Treatment Goals in the Management of Urinary Incontinence in Elderly

The impact of the LUTS and urinaryincontinence

Lower urinary tract symptoms (LUTS), includingurinary incontinence, are widely prevalent worldwide,and cause significant negative impact on the life of thepatients.¹   This negative effect is apparent across severaldomains of patients’ health-related quality-of-life(HRQOL), inclusive of an overall perception of bladderproblems, general health status and mental health.Possibly, the impact could be further related to theassociation of urinary incontinence with an increasedrisk of urinary tract infections (UTIs),²   pressure ulcers,falls, fractures, and sleep disturbances, all of which maylead to functional impairment and decline in overallhealth status of the affected individuals.³

Several psychological and social complicationsmay develop due to urinary incontinence; includingisolation, depression, anxiety, impaired sexual function,decreased work productivity, increased functionaldependency, and increased caregivers’ burden.³   Datain this context clearly show that men and women withLUTS report low levels of HRQOL and high levels ofanxiety and depression.^4,5    Herein, significant predictorsof anxiety in women include nocturia, urgency, stressurinary incontinence, leaking during sexual activity,weak stream and split stream; and in men, nocturia,urgency, incomplete emptying and bladder pain(Table 1). Likewise, weak stream, urgency and stressurinary incontinence are significant for depressionin women, and perceived frequency and incompleteemptying are significant for men (Table 2).Overall, burden from incontinence symptoms maybe higher in women than men, whereas the opposite

seem true for voiding and post-micturition symptoms.⁴   Nevertheless, storage symptoms could be significantlymore associated with greater perceived bladder impactin both men and women, and at individual level,urgency urinary incontinence is the most bothersomefor both genders.^4,6   The evidence conforms that bothmen and women with urgency urinary incontinencereport moderate or major bother more frequentlythan individuals with other LUTS. In simple terms,while urinary urgency is the most common troublingsymptom; for individuals, urgency incontinence ismost likely to be rated as bothersome. At populationlevel, the most prevalent bothersome symptoms areurgency, stress urinary incontinence, and nocturia.These symptoms cause substantial personal andsocietal expenditures,⁷   and the bother increases assymptoms increases both in number and severity.⁶

Global and Indian epidemiological trends

Worldwide prevalence estimates clearly suggest thatLUTS and urinary incontinence are highly prevalentconditions worldwide. Data in this context suggestthat an estimated 45.2%, 10.7%, 8.2% and 21.5% of the 2008 worldwide population (4.3 billion) wasaffected by at least one LUTS, overactive bladder(OAB), urinary incontinence and LUTS suggestive ofbladder outlet obstruction (LUTS/BOO), respectively.Further, the numbers of affected individuals areprojected to increase with time, and it is anticipatedthat the worldwide prevalence of urinary incontinencewill increase from 8.2% in 2008 to 8.5% by 2018. Itis predicted that by 2018, an estimated 2.3 billionindividuals will be affected by at least one LUTS(18.4%, increase), 546 million by OAB (20.1%), 423million by urinary incontinence (21.6%) and 1.1 billionby LUTS/BOO (18.5%).⁸   In absolute numbers, a greaterproportion of this increase in burden is anticipated inthe developing regions, especially Asia (Figure 1).⁸

In India as well, burden and bother of urinaryincontinence could match the global trends, but sincethere are few community-based epidemiologicalstudies on urinary incontinence in India, precise datais lacking, especially relating to prevalence of urinarycontinence in men. In most of the Indian patients,especially in females, such negligent attitude towardsthe symptoms and late presentation to seek medicalcare is frequently attributable to unawareness,shyness, lack of education and motivation, and lackof easily accessible medical care.⁹   Some studiesconducted in women population however corroboratethe prevalent burden of urinary incontinence in Indiansociety. However, these percentages of people whosuffer from urinary incontinence and seek treatmentare few, possibly demonstrating the ‘tip of ice berg phenomenon’. A cross-sectional descriptive studydesigned to estimate age-specific prevalence and riskfactors of urinary incontinence among women aged35 ≥ years in a rural area noted that in a sample of552 women, 53 (10%) reported episodes of urinaryincontinence; of which 57% had symptoms of stressincontinence, 23% of urge, and 20% mixed symptoms.10In another cross-sectional design that collected datafrom a sample of 598 community dwelling women(age, 20 to 60 years) in a selected Indian district,the prevalence of urinary incontinence approached33.8%.¹¹

Types of urinary incontinence

LUTS are divided into storage symptoms and voidingsymptoms; and urinary incontinence is a storagesymptom defined by the incontinence society as“the complaint of any involuntary urinary leakage”.Urinary incontinence may be further defined and subcategorizedaccording to the patient’s main symptoms,as stress or urgency urinary incontinence (Table 3).^3,12   Herein, urge incontinence is characterized by leakageaccompanied or immediately preceded by urgencycharacterizes, whilst stress incontinence is associatedwith effort, exertion, sneezing or coughing.

Urge urinary incontinence is the most commoncause of incontinence in the elderly, pathophysiologyof which is primarily attributable to detrusor muscleover-activity, resulting in uncontrolled, uninhibited,or involuntary bladder muscle contractions.¹³   Oftenthe terms OAB and urge incontinence are used interchangeably; however, they describe two differentconditions. OAB is characterized by the storagesymptoms of urgency, with or without urgencyincontinence, usually with frequency and nocturia. Itis thus a symptom syndrome that includes frequency,urgency, and nocturia; and these can all occur withor without urge incontinence. Nevertheless, despitethe definitions being distinct, the two conditions -OAB and urge incontinence – are treated in the samemanner, because subsets of patients with OAB, with itshallmark symptom of urgency, also have urge urinaryincontinence.¹⁴

Stress incontinence in women is primarilyattributable to bladder sphincter dysfunction, whichresults in leakage of urine at inappropriate times. Purestress incontinence may be devoid of urgency andnocturia. However, many of such patients may havemixed forms of incontinence with features of urgency.In most such cases, or otherwise when features ofboth stress and urge incontinence are simultaneouslypresent in a patient, the term mixed incontinence ismore appropriate.¹⁵

Pathophysiological basis of incontinence symptoms

Maintenance of continence is a multifacetedmechanism, which requires an appropriately functioninglower urinary tract. Nevertheless, the function andphysiology of lower urinary tract is complicated, and is not completely understood. In individuals with normalphysiology, sympathetic nervous system activation aidsin closing the bladder neck; the bladder fills withoutleakage while the parasympathetic nervous system is inhibited.³   As the bladder fills and pressure rises, thereis an increase in parasympathetic tone, which causesthe detrusor muscle to contract and the bladder toempty. The main neurotransmitter involved in bladdercontraction is acetylcholine that acts at the muscarinicreceptors. Usually, muscarinic 2 receptors are found inthe lower urinary tract; however, muscarinic 3 receptorsare thought to have a larger role in bladder emptying.Alpha-adrenergic receptors are involved in urethralsmooth muscle control.3 Often, multiple causes maybe present in individuals with urinary incontinence(Figure 2).^13,16

Elderly: The vulnerable population

Aging is a consistent risk factor, reported for urinaryincontinence in both men and women, and hencethe prevalence of urinary incontinence is projected toincrease with the aging population.³   In conformity tothis, urinary incontinence and LUTS are seen highlyprevalent in late life, and are strongly associated withfrailty as well. Pathologically, this high occurrence ofurinary incontinence in the elderly could be becauseaging is associated with several physiologic changes,which may contribute to development of thisurinary problem in older population. These changesencompass decreases in bladder compliance, bladdercapacity, urethral closing pressure, and ability topostpone voiding; increases in involuntary detrusorcontractions, post void residual (PVR), and frequencyof voiding; and prostatic enlargement (in men) andweakened pelvic floor musculature (in women). Inaddition, chronic disease burden and comorbid statescan also contribute to urinary incontinence in theelderly.

The prevalence of urinary incontinence is about 2–3times more common in women than in men until 80 yearsof age, after which the rates are usually similar. Usuallyit is seen that in older women, mixed incontinence ismore common, accounting for approximately 50% ofall cases. In contrast, urinary incontinence in men has alater and more sudden onset than in women. Especially,it is noted that incontinence is extremely commonamong individuals living in the long-term care in formof urgency incontinence.17 Estimates in this regardhave suggested that up to 30% of community-dwellingolder adults may be affected by urinary incontinence,whereas this proportion increases to more than 50% innursing home residents.¹⁸

Clinical evaluation of urinary incontinence in elderly

Effective assessment is the initial and key step ineffective management of urinary incontinence as itwould help in treatment decision making, based onindividual needs.¹⁹   This may be facilitated by a thoroughmedical and drug history to determine contributingfactors for urinary incontinence. Generally, for themajority of patients presenting with urgency andfrequency, referral for investigations is not necessarybecause history and physical examination can identifypossible reversible causes in most cases. However,since symptoms may not be exclusive, and if noreversible cause is identified, other lower urinary tractpathology should be excluded by examination.^13,20

A foremost step in this work-up is to determine thetype of incontinence, and the urgency with which itshould be treated. The urologist needs to distinguishthe irritative (frequency, nocturia urgency, urgeincontinence) from obstructive (hesitancy, intermittency,weak stream) LUTS.²¹   Such determinations can bemade using simple questionnaires, an assessmentof other medical problems possibly contributing toincontinence, a discussion of the effect of symptomson patient’s QOL, a review of patient’s completedvoiding diary, and a complete physical examinationto identify possible etiology. Other components ofevaluation include laboratory tests, urinalysis, pad/cotton-swab testing; and measurement of postvoidresidual urine volume (PVR) to detect overflowbladder (Box 1).^22,23,24,25         Regardless, the diagnosis andmanagement would be more complex in the elderlypopulation due to a myriad of associated disease andhost related factors.

Challenges in assessment

There exist several challenges in the assessment andcontrol of urinary incontinence in the elderly, and amajor factor is the non-reporting or under-reportingof the symptoms by patients. Many elderly peopleassume incontinence as a normal part of the agingprocess and do not report it to their doctors. This isseen despite the problem being socially distressing,with a high degree of discomfort. Though it severelyimpacts the quality-of-life, patients, especially women,do not usually discuss the problems with others orduring visit to a doctor for treatment, and often preferto remain ‘silent sufferers’ of the problem.²

Besides, the actual severity of leakage couldrange from complete bladder emptying to loss ofdrops of urine. This together with technical problemsin urodynamic studies may pose difficulties inassessment. Urodynamics play an important role indefining the bladder and/or outlet dysfunction andhelp direct one’s therapy.²⁶   However, most urodynamicstudies are performed when the patient is awake.18 Thisis to allow direct patient assessment of the sensationsof filling and urge to void; but the method may notbe feasible in some elderly patients since it requiressound orientation, good cognition, and active patientparticipation.

Furthermore, when interpreting urodynamic datain the elderly, it is important to realize that normalage-related physiologic changes may significantlyalter the measured urodynamic parameters; and maybe present independently of the patient’s presentingsymptoms. Several normal age-related changes occurin the lower urinary tract, including the developmentof uninhibited detrusor contractions; an increase innocturnal fluid excretion; prostatic enlargement inmen; urethral shortening and sphincter weakening inwomen; a decrease in bladder capacity in both sexes;and possibly a decrease in detrusor contractility.¹⁸   Inaddition, elderly patients may also have associatedillnesses, with direct or indirect influence on lowerurinary tract; and such multiplicity of conditions and/or co-medications will make assessment and therapyfurther complex.

Treatment goals and approaches in patients with urinary incontinence

A urologist’s goal in treating incontinence in theelderly is to restore a socially acceptable level ofurinary continence, and this can be accomplishedby combination of several non-pharmacological andpharmacological approaches.¹⁸   In general, a steppedcare approach is advocated that starts with from leastinvasive interventions, and invasive interventions arereserved for individuals that have not responded toother treatments.²⁷

Lifestyle and behavioral modifications

Non-pharmacological and behavioral strategiesare important in the overall management of urinaryincontinence. Especially in the elderly population,they are the first-line treatment of choice, possiblybecause of lack of adverse effects, and an ease ofimplementation. Frequently advocated lifestylemodifications for urinary incontinence include smokingcessation, caffeine and alcohol reduction, weightloss, and modifying the fluid intake.3 Bladder trainingand pelvic muscle rehabilitation (also referred to asKegel exercises) are behavioral techniques, the goalof which is to achieve a satisfactory voiding pattern.Bladder training constitutes an urge suppressiontechnique; whereas in pelvic muscle rehabilitation,repetitive contraction and relaxation of the pelvicfloor muscles is used to improve the reflex inhibitionof involuntary detrusor contractions and enhance theability to voluntarily contract the external sphincter.An important limitation associated with such lifestyleand behavioral interventions is that their effectivenessand success largely depends on patient motivation, functional capacity, and cognitive function, and hencethey may not be widely applicable in all subgroups ofpatients with urinary incontinence. Also, they can befrequently time consuming.

Importance of drug therapy

Pharmacotherapy is frequently required and addedto non-pharmacological or behavioral therapyto help alleviate the symptoms in patients withurinary incontinence. The response to drug therapymay however vary depending upon the type ofincontinence. In this regard, it is generally consideredthat patients with urge incontinence respond wellto pharmacotherapy, whereas limited or conflictingevidence exists for use of medications in pure stressincontinence. Careful selection of patients is thereforeimportant to optimize treatment outcomes inindividual cases.

Anticholinergic agents for urinary incontinence in elderly: A dilemma

Anticholinergic drugs are a commonly prescribed drugclass in patients with urge incontinence, which attemptto control bladder detrusor muscle overactivity, helprelax bladder muscles, and prevent bladder spasmsby their action on bladder muscarinic (M) receptors;consequently resulting in a reduction in urgencysymptoms and improvements in bladder control.Nevertheless, there are several common adverse effectsof these medications, which may be a limitation.²⁸   This is because muscarinic receptors are also located inother organ systems, and anti-muscarinic drugs arefrequently non-selective. These drugs may thereforebe associated with several peripheral and centraladverse reactions (Table 4).¹³   Especially, some adverseeffects, such as confusion, delirium, constipation,memory loss, and acute urinary retention (AUR) in overflow incontinence, are of particular concern inthe more vulnerable elderly population.²⁹   They mayprecipitate urinary retention by inhibiting detrusorcontractility, and therefore warrant caution in menwith underlying urinary obstruction. Furthermore,elderly patient are often on polytherapy. This mightincrease the risk of anticholinergic side effects in suchpatients, seeing that most medications administeredfor depression, allergies, Parkinson disease and OABhave anticholinergic properties.³⁰   In all, administrationof anticholinergic agents in elderly patients withurinary incontinence is a contentious issue, and shouldbe considered cautiously on individual basis.

Flavoxate: A preferred front-line antispasmodic

Antispasmodic drugs have proven to be effectivein suppressing premature detrusor contractions,enhancing bladder storage, and relieving symptomsof OAB, and are therefore indicated in this condition.Flavoxate is the first drug in this class to be approved forOAB by the Food and Drug Administration (FDA), andhas been used extensively in the treatment of urinarydisorders characterized by smooth muscle spasm.^31,32     This flavone derivative is known to possess potentsmooth muscle relaxant properties till the normalstate, and having major application in the treatment ofurge incontinence and OAB, supported by an excellenttolerability and a valid therapeutic efficacy.³³   Themechanism of action of flavoxate could be considereda superimposition of several beneficial effects.³⁴   Flavoxate hydrochloride is an antispasmodic agentwhich exerts an inhibition of the phosphodiesterases,a moderate calcium antagonistic activity, and a localanesthetic effect.³⁵   It has demonstrated moderate antihistaminiceffect and mild analgesic effect as well.

A paramount differentiating property of flavoxateis the clear enhancement of bladder compliancecombined with unchanged contractility.³²   Severalurodynamic studies have shown that flavoxatecauses significant increases in the bladder volumecapacity (BVC), with greater results compared toother drugs.35 Consequently, flavoxate relieves thebothersome symptoms of frequency, incontinence,nocturia, dysuria, and urgency, and improves thedrainage capacity by normalizing detrusor activity.³²   The important feature of flavoxate treatment – thatit significantly increases the bladder capacity in OABpatients, without increasing the residual urine volume- could be significant benefit in the elderly who are more prone to AUR.³⁶   It can be used either alone or incombination with an alpha-1 adrenoreceptor blockerto reduce the symptoms of OAB/LUTS.

Furthermore, the efficiency of flavoxate mayincrease with rising dose of the drug. In a double-blind,randomized, parallel-group trial, flavoxate at a dailydosage of 600 mg was compared to a daily dosageof 1200 mg for the treatment of unstable bladder in 27 patients for 4 weeks.³⁷   Results showed that bothschedules were equally successful clinically. However,in urodynamic terms, particularly with respect touninhibited detrusor contractions, 1200 mg/day wassignificantly superior to 600 mg/day. Tolerability wasexcellent for both the regimens.

In clinical trials, both versus placebo or versus activecomparators, flavoxate treatment was associated witha significant improvement in different LUTS, such asdiurnal and night frequency, urgency and urinaryincontinence, suprapubic pain, dysuria, hesitancy andburning.³⁵   A double-blind multiclinic crossover studycompared the efficacy and tolerance of a 4-weektreatment course with flavoxate, given orally at 1200mg/day, with that of oxybutynin, 15 mg/day orally, inwomen with idiopathic motor or sensory urgency.³⁸   Ofthe 50 patients included in the study, 41 (20 affectedby sensory urgency and 21 by motor urgency)completed both courses of treatment and wereevaluated for efficacy utilizing clinical and urodynamiccriteria. According to the patients, flavoxate cured orgreatly improved the syndrome in 81.6% of cases,while oxybutynin produced the same effects in 78.9%.Furthermore, of the 41 patients who received bothtreatment courses, 11 (26.8%) experienced adversereactions with flavoxate, compared to 37 (90.2%)with oxybutynin treatment. Of note, five patients,not included in the efficacy evaluation, interruptedthe treatment because of side effects while takingoxybutynin, whereas no patients stopped while takingflavoxate. The severity of the side effects recordedduring oxybutynin treatment was significantly greaterthan during treatment with flavoxate.³⁸

Gaudenz and Weil³⁹   made a comparison offlavoxate, emepronium, propantheline and a placebofor treatment of urinary incontinence due to bladderinstability in several hundred cases of motor urgeincontinence in the females; and noted efficacy andtolerability for flavoxate. In a study by Gu FL et al⁴⁰   ,which involved 336 evaluable patients, flavoxatecompletely cured or improved symptoms of urgency/incontinence in about 2/3rd patients with urgency/incontinence of various types. Importantly, the drugwas effective in 77.4% of patients refractory to previousanticholinergic treatment.

Favorable safety profile of flavoxate

A number of years of clinical practice have proven theefficacy and tolerability of flavoxate administration inrelieving LUTS. Flavoxate is associated with an overallmore favourable safety profile than competitors.³⁵   Voiding, which is under cholinergic control, is notadversely affected by flavoxate hydrochloride,and there is no build-up in post-voiding residualurine volumes during treatment with flavoxatehydrochloride. This drug, therefore, does not showtypical anticholinergic effects.³²   Such favorabletolerability profile suggests its wide applicability insubpopulations of patients with OAB and urinaryincontinence. The drug has no antimuscarinic activity,and is largely devoid of antimuscarinic/anticholinergicside effects seen with other drugs (Table 5).^31,37     In fact,Gu FL et al⁴⁰   documented that adverse events occurredin their study only in 1.3% patients with urgency andurge incontinence treated with flavoxate. Flavoxate issafe for long-term treatment and improves quality-oflife.This tolerability profile is maintained even at highdoses of up to 1200 mg/day and during long-termtreatment of up to 180 days), and is important becauseproblems such as urinary incontinence require chronicdrug administration.³²

Conclusion

Urinary incontinence is a common global problemthat is expected to rise in future with the agingpopulation. The disease is associated with considerablephysiological and societal impact, causing significantburden and affecting the overall quality-of-life of thepatients. However, it is often under-reported and undertreated.Especially, the elderly population is vulnerableto developing urinary incontinence due to severalphysiological changes that affect the functioning oflower urinary tract; though it should not be assumeda normal consequence of aging. Assessment andtreatment of urinary incontinence is usually complexbecause of several host related factors. Regardless, thetreatment approach is simple in that it should start withnon-pharmacological or behavioral interventions. Drugtherapy is combined with behavioral modification toaugment the therapeutic benefits. However, initiationof drug therapy requires careful considerable as elderlyare not only physiologically vulnerable but might behaving comorbidities and receiving other drugs aswell. In many such cases with urinary incontinence,flavoxate’s favorable tolerability and efficacy, proventhrough several years of clinical use, makes it a viableoption for use in subpopulations of patients. Especially,flavoxate is free from side effects of anticholinergicmedications. Using flavoxate over the anticholinergicshas following advantages: i) no anti-cholinergic sideeffects; ii) flavoxate improves bladder volume capacity;iii) reduces post void bladder volume; iv) no risk ofurinary retention. Overall, treatment should be tailoredaccording to individual needs of the patients, with aimto maximize the treatment benefits and improve thequality-of-life.

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