition.

Men, n409717041280 427144914632883433 
Perception of bladder condition, n (%)
n393116511231 411136114102803281 
Does not cause me any problems at all3646 (92.8)1287 (77.9) 820 (66.6) 275 (66.9) 538 (39.5) 648 (46.0)119 (42.4) 559 (17.0)<0.001
Causes me:         
Some very minor problems 274 (7.0) 325 (19.7) 319 (25.9) 132 (32.2) 570 (41.9) 624 (44.3)117 (41.8)1149 (35.0) 
Some minor problems   5 (0.1)  33 (2.0)  63 (5.2)   3 (0.8) 183 (13.5)  118 (8.4) 34 (12.0) 864 (26.3) 
Moderate problems   0   6 (0.3)  23 (1.8)   1 (0.1)  59 (4.4)  16 (1.1)  9 (3.4) 604 (18.4) 
Severe problems   1 (0.0)   0   6 (0.5)   0   7 (0.5)   4 (0.3)  1 (0.5)  86 (2.6) 
Many severe problems   4 (0.1)   0   0   0   3 (0.3)   0  0  19 (0.6) 
IPSS QL, n (%)  1278  1462   
 Delighted2334 (57.0) 523 (30.7) 299 (23.4) 121 (28.4) 133 (9.2) 172 (11.8) 34 (11.9)  77 (2.2)<0.001
 Pleased1203 (29.4) 623 (36.6) 387 (30.3) 140 (32.8) 275 (19.0) 381 (26.1) 59 (20.3) 261 (7.6) 
 Mostly satisfied 406 (9.9) 390 (22.9) 346 (27.1) 127 (29.7) 477 (32.9) 498 (34.0) 81 (28.1) 805 (23.4) 
 Mixed, about equally satisfied and dissatisfied  118 (2.9) 145 (8.5) 167 (13.0)  31 (7.2) 386 (26.6) 329 (22.5) 78 (27.1)1124 (32.7) 
 Mostly dissatisfied   9 (0.2)  10 (0.6)  45 (3.5)   8 (1.9)  114 (7.9)  57 (3.9) 27 (9.3) 711 (20.7) 
 Unhappy  16 (0.4)   11 (0.6)  25 (1.9)   0  44 (3.1)  24 (1.7)  5 (1.8) 341 (9.9) 
 Terrible  10 (0.2)   2 (0.1)  10 (0.8)   0  19 (1.3)   2 (0.1)  4 (1.4) 115 (3.3) 
Mean (sd) OABq-SF†  98.5 (2.6)  97.5 (3.5)  94.1 (9.3)  97.3 (3.6)  89.8 (11.0)  94.9 (6.3) 90.9 (10.0)  77.7 (19.3)<0.001
Women, n4006 8223545 1432340 3115744120 
Perception of bladder condition, n (%)
n3832 7913393 1382229 301 5493927 
Does not cause me any problems at all3226 (84.2) 520 (65.8)1312 (38.7)  75 (54.3) 523 (23.5) 116 (38.5)107 (19.4) 303 (7.7)<0.001
Causes me:         
Some very minor problems 587 (15.3) 249 (31.4)1412 (41.6)  52 (37.4) 946 (42.5) 148 (49.0)218 (39.7)1039 (26.4) 
Some minor problems   11 (0.3)  18 (2.3) 472 (13.9)   9 (6.8) 457 (20.5)  27 (9.0)129 (23.5)1024 (26.1) 
Moderate problems   8 (0.2)   3 (0.4) 168 (4.9)   2 (1.5) 242 (10.9)   8 (2.7) 84 (15.3)1126 (28.7) 
Severe problems   0   0  23 (0.7)   0  54 (2.4)   2 (0.8) 10 (1.8) 354 (9.0) 
Many severe problems   0   0   7 (0.2)   0   5 (0.2)   0  2 (0.3)  82 (2.1) 
IPSS QL, n (%)3998 8213542 1412334  311570 4117 
 Delighted1997 (49.9) 228 (27.8) 459 (13.0)  30 (21.0) 133 (5.7)  23 (7.2) 21 (3.6)  44 (1.1)<0.001
 Pleased1155 (28.9) 267 (32.5) 761 (21.5)  44 (31.5) 312 (13.4)  54 (17.4) 61 (10.7) 160 (3.9) 
 Mostly satisfied 596 (14.9) 226 (27.6)1031 (29.1)  41 (29.3) 624 (26.7) 135 (43.3)133 (23.3) 570 (13.9) 
 Mixed, about equally satisfied and dissatisfied 192 (4.8)  79 (9.6) 874 (24.7)  20 (14.4) 750 (32.1)  72 (23.1)187 (32.8)1302 (31.6) 
 Mostly dissatisfied  19 (0.5)   7 (0.9) 275 (7.8)   5 (3.3) 299 (12.8)  18 (5.8)100 (17.6) 949 (23.0) 
 Unhappy  20 (0.5)   5 (0.6) 106 (3.0)   1 (0.4) 171 (7.3)   8 (2.5) 52 (9.1) 663 (16.1) 
 Terrible  20 (0.5)  10 (1.2)  36 (1.0)   0 (0.0)  45 (1.9)   2 (0.8) 16 (2.9) 429 (10.4) 
Mean (sd) OABq-SF‡  97.9 (3.2)  96.2 (4.7)  91.6 (11.3)  95.5 (5.3)  85.0 (15.6)  92.3 (8.9) 82.5 (16.3)  69.1 (23.1)<0.001

The pattern was similar for generic health status and anxiety and depression (Table 3). The mean PCS and MCS scores were highest (indicating better health) among men and women with no/minimal LUTS and lowest among those with voiding + storage + postmicturition symptoms. The mean scores on the HADS-A and HADS-D and proportions of participants with clinical levels of anxiety and depression (HADS-A ≥ 8; HADS-D ≥ 8) also followed this pattern. Rates of clinical anxiety and clinical depression were highest in the voiding + storage + postmicturition group (HADS-A ≥ 8, men 35.9%, women 53.3%; HADS-D ≥ 8, men 29.8%, women 37.6%) and lowest in the no/minimal LUTS group (HADS-A ≥ 8, men 10.7%, women 18%; HADS-D ≥ 8, men 8.4%, women 9.7%) but were also elevated in the other LUTS subgroups (HADS-A ≥ 8 15.4–26.4% in men and 26.6–38.2% in women; HADS-D ≥ 8 10.2–18.0% in men and 13.3–26.3% in women).

Table 3.  Generic health status, anxiety and depression by LUTS occurring at least sometimes*
VariableNo LUTSV onlyS onlyPM onlyV + SV + PMS + PMV + S + PMP
  1. *All numbers presented are weighted; subgroups might or might not equal total N because of rounding or weighted values. Men: †significant differences (P <0.001) between PCS means: No LUTS vs V, No LUTS vs S, No LUTS vs V + S, no LUTS vs V + P, no LUTS vs S + P, no LUTS vs V + S + P, V vs S, V vs V + S, V vs V + S + P, S vs P, S vs V + S, S vs V + S + P, P vs V + S, P vs V + P, P vs V + S + P, V + S vs V + P, V + S vs V + S + P, V + P vs V + S + P, S + P vs V + S + P. ‡Significant differences between MCS means: no LUTS vs V, No LUTS vs S, no LUTS vs V + S, no LUTS vs V + P, no LUTS vs V + P, no LUTS vs S + P, no LUTS vs V + S + P, V vs V + P, V + V + S + P, S vs V + P, S vs V + S + P, P vs V + S + P, V + S vs V + S + P, V + P vs V + S + P, S + P vs V + S + P. §In the USA version response options to HADS-A item ‘I can sit at ease and feel relaxed’ were incorrect. The mean of an individual’s anxiety items was substituted for this item in scoring the USA data. Significant differences between HADS-A score means: no LUTS vs V, no LUTS vs S, no LUTS vs V + S, no LUTS vs V + P, no LUTS vs V + P, no LUTS vs S + P, no LUTS vs V + S + P, V vs V + P, V vs V + S + P, S vs V + S. ¶Missing responses not included in these frequencies and calculations. Significant differences between HADS-D score means: no LUTS vs V, no LUTS vs S, no LUTS vs V + S, no LUTS vs V + P, no LUTS vs S + P, no LUTS vs V + S + P, V vs V + S, V vs V + P, V vs V + S + P, S vs V + S, S vs V + P, S vs V + S + P, P vs V + S, P vs V + P, P vs V + S + P, V + S vs V + S + P, V + P vs V + S + P, S + P vs V + S + P. Women: †Significant differences between PCS means: no LUTS vs S, no LUTS vs V + S, no LUTS vs V + P, no LUTS vs S + P, no LUTS vs V + S + P, V vs S, V vs V + S, V vs S + P, V vs V + S + P, S vs V + S, S vs S + P, S vs V + S + P, P vs V + S, P vs S + P, P vs V + S + P, V + S vs V + S + P, V + P vs S + P, V + P vs V + S + P, S + P vs V + S + P. ‡Significant differences between MCS means: no LUTS vs V, no LUTS vs S, no LUTS vs V + S, no LUTS vs V + P, no LUTS vs S + P, no LUTS vs V + S + P, V vs S, V vs S + P, V vs V + S + P, S vs V + S, S vs V + P, S vs S + P, S vs V + S + P, P vs S + P, P vs V + S + P, V + S vs V + S + P, S + P vs V + S + P; §Significant differences between HADS-A score means: no LUTS vs V, no LUTS vs S, no LUTS vs P, no LUTS vs V + P, no LUTS vs S + P, no LUTS vs V + S + P, V vs S, V vs V + S, V vs S + P, V vs V + S + P, S vs V + S, S vs V + P , S vs S + P, S vs V + S + P, P vs V + S + P, V + S vs V + S + P, V + P vs V + S + P, S + P vs V + S + P ¶Missing responses not included in these frequencies and calculations. Significant differences between HADS-D score means: no LUTS vs V, no LUTS vs S, no LUTS vs V + P, no LUTS vs S + P, no LUTS vs V + S + P, V vs S, V vs V + S, V vs S + P, V vs V + S + P, S vs V + S, S vs S + P, S vs V + S + P, P vs V + S, P vs S + P, P vs V + S + P, V + S vs V + S + P, V + P vs V + S + P, S + P vs V + S + P. V, voiding; S, storage; PM, postmicturition.

Men, n409717041280427144914632883433 
Mean(sd)         
SF-12         
 PCS  51.4 (8.8)  49.8 (9.8)  47.5 (11.1) 51.0 (8.0)  45.9 (11.7)  48.6 (10.3) 48.4 (8.7)  42.5 (12.4)<0.001
 MCS  53.0 (8.4)  51.5 (8.9)  51.3 (10.1) 50.8 (7.9)  50.4 (10.4)  49.4 (9.8) 49.6 (9.9)  46.4 (11.9)<0.001
HADS         
 HADS-A§   3.3 (3.3)   4.2 (3.5)   3.9 (3.8)  4.3 (3.4)   4.6 (3.9)   5.3 (4.0)  4.7 (4.0)   6.4 (4.6)<0.001
 HADS-A ≥ 8, n (%) 436 (10.7) 264 (15.8) 194 (15.4) 68 (16.0) 296 (20.6) 379 (26.4) 62 (21.7)1209 (35.9)<0.001
 HADS-D   2.6 (3.0)   3.2 (3.0)   3.3 (3.3)  3.3 (3.0)   4.0 (3.5)   4.1 (3.3)  4.0 (3.5)   5.6 (4.1)<0.001
 HADS-D ≥ 8, n (%) 341 (8.4) 173 (10.2) 153 (12.0) 51 (12.1) 234 (16.2) 244 (16.7) 51 (18.0) 1017 (29.8)<0.001
Women, n4006 82235451432340 3115744120 
Mean (sd)         
SF-12         
 PCS  50.5 (9.2)  48.8 (9.9)  46.5 (11.2) 49.7 (9.5)  44.5 (12.0)  46.6 (11.3) 43.4 (11.7)  40.0 (13.0)<0.001
 MCS  51.9 (8.9)  49.5 (10.2)  50.1 (10.5) 50.7 (8.6)  47.5 (11.1)  46.6 (11.8) 46.3 (11.7)  44.0 (12.7)<0.001
HADS         
 HADS-A§   4.4 (3.7)   5.6 (4.0)   5.4 (4.1)  5.9 (3.7)   6.7 (4.4)   6.4 (4.1)  6.9 (4.2)   8.4 (4.9)<0.001
 HADS-A ≥ 8, n (%) 715 (18.0) 233 (28.5) 933 (26.6) 39 (27.9) 878 (38.1)  115 (37.2)216 (38.2)2175 (53.3)<0.001
 HADS-D   2.9 (3.0)   3.7 (3.1)   3.8 (3.4)  3.6 (3.0)   4.8 (3.7)   4.5 (3.6)  5.1 (3.7)   6.4 (4.2)<0.001
 HADS-D ≥ 8, n (%) 386 (9.7) 109 (13.3) 525 (14.9) 15 (10.3) 525 (22.5)  58 (18.8)151 (26.3)1542 (37.6)<0.001

Results of the logistic regression analyses conducted separately in men and women to examine associations of overall perception of bladder problems, anxiety and depression are described for each outcome in Table 4. For the initial models, each LUTS frequency and bother variable was included in the model; however, multi-collinearity issues raised concerns with this modelling approach. As such, individual LUTS frequency and symptom bother models were assessed separately, with similar results. For purposes of simplicity, only the individual symptom bother models are presented (Table 4).

Table 4.  A summary of logistic regressions for perception of bladder condition, anxiety and depression
CovariatesImpact of bladder condition (PPBC at least moderate)Anxiety (HADS-A ≥ 8)Depression (HADS-D ≥ 8)
MenWomenMenWomenMenWomen
  1. * P <0.01, ** P <0.001. BMI, Body Mass Index. SUI, stress urinary incontinence. PM, postmicturition.

Age +**********
Hispanic vs white      
Other vs white      
Asian vs white      
Black vs white      
BMI +****+*+**
No. of comorbid conditions+**+**+**+**+**+**
Sweden vs USA+**+******* 
UK vs USA****+**+**  
Voiding symptom bother      
Weak stream+**  +* +*
Split stream   +**  
Intermittency      
Hesitancy      
Straining      
Terminal dribble      
Storage symptom bother      
Perceived frequency+**+**  +** 
Nocturia+**+**+**+**  
Urgency+**+**+**+** +*
Urgency with fear of leaking+**+**    
Urgency incontinence +**    
SUI (laugh, sneeze, cough)SUI (physical activities) +**+** +** +**
Leak for no reason +**    
Nocturnal enuresis +**    
Leak during sexual activity+*+* +*  
PM symptom bother      
Incomplete emptying+**+**+**+**+* 
PM incontinence      
Other symptom bother      
Bladder area pain  +*   
Dysuria      

When examining predictors of higher levels of perceived bladder problems (at least moderate on PPBC), several storage LUTS were highly significant for both men and women (Table 4). Among men, the bother associated with the storage symptoms of perceived frequency, nocturia, urgency, urgency with fear of leaking, and leaking during sexual activity were all significantly related to greater bladder impact (all P < 0.001). Additional LUTS that were also associated with higher levels of perceived bladder problems were weak stream and incomplete emptying. Age and race were not associated with worsening bladder impact, whereas the number of comorbid conditions and being from Sweden were associated. Men in the USA were more likely than men in the UK to report greater bladder problems. Among women, the bother associated with all storage symptoms, which is suggestive of OAB, was significantly associated with higher levels of perceived bladder problems (all P < 0.001 except leaking during sexual activity, for which P < 0.01). Incomplete emptying, increasing age, number of comorbid conditions and increased BMI were also associated with higher levels of perceived bladder problems. As with men, Swedish women reported greater bladder problems and women in the UK reported fewer problems than women in the USA.

In the clinical anxiety models (HADS-A ≥ 8), younger age and lower BMI were significantly associated with clinical anxiety for both men and women, as was an increasing number of comorbid conditions (Table 4). Bother related to nocturia, urgency, incomplete emptying and bladder area pain were the only LUTS that were significantly associated with anxiety in men, whereas bother associated with weak stream, split stream, nocturia, urgency, stress urinary incontinence (SUI; sneeze, cough), leaking during sexual activity, and incomplete emptying were significantly associated with anxiety in women. Swedish men and women were less likely than men and women in the USA to report anxiety, but men and women in the UK were more likely than their counterparts in the USA to report anxiety.

The depression models were similar to the anxiety models, but with fewer LUTS having an association with clinically relevant depression (HADS-D ≥ 8). Among men, the bother associated with perceived frequency and incomplete emptying was associated with depression, whereas among women, the bother associated with weak stream, urgency, and SUI (sneeze, cough) was associated with depression. Younger age, increased BMI and increasing number of comorbid conditions were also significantly associated with depression; however, no country differences were present except for Swedish men being less likely to have clinically relevant depression than men in the USA.

The predictive fit of all models was quite good. Among women, c-indices were 0.94 for bladder condition impact, 0.76 for anxiety and 0.81 for depression. Among men, values were 0.95 for bladder condition impact, 0.78 for anxiety and 0.80 for depression.

DISCUSSION

In this study, men and women with multiple storage, voiding and postmicturition symptoms reported the lowest levels of urinary-specific HRQL and generic health, and had the highest rates of clinical anxiety and depression. Mean PCS and MCS (SF-12) scores in men and women with voiding + storage + postmicturition symptoms were well below USA norms (USA population mean, 50), indicating below-average health status (PCS, men 42.5, women, 40; MCS, men 46.4, women 44). The physical health status of women with all three categories of LUTS was lower than that for 84% of the USA population, and physical health status among men was only slightly better.

This diminished health status is consistent with previous research in studies evaluating the effects of subsets of LUTS, including BPH and OAB. Robertson et al.[14] found that increases in IPSS were associated with statistically significant reductions in SF-12 PCS and MCS. Using the SF-36, a longer version of the SF-12, Abrams et al.[6] found lower levels of HRQL for patients with OAB than in those with diabetes, and Welch et al.[20] found that men with severe LUTS (defined as a score of 20–35 on the AUA Symptom Index) had lower scores on many indices, most notably vitality/energy, role functioning, and mental health, than men with gout, hypertension, angina, or diabetes. Building on these previous findings, the present study shows that the greatest impairments in generic health status are evident in individuals with storage, voiding and postmicturition symptoms.

Not surprisingly, the greater number of different types of LUTS experienced increased the level of perceived bladder problems. The PPBC is a useful assessment of overall bladder condition that is quite discriminative by LUTS subgroups. The bother associated with storage symptoms has a profound impact on perceived bladder problems, with a worsened condition significantly associated with bothersome storage symptoms. Although not previously examined in the manner of the present study, previous research showed storage symptoms to be more bothersome than other LUTS, particularly when incontinence is implicated [5,37,38]. Given that both men and women commonly experience LUTS, including BPH and OAB, proactively asking a question like the PPBC (‘How bothered are you by your bladder condition?’) can provide important information about overall impact on patients.

In parallel, those with multiple storage, voiding and postmicturition LUTS were most likely to report clinically relevant levels of anxiety and depression, with 35.9% of men and 53.3% of women meeting screening criteria for clinical anxiety (HADS-A ≥ 8), and 29.8% of men and 37.6% of women meeting criteria for clinical depression (HADS-D ≥ 8). Rates of anxiety and depression were also elevated in the other LUTS subgroups (HADS-A ≥ 8 of 15.4–26.4% in men and 26.6–38.2% in women; HADS-D ≥ 8 of 10.2–18.0% in men and 13.3–26.3% in women). Although these HADS scores do not correspond exactly to mental disorders defined by International Classification of Diseases, 10th edition, or Diagnostic and Statistical Manual of Mental Disorders, 10th edition, these worrisome high rates suggest that a substantial proportion of men and women with LUTS are in need of mental health evaluation and treatment.

This robust association of depression and clinical anxiety with LUTS affects not only overall patient HRQL but also seriously affects healthcare economics, with rising healthcare costs and increasing complications. This increase in psychiatric morbidity needs further assessment in a longitudinal study and requires efforts to increase the awareness in the medical community to ensure the early diagnosis and appropriate management of these conditions. Because men with storage, voiding and postmicturition LUTS (or voiding and storage symptoms) probably have either OAB and/or underlying BPH leading to BOO, a comprehensive assessment of these individuals should include not only all LUTS, but an assessment of an individual’s HRQL and mental health status, with referrals as indicated. Similarly, women with multiple LUTS, including OAB and incontinence, should receive a comprehensive assessment for underlying pathophysiology and mental health referral as needed.

There are several limitations to this study. First, the data are cross-sectional and the temporal relationship between LUTS and depression and anxiety (as well as between LUTS and physical and mental health status) is unknown. Findings regarding changes in HRQL with changes in LUTS via longitudinal research have been mixed, with some studies showing that changes in symptoms were associated with changes in LUTS-related bother [39] and psychological morbidity [27], whereas other findings showed that changes in LUTS are not associated with changes in generic HRQL [40]. More longitudinal research is needed to assess the temporal relationship of LUTS and anxiety and depression. Secondly, assessment in this study was based exclusively on self-report, and clinically significant levels of anxiety and depression might not correspond to clinical diagnoses or results obtained using clinician-administered diagnostic interview techniques.

Importantly, the burden of LUTS increases with increasing number and types of LUTS. Storage symptoms have a greater overall impact on the bladder than voiding or postmicturition symptoms; however, a combination of symptoms from two or more categories is common and has a negative effect on HRQL and mental health. Regardless of whether LUTS are causal factors that contribute to depression and anxiety, or are secondary to them, the high levels of psychiatric morbidity in patients with multiple LUTS warrants further research and medical assessment of patients suffering from common LUTS-related conditions, such as BOO, BPH and OAB.

ACKNOWLEDGEMENTS

Additional editorial support was provided by Tracy Johnson and Janet E. Matsuura, PhD, at Complete Healthcare Communications, Inc., and was funded by Pfizer Inc. This research was supported by funding from Pfizer Inc.

CONFLICT OF INTEREST

Karin Coyne, Chris Sexton, and Christine Thompson are employees of United BioSource Corporation, who are scientific consultants to Pfizer. Alan Wein is a scientific consultant with Allergan, Astellas, Novartis, and Pfizer. Andrea Tubaro is a scientific consultant for Astellas, GlaxoSmithKline, Novartis, and Ferring. Zoe Kopp and Lalitha Aiyer are employees of Pfizer Inc.

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