A longitudinal study over 5 to 10 years of clinical outcomes in women with idiopathic detrusor overactivity

Authors


Dr AR Morris, Department of Obstetrics and Gynaecology, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia. Email alastair.morris@btinternet.com

Abstract

Objective  To evaluate the long-term clinical outcome in women with idiopathic detrusor overactivity (IDO) and to identify significant prognostic factors.

Design  Longitudinal study incorporating retrospective case note review and a postal questionnaire.

Setting  Tertiary referral urogynaecology clinic in Australia.

Population  Women with a sole urodynamic diagnosis of IDO.

Methods  Audit of urodynamic records and case notes. Postal questionnaire incorporating validated disease-specific quality-of-life (QoL) instruments.

Main outcome measure  Subjective assessment of overall improvement on a 4-point scale followed by scoring of short forms of the urogenital distress inventory and incontinence impact questionnaire.

Results  One hundred and thirty two women were identified following examination of 1975 consecutive records with 76 (67%) returning questionnaires. Median follow up was 8 years (6–9), and the duration of symptoms was 13 years (9–18). Improvement was achieved in 25 (35%) women. Disease symptoms fluctuated in severity and QoL were worse in nonresponders to therapy (P < 0.0001). Urge incontinence at presentation was associated with treatment failure (P= 0.001) as was nocturia (P= 0.04), but urodynamic variables were not associated with outcome. Only 3 of 46 (6.5%) women not responding to therapy thought that their symptoms would improve with time.

Conclusions  IDO seldom resolves and fluctuates in severity. Individual response is unpredictable, although the presence of urge incontinence is associated with a significantly worse prognosis.

Introduction

The symptoms of idiopathic detrusor overactivity (IDO), such as frequency, urgency, nocturia, with or without urge incontinence, become steadily more common as age advances.1 Thus, as our population demographics shift towards the elderly, the total ‘burden of disease’ for this condition will increase.2 If we regard IDO as a chronic, largely incurable condition, the cost implications will be greater than if IDO is considered an acute, treatable form of incontinence.

Although the literature contains many studies comparing the efficacy of different anticholinergic medications, they generally report short-term data of variable quality. Although limited data about the medium-term treatment response of women with detrusor overactivity (DO) have been published,3 a long-term longitudinal study of women with urodynamically proven IDO has not yet been undertaken.

Although women with the overactive bladder (OAB) symptom complex describe similar symptoms to those with IDO, women with OAB will not have undergone urodynamic assessment. As such, the two terms should not be used interchangeably and outcomes may differ. Little medium-term data has been published for women with OAB,4 and such women are not considered in this paper.

The main aim of this study was to assess the clinical outcome among a cohort of women with IDO over a period of 5–10 years. A subsidiary aim was to compare the clinical course of those with different urodynamic forms of the condition. In addition, the study aimed to define the typical pattern of disease symptoms over this time (e.g. progressive worsening versus an undulating course). The clinical symptoms or aspects of the women’s personal/family history associated with a poor outcome were also analysed.

Methods

A longitudinal study was undertaken in a cohort of women with urodynamically proven DO who had initially attended a tertiary referral urogynaecology clinic between 1992 and 1997. The study was carried out in two parts. First, the clinic notes were audited as to number of visits and number of treatments, the response to treatment and whether the woman was discharged from review or just failed to attend the next scheduled visit (called the ‘last clinic review’). Second, a questionnaire that assessed the current status of the bladder complaint, together with two short quality-of-life (QoL) instruments, was sent to all women, so that the duration of this follow up was 5–10 years after the first visit. Local ethical committee approval was obtained. Details of each part of the study methods are described below.

Last clinic review methodology

Women either with phasic DO or those with urodynamic features of reduced bladder compliance were identified by searching urodynamic records and case notes of all female patients who first attended over the 5-year index period. Only those women in whom either of these was the sole urodynamic finding were included in the study. When this study was commenced, the International Continence Society (ICS) defined ‘phasic’ DO and described the characteristic appearance of a bladder with reduced compliance—the latter being a linear pressure rise that persisted when filling ceased.5 However, in the most recent revision of these guidelines, reduced bladder compliance was not considered.6

The clinic was established by a single-handed urogynaecologist who managed all women and performed all urodynamic testing in the 5 years following its foundation with very limited registrar support. A standard treatment protocol was applied for women with symptoms of OAB. At the first visit, detailed bladder training instructions were given based upon the 72-hour frequency volume chart (FVC) routinely sent out for prior to the first visit. A videotape about bladder training, constructed by the urogynaecologist, was given. Women were trained to contract their pelvic floor muscle (PFM) when trying to inhibit the premature desire to void, based on digital assessment of PFM strength.7 A mid-stream urine was cultured, postmenopausal women with signs of vaginal atrophy were given topical vaginal estrogen therapy and a trial of anticholinergic therapy was started, with the first-line agent being oxybutynin. Unless symptoms were mild, urodynamic testing by medium fill cystometry was booked for the second visit (usually 6–10 weeks later).

At subsequent follow up, the dose of anticholinergic was titrated against adverse effects, and other agents such as imipramine or tolterodine (on a named patient basis) were given. If the woman continued with debilitating frequency urgency/urge leak for more than 12 months despite bladder training plus two or more anticholinergics, then cystodistension was offered. If this was not helpful, then other treatments such as transcutaneous electrical nerve stimulation or electroacupuncture (Stoller Afferent Nerve Stimulator) were considered.8,9

At each follow up visit, it was routine practice to ask women by what percentage their symptoms had improved or worsened. The woman was asked to consider that at their first visit symptoms were defined as ‘100% bad’. A 24-hour FVC, given prior to each follow up visit was used to verify the patient’s identification of percentage change. Subsequent outcomes were defined as shown in Table 1.

Table 1.  Categorisation of patients’ outcomes at time of last clinic visit
Findings in case notesCategory
Cured or 75% improvement documentedCured
Significantly better or 50–74% improvement documentedMuch improved
Little benefit or 10–49% improvement documentedLittle help
No benefit or <10% improvement documentedNo help

Long-term follow up methodology

After checking the current addresses of the index group, a questionnaire was sent to each woman together with an explanatory letter outlining the purpose of the study, its voluntary confidential nature and a stamped return envelope. If no reply had been obtained after 1 month, a further questionnaire with a different cover letter was sent. If this did not elicit a response, a phone call was made to the patient’s last known telephone number.

The questionnaire was designed to provide both objective and subjective assessment of DO symptoms. Objective data were obtained by incorporating two validated disease-specific QoL instruments—the short forms of the urogenital distress inventory (UDI) and the incontinence impact questionnaire (IIQ).10 Subjective assessment of the value of all treatments was made by asking women to report the change in their condition using defined response categories: ‘cured’, ‘improved a lot’, ‘improved a little’ and ‘not helped at all’. Other questions invited subjective assessment of individual symptoms, the clinical course of the disease and recent changes to overall health that could influence lower urinary tract (LUT) function, the degree of bother they caused and whether the woman believed that their DO would ever improve or entirely resolve in the future. Women were also asked for further details about family members who were now known to suffer from similar LUT symptoms (but who did not do so when the woman was first seen). The questionnaire was pilot tested in a group of 20 women then refined, but the validated QoL instruments remained unchanged.

To facilitate analysis at either end point, women who were categorised as ‘cured’ or ‘much improved’ were grouped together as treatment ‘responders’. Conversely, women who found treatment as ‘little help’ or ‘no help’ were grouped and called ‘nonresponders’.

Statistical analysis

The data were double entered into a spreadsheet by a single individual and the first author checked the completed file. Analysis was performed using SPSS version 11.0 (Graduate edition) (SPSS Inc., Chicago, IL, USA). All data were tested for normality using the Shapiro–Wilk test. Student’s t test was used for normally distributed data (presented as mean/SD), while the Wilcoxon signed-rank test or Mann–Whitney U (MW-U) test were used for nonparametric paired and unpaired data, respectively (presented as median/interquartile range). Analysis of ordinal data was by the chi-square test (χ2) or by Fisher’s exact test (FET) if more than 25% of the numerators or denominators be five or less. Data for responders to therapy are presented before that of nonresponders unless otherwise indicated.

Results

Between 1992 and 1997, 1975 women attended the clinic for the first time (Figure 1). Of these, 1320 (67%) women underwent cystometry with IDO the sole urodynamic diagnosis in 132 (10%).

Figure 1.

Women participating in the study.

Clinical features of phasic DO versus low-compliance bladder

Clinical and demographic data are described in Table 2. Among the whole patient group, 75 (57%) had phasic DO and 57 (43%) had low-compliance bladder. Both groups reported similar symptoms with the exception of bedwetting, which occurred more frequently among those with phasic DO both at the last visit (16 of 70 [23%] versus 3 of 51 [6%], χ2= 6.42, P= 0.01) and at 5–10 years (8 of 40 [20%] versus 1 of 36 [3%], χ2= 5.38, P= 0.02). Therefore, as demographic data and clinical outcomes among women with both subtypes of DO were similar, they were combined for the remainder of the analysis reported below.

Table 2.  Demographic and clinical data from women with phasic DO and low-compliance bladder
 Phasic DOReduced bladder complianceSignificance
Age of onset of symptoms52 years (32–70)47 years (32–67)MW-U, P= 0.56
Duration of symptoms prior to first attendance5 years (2–10)4 years (1–10)MW-U, P= 0.37
Urge incontinence61 of 75 (81%)39 of 57 (68%)χ2= 2.27, P= 0.13
Nocturia19 of 75 (25%)15 of 57 (26%)χ2= 0, P= 1
Responded to treatment when last seen36 of 75 (47%)29 of 57 (51%)χ2= 0.04, P= 0.85
Responded to treatment at long-term follow up14 of 38 (37%)11 of 33 (33%)χ2= 0.09, P= 0.75

Results at time of last visit to the clinic

Of the 132 women with IDO, 65 (49%) were classified as having responded to treatment. The proportions in each of the four outcome categories are shown in Table 3. The age of onset of symptoms of DO occurred at similar ages in the responders (53 years [30–68]) and in the nonresponders (48 years [33–70] [MW-U = 0.04, P= 0.97]). Responders had disease of a similar duration (6.4 years [2.7–12.7]) to nonresponders (5.7 years [2.1–10.8] MW-U, P= 0.07) as calculated from the time of onset of symptoms to the date of their last clinic review.

Table 3.  Outcome by category at time of last visit to the pelvic floor unit and following questionnaire administration
Final outcome groupsLast review appointment (n= 132)After questionnaire administration (n= 71)
Responded
Cured28 (21%) 49%5 (7%) 35%
Much improved37 (28%)20 (28%)
Not responded
Little improved32 (24%) 51%30 (42%) 65%
No improvement35 (27%)16 (23%)

The common adult and childhood LUT symptoms, recorded at the first presentation are shown in Table 4 for each outcome group. Symptoms of childhood LUT dysfunction were quite common in this cohort, with a history of childhood nocturnal enuresis obtained from 26 (29%) and daytime incontinence from 8 (9%). These symptoms were significantly more common in women with a poor outcome (Table 4). Of those symptoms typically described by adults, only nocturnal enuresis was associated with failure of treatment at this time. Both groups could recall similar number of siblings who wet (2 of 17 [12%] versus 3 of 25 [12%], A = 2.02, P= 0.68).

Table 4.  Symptoms at first presentation to the pelvic floor unit
SymptomTotal number of women who could be categorisedRespondersNonresponderχ2P
PresentNot presentPresentNot present
Frequency128412344200.320.58
Urgency12859554101.190.17
Urge incontinence127461754102.450.12
Stress leak126184515480.370.54
Nocturnal enuresis12155714545.600.02
Nocturia121184316140.120.72
Leak on hearing running water118293132260.550.46
Nocturnal enuresis >age 58993617254.280.04
Daywetting >age 5881457355.570.02

No significant differences was identified between responders and nonresponders from standard baseline parameters, obtained either from the FVC (voids per day, urge episodes, urge incontinence episodes) or from cystometric assessment (data not shown). Previous hysterectomy did not influence outcome. A total of 41 women had undergone either abdominal or vaginal hysterectomy before being seen for the first time, and of these, 23 (56%) responded to treatment compared with 42 of 91 (46%) who did not (χ2= 1.11, P= 0.29). Likewise, a past history of irritable bowel syndrome (5 of 56 [9%] versus 1 of 47 [2%], A = 3.23, one-sided P= 0.14) or recurrent cystitis (n= 26, χ2= 0.02, P= 0.88) was not associated with outcome.

Long-term follow up at 5–10 years

Initial demographic data

A total of 76 questionnaires were returned, a response rate of 67% (Figure 1). Demographic variables among those returning the questionnaire (participants) and among those not returning it (nonparticipants) were similar (parity, menopausal status, symptoms at presentation, the age at which they first occurred and childhood/family histories of LUT dysfunction parameters relating to the FVC/urodynamic tests). The duration of symptoms up until the time of their last clinic review for participants (who completed the questionnaire) and nonparticipants (who did not complete the questionnaire) was similar (6.5 years [2.5–12.5] versus 5.5 years [2–12], MW-U, P= 0.50]. However, participants had more review appointments than nonparticipants (5 [3–9] versus 3 [2–6] MW-U, P= 0.01) and were also treated for a greater duration (10 months [2–42] versus 6 months [2–14], MW-U P= 0.03).

Of the 76 returned questionnaires, the data set was incomplete in 5 cases, yielding 71 full responses (93%). The median duration of follow up from first attendance at the clinic until completion of the questionnaire was 8 years (6–9). Overall, as shown in Table 3, 35% of women responded to treatment, representing a decrease of 14% in the treatment response from that determined at the last clinic review.

The median duration of clinical disease for those participating in the study was 13 years (9–18), with responders reporting symptoms for significantly less time (10 years [7–16] versus 15 years [10–18] MW-U, P= 0.049). The median number of therapies received by the group was 3 (2–4), with 20% having had only one treatment and 25% having had more than four treatments. The number of treatments received by responders, 2 (1–5), was not significantly different to the number of treatments given to nonresponders, 3 (2–5), P= 0.17. Cystodistension was performed in 24 (34%) women.

Variables influencing treatment outcomes

The likelihood of responding to treatment was not associated with age at symptom onset (49 years [30–63]) versus 44 years [27–59] MW-U, P= 0.51). However, urge incontinence was described significantly less often in responders than nonresponders (15 of 25 [60%] versus 40 of 46 [87%] χ2= 6.74, P= 0.001). Responders also described nocturia less frequently (7 of 25 [28%] versus 24 of 46 [52%] χ2= 4.18, P= 0.04).

Women in both outcome groups had a similar number of affected first-degree family members (11 of 26 [42%] versus 14 of 46 [30%] χ2= 0.9, P= 0.34) as recorded on the follow-up questionnaire. Childhood history had been ascertained for 50 of the 71 (70%) women. Bedwetting was associated with nonresponse to treatment at last clinic review, but this was not the case at 5–10 years (13 of 36 [36%] versus 4 of 14 [29%], χ2= 0.25, P= 0.61). Although daytime incontinence beyond age 5 was noted more frequently among nonresponders, this did not reach significance (0 of 14 [0%] versus 6 of 36 [17%], FET, A = 1.68, one-sided P= 0.12).

Baseline FVC and cystometric testing did not predict outcome. Both QoL tests (UDI and IIQ) that were contained in the questionnaire provided objective data confirming nonresponders had a greater severity of symptoms (P≤ 0.001) (Table 5).

Table 5.  QoL scores among women completing the follow-up questionnaire
IndexResponded to treatmentNonresponder to treatmentMW-U, P
UDI18 (10–35)44 (27–61)0.001
IIQ10 (0–26)33 (19–59)<0.001

Reported course of disease

The majority of women reported that their disease fluctuated in severity, Figure 2. Of those who did not respond to therapy, the majority indicated that their symptoms had continued to worsen with age (27 of 46 [59%]). In addition, the majority of these nonresponders (29 of 46 [63%]) either ‘disagreed’ or ‘strongly disagreed’ that improvement would ever be achieved. Only 3 of 46 (6.5%) women believed that their symptoms would improve with time and none believed that their symptoms would ever resolve completely.

Figure 2.

Perceived course of disease among all women responding to the questionnaire (n= 75).

The majority of participants, 45 of 75 (60%), believed that symptoms of DO influenced their QoL. As shown in Figure 3, this view was held by significantly more women who did not respond to treatment (7 of 25 [28%] versus 36 of 46 [78%], χ2= 17.13, P < 0.0001). Following participation in the study, four women returned to the clinic for further treatment due to the severity of their symptoms.

Figure 3.

Response by outcome group to the statement ‘my bladder problem has no influence on my quality of life’ (n= 75). (Responders in black, n= 25; nonresponders in stripe, n= 46).

In view of the fact that the outcome was unknown for 42 women (37 nonparticipants plus 5 who did not complete all the questions), we repeated the analysis of outcome assuming that each of these women either responded to therapy or did not respond to therapy. On the basis that all 42 women responded to therapy, this represents a maximum response of 59% (67 of 113 women). Conversely, if all unknown women were nonresponders to therapy, then they would form 78% (88 of 113) of the group and only 22% of women would have been helped by treatment.

Discussion

This longitudinal study describes, for the first time, the clinical outcome in female patients with a sole urodynamic diagnosis of IDO over a prolonged period (median of 8 years). At the present time, only one other study in the published literature has described some aspects of the course of DO over a comparable period.3 Other papers have addressed the condition now defined as OAB, although some of the women in these studies would have been shown to have had DO if urodynamic assessment had been performed.4

The primary outcome of this study was the clinical status of each woman at the time of the last clinic review appointment and then after questionnaire administration completed between 5 and 10 years later. The overall response rate to the questionnaire of 67% was high, particularly in view of the length of follow up that this study entailed. It was hoped that this data would help gynaecologists, and other relevant clinicians, to begin to answer questions that female patients commonly ask, such as ‘will I get better’ and ‘how long will I need to take my tablets for’.

As pointed out, this study was commenced when the 1988 ICS definitions were current.5 As such, the urodynamic features of reduced bladder compliance were considered a separate entity at that time. After our study was commenced, a subsequent ICS guideline was published, and this was no longer the case.6 Nevertheless, many clinicians appear to continue to report it and believe that they can readily distinguish it from phasic DO based upon the characteristic appearances of each during the filling phase of cystometry. However, the marked difference in appearance of each at cystometry raises the controversy as to whether they have different aetiologies. Certainly, the urodynamic finding of reduced bladder compliance is not observed on ambulatory urodynamic testing. Nevertheless, several observations can be made from our study. For the first time, we have shown that phasic DO and reduced bladder compliance may be indistinguishable in terms of the course of the disease. Counselling of women should therefore be similar. Although no difference was noted in the age of onset of symptoms for both groups of women, those with phasic DO were significantly more likely to bedwet. Bedwetting remained a problem among significantly more women with phasic DO throughout their life, as indicated by symptoms on the follow-up questionnaire. Thus, the underlying pathophysiology may vary, but the clinical course appeared similar thus the outcome data could be pooled.

The success of the treatments offered to our women was disappointing. At the time of the last clinic review, only half the women were categorised as having ‘responded’ to therapy when compared with their baseline status. Six years later, the response rate had decreased to 35%. As previously outlined, categorisation as a ‘responder’ indicated a >50% improvement in symptoms from the time of the first visit. As such, there was still-room for considerable improvement among many women—an improvement that most would be keen to try to achieve. Almost all women were treated with anticholinergic medication, but at the time of this study, more recently developed pharmacological agents (e.g. tolterodine, propiverine and solifenacin) were not freely available within Australia. Some women may have had a better outcome if more effective drugs had been available. However, although the lack of newer drugs is unfortunate for an individual woman, from the perspective of a longitudinal study, it reduces the confounding effect that a range of medication brings.

Childhood nocturnal enuresis was present in 29% of women at their first visit with a further 9% having suffered daytime incontinence as a child. Although similar data were not gathered from a control group of women with stable bladders, these proportions are higher than that would be expected in the general Australian population.11 Both nocturnal enuresis and daytime incontinence were associated with adverse outcome at the last clinic review. In early childhood, these individuals cannot be distinguished from other children as incontinence of urine is physiologically normal until full bladder control is achieved around 4–5 years of age. However, our data suggest that by early adulthood an abnormal pattern of LUT function is present in many women who are later diagnosed as having DO.

Of those completing the questionnaire, 28% indicated that they had experienced bedwetting as children and still continued to do so. This level of bedwetting is much greater than previous work would have predicted. For example, Bower et al (1996) observed an overall rate of 15% for nocturnal enuresis among 2292 male and female Australian children aged 5–12 years.11 Of those affected, the majority (60%) were male children. Most of studies have suggested that nocturnal enuresis in children largely resolves by adolescence and that less than 1% of adults will still suffer this condition.11 It is unfortunate that this symptom was not improved by treatments for DO and suggests that these women may have an intrinsic defect in the control of their LUT.

Data obtained from the questionnaire have, for the first time, described the perceived course of DO from a patient’s perspective. The majority (45%) believed that the severity of their symptoms waxed and waned over time. Consequently, it is likely that some women were discharged from review, after apparently successful treatment, only for their symptoms to recur. Should they not seek further treatment at that time it is likely that the clinician would remain ignorant of their deterioration and be left with an over optimistic impression of the value of therapy.

A further striking feature of the data is the dismal outlook that many women have as regards future prognosis. This was observed among responders and nonresponders to treatment. Only 8% of ‘responders’ believed that their symptoms would resolve entirely as did 6.5% of ‘nonresponders’. The latter group were also pessimistic that any improvement would be achieved in the future as regards their bladder symptoms. The symptoms of DO affected the QoL of many individuals in each outcome group, although proportionally more of those not responding indicated that this was the case. In addition, most women felt that their symptoms had become worse with age. It was anticipated that increasing age would result in other medical conditions arising such that the relative importance of LUT symptoms would diminish. Although no baseline data were recorded to ascertain the relative importance of these symptoms at the first visit, over half of those not responding to treatment believed that they were their most bothersome health problem at present.

Before concluding, there are several aspects of this study that should be addressed. The response rate of 67% is high for a study of women over a period of 5–10 years. However, this means that the outcomes of 33% of our women remain unknown, which is unfortunate. The women reported here all had an urodynamic diagnosis of IDO, which represented a rate of 10% for our clinic population. However, larger studies of consecutive women having cystometry suggest that IDO is identified in approximately 18%.12 Why the diagnosis of IDO seems relatively under-represented in our study population is unknown as all women were recruited from a tertiary level urogynaecology service. By incorporation of QoL instruments into the questionnaire, it was possible to obtain an objective assessment of outcome, but unfortunately, baseline data were not available. When the study was commenced, QoL data were rarely gathered, although the current literature shows this is clearly no longer the case. Neither was it possible to obtain data on compliance with therapy in terms of how long individual medications were taken for and the reasons for ceasing. These are all issues that should be addressed in future prospective studies designed to confirm the data presented here.

Conclusion

In this study, less than 50% of women achieved what they considered to be a cure and most did not believe their symptoms would ever resolve completely. This study establishes phasic and low-compliance bladder as indistinguishable forms of the disease both in terms of overall clinical course. Urge incontinence is associated with a poor prognosis, reflecting profound disturbance in the control of micturition. Daytime incontinence in childhood appears to further worsen prognosis.

Contribution to authorship

A.R.M. designed the study protocol, obtained ethical approval, created the data collection forms, audited the case notes, collected/analysed the data and significantly contributed to the writing of the paper. J.I.W. reviewed the design of the study, advised on statistical analysis and significantly contributed to the writing of the paper. K.H.M. supervised the study and significantly contributed to the design, analysis of data and writing of the paper.

Ethics approval

Approval was obtained from the ethics committee of South Eastern Sydney Area Health Service.

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