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The Impact of Detrusor Overactivity on Bladder Function in Younger and Older Women
The Impact of Detrusor Overactivity on Bladder Function in Younger and Older Women Mathias H.-D. Pfisterer,* Derek J. Griffiths,† Lisa Rosenberg, Werner Schaefer‡ and Neil M. Resnick From the Division of Geriatric Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, and Bethanien-Krankenhaus, Geriatric Center of the University of Heidelberg (MHDP), Heidelberg, Germany
Purpose: We examined the relationship of DO and aging, and bladder function in female volunteers. Materials and Methods: We recruited 85 cognitively competent, fully functional female volunteers who were 22 to 90 years old (median age 54) with and without symptoms suggestive of DO. Comprehensive assessment included a bladder diary, uroflowmetry and videourodynamics. We examined predefined urodynamic and diary variables for associations with DO and age, summarizing results in the 3 subgroups no DO, intermediate DO and clinically relevant DO. Results: Compared to women without DO those with DO showed a decrease in maximum cystometric capacity (558 vs 448 ml), mean daytime voided volume (260 vs 175 ml) and volume at strong desire to void (363 vs 283 ml) but an increase in maximum isovolumetric pressure (41 vs 64 cm H2O) and maximum detrusor pressure during involuntary contraction (intermediate and relevant DO 22 and 37 cm H2O, respectively). The positive association between increased detrusor contraction strength and DO was present at younger ages but absent in older subjects. Maximum urethral closure pressure and detrusor contraction strength decreased significantly with age. Conclusions: From young adulthood to old age DO appears to affect bladder function parameters. It is associated with decreased bladder capacity and increased bladder sensation. Moreover, in younger adults DO is also associated with increased detrusor contraction strength, which is an association not seen in older individuals. This age associated loss of muscle function may be related to sarcopenia, implying that different treatments may be appropriate in older adults. Key Words: urinary tract, bladder, urodynamics, aging, female
rge incontinence and DO are a source of considerable morbidity, especially in the elderly population,1 and they impair quality of life. Because DO becomes much more common in old age, it is difficult to disentangle its effects from those of aging alone. For example, in young and middle-aged women DO is associated with increased detrusor contractility2,3 but in the elderly population observations are inconclusive.4,5 Moreover, in older individuals sphincter function, urine output and sensation may modify the clinical manifestation of DO.6 Published data concerning DO associated changes in bladder function are derived primarily from studies of symptomatic patients.2– 6 Few studies cover the spectrum from asymptomatic and healthy subjects without DO to subjects with clear DO and consonant symptoms. Still fewer include an age range wide enough to allow the evaluation of age related changes.
U
Submitted for publication June 17, 2005. Study received local Institutional Review Board approval. Supported by United States Public Health Service Grants R01AG20629 and P01-AG04390, and a mid career fellowship in geriatrics from the Robert Bosch Foundation, Germany (MHDP). * Correspondence: Kontinenzberatungsstelle Bethanien-Krankenhaus, Geriatrisches Zentrum, Rohrbacherstrasse 149, 69126 Heidelberg, Germany (e-mail: [email protected]). † Financial interest and/or other relationship with Laborie Medical Technologies. ‡ Financial interest and/or other relationship with Eli Lilly and Sanofi Aventis.
0022-5347/06/1755-1777/0 THE JOURNAL OF UROLOGY® Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION
Therefore, we examined the impact of DO on bladder function while controlling for age in a group of select 22 to 90-year-old volunteers with and without DO. We included only women to avoid the confounding effect of urethral obstruction. We clarified the role of DO in abnormalities of bladder function in young and old populations. Based on clinical experience and the literature we hypothesized that in the presence of DO bladder capacity and micturition volume would be smaller,2,6 while micturition frequency, bladder sensation,6 detrusor contractility (contraction strength)2,3,5 and urethral sphincter function would be greater.3 MATERIALS AND METHODS This was a secondary analysis of data collected for a study of DO and aging, and approved by the local Institutional Review Board. Data were obtained on adult female volunteers 20 years and younger who were recruited through advertising. In each age decade efforts were made to recruit an equal number of subjects with or without OAB symptoms. Exclusion criteria were dementia, neurological disease, current urinary tract infection, history of pelvic irradiation, bladder cancer, vitamin B12 deficiency or alcohol abuse, abdominoperineal resection, radical hysterectomy or the use of agents given for bladder problems that could not be stopped for 2 weeks. Assessment included detailed history, physical examination and a 3-day bladder diary.6 Videourodynamic testing
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Vol. 175, 1777-1783, May 2006 Printed in U.S.A. DOI:10.1016/S0022-5347(05)00985-7
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IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION
included free uroflowmetry and nonstraining PVR, measured twice, fluoroscopically monitored cystometry with filling at 30 ml per minute using room temperature Cystografin™ with measurement of intravesical and abdominal pressure, urethral pressure profilometry, isovolumetric testing, seated pressure flow studies and final PVR. No limit on bladder volume was imposed other than subject discomfort. The provocation of DO or incontinence was done by coughing, suprapubic tapping, running water, hand washing, catheter manipulation, posture change from supine to standing, the Valsalva maneuver, heel jouncing and a 2-minute wait with a full bladder after sitting on a commode. Methods and definitions conform to the standards recommended by the International Continence Society7,8 except for DO classification, detrusor contraction strength and involuntary dpdet/dt, as discussed. To quantify detrusor contraction strength during voiding we used pdet.isv and PIP1. We measured pdet.isv in 1 or more of 3 ways, including by interrupting voiding with a balloon catheter or voluntarily (stop test), or by attempting to void against a balloon blocked outlet. The greatest of these 3 values was considered pdet.isv. PIP1, a modification9 of the Schaefer contractility parameter detrusor strength coefficient,10 was used to estimate pdet.isv from the pressure flow study without interrupting flow. DO is defined as the urodynamic observation of involuntary bladder contraction during the filling phase.7,8 DO is believed to underlie OAB symptoms, such as urgency, urge incontinence, increased frequency and nocturia. The association with symptoms is not perfect since some symptom-free volunteers show DO on urodynamic testing, while some symptomatic patients do not even with provocation.11,12 Consequently DO must be judged in the context of the symptoms. To quantify to what extent the urodynamic observation of DO or no DO was supported symptomatically we ranked subjects blindly using a new DO⫹ scale. We devised DO⫹ before the analysis, basing factors and weights on our clinical experience (see Appendix). The DO⫹ value range was 8 to ⫺6. Scores of 8 required DO incontinence during urodynamic testing, and congruent symptoms and bladder diary findings. Scores of ⫺6 required a stable bladder during urodynamic testing despite provocation with neither symptoms nor a suggestion of DO by history or bladder diary. Values close to zero implied that symptoms and urodynamics were not entirely consistent. Content validity was ensured by basing the score on International Continence Society definitions of OAB syndrome and DO. Face validity was confirmed by 5 experts. Internal consistency was assessed by Cronbach’s ␣, which was 0.77. The score in each subject was generated by a computerized algorithm using information from the bladder diary, videourodynamic study and history. The lower of at least 2 PVR values obtained after nonstraining free uroflowmetry was used in the analyses. The dpdet/dt is the rate of increase in detrusor pressure measured in a 2-second period. For each subject with DO the highest value was recorded.
Statistics SPSS 11.5 (SPSS, Chicago, Illinois) was used for statistical analysis. Select urodynamic and diary variables were grouped into predefined domains representing various as-
pects of lower urinary tract function (table 1). We used multiple linear regression analysis to examine associations of the variables in each domain with age and DO. We used  to compare the associations of DO and age with the different variables. Voiding frequency was examined for an association with age only since frequency contributed directly to the DO⫹ score. Statistical significance was considered at 2-tailed p ⬍0.05. For results significant on regression analysis we performed ANOVA to assess the interaction between DO⫹ score and age. For display purposes we summarized values of the variables in 3 subgroups, namely no DO—DO⫹ score ⫺3 or less, intermediate DO—score greater than ⫺3 to less than 3 and clinically relevant DO—score 3 or greater.
RESULTS All 85 women 22 to 90 years old (median age 54) were cognitively intact, mobile and fully functional with similar values in each of the 3 DO⫹ groups and no significant differences in age across groups (table 2 and fig. 1). As intended, approximately half of the subjects had symptoms suggestive of DO and 42 of the 85 showed DO on urodynamics. Urge incontinence was reported in the bladder diary by 27% of the subjects with significant differences among the no, intermediate and clinically relevant DO groups (0%, 26% and 58%, respectively). None of the subjects was receiving specific bladder relaxant medication. A total of only 4 subjects in all 3 groups used a medication other than estrogen that might have affected bladder or sphincter function (table 2). Table 1 lists urodynamic and bladder diary variables grouped by domain. The percent of missing values was between 0% and 6% for all variables except pressure flow results (9%) and isovolumetric testing (27%). The missing 27% of values did not differ significantly from the remainder in demographics, DO⫹ score or other contractility measures. Table 3 lists associations with DO and age.
Urine Production and Micturition Frequency Diurnal and 24-hour urine production, and the proportion of urine excreted at night were not associated with DO⫹ (tables 1 and 3). As expected, micturition frequency differed among the groups.
Bladder Capacity All bladder capacity variables decreased with increasing evidence of DO, significantly so for maximum cystometric capacity and mean daytime voided volume (tables 1 and 3, and fig. 2). No bladder capacity variable depended significantly on age (table 3).
Bladder Sensation Bladder sensation appeared to occur at smaller volumes in subjects with DO (tables 1 and 3). In particular volume at strong desire to void became significantly smaller with increasing evidence of DO, implying increased sensation (table 3 and fig. 2). In contrast, regardless of which of the 3 sensation variables was used, bladder sensation decreased significantly with age (table 3).
IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION
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TABLE 1. Bladder and sphincter function variables by DO⫹ group Domain (variables) Urine production: 24-Hr (ml) Diurnal (ml) Nocturnal (% total) No. micturition frequency: Daytime Nocturnal Bladder capacity (ml): Max cystometric capacity* Max bladder diary voided vol Mean daytime bladder diary voided vol* Bladder sensation (ml): First filling First void desire Strong void desire* Detrusor contractility: pdet.isv (cm H2O)* PIP1 (cm H2O) PVR after pressure flow study (ml)* Free uroflow study lowest PVR (ml) Other voiding/outlet parameters: Free uroflow Qmax (ml/sec) Pressure flow study Qmax (ml/sec) pdet.Qmax (cm H2O) Abrams-Griffiths No. Involuntary contraction characteristics (42 pts): Bladder vol at first contraction (ml) First pdet.max (cm H2O) Highest pdet.max (cm H2O)* Highest dpdet/dt* Mechanical filling parameters (cm H2O):* Compliance Max minus baseline pressure Urethral sphincter function: Functional urethral profile length (cm) Max urethral closure pressure (cm H2O) Voluntary striated sphincter pressure increase (cm H2O)
Mean All Subjects ⫾ SD
Mean No DO ⫾ SD
Mean Intermediate DO ⫾ SD
Mean Relevant DO ⫾ SD
1,765 ⫾ 758 1,228 ⫾ 589 31 ⫾ 12
1,730 ⫾ 733 1,195 ⫾ 532 30 ⫾ 10
1,703 ⫾ 759 1,205 ⫾ 613 32 ⫾ 14
1,880 ⫾ 806 1,295 ⫾ 640 33 ⫾ 12
7.5 ⫾ 2.8 0.8 ⫾ 1.0
6.2 ⫾ 1.8 0.5 ⫾ 0.8
7.3 ⫾ 2.9 0.7 ⫾ 0.7
9.1 ⫾ 2.8 1.4 ⫾ 1.2
493 ⫾ 182 482 ⫾ 187 219 ⫾ 97
558 ⫾ 173 479 ⫾ 167 260 ⫾ 118
461 ⫾ 157 415 ⫾ 155 215 ⫾ 74
448 ⫾ 199 461 ⫾ 171 175 ⫾ 74
118 ⫾ 78 179 ⫾ 100 317 ⫾ 132
130 ⫾ 83 196 ⫾ 98 363 ⫾ 134
107 ⫾ 64 169 ⫾ 102 303 ⫾ 122
118 ⫾ 89 173 ⫾ 103 283 ⫾ 134
52 ⫾ 36 51 ⫾ 13 22 ⫾ 72 10 ⫾ 20
41 ⫾ 16 51 ⫾ 12 2 ⫾ 10 8 ⫾ 13
50 ⫾ 36 49 ⫾ 11 15 ⫾ 33 7 ⫾ 10
64 ⫾ 48 55 ⫾ 17 54 ⫾ 121 17 ⫾ 31
25 ⫾ 12 22 ⫾ 9 29 ⫾ 12 ⫺15 ⫾ 24
27 ⫾ 12 23 ⫾ 9 27 ⫾ 9 ⫺20 ⫾ 21
23 ⫾ 10 22 ⫾ 8 27 ⫾ 9 ⫺17 ⫾ 20
26 ⫾ 13 22 ⫾ 10 32 ⫾ 17 ⫺12 ⫾ 29
340 ⫾ 162 19 ⫾ 10 22 ⫾ 10 3.5 ⫾ 2.4
396 ⫾ 230 28 ⫾ 21 37 ⫾ 32 5.1 ⫾ 3.9
374 ⫾ 206 25 ⫾ 18 31 ⫾ 26 4.5 ⫾ 3.5
Not applicable Not applicable Not applicable Not applicable
153 ⫾ 145 3.4 ⫾ 2.4
215 ⫾ 176 3.0 ⫾ 2.7
137 ⫾ 134 3.2 ⫾ 2.1
106 ⫾ 91 3.9 ⫾ 2.4
3.3 ⫾ 0.8 62 ⫾ 27 34 ⫾ 22
3.4 ⫾ 0.9 63 ⫾ 24 33 ⫾ 23
3.4 ⫾ 0.5 64 ⫾ 28 38 ⫾ 20
3.2 ⫾ 0.9 59 ⫾ 29 30 ⫾ 23
* Significant association with DO⫹ score (p ⬍0.05).
Detrusor Contractility Contraction strength variables decreased with age (table 3 and fig. 3, B). In contrast, pdet.isv increased significantly with increasing evidence of DO from a mean of 41 cm H2O in subjects with no DO to 64 cm H2O in the group with clinically relevant DO (p ⫽ 0.009, table 1 and fig. 3, A). PIP1 showed similar but less pronounced behavior (p ⫽ 0.06). PVR determined after pressure flow study was slightly greater in subjects with DO. There was no significant association between PVR and either contraction strength variable, possibly reflecting the variability of PVR determination. Involuntary Contraction Characteristics Associations could be calculated only in subjects with DO on urodynamics. Whether determined from the first or strongest contraction, involuntary contraction pdet.max decreased with age and increased with DO, while dpdet/dt showed similar behavior (table 3). Interaction Between DO and Age ANOVA revealed that the statistical interaction between DO⫹ and age contributed significantly to the variance of pdet.max in involuntary contraction and involuntary dpdet/dt (p ⫽ 0.002 and 0.008, respectively). The interaction was similar for pdet.isv and voiding pressure pdet.Qmax (p ⫽ 0.064 and 0.091, respectively). All of these variables express the
strength or briskness of a detrusor contraction during voiding or during DO. Thus, the interactions suggest that the associations between contraction strength and DO may be different in younger and older subjects. Figure 4 shows 2 examples. In younger subjects (20 to 39 years old) each contraction strength variable tended to increase with increasing evidence of DO. In older subjects (60 years or older) contraction strength failed to increase with increasing evidence of DO. Other Filling Parameters Bladder compliance showed some dependence on DO ( ⫽ 0.364, p ⫽ 0.001). However, it was always well within the normal range. Urethral Sphincter Function There was no significant association between any urethral sphincter variable and DO. Maximum urethral closure pressure decreased significantly with age (table 3). It showed a positive bivariate association with pdet.max at the first involuntary contraction (r ⫽ 0.45, p ⫽ 0.005). DISCUSSION In accordance with previous observations2,3 these data suggest that detrusor contraction strength is greater in subjects with DO (table 1 and fig. 3, A). However, detrusor contrac-
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IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION TABLE 2. Sample characteristics by DO⫹ group
No. subjects General health/function: Mean age ⫾ SD Age range (median) % White/black Mini Mental State Examination (Mean ⫾ SD) Urogenital history: Mean no. vaginal deliveries ⫾ SD Mean American Urological Association symptom index ⫾ SD* No. bladder surgery (suspension) No. abdominal or vaginal hysterectomy No. estrogen medication† No. drugs with potential to decrease detrusor activity‡ No. urogenital examination: Urodynamic stress urinary incontinence† Grade I–II uterine descensus Mild cystourethrocele Grade I rectocele DO: No. DO (%)†,§ No. DO incontinence (%)† Mean DO⫹ score ⫾ SD
All Subjects
No DO
Intermediate DO
Relevant DO
85
28
31
26
53.5 ⫾ 17 21.8–89.6 (54.2) 75/21 29.0 ⫾ 1.2
50.3 ⫾ 16 21.8–80.1 (51.8) 75/18 29.3 ⫾ 0.9
54.7 ⫾ 16 22.2–79.8 (56.9) 71/29 29.1 ⫾ 0.8
55.7 ⫾ 19 22.4–89.6 (56.1) 81/15 28.5 ⫾ 1.6
1.6 ⫾ 1.8 4.7 ⫾ 4.1
1.9 ⫾ 1.6 10.1 ⫾ 5.4
1.6 ⫾ 1.7 13.0 ⫾ 4.5
8 16 31 4
0 3 6 2
5 6 8 1
3 7 17 1
13
4
8
1
5 25 12
1 4 0
3 11 7
1 10 5
42 (49) 23 (27) ⫺0.3 ⫾ 4.2
0 0 ⫺5.2 ⫾ 0.8
16 (52) 3 (10) ⫺0.1 ⫾ 1.3
26 (100) 20 (77) 4.9 ⫾ 1.4
1.7 ⫾ 1.7 9.2 ⫾ 5.8
No subjects were on specific bladder relavants or anticholinergics. * Significant difference among groups (Kruskal-Wallis test p ⬍0.05). † Significant difference among groups (chi-square test p ⬍0.05). ‡ Amitryptyline or hyoscyamine (low dose or nightly). § Intentionally selected to have symptoms suggesting DO in half of subjects.
tility also appears to decrease with age (table 3 and fig. 3, B). These opposite associations seem to underlie the relationship between detrusor contraction strength and DO, which was observed at younger ages but seems to have been absent in older subjects (fig. 4). Although cause and effect could not be disentangled in this cross-sectional study and our sample size was not large, the age related difference in the relationship was similar and statistically significant or almost significant for urodynamic variables that measure contractility in 4 ways (fig. 4). Moreover, these relationships remained even when outliers with the highest pdet.isv or pdet.max values were omitted (fig. 4). Thus, it appears that in younger but
FIG. 1. Subject age in 3 DO⫹ groups. Age was used as continuous variable in regression analyses. y, years.
not in older subjects detrusor contraction strength tends to be higher in those with DO. The lack of an apparent increase in detrusor contractility in aged bladders with DO has several possible explanations: Although it was a consistent finding in our subjects, it may still be spurious and should be confirmed by others. If corroborated, it may reflect confounding by conditions such as diabetes mellitus, B12 deficiency or spinal stenosis, which are common in the elderly population and independently lead to decreased detrusor contractility. However, such diseases were excluded in this study. Another possibility is that the mediator(s) of increased contractility in the context of DO, eg growth factors and cytokines, may decrease with age. However, since caveolae, bladder weight and smooth muscle density decrease with age,13,14 it is possible that the aged detrusor does not have the reserve capacity to develop higher contraction strength in the setting of DO because of age related muscle loss (sarcopenia). Whichever explanation is correct, this failure to increase contractility in DO may be the beginning of a progression to incomplete emptying, that is to detrusor hyperactivity with impaired contractile function, a common condition in frail elderly individuals.4 The observation of an age associated decrease in maximum urethral closure pressure may reflect an age associated loss of striated muscle in the female urethra.15 It was suggested that DO is related to increased urethral outlet resistance due to sphincter hypertrophy.3 However, in our subjects with DO there was no evidence of increased sphincter function and no clear evidence of increased outflow resistance by pressure flow testing (tables 1 and 3). This study shows that maximum urethral closure pressure and the amplitude pdet.max of involuntary contractions are positively associated (p ⫽ 0.005). Possibly in elderly women urethral sphincter weakness limits the pressure that
IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION
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TABLE 3. Age and DO⫹ score , and interaction significance Association With DO () Urine production: 24-Hr Diurnal Nocturnal Micturition frequency:* Daytime Nocturnal Bladder capacity: Max cystometric capacity Max bladder diary voided vol Mean daytime bladder diary voided vol Cystometry bladder sensation: First filling First void desire Strong void desire Detrusor contractility: pdet.isv PIP1 PVR after pressure flow study Lowest free uroflow PVR Other voiding/outlet parameters: Free uroflow Qmax Pressure flow study Qmax pdet.Qmax Abrams-Griffiths No. Involuntary contraction characteristics (42 pts): Bladder vol at first contraction First pdet.max Highest pdet.max Highest dpdet/dt Mechanical filling parameters: Compliance Max minus baseline pressure Urethral sphincter function: Functional urethral profile length Max urethral closure pressure Voluntary striated sphincter pressure increase
p Value
0.152 0.159 0.057
⫺0.088 ⫺0.126 ⫺0.302 0.317 0.195 0.308 0.163 ⫺0.030 ⫺0.016 0.233 0.140 0.133 0.245 0.343 0.307 ⫺0.364 0.188 ⫺0.090 0.008 0.008
p Value
⫺0.095 ⫺0.181 0.355
⬍0.01
DO/Age Interaction p Value
⫺0.038 0.201
Not applicable Not applicable ⫺0.301 ⫺0.202 ⫺0.364
Association With AGE ()
⬍0.01 ⬍0.01
0.133 0.082 ⫺0.040
⬍0.01
0.445 0.432 0.327
⬍0.001 ⬍0.001 ⬍0.01
⫺0.342 ⫺0.463 0.100 0.086
⬍0.01 ⬍0.001
⬍0.01 ⬍0.01
⬍0.05
⬍0.05 ⬍0.05 ⬍0.01
0.064
⫺0.151 ⫺0.309 ⫺0.282 0.085
⬍0.01 ⬍0.05
0.091
0.153 ⫺0.367 ⫺0.401 ⫺0.423
⬍0.05 ⬍0.01 ⬍0.01
0.002 0.008
0.131 ⫺0.002 ⫺0.052 ⫺0.626 ⫺0.173
⬍0.001
* Bivariate correlation with age.
can be attained in an involuntary contraction.6 However, even when this postulated pop-off valve mechanism is excluded by blocking the bladder outlet with a balloon, older
FIG. 2. In 3 DO⫹ groups values of 3 volume parameters in 3-day bladder diary, namely maximum cystometric bladder capacity, volume at strong desire to void during filling cystometry and mean daytime voided volume, showed significant decrease with DO (p ⬍0.05).
subjects were still unable to generate high detrusor pressures (fig. 3, A). This again shows an age related decrease in detrusor muscle function, just as for the striated urethral sphincter. The rodent detrusor and its innervation are sensitive to prolonged ovarian hormonal deficiency, contributing to impaired contractility.16 To our knowledge it is unknown whether the human detrusor behaves similarly. As postulated, micturition frequency increases and bladder sensation becomes stronger in the setting of DO. Simi-
FIG. 3. Mean and 95% CI of detrusor contraction strength parameter pdet.isv. A, in 3 DO groups. B, in age groups 20 to 39, 40 to 59 and 60 years or older. There was significant increase in pdet.isv with increasing evidence of DO ( ⫽ 0.317, p ⫽ 0.009) and significant decrease with age ( ⫽ ⫺0.342, p ⫽ 0.005).
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IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION reserve. This age associated loss of muscle function may be related to sarcopenia, implying that different treatments may be appropriate in older adults. APPENDIX DOⴙ score Score Source Parameter Detailed history: Urge incontinence Frequency 9/day or greater ⫹ nocturia 2/night or greater ⫹ urgency/precipitancy 72-hr bladder diary: Frequency 9/day or greater ⫹ nocturia 2/night or greater Urge leakage Videourodynamic study: DO DO incontinence DO⫹ score range
FIG. 4. Scatterplots and regression lines in age groups 20 to 39, 40 to 59 and 60 years or older. Associations between contraction strength and DO were different in younger and older subjects, and pdet.Qmax and involuntary dpdet/dt showed similar behavior. A, pdet.isv vs DO⫹ score. B, involuntary contraction pdet.max vs DO⫹ score.
larly, bladder capacity decreases with increasing evidence of DO. However, bladder capacity shows no significant dependence on age per se. The common observation that bladder capacity tends to decrease with age seems to reflect the increasing prevalence of DO in old age. The fact that neural aspects such as bladder sensation as well as muscular aspects such as detrusor contractility become stronger in the setting of DO suggests that neurogenic and myogenic mechanisms may have a role in DO (table 3).17,18 To our knowledge this is the first comprehensive evaluation of the effects of DO, aging and their interactions on lower urinary tract function. Nevertheless, the study has limitations. Because of the selection criteria and the crosssectional nature of the study, the sample is not representative of any particular population. However, subject baseline characteristics reflect the typical, cognitively intact, functionally independent American female. Furthermore, the values of urodynamic and bladder function parameters are consistent with those in previously published results.19,20 There was a higher proportion of subjects on estrogen medication in the group with clinically relevant DO than in the other 2 groups. Physicians may prescribe estrogen more often to patients with OAB or prescribed estrogen may be related to the development of DO. Whichever interpretation is correct, our conclusions are unaffected because the effects of age and DO were still present in the regression model after controlling for estrogen medication use. Additional research on the effects of aging and DO on bladder function will help substantiate our conclusions. CONCLUSIONS From young adulthood to old age DO appears to affect bladder function parameters. It is associated with decreased bladder capacity and increased bladder sensation. Moreover, in younger adults DO is also associated with increased detrusor contraction strength, which is an association not seen in older individuals, perhaps reflecting a lack of detrusor
No
?
Yes
⫺1 ⫺1
0 0
1 1
⫺1
0
1
⫺1
0
1
⫺2 0
0 0 ⫺6–8
2 2
Abbreviations and Acronyms
 ⫽ standardized regression coefficient (multiple linear regression model) DO ⫽ detrusor overactivity dpdet/dt ⫽ contraction velocity OAB ⫽ overactive bladder pdet.isv ⫽ maximum isovolumetric pressure pdet.max ⫽ maximum detrusor pressure pdet.Qmax ⫽ voiding pressure/pressure at Qmax PIP1 ⫽ projected isovolumetric detrusor pressure PVR ⫽ post-void residual urine Qmax ⫽ maximum flow rate
REFERENCES 1. Resnick, N. M.: Urinary incontinence. Lancet, 346: 94, 1995 2. Cucchi, A., Siracusano, S., Guarnaschelli, C. and Rovereto, B.: Voiding urgency and detrusor contractility in women with overactive bladders. Neurourol Urodyn, 22: 223, 2003 3. Digesu, G. A., Hutchings, A., Salvatore, S., Selvaggi, L., Milani, R. and Khullar, V.: Pressure flow study: a useful diagnostic test of female lower urinary tract symptoms. Neurourol Urodyn, 23: 104, 2004 4. Resnick, N. M. and Yalla, S. V.: Detrusor hyperactivity with impaired contractile function. An unrecognized but common cause of incontinence in elderly patients. JAMA, 257: 3076, 1987 5. Griffiths, D. J., McCracken, P. N., Harrison, G. M., Gormley, E. A. and Moore, K. N.: Urge incontinence and impaired detrusor contractility in the elderly. Neurourol Urodyn, 21: 126, 2002 6. Miller, K. L., DuBeau, C. E., Bergmann, M., Griffiths, D. J. and Resnick, N. M.: Quest for a detrusor overactivity index. J Urol, 167: 578, 2002 7. Abrams, P., Cardozo, L., Fall, M., Griffiths, D., Rosier, P., Ulmsten, U. et al: The standardisation of terminology in lower urinary tract function: report from the standardisation subcommittee of the International Continence Society. Am J Obstet Gynecol, 189: 116, 2002 8. Schaefer, W., Abrams, P., Liao, L., Mattiasson, A., Pesce, F., Spangberg, A. et al: Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn, 21: 261, 2002
IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION 9. Tan, T. L., Bergmann, M. A., Griffiths, D. and Resnick, N. M.: Stop test or pressure-flow study? Measuring detrusor contractility in older females. Neurourol Urodyn, 23: 184, 2004 10. Schäfer, W. and Sterling, A. M.: Simple analysis of voiding function by coefficients: obstruction coefficient, OCO, and detrusor strength coefficient, DECO. In: Proceedings of the 25th Annual Meeting of the International Continence Society, p. 338, 1995 11. Brocklehurst, J. C. and Dillane, J. B.: Studies of the female bladder in old age. I. Cystometrograms in non-incontinent women. Gerontol Clin (Basel), 8: 285, 1966 12. Diokno, A. C., Brown, M. B., Brock, B. M., Herzog, A. R. and Normolle, D. P.: Clinical and cystometric characteristics of continent and incontinent noninstitutionalized elderly. J Urol, 140: 567, 1988 13. Lepor, H., Sunaryadi, I., Hartanto, V. and Shapiro, E.: Quantitative morphometry of the adult human bladder. J Urol, 148: 414, 1992 14. Aygen, E. M., Ekmekcioglu, O. and Basbug, M.: The menopause and bladder weight. Int Urogynecol J Pelvic Floor Dysfunct, 10: 316, 1999 15. Perucchini, D., DeLancey, J. O., Ashton-Miller, J. A., Galecki, A. and Schaer, G. N.: Age effects on urethral striated muscle. II. Anatomic location of muscle loss. Am J Obstet Gynecol, 186: 356, 2002 16. Zhu, Q., Ritchie, J., Marouf, N., Dion, S. B., Resnick, N. M., Elbadawi, A. et al: Role of ovarian hormones in the pathogenesis of impaired detrusor contractility: evidence in ovariectomized rodents. J Urol, 166: 1136, 2001 17. Haferkamp, A., Dorsam, J., Resnick, N. M., Yalla, S. V. and Elbadawi, A.: Structural basis of neurogenic bladder dysfunction. II. Myogenic basis of detrusor hyperreflexia. J Urol, 169: 547, 2003 18. Elbadawi, A., Yalla, S. V. and Resnick, N. M.: Structural basis of geriatric voiding dysfunction. III. Detrusor overactivity. J Urol, 150: 1668, 1993 19. Malone-Lee, J. and Wahedna, I.: Characterisation of detrusor contractile function in relation to old age. Br J Urol, 72: 873, 1993
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20. Madersbacher, S., Pycha, A., Schatzl, G., Mian, C., Klingler, C. H. and Marberger, M.: The aging lower urinary tract: a comparative urodynamic study of men and women. Urology, 51: 206, 1998
EDITORIAL COMMENT Symptomatic DO can have significant negative impacts on overall and health related quality of life, particularly in older adults. The prevalence of DO increases with age. In this cross-sectional study the authors noted a positive association between increased detrusor contraction strength and clinically relevant DO in younger women. However, this association was not observed in elderly subjects. Detrusor contraction strength and maximum urethral closure pressure decreased significantly with age even in the face of symptomatic DO. Although the cross-sectional design precluded the verification of direct causality, these findings support the hypothetical relationship between the observed physiological changes and the potential development of the detrusor hyperactivity with impaired contractility complex in geriatric patients. It is also well recognized that urodynamic assessment and clinical symptoms do not always correlate in patients with DO. The authors present an intriguing new instrument, the DO⫹ scale, for the categorical assessment of DO. This validated, multidimensional tool combines information from clinical history, voiding diaries and urodynamic parameters to create a ranked score of the agreement between signs and symptoms. This instrument has great potential usefulness and additional research will help clarify its role in the assessment of patients with DO. Tomas L. Griebling Department of Urology and Center on Aging University of Kansas Kansas City, Kansas
Purpose: We examined the relationship of DO and aging, and bladder function in female volunteers. Materials and Methods: We recruited 85 cognitively competent, fully functional female volunteers who were 22 to 90 years old (median age 54) with and without symptoms suggestive of DO. Comprehensive assessment included a bladder diary, uroflowmetry and videourodynamics. We examined predefined urodynamic and diary variables for associations with DO and age, summarizing results in the 3 subgroups no DO, intermediate DO and clinically relevant DO. Results: Compared to women without DO those with DO showed a decrease in maximum cystometric capacity (558 vs 448 ml), mean daytime voided volume (260 vs 175 ml) and volume at strong desire to void (363 vs 283 ml) but an increase in maximum isovolumetric pressure (41 vs 64 cm H2O) and maximum detrusor pressure during involuntary contraction (intermediate and relevant DO 22 and 37 cm H2O, respectively). The positive association between increased detrusor contraction strength and DO was present at younger ages but absent in older subjects. Maximum urethral closure pressure and detrusor contraction strength decreased significantly with age. Conclusions: From young adulthood to old age DO appears to affect bladder function parameters. It is associated with decreased bladder capacity and increased bladder sensation. Moreover, in younger adults DO is also associated with increased detrusor contraction strength, which is an association not seen in older individuals. This age associated loss of muscle function may be related to sarcopenia, implying that different treatments may be appropriate in older adults. Key Words: urinary tract, bladder, urodynamics, aging, female
rge incontinence and DO are a source of considerable morbidity, especially in the elderly population,1 and they impair quality of life. Because DO becomes much more common in old age, it is difficult to disentangle its effects from those of aging alone. For example, in young and middle-aged women DO is associated with increased detrusor contractility2,3 but in the elderly population observations are inconclusive.4,5 Moreover, in older individuals sphincter function, urine output and sensation may modify the clinical manifestation of DO.6 Published data concerning DO associated changes in bladder function are derived primarily from studies of symptomatic patients.2– 6 Few studies cover the spectrum from asymptomatic and healthy subjects without DO to subjects with clear DO and consonant symptoms. Still fewer include an age range wide enough to allow the evaluation of age related changes.
U
Submitted for publication June 17, 2005. Study received local Institutional Review Board approval. Supported by United States Public Health Service Grants R01AG20629 and P01-AG04390, and a mid career fellowship in geriatrics from the Robert Bosch Foundation, Germany (MHDP). * Correspondence: Kontinenzberatungsstelle Bethanien-Krankenhaus, Geriatrisches Zentrum, Rohrbacherstrasse 149, 69126 Heidelberg, Germany (e-mail: [email protected]). † Financial interest and/or other relationship with Laborie Medical Technologies. ‡ Financial interest and/or other relationship with Eli Lilly and Sanofi Aventis.
0022-5347/06/1755-1777/0 THE JOURNAL OF UROLOGY® Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION
Therefore, we examined the impact of DO on bladder function while controlling for age in a group of select 22 to 90-year-old volunteers with and without DO. We included only women to avoid the confounding effect of urethral obstruction. We clarified the role of DO in abnormalities of bladder function in young and old populations. Based on clinical experience and the literature we hypothesized that in the presence of DO bladder capacity and micturition volume would be smaller,2,6 while micturition frequency, bladder sensation,6 detrusor contractility (contraction strength)2,3,5 and urethral sphincter function would be greater.3 MATERIALS AND METHODS This was a secondary analysis of data collected for a study of DO and aging, and approved by the local Institutional Review Board. Data were obtained on adult female volunteers 20 years and younger who were recruited through advertising. In each age decade efforts were made to recruit an equal number of subjects with or without OAB symptoms. Exclusion criteria were dementia, neurological disease, current urinary tract infection, history of pelvic irradiation, bladder cancer, vitamin B12 deficiency or alcohol abuse, abdominoperineal resection, radical hysterectomy or the use of agents given for bladder problems that could not be stopped for 2 weeks. Assessment included detailed history, physical examination and a 3-day bladder diary.6 Videourodynamic testing
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Vol. 175, 1777-1783, May 2006 Printed in U.S.A. DOI:10.1016/S0022-5347(05)00985-7
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IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION
included free uroflowmetry and nonstraining PVR, measured twice, fluoroscopically monitored cystometry with filling at 30 ml per minute using room temperature Cystografin™ with measurement of intravesical and abdominal pressure, urethral pressure profilometry, isovolumetric testing, seated pressure flow studies and final PVR. No limit on bladder volume was imposed other than subject discomfort. The provocation of DO or incontinence was done by coughing, suprapubic tapping, running water, hand washing, catheter manipulation, posture change from supine to standing, the Valsalva maneuver, heel jouncing and a 2-minute wait with a full bladder after sitting on a commode. Methods and definitions conform to the standards recommended by the International Continence Society7,8 except for DO classification, detrusor contraction strength and involuntary dpdet/dt, as discussed. To quantify detrusor contraction strength during voiding we used pdet.isv and PIP1. We measured pdet.isv in 1 or more of 3 ways, including by interrupting voiding with a balloon catheter or voluntarily (stop test), or by attempting to void against a balloon blocked outlet. The greatest of these 3 values was considered pdet.isv. PIP1, a modification9 of the Schaefer contractility parameter detrusor strength coefficient,10 was used to estimate pdet.isv from the pressure flow study without interrupting flow. DO is defined as the urodynamic observation of involuntary bladder contraction during the filling phase.7,8 DO is believed to underlie OAB symptoms, such as urgency, urge incontinence, increased frequency and nocturia. The association with symptoms is not perfect since some symptom-free volunteers show DO on urodynamic testing, while some symptomatic patients do not even with provocation.11,12 Consequently DO must be judged in the context of the symptoms. To quantify to what extent the urodynamic observation of DO or no DO was supported symptomatically we ranked subjects blindly using a new DO⫹ scale. We devised DO⫹ before the analysis, basing factors and weights on our clinical experience (see Appendix). The DO⫹ value range was 8 to ⫺6. Scores of 8 required DO incontinence during urodynamic testing, and congruent symptoms and bladder diary findings. Scores of ⫺6 required a stable bladder during urodynamic testing despite provocation with neither symptoms nor a suggestion of DO by history or bladder diary. Values close to zero implied that symptoms and urodynamics were not entirely consistent. Content validity was ensured by basing the score on International Continence Society definitions of OAB syndrome and DO. Face validity was confirmed by 5 experts. Internal consistency was assessed by Cronbach’s ␣, which was 0.77. The score in each subject was generated by a computerized algorithm using information from the bladder diary, videourodynamic study and history. The lower of at least 2 PVR values obtained after nonstraining free uroflowmetry was used in the analyses. The dpdet/dt is the rate of increase in detrusor pressure measured in a 2-second period. For each subject with DO the highest value was recorded.
Statistics SPSS 11.5 (SPSS, Chicago, Illinois) was used for statistical analysis. Select urodynamic and diary variables were grouped into predefined domains representing various as-
pects of lower urinary tract function (table 1). We used multiple linear regression analysis to examine associations of the variables in each domain with age and DO. We used  to compare the associations of DO and age with the different variables. Voiding frequency was examined for an association with age only since frequency contributed directly to the DO⫹ score. Statistical significance was considered at 2-tailed p ⬍0.05. For results significant on regression analysis we performed ANOVA to assess the interaction between DO⫹ score and age. For display purposes we summarized values of the variables in 3 subgroups, namely no DO—DO⫹ score ⫺3 or less, intermediate DO—score greater than ⫺3 to less than 3 and clinically relevant DO—score 3 or greater.
RESULTS All 85 women 22 to 90 years old (median age 54) were cognitively intact, mobile and fully functional with similar values in each of the 3 DO⫹ groups and no significant differences in age across groups (table 2 and fig. 1). As intended, approximately half of the subjects had symptoms suggestive of DO and 42 of the 85 showed DO on urodynamics. Urge incontinence was reported in the bladder diary by 27% of the subjects with significant differences among the no, intermediate and clinically relevant DO groups (0%, 26% and 58%, respectively). None of the subjects was receiving specific bladder relaxant medication. A total of only 4 subjects in all 3 groups used a medication other than estrogen that might have affected bladder or sphincter function (table 2). Table 1 lists urodynamic and bladder diary variables grouped by domain. The percent of missing values was between 0% and 6% for all variables except pressure flow results (9%) and isovolumetric testing (27%). The missing 27% of values did not differ significantly from the remainder in demographics, DO⫹ score or other contractility measures. Table 3 lists associations with DO and age.
Urine Production and Micturition Frequency Diurnal and 24-hour urine production, and the proportion of urine excreted at night were not associated with DO⫹ (tables 1 and 3). As expected, micturition frequency differed among the groups.
Bladder Capacity All bladder capacity variables decreased with increasing evidence of DO, significantly so for maximum cystometric capacity and mean daytime voided volume (tables 1 and 3, and fig. 2). No bladder capacity variable depended significantly on age (table 3).
Bladder Sensation Bladder sensation appeared to occur at smaller volumes in subjects with DO (tables 1 and 3). In particular volume at strong desire to void became significantly smaller with increasing evidence of DO, implying increased sensation (table 3 and fig. 2). In contrast, regardless of which of the 3 sensation variables was used, bladder sensation decreased significantly with age (table 3).
IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION
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TABLE 1. Bladder and sphincter function variables by DO⫹ group Domain (variables) Urine production: 24-Hr (ml) Diurnal (ml) Nocturnal (% total) No. micturition frequency: Daytime Nocturnal Bladder capacity (ml): Max cystometric capacity* Max bladder diary voided vol Mean daytime bladder diary voided vol* Bladder sensation (ml): First filling First void desire Strong void desire* Detrusor contractility: pdet.isv (cm H2O)* PIP1 (cm H2O) PVR after pressure flow study (ml)* Free uroflow study lowest PVR (ml) Other voiding/outlet parameters: Free uroflow Qmax (ml/sec) Pressure flow study Qmax (ml/sec) pdet.Qmax (cm H2O) Abrams-Griffiths No. Involuntary contraction characteristics (42 pts): Bladder vol at first contraction (ml) First pdet.max (cm H2O) Highest pdet.max (cm H2O)* Highest dpdet/dt* Mechanical filling parameters (cm H2O):* Compliance Max minus baseline pressure Urethral sphincter function: Functional urethral profile length (cm) Max urethral closure pressure (cm H2O) Voluntary striated sphincter pressure increase (cm H2O)
Mean All Subjects ⫾ SD
Mean No DO ⫾ SD
Mean Intermediate DO ⫾ SD
Mean Relevant DO ⫾ SD
1,765 ⫾ 758 1,228 ⫾ 589 31 ⫾ 12
1,730 ⫾ 733 1,195 ⫾ 532 30 ⫾ 10
1,703 ⫾ 759 1,205 ⫾ 613 32 ⫾ 14
1,880 ⫾ 806 1,295 ⫾ 640 33 ⫾ 12
7.5 ⫾ 2.8 0.8 ⫾ 1.0
6.2 ⫾ 1.8 0.5 ⫾ 0.8
7.3 ⫾ 2.9 0.7 ⫾ 0.7
9.1 ⫾ 2.8 1.4 ⫾ 1.2
493 ⫾ 182 482 ⫾ 187 219 ⫾ 97
558 ⫾ 173 479 ⫾ 167 260 ⫾ 118
461 ⫾ 157 415 ⫾ 155 215 ⫾ 74
448 ⫾ 199 461 ⫾ 171 175 ⫾ 74
118 ⫾ 78 179 ⫾ 100 317 ⫾ 132
130 ⫾ 83 196 ⫾ 98 363 ⫾ 134
107 ⫾ 64 169 ⫾ 102 303 ⫾ 122
118 ⫾ 89 173 ⫾ 103 283 ⫾ 134
52 ⫾ 36 51 ⫾ 13 22 ⫾ 72 10 ⫾ 20
41 ⫾ 16 51 ⫾ 12 2 ⫾ 10 8 ⫾ 13
50 ⫾ 36 49 ⫾ 11 15 ⫾ 33 7 ⫾ 10
64 ⫾ 48 55 ⫾ 17 54 ⫾ 121 17 ⫾ 31
25 ⫾ 12 22 ⫾ 9 29 ⫾ 12 ⫺15 ⫾ 24
27 ⫾ 12 23 ⫾ 9 27 ⫾ 9 ⫺20 ⫾ 21
23 ⫾ 10 22 ⫾ 8 27 ⫾ 9 ⫺17 ⫾ 20
26 ⫾ 13 22 ⫾ 10 32 ⫾ 17 ⫺12 ⫾ 29
340 ⫾ 162 19 ⫾ 10 22 ⫾ 10 3.5 ⫾ 2.4
396 ⫾ 230 28 ⫾ 21 37 ⫾ 32 5.1 ⫾ 3.9
374 ⫾ 206 25 ⫾ 18 31 ⫾ 26 4.5 ⫾ 3.5
Not applicable Not applicable Not applicable Not applicable
153 ⫾ 145 3.4 ⫾ 2.4
215 ⫾ 176 3.0 ⫾ 2.7
137 ⫾ 134 3.2 ⫾ 2.1
106 ⫾ 91 3.9 ⫾ 2.4
3.3 ⫾ 0.8 62 ⫾ 27 34 ⫾ 22
3.4 ⫾ 0.9 63 ⫾ 24 33 ⫾ 23
3.4 ⫾ 0.5 64 ⫾ 28 38 ⫾ 20
3.2 ⫾ 0.9 59 ⫾ 29 30 ⫾ 23
* Significant association with DO⫹ score (p ⬍0.05).
Detrusor Contractility Contraction strength variables decreased with age (table 3 and fig. 3, B). In contrast, pdet.isv increased significantly with increasing evidence of DO from a mean of 41 cm H2O in subjects with no DO to 64 cm H2O in the group with clinically relevant DO (p ⫽ 0.009, table 1 and fig. 3, A). PIP1 showed similar but less pronounced behavior (p ⫽ 0.06). PVR determined after pressure flow study was slightly greater in subjects with DO. There was no significant association between PVR and either contraction strength variable, possibly reflecting the variability of PVR determination. Involuntary Contraction Characteristics Associations could be calculated only in subjects with DO on urodynamics. Whether determined from the first or strongest contraction, involuntary contraction pdet.max decreased with age and increased with DO, while dpdet/dt showed similar behavior (table 3). Interaction Between DO and Age ANOVA revealed that the statistical interaction between DO⫹ and age contributed significantly to the variance of pdet.max in involuntary contraction and involuntary dpdet/dt (p ⫽ 0.002 and 0.008, respectively). The interaction was similar for pdet.isv and voiding pressure pdet.Qmax (p ⫽ 0.064 and 0.091, respectively). All of these variables express the
strength or briskness of a detrusor contraction during voiding or during DO. Thus, the interactions suggest that the associations between contraction strength and DO may be different in younger and older subjects. Figure 4 shows 2 examples. In younger subjects (20 to 39 years old) each contraction strength variable tended to increase with increasing evidence of DO. In older subjects (60 years or older) contraction strength failed to increase with increasing evidence of DO. Other Filling Parameters Bladder compliance showed some dependence on DO ( ⫽ 0.364, p ⫽ 0.001). However, it was always well within the normal range. Urethral Sphincter Function There was no significant association between any urethral sphincter variable and DO. Maximum urethral closure pressure decreased significantly with age (table 3). It showed a positive bivariate association with pdet.max at the first involuntary contraction (r ⫽ 0.45, p ⫽ 0.005). DISCUSSION In accordance with previous observations2,3 these data suggest that detrusor contraction strength is greater in subjects with DO (table 1 and fig. 3, A). However, detrusor contrac-
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IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION TABLE 2. Sample characteristics by DO⫹ group
No. subjects General health/function: Mean age ⫾ SD Age range (median) % White/black Mini Mental State Examination (Mean ⫾ SD) Urogenital history: Mean no. vaginal deliveries ⫾ SD Mean American Urological Association symptom index ⫾ SD* No. bladder surgery (suspension) No. abdominal or vaginal hysterectomy No. estrogen medication† No. drugs with potential to decrease detrusor activity‡ No. urogenital examination: Urodynamic stress urinary incontinence† Grade I–II uterine descensus Mild cystourethrocele Grade I rectocele DO: No. DO (%)†,§ No. DO incontinence (%)† Mean DO⫹ score ⫾ SD
All Subjects
No DO
Intermediate DO
Relevant DO
85
28
31
26
53.5 ⫾ 17 21.8–89.6 (54.2) 75/21 29.0 ⫾ 1.2
50.3 ⫾ 16 21.8–80.1 (51.8) 75/18 29.3 ⫾ 0.9
54.7 ⫾ 16 22.2–79.8 (56.9) 71/29 29.1 ⫾ 0.8
55.7 ⫾ 19 22.4–89.6 (56.1) 81/15 28.5 ⫾ 1.6
1.6 ⫾ 1.8 4.7 ⫾ 4.1
1.9 ⫾ 1.6 10.1 ⫾ 5.4
1.6 ⫾ 1.7 13.0 ⫾ 4.5
8 16 31 4
0 3 6 2
5 6 8 1
3 7 17 1
13
4
8
1
5 25 12
1 4 0
3 11 7
1 10 5
42 (49) 23 (27) ⫺0.3 ⫾ 4.2
0 0 ⫺5.2 ⫾ 0.8
16 (52) 3 (10) ⫺0.1 ⫾ 1.3
26 (100) 20 (77) 4.9 ⫾ 1.4
1.7 ⫾ 1.7 9.2 ⫾ 5.8
No subjects were on specific bladder relavants or anticholinergics. * Significant difference among groups (Kruskal-Wallis test p ⬍0.05). † Significant difference among groups (chi-square test p ⬍0.05). ‡ Amitryptyline or hyoscyamine (low dose or nightly). § Intentionally selected to have symptoms suggesting DO in half of subjects.
tility also appears to decrease with age (table 3 and fig. 3, B). These opposite associations seem to underlie the relationship between detrusor contraction strength and DO, which was observed at younger ages but seems to have been absent in older subjects (fig. 4). Although cause and effect could not be disentangled in this cross-sectional study and our sample size was not large, the age related difference in the relationship was similar and statistically significant or almost significant for urodynamic variables that measure contractility in 4 ways (fig. 4). Moreover, these relationships remained even when outliers with the highest pdet.isv or pdet.max values were omitted (fig. 4). Thus, it appears that in younger but
FIG. 1. Subject age in 3 DO⫹ groups. Age was used as continuous variable in regression analyses. y, years.
not in older subjects detrusor contraction strength tends to be higher in those with DO. The lack of an apparent increase in detrusor contractility in aged bladders with DO has several possible explanations: Although it was a consistent finding in our subjects, it may still be spurious and should be confirmed by others. If corroborated, it may reflect confounding by conditions such as diabetes mellitus, B12 deficiency or spinal stenosis, which are common in the elderly population and independently lead to decreased detrusor contractility. However, such diseases were excluded in this study. Another possibility is that the mediator(s) of increased contractility in the context of DO, eg growth factors and cytokines, may decrease with age. However, since caveolae, bladder weight and smooth muscle density decrease with age,13,14 it is possible that the aged detrusor does not have the reserve capacity to develop higher contraction strength in the setting of DO because of age related muscle loss (sarcopenia). Whichever explanation is correct, this failure to increase contractility in DO may be the beginning of a progression to incomplete emptying, that is to detrusor hyperactivity with impaired contractile function, a common condition in frail elderly individuals.4 The observation of an age associated decrease in maximum urethral closure pressure may reflect an age associated loss of striated muscle in the female urethra.15 It was suggested that DO is related to increased urethral outlet resistance due to sphincter hypertrophy.3 However, in our subjects with DO there was no evidence of increased sphincter function and no clear evidence of increased outflow resistance by pressure flow testing (tables 1 and 3). This study shows that maximum urethral closure pressure and the amplitude pdet.max of involuntary contractions are positively associated (p ⫽ 0.005). Possibly in elderly women urethral sphincter weakness limits the pressure that
IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION
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TABLE 3. Age and DO⫹ score , and interaction significance Association With DO () Urine production: 24-Hr Diurnal Nocturnal Micturition frequency:* Daytime Nocturnal Bladder capacity: Max cystometric capacity Max bladder diary voided vol Mean daytime bladder diary voided vol Cystometry bladder sensation: First filling First void desire Strong void desire Detrusor contractility: pdet.isv PIP1 PVR after pressure flow study Lowest free uroflow PVR Other voiding/outlet parameters: Free uroflow Qmax Pressure flow study Qmax pdet.Qmax Abrams-Griffiths No. Involuntary contraction characteristics (42 pts): Bladder vol at first contraction First pdet.max Highest pdet.max Highest dpdet/dt Mechanical filling parameters: Compliance Max minus baseline pressure Urethral sphincter function: Functional urethral profile length Max urethral closure pressure Voluntary striated sphincter pressure increase
p Value
0.152 0.159 0.057
⫺0.088 ⫺0.126 ⫺0.302 0.317 0.195 0.308 0.163 ⫺0.030 ⫺0.016 0.233 0.140 0.133 0.245 0.343 0.307 ⫺0.364 0.188 ⫺0.090 0.008 0.008
p Value
⫺0.095 ⫺0.181 0.355
⬍0.01
DO/Age Interaction p Value
⫺0.038 0.201
Not applicable Not applicable ⫺0.301 ⫺0.202 ⫺0.364
Association With AGE ()
⬍0.01 ⬍0.01
0.133 0.082 ⫺0.040
⬍0.01
0.445 0.432 0.327
⬍0.001 ⬍0.001 ⬍0.01
⫺0.342 ⫺0.463 0.100 0.086
⬍0.01 ⬍0.001
⬍0.01 ⬍0.01
⬍0.05
⬍0.05 ⬍0.05 ⬍0.01
0.064
⫺0.151 ⫺0.309 ⫺0.282 0.085
⬍0.01 ⬍0.05
0.091
0.153 ⫺0.367 ⫺0.401 ⫺0.423
⬍0.05 ⬍0.01 ⬍0.01
0.002 0.008
0.131 ⫺0.002 ⫺0.052 ⫺0.626 ⫺0.173
⬍0.001
* Bivariate correlation with age.
can be attained in an involuntary contraction.6 However, even when this postulated pop-off valve mechanism is excluded by blocking the bladder outlet with a balloon, older
FIG. 2. In 3 DO⫹ groups values of 3 volume parameters in 3-day bladder diary, namely maximum cystometric bladder capacity, volume at strong desire to void during filling cystometry and mean daytime voided volume, showed significant decrease with DO (p ⬍0.05).
subjects were still unable to generate high detrusor pressures (fig. 3, A). This again shows an age related decrease in detrusor muscle function, just as for the striated urethral sphincter. The rodent detrusor and its innervation are sensitive to prolonged ovarian hormonal deficiency, contributing to impaired contractility.16 To our knowledge it is unknown whether the human detrusor behaves similarly. As postulated, micturition frequency increases and bladder sensation becomes stronger in the setting of DO. Simi-
FIG. 3. Mean and 95% CI of detrusor contraction strength parameter pdet.isv. A, in 3 DO groups. B, in age groups 20 to 39, 40 to 59 and 60 years or older. There was significant increase in pdet.isv with increasing evidence of DO ( ⫽ 0.317, p ⫽ 0.009) and significant decrease with age ( ⫽ ⫺0.342, p ⫽ 0.005).
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IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION reserve. This age associated loss of muscle function may be related to sarcopenia, implying that different treatments may be appropriate in older adults. APPENDIX DOⴙ score Score Source Parameter Detailed history: Urge incontinence Frequency 9/day or greater ⫹ nocturia 2/night or greater ⫹ urgency/precipitancy 72-hr bladder diary: Frequency 9/day or greater ⫹ nocturia 2/night or greater Urge leakage Videourodynamic study: DO DO incontinence DO⫹ score range
FIG. 4. Scatterplots and regression lines in age groups 20 to 39, 40 to 59 and 60 years or older. Associations between contraction strength and DO were different in younger and older subjects, and pdet.Qmax and involuntary dpdet/dt showed similar behavior. A, pdet.isv vs DO⫹ score. B, involuntary contraction pdet.max vs DO⫹ score.
larly, bladder capacity decreases with increasing evidence of DO. However, bladder capacity shows no significant dependence on age per se. The common observation that bladder capacity tends to decrease with age seems to reflect the increasing prevalence of DO in old age. The fact that neural aspects such as bladder sensation as well as muscular aspects such as detrusor contractility become stronger in the setting of DO suggests that neurogenic and myogenic mechanisms may have a role in DO (table 3).17,18 To our knowledge this is the first comprehensive evaluation of the effects of DO, aging and their interactions on lower urinary tract function. Nevertheless, the study has limitations. Because of the selection criteria and the crosssectional nature of the study, the sample is not representative of any particular population. However, subject baseline characteristics reflect the typical, cognitively intact, functionally independent American female. Furthermore, the values of urodynamic and bladder function parameters are consistent with those in previously published results.19,20 There was a higher proportion of subjects on estrogen medication in the group with clinically relevant DO than in the other 2 groups. Physicians may prescribe estrogen more often to patients with OAB or prescribed estrogen may be related to the development of DO. Whichever interpretation is correct, our conclusions are unaffected because the effects of age and DO were still present in the regression model after controlling for estrogen medication use. Additional research on the effects of aging and DO on bladder function will help substantiate our conclusions. CONCLUSIONS From young adulthood to old age DO appears to affect bladder function parameters. It is associated with decreased bladder capacity and increased bladder sensation. Moreover, in younger adults DO is also associated with increased detrusor contraction strength, which is an association not seen in older individuals, perhaps reflecting a lack of detrusor
No
?
Yes
⫺1 ⫺1
0 0
1 1
⫺1
0
1
⫺1
0
1
⫺2 0
0 0 ⫺6–8
2 2
Abbreviations and Acronyms
 ⫽ standardized regression coefficient (multiple linear regression model) DO ⫽ detrusor overactivity dpdet/dt ⫽ contraction velocity OAB ⫽ overactive bladder pdet.isv ⫽ maximum isovolumetric pressure pdet.max ⫽ maximum detrusor pressure pdet.Qmax ⫽ voiding pressure/pressure at Qmax PIP1 ⫽ projected isovolumetric detrusor pressure PVR ⫽ post-void residual urine Qmax ⫽ maximum flow rate
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IMPACT OF DETRUSOR OVERACTIVITY ON BLADDER FUNCTION 9. Tan, T. L., Bergmann, M. A., Griffiths, D. and Resnick, N. M.: Stop test or pressure-flow study? Measuring detrusor contractility in older females. Neurourol Urodyn, 23: 184, 2004 10. Schäfer, W. and Sterling, A. M.: Simple analysis of voiding function by coefficients: obstruction coefficient, OCO, and detrusor strength coefficient, DECO. In: Proceedings of the 25th Annual Meeting of the International Continence Society, p. 338, 1995 11. Brocklehurst, J. C. and Dillane, J. B.: Studies of the female bladder in old age. I. Cystometrograms in non-incontinent women. Gerontol Clin (Basel), 8: 285, 1966 12. Diokno, A. C., Brown, M. B., Brock, B. M., Herzog, A. R. and Normolle, D. P.: Clinical and cystometric characteristics of continent and incontinent noninstitutionalized elderly. J Urol, 140: 567, 1988 13. Lepor, H., Sunaryadi, I., Hartanto, V. and Shapiro, E.: Quantitative morphometry of the adult human bladder. J Urol, 148: 414, 1992 14. Aygen, E. M., Ekmekcioglu, O. and Basbug, M.: The menopause and bladder weight. Int Urogynecol J Pelvic Floor Dysfunct, 10: 316, 1999 15. Perucchini, D., DeLancey, J. O., Ashton-Miller, J. A., Galecki, A. and Schaer, G. N.: Age effects on urethral striated muscle. II. Anatomic location of muscle loss. Am J Obstet Gynecol, 186: 356, 2002 16. Zhu, Q., Ritchie, J., Marouf, N., Dion, S. B., Resnick, N. M., Elbadawi, A. et al: Role of ovarian hormones in the pathogenesis of impaired detrusor contractility: evidence in ovariectomized rodents. J Urol, 166: 1136, 2001 17. Haferkamp, A., Dorsam, J., Resnick, N. M., Yalla, S. V. and Elbadawi, A.: Structural basis of neurogenic bladder dysfunction. II. Myogenic basis of detrusor hyperreflexia. J Urol, 169: 547, 2003 18. Elbadawi, A., Yalla, S. V. and Resnick, N. M.: Structural basis of geriatric voiding dysfunction. III. Detrusor overactivity. J Urol, 150: 1668, 1993 19. Malone-Lee, J. and Wahedna, I.: Characterisation of detrusor contractile function in relation to old age. Br J Urol, 72: 873, 1993
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EDITORIAL COMMENT Symptomatic DO can have significant negative impacts on overall and health related quality of life, particularly in older adults. The prevalence of DO increases with age. In this cross-sectional study the authors noted a positive association between increased detrusor contraction strength and clinically relevant DO in younger women. However, this association was not observed in elderly subjects. Detrusor contraction strength and maximum urethral closure pressure decreased significantly with age even in the face of symptomatic DO. Although the cross-sectional design precluded the verification of direct causality, these findings support the hypothetical relationship between the observed physiological changes and the potential development of the detrusor hyperactivity with impaired contractility complex in geriatric patients. It is also well recognized that urodynamic assessment and clinical symptoms do not always correlate in patients with DO. The authors present an intriguing new instrument, the DO⫹ scale, for the categorical assessment of DO. This validated, multidimensional tool combines information from clinical history, voiding diaries and urodynamic parameters to create a ranked score of the agreement between signs and symptoms. This instrument has great potential usefulness and additional research will help clarify its role in the assessment of patients with DO. Tomas L. Griebling Department of Urology and Center on Aging University of Kansas Kansas City, Kansas