The Effect of Age on Lower Urinary Tract Function: A Study in Women

Pfisterer MDH, Griffiths DJ, Schaefer W, Resnick NM.
J Am Geriatr Soc. 2006; 54: 405-412.

MJ Strauhal, PT, BCB-PMD

October 9, 2013

Primary Aim:  To identify age-associated changes in female lower urinary tract (LUT) function across a wide age spectrum, controlling for detrusor overactivity (DO).  DO is common in old age, but may not represent normal aging.

 Subjects:  Ambulatory, nondemented, community-dwelling females with and without bladder symptoms suggestive of DO who were recruited by local advertising; efforts were made to recruit equal numbers of subjects in each age bracket who did and did not have symptoms of overactive bladder (OAB).

• Exclusion criteria: dementia, Alzheimer’s disease, diabetes mellitus, neurological disease (such as stroke, MS, Parkinson’s), disc disease, SCI or malformations resulting in gross neuropathy, detrusor-sphincter dyssynergia, current UTI, history of pelvic irradiation or bladder cancer, history of vitamin B12 deficiency, history of ETOH abuse, radical hysterectomy, abdominoperineal resection, agents acting on cholinergic or sympathetic nervous system that were given for bladder problems that could not be stopped for 2 weeks

Study Design:  Secondary analysis of a cross-sectional study of DO and aging; subjects were stratified by age group and presence of DO; ages evenly distributed across a wide range and in each decade approximately ½ had symptoms suggestive of DO (this was to control for its possible confounding effect)

Methods:  Methods, definitions, and units conformed to the standards recommended by the ICS

• Detailed clinical evaluation
• Detailed history and physical exam (including neuro and cognitive testing)
• A 3-day bladder diary including voiding times, voided volumes; timing, severity (to permit quantification of urine production they imputed 5 ml=mild, 15ml=moderate, 60ml=severe) and description of leakage episodes; bed and waking times
• Urodynamic study (UDS) including noninstrumented uroflowmetry, US and catheterized PVR (values were the lowest of 2 or 3 values after nonstrained free uroflows performed in private), fluoroscopically monitored provocation cystometry at 30ml/min (using Cystografin which is a radiopaque contrast agent) and simultaneous monitoring of abdominal pressure
• Isovolumetric testing (this measure the strength of the detrusor or “build up in pressure” during occlusion of the urethra NOT during voiding)
• Detrusor contractility has 2 aspects, which appear independent of each other:
• The strength of the detrusor (measured by isovolumetric testing)
• Whether the contraction is adequately sustained (measured by PVR)
• Also tested by UDS were the urethral pressure profilometry during rest, reflex testing, volitional squeeze, straining, and coughing; and seated pressure-flow study
• Provocation of DO or UI included coughing, suprapubic tapping, running water, hand washing, catheter manipulation, change of posture from supine to standing, heel jouncing, and 2 minute wait with full bladder after sitting on commode
• Detrusor contraction during void was quantified by using the projected isovolumetric detrusor pressure (modified Schaefer detrusor strength coefficient or DECO)
• Creatinine clearance was calculated using the Cockcroft-Gault equation
• Serum creatinine is an endogenous marker of glomerular filtration and is used to estimate glomerular filtration rate (GFR)
• GFR declines with age, even in the absence of kidney disease
• Lean muscle mass (which typically decreases with age )and dietary intake (especially decreased dietary protein intake which is also common in the elderly) can affect creatinine measurements
• Normal values for women younger than 40 years is 87-107 ml/min (88-128 ml/min) and will decrease by 6.5 ml/min for every 10 years past the age of 20
• DO+ score was devised to incorporate both clinical and UDS data; computed blinded
• This was to quantify the degree to which UDS either supported or did not support reports of symptoms of urgency, urge UI, frequency, nocturia
• Some symptom free patients have UDS observed DO
• Some patients with OAB symptoms do not have UDS DO
• DO+ scores ranged from 8 (subjects who had UI due to DO on UDS and had bladder diaries congruent with OAB) to -6 (subjects who had no UDS DO and no symptoms of OAB on diary; values close to 0 implied that symptoms and UDS were not entirely consistent
• DO+ was used in the statistical analysis to identify the effects of DO contrasted to other effects of aging
• Content and face validity ensured
• Cronbach alpha was 0.77 (indicating good internal consistency)
• Selected UDS and diary variables were grouped into 5 predefined domains and 2 miscellaneous categories and summarized in 3 subgroups (aged 20-39, 40-59, and > 60)

o   Multiple linear regression analysis was used to examine the association between these variables and age and DO

o   Standardized beta coefficients were presented to compare the association of age across different variables

o   Bivariate association with age only was presented for daytime and nocturnal voiding frequency

o   Statistical significance was taken at 2-tailed P<.05

Results:

• Subjects: 396 subjects were screened, 109 qualified and agreed to participate, 8 excluded after clinical evaluation, 16 withdrew consent, leaving 85 women who completed the UDS
• 42% were aged 60 or olderà 14 of these were 70 and olderà 4 of these were 80 and olderà these 4 used a medication that could affect the bladder or sphincter but analysis remained the same whether these 4 were included or not
• Table 1
• Urine production
• 24 hour: WNL, little change with age
• Diurnal:  WNL, little change with age
• Nocturnal: increased significantly with age (beta=0.36; P=.001)
• Mean # of nocturnal voids remained < one even in the oldest group, however there were none in the group with DM or CHF
• Bladder capacity and total urine production remained constant, so other factors such as hormonal changes or decreased renal function may have been responsible
• But, no significant difference between nocturnal voiding frequency, nocturnal urine production, and creatinine clearance in study subjects
• Micturition frequency- “no striking association with age”
• Daytime:  average 8 voids/day or fewer, no association with age
• DO did increase micturition frequency
• Nocturnal:  had a skewed distribution (distortion of the normal bell curve due to extreme scores in the data), but mean # of nocturnal voids remained < 1
• Bladder capacity (see also Figure 1)
• Neither UDS or max amount voided on bladder diary showed significant change with age
• Max cystometric bladder capacity was approximately 100 ml smaller in those with DO and symptoms of OAB
• Bladder sensation (see also Figure 1)
• Appears to decline with age for first sensation to void, first desire to void (shown in Figure 1) and strong desire to void
• Because adequate sensory input is necessary for conscious bladder control, this is clinically relevant
• The larger the volume at which a person realizes the need to void, the shorter is the warning period during which she can defer and void at her convenience (this effect will be greater in those with DO or OAB and may be associated with more severe UUI)
• May reflect the secular effect of a larger # of deliveries and potentially more damaging obstetric methods in the older women, but it was also present in a subgroup of nulliparous subjects
• Corresponding volumes increased by approximately 100 ml from the youngest to the oldest group
• Volume at strong desire to void was approximately 100 ml smaller (implying stronger sensation) in those with DO regardless of age
• Still present in subanalysis of 28 nulliparous women in the study
• Detrusor contractility (see also Figure 2)
• Negatively associated with age, even if controlling for DO
• Detrusor contraction strength (projected isovolumetric pressure- PIP1) declined with age (62 cmH2O youngest group to 42 cm H2O oldest group)
• May reflect histological and ultrastructural changes in the bladder
• Membrane changesà decrease of caveolae leading to abnormal excitation-contraction coupling, or a decrease of acetylcholine release
• Animal models have shown a decline in estrogen leads to a loss of caveolae and development of a dense band pattern of the detrusor
• May reflect myogenic or neurogenic changes, or both
• Lowest PVR volume did not increase significantly with age
• “Despite decreased detrusor strength, bladder emptying remained surprisingly efficient into early old age.”
• Population-based studies have shown that PVR remained less than 100 ml in 90% of elderly women
• The end of physiologic reserve (in the absence of other pathologies) may not be reached until advanced age and may lead to an increased prevalence of detrusor hyperactivity (overactivity) during filling with impaired contractility (DHIC) or detrusor underactivity during voiding which is common in subjects older than those in the present study
• Other voiding parameters (see also Figure 2)
• Max voided flow rates declined with age during both pressure-flow study (transurethral catheter in situ) and free uroflow
• Detrusor pressure at max flow declined with age
• Urethral sphincter function
• Functional urethral profile length did not change with age
• Max urethral closure pressure (MUCP) showed steady and highly significant decrease with age (89 cm H2O in  youngest group to 45 H2O in oldest group)
• Age effect still present and regression model after controlling for race (higher proportion of African-Americans in the younger group- see Table 2) and for # of pregnancies and deliveries and in subanalysis of 28 nulliparous women in the study
• May reflect an age-associated loss of striated muscle in the female urethra (see reference #47)
• May set the stage for more severe urge UI in old age

Discussion:

• Data from this study reveals age-associated changes in the female LUT
• The common belief that bladder capacity shrinks with age may be related to DO rather than to aging
• Study done on women, but authors felt there was no reason to believe that findings would not apply to men as well
• Limitations:
• Oldest subgroup had a mean age of 69, so results may not apply to the oldest old
• The assumption that changes in the LUT (other than DO) represent aging
• Findings may reflect still undiscovered factors
• Drugs with a possible effect of detrusor activity were taken only be the oldest group
• Only 4 of the subjects
• Linear regression did not show significant change if these subjects were excluded
• Estrogen status was not studied and some changes attributed to “normal” aging may be related to a decline in estrogen levels
• Significant differences between groups in mean numbers of pregnancies and vaginal deliveries
• Inclusion of these variables had no effect on the interpretation of the regression models
• Cross-sectional study and sample is not reflective of any particular population
• Longitudinal studies need to be performed to confirm the findings
• Strengths:
• Few studies have tried to define the normal changes that occur with aging in the LUT using detailed UDS, a sufficient # of subjects, and with consideration of the potential confounding effects of medication or DO
• Baseline characteristics for each group reflect the typical, cognitively intact, functionally independent, American female with a BMI of 27, typical age-related creatinine clearance, and typical number of pregnancies
• The values of UDS and bladder function parameters are consistent with studies published from other countries
• They accounted for missing data (between 0-6% for each variable, low pressure flow was 9%)

Clinical Application:

• Based on the results of this study, what changes might you make regarding instructions provided to both younger and older patients?
• What other variables do you wish the researchers had looked at?
• Do you have ideas regarding why nocturnal urine production increases with age, even in healthy older subjects?

Additional Reading:

• Trowbridge ER, Wei JT, Fenner DE, Ashton-Miller JA, DeLancey JOL.  Effects of aging on lower urinary tract and pelvic floor function in nulliparous women.  Obstet Gynecol. 2007; 109: 715-720.
• Cross-sectional study evaluating the effects of aging on LUT controlling for parity, but not for DO
• 82 nulliparous women aged 21-70 years
• Increasing age was associated with decreasing MUCPà 15 cmH2O decrease in pressure per decade
• Women aged 61-70 years have only 40% MUCP of that observed at age 21-30
• However, at any given age there may be large variationsà in their subjects, at age 50 there were women with pressures as low as 40 cmH2O and as high as 110 cmH2O
• Increasing age was not associated with levator ani (LA) function as measured by vaginal closure force with an instrumented speculum
• This surprised the researchers because of:
• Well-known age-related loss that occurs in striated muscle cross-sectional areas
• Loss of urethral striated muscle (same reference #47 as above)
• However, LA is predominately slow twitch fibers which are largely unaffected by age
• Morris VC, Murray MP, DeLancey JO, Ashton-Miller JA.  A comparison of the effect of age on levator ani and obturator internus muscle cross-sectional areas and volumes in nulliparous women.  Neurourol Urodyn. 2012; 31: 481-486.
• MRI images of 15 healthy younger (aged 21-25 years) and 12 healthy older (aged >63 years) nulliparous women
• Muscle volumes were calculated
• The effects of age did not reach statistical significance for decrease in max cross-sectional area or volume in LA, but did with OI