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Contents: Urogynecology: Original Research

The Burden of Nocturia Among Middle-Aged and Older Women

Hsu, Amy MD; Nakagawa, Sanae MA; Walter, Louise C. MD; Van Den Eeden, Stephen K. PhD; Brown, Jeanette S. MD; Thom, David H. MD, PhD; Lee, Sei J. MD, MAS; Huang, Alison J. MD

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doi: 10.1097/AOG.0000000000000600
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Nocturia is common among middle-aged and older adults, with up to half reporting waking to urinate at least once per night.1–3 In addition to poor sleep, nocturia has been linked to decreased mental and somatic health, falls and fractures, and increased mortality in some populations.4–7

Among older men, nocturia may occur from impaired bladder emptying as a result of prostatic hyperplasia,8 although other factors influencing nocturnal urine production and regulation of bladder function may play a role.9,10 Among older women, however, the prevalence and severity of nocturia are not as well described, the determinants of nocturia are not as well understood, and many clinicians caring for women are at a loss to explain why some female patients wake up multiple times to urinate but not others.

Nocturia may have received relatively less attention in women's health as a result of the view of nocturia as resulting from another primary disorder rather than a clinical entity in its own right.11 Although nocturia can develop in the setting of an overactive bladder12 and polyuria,1 women may also report nocturia without urgency or urinary frequency during the day.

To better understand the prevalence, predictors, and effects of nocturia in women, we examined the age- and race-specific prevalence of nocturnal voiding and the overlap between nocturnal voiding and other common urinary tract symptoms in an ethnically diverse, community-dwelling population of middle-aged and older women. We also examined duration of nocturia, demographic and clinical factors associated with nocturia, and predictors of greater subjective bother and disruptiveness from nocturia.

MATERIALS AND METHODS

This research was conducted within a multiethnic, observational cohort study of risk factors for urinary tract dysfunction in community-dwelling middle-aged and older women, the Reproductive Risks of Incontinence Study at Kaiser. Details about Reproductive Risks of Incontinence Study at Kaiser and participant recruitment have been reported previously.13 Participants were female members of Kaiser Permanente Northern California, an integrated health care delivery system serving 25–30% of the northern California population. To be eligible for the study, women had to be at least 40 years of age, to have enrolled in Kaiser Permanente Northern California before age 21 years, and to have had at least half of any childbirth events at a Kaiser Permanente Northern California facility. Women were randomly sampled from within age and race–ethnicity strata to achieve an overall composition of approximately 20% black, 20% Latina, 20% Asian, and 40% white. No symptoms or history of urinary tract dysfunction were required, but approximately 20% of participants were recruited from the Kaiser Permanente Northern California Diabetes Registry to enrich the participation in the Reproductive Risks of Incontinence Study at Kaiser by women with diabetes. In contrast, the general prevalence of diabetes in California is 13% in those 45–64 years old and 22% in those 65–74 years old.14

This study focused on the third wave of Reproductive Risks of Incontinence Study at Kaiser involving home-based study visits conducted between November 2008 and April 2012. The Reproductive Risks of Incontinence Study at Kaiser cohort was initially interviewed and examined between October 1999 and February 2003 and a follow-up interview took place between January 2003 and January 2008. Of the 4,819 women who were contacted to assess eligibility, 3,438 (71%) were found to be preliminarily eligible, 2,468 of these (72%) consented to participate, and 2,016 (82%) of these completed a study visit. Fifty-nine percent of eligible women completed the study. Additionally, a subset of 454 (23%) of Reproductive Risks of Incontinence Study at Kaiser 3 participants also provided data on nocturia 5 years earlier as part of Reproductive Risks of Incontinence Study at Kaiser 2. All participants provided informed consent before data collection. The institutional review boards of the University of California at San Francisco and the Kaiser Foundation Research Institute approved all study procedures.

Nocturnal voiding frequency was assessed using structured, interviewer-administered questionnaire items previously used in large epidemiologic studies.15 To minimize missing data and encourage accurate responses, trained female interviewers administered the questions about lower urinary tract symptoms and probed participants to clarify responses when appropriate. Participants were asked to indicate the number of times they urinated at night (“from the time you go to bed until the time you get up in the morning”) during a typical week. Consistent with past research suggesting that nocturnal voiding does not become clinically bothersome until it occurs more than once per night,16–19 women were considered to have “clinically significant” nocturia if they reported needing to urinate two or more times per night. To further assess the subjective bothersomeness and functional disruptiveness of nocturia, participants were also asked, “How much has this frequency of nighttime urination bothered you?” and “How much has this frequency of nighttime urination interfered with your day-to-day activities?” with response options including “not at all,” “slightly,” “moderately,” “quite a bit,” and “extremely.”

Other urinary tract symptoms were assessed with interviewer-administered structured questionnaire items validated against a detailed bladder diary.20 To assess urgency incontinence, women were asked about urine leakage associated with an overwhelming urge to urinate or difficulty holding urine. To assess stress incontinence, participants were asked about urine leakage associated with physical activity such as coughing, lifting, sneezing, or exercise. Women were considered to have weekly urgency incontinence or stress incontinence if they reported symptoms occurring at least four times per month in the past 3 months. Incontinence that occurred at least four times per month but was not associated with an urge to urinate or with physical activity was classified as “other or unclassifiable incontinence.” Daytime frequency was defined as urinating eight or more times during daytime hours (“from the time you get up in the morning to the time that you go to bed at night”) in a typical week.16

Demographic and clinical characteristics were assessed using participant-administered questionnaires, physical examination, performance testing, or abstraction of records from Kaiser Permanente Northern California databases. Race–ethnicity was assessed by self-report. Reproductive and gynecologic histories were ascertained by asking participants about all vaginal and cesarean deliveries, history of hysterectomy and oophorectomy, time elapsed since their last menses, and whether they experienced hot flushes in the past month. Chronic health conditions were assessed primarily with participant report of prior physician diagnoses, although diagnoses of diabetes were confirmed with review of clinical records indicating use of a glycemic control medication, fasting blood glucose of 126 mg/dL or higher, or elevated hemoglobin A1c level greater than 7.0% on one or more occasions. Depression symptoms were assessed using the depression subscale of the Hospital Anxiety and Depression Scale.21 Body mass index was calculated as weight (kg)/[height (m)]2. Cognitive function was assessed using the Mini-Mental State Examination.22 Physical mobility was assessed using the Timed Up-and-Go Test, where participants were timed while asked to rise from a seated position, walk 3 m, turn around, walk back to the chair, and sit down.23

Medication use was abstracted from Kaiser Permanente Northern California electronic pharmacy databases for participants who filled at least 80% of their medications at a Kaiser Permanente Northern California pharmacy. For participants who filled less than 80% of their prescriptions at a Kaiser Permanente Northern California pharmacy, study interviewers reviewed participants' medication lists and bottles in their homes.

Descriptive statistics were used to examine the overall distribution of nocturnal voiding frequency among participants stratified by age group and race–ethnicity. The prevalence of other urinary tract symptoms among women with and without clinically significant nocturia was compared using χ2 tests. Among participants who reported urinating at least once per night, we examined the distribution of 1) self-reported bother associated with nocturia; and 2) effect of nocturia on day-to-day activities stratified by nocturnal voiding frequency. Among participants reporting clinically significant nocturia in Reproductive Risks of Incontinence Study at Kaiser 3, we also examined the proportion who reported nocturia 5 years year earlier during Reproductive Risks of Incontinence Study at Kaiser 2.

Multivariable logistic regression models assessed potential risk factors of nocturia, including demographics (age, race–ethnicity, relationship status, education), gynecologic variables (parity, hysterectomy, oophorectomy, menopausal status, experience of hot flushes in the past month), common chronic medical conditions (diabetes, hypertension, heart disease, stroke, depression), selected medications (diuretics, systemic and vaginal estrogen, tricyclic antidepressants, calcium channel blockers), physical examination and testing (body mass index, Timed Up-and-Go test, Mini-Mental State Examination), and smoking and alcohol use. All potential risk factors were included in multivariable models regardless of association with nocturia in bivariate analysis.

Finally, additional multivariable logistic regression models examined characteristics associated with being at least “moderately” bothered by nocturia, including a limited set of predictor variables including age, race–ethnicity, relationship status, depression and anxiety, physical mobility, cognitive function, and frequency of nocturnal voiding. All analyses were performed using SAS 9.3.

RESULTS

Demographic and clinical characteristics of the 2,016 participants are summarized in Table 1. Mean age was 56 years (standard deviation 9 years), and more than half of the cohort self-identified as racial or ethnic minorities (22% black, 23% Latina, 20% Asian). Thirty-four percent (n=692) of women reported clinically significant nocturia, defined as voiding two or more times per night.

Table 1
Table 1:
Demographic and Clinical Characteristics of the Study Population (N=2,016)

Overall frequency of nocturnal voiding increased with age (P for linear trend using ordinal regression by age <.001) (Table 2). However, more than 20% of women younger than age 50 years still reported clinically significant nocturia. Overall frequency of nocturnal voiding was higher in black and Latina women compared with white women (P<.001 for heterogeneity using ordinal regression) with 9% of black and 7% of Latina women reporting needing to urinate four or more times per night compared with 4% of white women.

Table 2
Table 2:
Age- and Race-Specific Prevalence of Nocturnal Voiding

The majority of women with clinically significant nocturia reported one or more concomitant lower urinary tract symptoms, including weekly urgency incontinence (32%), stress incontinence (28%), daytime frequency (34%) (Table 3). Nevertheless, more than one third of participants had “isolated nocturia” in the absence of other clinically significant urinary symptoms. Furthermore, approximately half of women without clinically significant nocturia reported one or more other urinary symptoms.

Table 3
Table 3:
Self-Reported Lower Urinary Tract Symptoms in Women With and Without Clinically Significant Nocturia*

Greater frequency of nocturnal voiding was associated with greater subjective bothersomness and disruptiveness from nocturia (Fig. 1). P values for the linear trend of nocturnal voiding on being at least moderately bothered and affected day-to-day activities were both <.001. Of 1,407 women who reported at least one voiding episode per night during an average week, 334 (24%) reported being moderately or more bothered by their nocturnal voiding and approximately 122 (9%) of women reported that their nocturnal voiding had at least a moderate effect on their day-to-day activities. Nevertheless, only 12% of those with four or more episodes of nocturnal voiding reported being “extremely” bothered, and only 4% of those with this level of nocturia reported that their symptoms interfered “extremely” with their day-to-day activities.

Fig. 1
Fig. 1:
Distribution of bother (A) and disruptiveness of day-to-day activities (B) from nocturia by voiding frequency. P<.001 for test of linear trend of nocturnal voiding on the proportion of participants who reported being at least “moderately” bothered by nocturia or who reported that nocturia had at least a “moderate” effect on day-to-day activities using logistic regressions.Hsu. Nocturia in Middle-Aged and Older Women. Obstet Gynecol 2015.

Among the 692 women who reported clinically significant nocturia in Reproductive Risks of Incontinence Study at Kaiser 3, a subset of 454 (66%) women also provided data on nocturnal voiding 5 years earlier as part of Reproductive Risks of Incontinence Study at Kaiser 2 (Fig. 2).13 Three hundred eight (68%) of those women also reported clinically significant nocturia during Reproductive Risks of Incontinence Study at Kaiser 2. Of these women, 143 (32%) had nocturia that was equally frequent, 74 (16%) had nocturia that was more frequent, and 91 (20%) had nocturia that was less frequent 5 years ago.

In multivariable analyses (Table 4), age was an independent predictor of nocturia with each 5-year increase in age associated with an estimated 21% increase in the odds of reporting nocturia. Additionally, women were more likely to have nocturia if they self-identified as black or Latina rather than white or had a history of hysterectomy, hot flushes in the past month, worse depressive symptoms, vaginal estrogen use, or decreased physical mobility. No evidence of interaction between postmenopausal status and use of estrogen or bilateral oophorectomy status was detected (P=.71 and .92, respectively).

Table 4
Table 4:
Adjusted Associations Between Demographic and Clinical Factors and Clinically Significant Nocturia*†

In multivariate analyses examining factors associated with more subjective bother from nocturia, women were more likely to report being at least moderately bothered if they had more frequent nocturnal voiding (odds ratio [OR] 2.63, 95% confidence interval [CI] 2.08–3.31 per each additional episode of nocturnal voiding) or higher depression scores (OR 1.09, 95% CI 1.02–1.15 per each 1-point increase in Hospital Anxiety and Depression Scale depression subscale score), controlling for age, race or ethnicity, relationship status, physical mobility, and cognitive function. Women who were at least moderately bothered had a mean of three (±1) episodes of voiding per night compared with two (±1) among women who were not at all or slightly bothered. Mean Hospital Anxiety and Depression Scale score was 4.3 (±3.3) among women who were at least moderately bothered compared with 3.4 (±3.0) among women who were not at all or slightly bothered. Among women with “isolated nocturia,” multivariate analyses controlling for the same covariates revealed the same two independent risk factors for at least moderate bothersomeness from “isolated nocturia”: number of episodes of nocturia (OR 2.69, 95% CI 1.72–4.21 per each additional nocturnal voiding episode) and depression (OR per each 1-point increase in Hospital Anxiety and Depression Scale depression subscale scores 1.19, 95% CI 1.04–1.34). Women with “isolated nocturia” who were at least moderately bothered had a mean of three (±1) episodes of voiding per night compared with two (±3) among women who were not at all or slightly bothered. Mean Hospital Anxiety and Depression Scale score was 4.7 (±3.2) among women who were at least moderately bothered compared with 3.1 (±2.7) among women who were not at all or slightly bothered.

DISCUSSION

In our study, more then one third of women reported clinically significant nocturia, indicating that nocturia may be as prevalent as other lower urinary tract symptoms that currently receive more attention in women's health. Although nocturnal voiding frequency was higher in older women and those from certain racial or ethnic minority groups, more than 20% of women younger than age 50 years and at least 30% of women from all racial or ethnic groups reported nocturnal voiding of at least two episodes in a typical night. Furthermore, approximately one third of women with clinically significant nocturia reported no other urinary tract symptoms, suggesting that nocturia is not exclusively explained by other established urinary tract disorders. Among those reporting clinically significant nocturia, more than 60% also reported nocturia 5 years earlier, suggesting that their nocturia was a longstanding or recurrent problem. These results highlight the need for increased awareness, screening, or both for nocturia in women, even in the absence of other urinary symptoms.

Consistent with prior studies suggesting that the effects of nocturia become significant only when individuals void two or more times per night,16–19 our data indicate that the bothersomeness and disruptiveness of nocturia increase substantially at this threshold. However, we observed a wide distribution of bother at each level of nocturnal voiding frequency with some women having very frequent nocturia yet finding their symptoms only mildly bothersome or disruptive. Furthermore, depression was strongly associated with finding nocturia to be bothersome, independent of nocturnal voiding frequency, suggesting that factors unrelated to bladder function may shape women's experience of nocturia.

Our study agrees with prior studies that show increased odds of nocturia with age, racial–ethnic minority status, and history of hysterectomy.5,24–27 We also found other factors such as depression, use of vaginal estrogen, and physical mobility that may contribute to risk of nocturia in community-dwelling women. Rather than focusing predominantly on women's urogynecologic history, clinicians may need to conduct a more comprehensive assessment.

Prior studies have found gynecologic factors such as parity24,27,28 and postmenopausal status28 to be associated with nocturia, which did not emerge as independent predictors of nocturia in our analyses. However, those studies were conducted in younger females,27 in less diverse populations,24 or had a smaller number of participants who reported nocturia.28 Other medical conditions and health factors such as obesity,25,29,30 diabetes,18,19,25 and diuretic use18,25 have also been reported to be associated with nocturia in prior research. Those studies were generally restricted to geriatric populations,18,26 included lower numbers of women with nocturia,19 or used a lower threshold of one or more episodes of nighttime voiding.25

There are several limitations of this research. First, assessment of nocturia and other urinary tract symptoms was based on structured questionnaires rather than voiding diaries or frequency volume charts. However, the questionnaire measures used in this research have been used in other large epidemiologic studies and have been shown to have good overall correlation with voiding diaries.20 Second, our outcome measure could not determine whether women were woken up by the need to urinate or were already awake as a result of other factors (such as pain, anxiety, hot flush, bed partner activity, or pre-existing insomnia) at the time they decided to void. Third, several risk factors that we identified for nocturia (eg, depression) are also known risk factors for insomnia,31 and their effects on women's risk of nocturia may possibly be mediated by direct effects on sleep quality. Fourth, medical conditions other than diabetes mellitus were assessed primarily by patient report rather than chart review. However, there is no intrinsic reason to believe that recall or report of other comorbid conditions would differ between women who have nocturia compared with women who do not have nocturia. Lastly, our study population consisted of long-time female enrollees in an integrated health care system in northern California and was enriched with women from racial or ethnic minorities and women with diabetes, which may affect the generalizability of our findings to women in other settings.

Our study highlights that nocturia is common and persistent among middle-aged and older women and a substantial proportion of women develop this problem in the absence of other established urinary tract disorders, suggesting that nocturia should not simply be viewed as a manifestation of another primary urinary tract disorder but as a potential clinical entity in its own right. Strategies for preventing and treating nocturia should address the wide array of factors that may exert indirect effects on urinary function.

Fig. 2
Fig. 2:
Women with clinically significant nocturia (n=692) who also provided data on nocturnal voiding in Reproductive Risks of Incontinence Study at Kaiser 2 (5 years prior).Hsu. Nocturia in Middle-Aged and Older Women. Obstet Gynecol 2015 .

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© 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.