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Prevalence of Nocturia in United States Men: Results From the National Health and Nutrition Examination Survey
Prevalence of Nocturia in United States Men: Results From the National Health and Nutrition Examination Survey Alayne D. Markland,*,† Camille P. Vaughan,‡,§ Theodore M. Johnson, II,储 Patricia S. Goode,¶ David T. Redden and Kathryn L. Burgio** From the Birmingham/Atlanta Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Birmingham, Alabama and Atlanta, Georgia (ADM, CPV, TMJ, PSG, DTR, KLB), and the School of Medicine (ADM, PSG, KLB), Center for Aging (ADM, PSG, KLB) and School of Public Health (DTR), University of Alabama at Birmingham, Birmingham, Alabama, and Emory University (CPV, TMJ), Atlanta, Georgia
Abbreviations and Acronyms BMI ⫽ body mass index BPE ⫽ benign prostatic enlargement LUTS ⫽ lower urinary tract symptoms NHANES ⫽ National Health and Nutrition Examination Survey POR ⫽ prevalence odds ratio Submitted for publication July 12, 2010. The Department of Veterans Affairs had no role in the collection, analysis and interpretation of the data, or the manuscript preparation, review or approval. Study received National Centers for Health Statistics Ethics Review Board approval. Supplementary material for this article can be obtained at http://www.aging.uab.edu/SubChannel/ Research/genito-urinary.aspx. * Correspondence: VA Medical Center, GRECC/ 11G, 700 19th St. S., Birmingham, Alabama 35233 (telephone: 205-934-3259; FAX: 205-558-7068; e-mail: [email protected]). † Recipient of a Veterans Health Administration Career Development Award (CDA-2). ‡ Recipient of a VA Rehabilitation Research and Development Career Development Award (CDA-1). § Financial interest and/or other relationship with Astellas. 储 Financial interest and/or other relationship with Pfizer and Vantia. ¶ Financial interest and/or other relationship with Pfizer. ** Financial interest and/or other relationship with Pfizer, Astellas and Johnson & Johnson.
See Editorial on page 781.
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Purpose: We estimated the prevalence of nocturia in the United States male population and identified associated factors. Materials and Methods: Data were analyzed for 5,297 men (20 years old or older) who participated in the 2005–2006 and 2007–2008 cycles of the NHANES, a cross-sectional survey of the United States noninstitutionalized population. Getting up 2 or more times at night to urinate was coded as nocturia. Potential factors included age, race/ethnicity, education, waist circumference, self-reported health status, chronic diseases, and prior diagnosis of benign prostatic enlargement and/or prostate cancer (men 40 years old or older). Prevalence and prevalence odds ratios were estimated from a multivariable logistic regression analysis using appropriate sampling weights. Results: The prevalence of nocturia was 21% (weighted 95% CI 19.3–23.0). Nocturia increased in prevalence with age (p ⬍0.001) from 8.2% (CI 6.7–10.2) in men 20 to 34 years old up to 55.8% (CI 51.3– 60.2) in men 75 years old or older. More nonHispanic black men had nocturia (30.2%, CI 26.7–34.1) than other racial/ethnic groups (20.1%, CI 18.1–22.1, p ⬍0.001). Significant factors included 10-year increase in age (POR 1.5, CI 1.5–1.6), nonHispanic black race/ethnicity (POR 2.0, CI 1.6 –2.7), fair/poor self-rated health (POR 1.5, CI 1.2–1.9), major depression (POR 2.5, CI 1.6 –3.9), hypertension (POR 1.4, CI 1.0 –1.9) and arthritis (POR 1.3, CI 1.0 –1.7). Among men 40 years old or older benign prostatic enlargement (POR 1.4, CI 1.1–1.8) and prostate cancer (POR 1.6, CI 1.0 –2.4) were associated with nocturia. Conclusions: After adjusting for age and race norms nocturia was common among United States men. NonHispanic black men had greater odds of nocturia even when controlling for other factors. Key Words: nocturia, male, prevalence, epidemiology, prostatic diseases NOCTURIA (waking at night to void1) is one of the most bothersome LUTS.2,3 In addition, frequent nocturia has been linked to poor self-rated health,4 negative effects on sleep,5 depression6 and falls.7 Recent epidemiological studies of nocturia have suggested that experiencing at least 2 episodes nightly is likely to cause significant bother.8
Few studies have assessed the prevalence of nocturia in a population based sample of adult men that includes significant ethnic or racial diversity.4,9 –13 Some population based studies of nocturia are specific to regional variations among different ethnic or racial groups,10 –13 but few are representative of the racial, ethnic
0022-5347/11/1853-0998/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 185, 998-1002, March 2011 Printed in U.S.A. DOI:10.1016/j.juro.2010.10.083
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RESEARCH, INC.
PREVALENCE OF NOCTURIA IN UNITED STATES MEN
and economic diversity in a nationally representative United States sample.4,9 Since 1999 the selection of participants for the NHANES has attempted to mirror the diverse population composition of the United States to provide reliable statistical estimates. It is important to compare these prevalence estimates with those of other populations worldwide and to identify risk factors that may warrant further investigation. Included in the NHANES 2005–2006 and 2007–2008 was a question that assessed the frequency of nocturia. Given the dearth of population based epidemiological data on nocturia among men in the United States, the goal of our analysis was to provide prevalence estimates and to identify independent risk factors for nocturia in men using data from this 4-year period.
METHODS NHANES 2005–2006 and 2007–2008 The NHANES program consists of cross-sectional health surveys conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention (http://www.cdc.gov/nchs/nhanes.htm). The NHANES provides estimates of the health status of the United States population by selecting a nationally representative sample of the noninstitutionalized population using a complex, stratified, multistage, probability cluster design. The NHANES 2005–2006 oversampled persons 60 years old or older, and black, Mexican American and low income white individuals to provide more reliable estimates for these groups. In the NHANES 2007–2008 all Hispanic groups were oversampled, not just Mexican Americans. The National Centers for Health Statistics Ethics Review Board approved the protocol and all participants provided written informed consent.
Procedures Participants were interviewed in their homes, and then underwent standardized physical examination including measurement of height, weight and abdominal girth, and a private interview at a mobile examination center. The interview included questions about symptoms of nocturia for all participants 20 years old or older. Men 40 years old or older were also asked questions related to prostate conditions during this private interview. To define nocturia we used the question, “During the past 30 days, how many times per night did you most typically get up to urinate, from the time you went to bed at night until the time you got up in the morning?” Response options included choices ranging from 0 to 4, or 5 or more. Nocturia was also categorized as 0, 1, 2 or 3 or more times per night, consistent with the International Continence Society definition of nocturia (1 or more times a night)1 and similar in wording to the validated nocturia question from the AUA symptom index.14 For prostate conditions the question “Have you ever been told by a doctor or health professional that you had an enlarged prostate gland?” defined BPE. The question “Have you ever been told by a doctor or health professional that you had prostate cancer?” identified those men who had prostate cancer.
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In interviews conducted in the household, participants self-reported race/ethnicity, which was then categorized as nonHispanic white, nonHispanic black, Hispanic (including Mexican American) and other/mixed race/ethnicity. Given the literature on nocturia and racial/ethnic differences among men,9 –13 nonHispanic black men were analyzed separately from all other racial/ethnic groups. Age was categorized in 15-year increments from ages 20 to 34 years and 10-year increments over the age of 35 years, with all participants 75 years old or older in the same category. Education was categorized as at least some level of high school education (including a General Education Development credential or equivalent) or more than high school. The poverty income ratio (an indicator of socioeconomic status that uses the ratio of income to the family’s poverty threshold set by the United States Census Bureau) was categorized as less than 1 (below the poverty threshold), 1 to 2 (1 to 2 times the poverty threshold) and more than 2 (more than 2 times the poverty threshold). From body measurements data BMI was calculated as weight in kilograms divided by height in meters squared and categorized as less than 25.0 (underweight/normal weight), 25.0 to 29.9 (overweight) and 30.0 or more (obese). Waist circumference was measured and recorded in cm. Waist circumference was then dichotomized as at or above the 75th percentile for the overall NHANES sample (109.7 cm). Data on disease status were ascertained through the question “Has a doctor or other health professional told you that you had [disease]?” In addition to hypertension 5 disease types identified as leading causes of death or morbidity in a prior NHANES analysis were also examined in this study, namely arthritis, cerebrovascular accident, chronic lower respiratory tract disease (self-reported emphysema, chronic bronchitis or asthma), coronary heart disease (coronary disease, angina or myocardial infarction) and diabetes mellitus (taking insulin and/or diabetic pills).15 These disease types were categorized as 0, 1 and 2 or more. Self-described general health status was defined by the question “Would you say that in general your health is excellent, very good, good, fair, or poor?” Responses to this question were aggregated into 2 categories of excellent, very good or good health vs fair or poor health. Depression was assessed in a private interview at the mobile examination centers using the validated Patient Health Questionnaire-9. This questionnaire yields scores from 0 to 27 and scores of 10 or greater are used to define major depression.16
Statistical Analysis The NHANES 2005–2006 and 2007–2008 data for participants 20 years old or older were combined to provide robust sample sizes. All analyses were calculated using STATA® 8.2, which incorporated the design effect, appropriate sample weights, and the stratification and clustering of the complex NHANES sample design.17 The sample weights adjust for unequal probabilities of selection and nonresponse. For this analysis we defined nocturia as occurring 2 or more times per night to capture nocturia that was clinically significant.8 Pearson’s chi-square test was used to assess the association between nocturia outcomes, and demographic and medical characteristics. Estimates with relative standard errors greater than 30% were identified as statistically unreliable. Multivariable logistic regression
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models were constructed using variables from the bivariate analyses that demonstrated statistically significant associations with nocturia (p ⬍0.1). Due to collinearity between BMI and waist circumference, the final multivariable model included waist circumference as a covariate. POR and 95% CIs were reported from the multivariable models with the level of statistical significance set at p ⬍0.05.
RESULTS Of the 7,274 men 20 years old or older in the NHANES 2005–2006 and 2007–2008 samples 5,297 completed the household interview (72.8%). Of these men 5,081 completed physical examinations for a response rate of 69.8%. Of these 5,081 men 638 were missing data on the nocturia question. Men who were missing nocturia data were not significantly different on age (p ⫽ 0.27) or survey cycle (p ⫽ 0.70), but were more likely to be nonHispanic black (13.6% vs 10.8%, p ⫽ 0.03) and less likely to have a high school education (9.8% vs 12.4%, p ⫽ 0.03). After eliminating these 638 cases our final analytic data set was comprised of 4,659 men. A total of 3,098 men were 40 years old or older and answered prostate condition questions. Overall 21.1% of the sample (95% CI 19.3, 23.0) experienced nocturia occurring 2 or more times at night and 7.8% (95% CI 6.7, 9.0) of these men had nocturia 3 or more times a night. A third of the sample (33.1%; 95% CI 30.6, 35.7) had nocturia 1 time per night. Based on age adjusted United States population counts from the NHANES, this represents more than 38 million men with nocturia occurring 2 or more times nightly. The prevalence of nocturia occurring 2 or more times nightly increased from 8.2% (95% CI 6.6, 10.2) in men 20 to 34 years old, to 55.8% (95% CI 51.3, 60.2) in those 75 years old or older. The figure depicts the linear progression in the prevalence of nocturia with age (p ⬍0.001). Factors significantly associated with nocturia in all men in the multivariable analysis (4,163) were a
Prevalence of nocturia occurring 1, 2, or 3 or more times per night among United States men, National Health and Nutrition Examination Survey, 2005–2006 and 2007–2008.
10-year age increment (POR 1.5; 95% CI 1.5, 1.6), nonHispanic black race/ethnicity (POR 2.0; 95% CI 1.6, 2.7), poor/fair self-rated health (POR 1.5; 95% CI 1.2, 1.9), major depression (POR 2.5; 95% CI 1.5, 3.9), hypertension (POR 1.4; 95% CI 1.0, 1.9) and arthritis (POR 1.3; 95% CI 1.0, 1.7). Men with more than a high school education and a better income status were less likely to report nocturia. Among men 40 years old or older (2,689) who were asked about prostate conditions, significant associated factors for nocturia also included the presence of BPE (POR 1.4; 95% CI 1.1, 1.8) and having prostate cancer (POR 1.6; 95% CI 1.0, 2.4). Education was no longer a significant factor when BPE and prostate cancer were included in the multivariable model. Having a self-reported history of stroke, cardiovascular disease, diabetes, chronic lung disease and a waist circumference at or above the 75th percentile were statistically significant factors for nocturia in the bivariate analysis, but were not significant in multivariable analyses.
DISCUSSION This analysis presents nationally representative, population based prevalence estimates and risk factors for nocturia in men 20 years old or older in the United States. The data indicate that nocturia occurring 2 or more times nightly is present in 1 of every 5 men. Other population based studies of nocturia in men concluded that between 10.3% and 25.2% of men have nocturia 2 or more times per night.4,9 –11 This variability in reported prevalence may be influenced by the age and ethnic diversity of the sampled population or the specificity of the question used to assess for the presence of nocturia. Our study, using 2 cycles of NHANES data, is unique in its use of a previously validated question to assess nocturia frequency that is common to those used in clinical practice, and in its use of a sample population of men that has geographic and economic diversity, and includes representative percentages of ethnic minorities in the United States. By 2050 more than a sixth of men in the United States will be 65 years old or older. Our results for older men reveal that more than half experience a frequency of nightly nocturia that is likely to be clinically significant. Consistent with other studies of nocturia in men and women, age was a significant independent risk factor even after adjustment for chronic diseases and multimorbidity associated with advancing age.9,13,18 Because nocturia may be a risk factor for other significant comorbid conditions (poor sleep, falls, depression), it is important to assess for the presence of frequent nocturia, particularly in older men. We found that nonHispanic black race/ethnicity was associated with nocturia on multivariable analysis, which is consistent with results from other
PREVALENCE OF NOCTURIA IN UNITED STATES MEN
epidemiological studies of nocturia that have included representative percentages of minorities.9,13 While socioeconomic factors could explain some of these differences, the increased risk among nonHispanic black men persisted after controlling for measures of education and income, as found in another study.19 The presence or absence of certain comorbid diseases was controlled for in the multivariable analysis. However, there may be other unmeasured conditions that could impact this difference such as the presence of obstructive sleep apnea. In addition, the severity of included conditions, particularly hypertension and diabetes, could affect the development of nocturia, and was not assessed in this analysis. Nocturia may result from conditions which lead to small volume voids (such as overactive bladder, BPE, urinary tract infections or inflammatory bladder conditions), excessive nighttime urine output (such as congestive heart failure, poorly controlled diabetes mellitus, nocturnal polyuria from loss of diurnal rhythm of arginine vasopressin, partial central vasopressin deficiency or peripheral edema) and/or sleep disorders (such as obstructive sleep apnea or periodic limb movement disorder). Furthermore, multiple causes for nocturia may coexist in an individual and further research is needed on all potential causes.2 Consistent with the pathophysiological basis for nocturia, we found that hypertension was associated with nocturia in the entire NHANES population of men. When controlling for waist circumference or BMI, diabetes was not associated with nocturia. The association with arthritis has not been reported consistently in previous studies of nocturia, although arthritis has been associated with increased severity of LUTS20 and incontinence.21 Among men 40 years old or older, self-report of BPE was associated with nocturia. It is interesting to note that we found an association of nocturia with a prior history of prostate cancer. Treatments for prostate cancer, such as prostatectomy and radiation, may increase LUTS in men. It is unclear if prostate cancer treatments increase nocturia specifically, or other symptoms such as urgency and frequency. The NHANES data did not contain sufficient numbers of men with prostate cancer to evaluate individual prostate cancer treatments, which definitely vary in impact on LUTS.
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Other studies have revealed that depression as well as poor self-rated health are independent risk factors for other LUTS in women and in men.4,6 Poor self-rated health is often a marker for mortality in older adults.22 Although causal associations between nocturia and poor self-rated health are not known, poor self-rated health and nocturia have been linked to mortality.12,22 Nocturia may lead to poor sleep and could be linked with depression. However, depression may also interfere with sleep quality and contribute to increased nocturia.23 Our study has some limitations. While the presence of nocturia was assessed using a validated question, the response depended upon self-report and did not include information that might be gained from a patient completed frequency volume chart that would allow insight into the etiology of nocturia.2 Using a definition of clinically significant nocturia occurring 2 or more times nightly we can directly compare population based prevalence estimates of nocturia in men in the United States to those of men in other countries. However, using a conservative definition may underestimate the prevalence of nocturia given the equal proportion of men with mild nocturia compared to those with more frequent nocturia. The variable BPE has several potential limitations including physician impression of symptoms, results of digital rectal examination (recognized to be of limited reliability and validity) or a patient’s own impression. As with most prevalence studies the NHANES sampled only the noninstitutionalized population. Lastly these cross-sectional data do not allow for the assessment of causality.
CONCLUSIONS Frequent nocturia affects a substantial proportion of men in the United States and prevalence increases with age. Risk factors associated with nocturia include advanced age, nonHispanic black race/ethnicity, major depression, fair/poor self-rated health, hypertension, and (among men 40 years old or older) BPE and prostate cancer. Identification of men who may have an increased risk of nocturia and providing treatment has important implications for improvement in quality of life.
REFERENCES 1. Van Kerrebroeck P, Abrams P, Chaikin D et al: The standardization of terminology in nocturia: report from the standardization subcommittee of the International Continence Society. BJU Int 2002; 90: 11. 2. DuBeau CE, Yalla SV and Resnick NM: Implications of the most bothersome prostatism symp-
tom for clinical care and outcomes research. J Am Geriatr Soc 1995; 43: 985. 3. Abrams P, Chapple C, Khoury S et al: Evaluation and treatment of lower urinary tract symptoms in older men. J Urol 2009; 181: 1779.
4. Coyne KS, Zhou Z, Bhattacharyya SK et al: The prevalence of nocturia and its effect on healthrelated quality of life and sleep in a community sample in the USA. BJU Int 2003; 92: 948. 5. Foley DJ, Vitiello MV, Bliwise DL et al: Frequent napping is associated with excessive daytime
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sleepiness, depression, pain, and nocturia in older adults: findings from the National Sleep Foundation ‘2003 Sleep in America’ Poll. Am J Geriatr Psychiatry 2007; 15: 344. 6. Kupelian V, Rosen RC, Link CL et al: Association of urological symptoms and chronic illness in men and women: contributions of symptom severity and duration–results from the BACH Survey. J Urol 2009; 181: 694. 7. Parsons JK, Mougey J, Lambert L et al: Lower urinary tract symptoms increase the risk of falls in older men. BJU Int 2009; 104: 63. 8. Tikkinen KA, Johnson TM 2nd, Tammela TL et al: Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol 2010; 57: 488. 9. Fitzgerald MP, Litman HJ, Link CL et al: The association of nocturia with cardiac disease, diabetes, body mass index, age and diuretic use: results from the BACH survey. J Urol 2007; 177: 1385. 10. Tikkinen KA, Tammela TL, Huhtala H et al: Is nocturia equally common among men and women? A population based study in Finland. J Urol 2006; 175: 596. 11. Lee YS, Lee KS, Jung JH et al: Prevalence of overactive bladder, urinary incontinence, and
lower urinary tract symptoms: results of Korean EPIC study. World J Urol 2009; Epub ahead of print. 12. Bing MH, Moller LA, Jennum P et al: Nocturia and associated morbidity in a Danish population of men and women aged 60-80 years. BJU Int 2008; 102: 808. 13. Burgio KL, Johnson TM 2nd, Goode PS et al: Prevalence and correlates of nocturia in community-dwelling older adults. J Am Geriatr Soc 2010; 58: 861. 14. Barry MJ, Fowler FJ Jr, O’Leary MP et al: The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol 1992; 148: 1549. 15. Weiss CO, Boyd CM, Yu Q et al: Patterns of prevalent major chronic disease among older adults in the United States. JAMA 2007; 298: 1160.
Nhanes/SurveyDesign/SampleDesign/intro.htm. Accessed July 7, 2010. 18. Johnson TM 2nd, Sattin RW, Parmelee P et al: Evaluating potentially modifiable risk factors for prevalent and incident nocturia in older adults. J Am Geriatr Soc 2005; 53: 1011. 19. Kupelian V, Link CL, Hall SA et al: JB: Are racial/ethnic disparities in the prevalence of nocturia due to socioeconomic status? Results of the BACH survey. J Urol 2009; 181: 1756. 20. Seim A, Hoyo C, Ostbye T et al: The prevalence and correlates of urinary tract symptoms in Norwegian men: the HUNT study. BJU Int 2005; 96: 88. 21. Tennstedt SL, Link CL, Steers WD et al: Prevalence of and risk factors for urine leakage in a racially and ethnically diverse population of adults: the Boston Area Community Health (BACH) Survey. Am J Epidemiol 2008; 167: 390.
16. Kroenke K, Spitzer RL and Williams JB: The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16: 606.
22. Strawbridge WJ and Wallhagen MI: Self-rated health and mortality over three decades: results from a time-dependent covariate analysis. Res Aging 1999; 21: 402.
17. National Center for Health Statistics, Centers for Disease Control and Prevention: Continuous NHANES Web Tutorial on Sampling Design. Available at http://www.cdc.gov/nchs/tutorials/
23. Hakkinen JT, Shiri R, Koskimaki J et al: Depressive symptoms increase the incidence of nocturia: Tampere Aging Male Urologic Study (TAMUS). J Urol 2008; 179: 1897.
Abbreviations and Acronyms BMI ⫽ body mass index BPE ⫽ benign prostatic enlargement LUTS ⫽ lower urinary tract symptoms NHANES ⫽ National Health and Nutrition Examination Survey POR ⫽ prevalence odds ratio Submitted for publication July 12, 2010. The Department of Veterans Affairs had no role in the collection, analysis and interpretation of the data, or the manuscript preparation, review or approval. Study received National Centers for Health Statistics Ethics Review Board approval. Supplementary material for this article can be obtained at http://www.aging.uab.edu/SubChannel/ Research/genito-urinary.aspx. * Correspondence: VA Medical Center, GRECC/ 11G, 700 19th St. S., Birmingham, Alabama 35233 (telephone: 205-934-3259; FAX: 205-558-7068; e-mail: [email protected]). † Recipient of a Veterans Health Administration Career Development Award (CDA-2). ‡ Recipient of a VA Rehabilitation Research and Development Career Development Award (CDA-1). § Financial interest and/or other relationship with Astellas. 储 Financial interest and/or other relationship with Pfizer and Vantia. ¶ Financial interest and/or other relationship with Pfizer. ** Financial interest and/or other relationship with Pfizer, Astellas and Johnson & Johnson.
See Editorial on page 781.
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Purpose: We estimated the prevalence of nocturia in the United States male population and identified associated factors. Materials and Methods: Data were analyzed for 5,297 men (20 years old or older) who participated in the 2005–2006 and 2007–2008 cycles of the NHANES, a cross-sectional survey of the United States noninstitutionalized population. Getting up 2 or more times at night to urinate was coded as nocturia. Potential factors included age, race/ethnicity, education, waist circumference, self-reported health status, chronic diseases, and prior diagnosis of benign prostatic enlargement and/or prostate cancer (men 40 years old or older). Prevalence and prevalence odds ratios were estimated from a multivariable logistic regression analysis using appropriate sampling weights. Results: The prevalence of nocturia was 21% (weighted 95% CI 19.3–23.0). Nocturia increased in prevalence with age (p ⬍0.001) from 8.2% (CI 6.7–10.2) in men 20 to 34 years old up to 55.8% (CI 51.3– 60.2) in men 75 years old or older. More nonHispanic black men had nocturia (30.2%, CI 26.7–34.1) than other racial/ethnic groups (20.1%, CI 18.1–22.1, p ⬍0.001). Significant factors included 10-year increase in age (POR 1.5, CI 1.5–1.6), nonHispanic black race/ethnicity (POR 2.0, CI 1.6 –2.7), fair/poor self-rated health (POR 1.5, CI 1.2–1.9), major depression (POR 2.5, CI 1.6 –3.9), hypertension (POR 1.4, CI 1.0 –1.9) and arthritis (POR 1.3, CI 1.0 –1.7). Among men 40 years old or older benign prostatic enlargement (POR 1.4, CI 1.1–1.8) and prostate cancer (POR 1.6, CI 1.0 –2.4) were associated with nocturia. Conclusions: After adjusting for age and race norms nocturia was common among United States men. NonHispanic black men had greater odds of nocturia even when controlling for other factors. Key Words: nocturia, male, prevalence, epidemiology, prostatic diseases NOCTURIA (waking at night to void1) is one of the most bothersome LUTS.2,3 In addition, frequent nocturia has been linked to poor self-rated health,4 negative effects on sleep,5 depression6 and falls.7 Recent epidemiological studies of nocturia have suggested that experiencing at least 2 episodes nightly is likely to cause significant bother.8
Few studies have assessed the prevalence of nocturia in a population based sample of adult men that includes significant ethnic or racial diversity.4,9 –13 Some population based studies of nocturia are specific to regional variations among different ethnic or racial groups,10 –13 but few are representative of the racial, ethnic
0022-5347/11/1853-0998/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 185, 998-1002, March 2011 Printed in U.S.A. DOI:10.1016/j.juro.2010.10.083
AND
RESEARCH, INC.
PREVALENCE OF NOCTURIA IN UNITED STATES MEN
and economic diversity in a nationally representative United States sample.4,9 Since 1999 the selection of participants for the NHANES has attempted to mirror the diverse population composition of the United States to provide reliable statistical estimates. It is important to compare these prevalence estimates with those of other populations worldwide and to identify risk factors that may warrant further investigation. Included in the NHANES 2005–2006 and 2007–2008 was a question that assessed the frequency of nocturia. Given the dearth of population based epidemiological data on nocturia among men in the United States, the goal of our analysis was to provide prevalence estimates and to identify independent risk factors for nocturia in men using data from this 4-year period.
METHODS NHANES 2005–2006 and 2007–2008 The NHANES program consists of cross-sectional health surveys conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention (http://www.cdc.gov/nchs/nhanes.htm). The NHANES provides estimates of the health status of the United States population by selecting a nationally representative sample of the noninstitutionalized population using a complex, stratified, multistage, probability cluster design. The NHANES 2005–2006 oversampled persons 60 years old or older, and black, Mexican American and low income white individuals to provide more reliable estimates for these groups. In the NHANES 2007–2008 all Hispanic groups were oversampled, not just Mexican Americans. The National Centers for Health Statistics Ethics Review Board approved the protocol and all participants provided written informed consent.
Procedures Participants were interviewed in their homes, and then underwent standardized physical examination including measurement of height, weight and abdominal girth, and a private interview at a mobile examination center. The interview included questions about symptoms of nocturia for all participants 20 years old or older. Men 40 years old or older were also asked questions related to prostate conditions during this private interview. To define nocturia we used the question, “During the past 30 days, how many times per night did you most typically get up to urinate, from the time you went to bed at night until the time you got up in the morning?” Response options included choices ranging from 0 to 4, or 5 or more. Nocturia was also categorized as 0, 1, 2 or 3 or more times per night, consistent with the International Continence Society definition of nocturia (1 or more times a night)1 and similar in wording to the validated nocturia question from the AUA symptom index.14 For prostate conditions the question “Have you ever been told by a doctor or health professional that you had an enlarged prostate gland?” defined BPE. The question “Have you ever been told by a doctor or health professional that you had prostate cancer?” identified those men who had prostate cancer.
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In interviews conducted in the household, participants self-reported race/ethnicity, which was then categorized as nonHispanic white, nonHispanic black, Hispanic (including Mexican American) and other/mixed race/ethnicity. Given the literature on nocturia and racial/ethnic differences among men,9 –13 nonHispanic black men were analyzed separately from all other racial/ethnic groups. Age was categorized in 15-year increments from ages 20 to 34 years and 10-year increments over the age of 35 years, with all participants 75 years old or older in the same category. Education was categorized as at least some level of high school education (including a General Education Development credential or equivalent) or more than high school. The poverty income ratio (an indicator of socioeconomic status that uses the ratio of income to the family’s poverty threshold set by the United States Census Bureau) was categorized as less than 1 (below the poverty threshold), 1 to 2 (1 to 2 times the poverty threshold) and more than 2 (more than 2 times the poverty threshold). From body measurements data BMI was calculated as weight in kilograms divided by height in meters squared and categorized as less than 25.0 (underweight/normal weight), 25.0 to 29.9 (overweight) and 30.0 or more (obese). Waist circumference was measured and recorded in cm. Waist circumference was then dichotomized as at or above the 75th percentile for the overall NHANES sample (109.7 cm). Data on disease status were ascertained through the question “Has a doctor or other health professional told you that you had [disease]?” In addition to hypertension 5 disease types identified as leading causes of death or morbidity in a prior NHANES analysis were also examined in this study, namely arthritis, cerebrovascular accident, chronic lower respiratory tract disease (self-reported emphysema, chronic bronchitis or asthma), coronary heart disease (coronary disease, angina or myocardial infarction) and diabetes mellitus (taking insulin and/or diabetic pills).15 These disease types were categorized as 0, 1 and 2 or more. Self-described general health status was defined by the question “Would you say that in general your health is excellent, very good, good, fair, or poor?” Responses to this question were aggregated into 2 categories of excellent, very good or good health vs fair or poor health. Depression was assessed in a private interview at the mobile examination centers using the validated Patient Health Questionnaire-9. This questionnaire yields scores from 0 to 27 and scores of 10 or greater are used to define major depression.16
Statistical Analysis The NHANES 2005–2006 and 2007–2008 data for participants 20 years old or older were combined to provide robust sample sizes. All analyses were calculated using STATA® 8.2, which incorporated the design effect, appropriate sample weights, and the stratification and clustering of the complex NHANES sample design.17 The sample weights adjust for unequal probabilities of selection and nonresponse. For this analysis we defined nocturia as occurring 2 or more times per night to capture nocturia that was clinically significant.8 Pearson’s chi-square test was used to assess the association between nocturia outcomes, and demographic and medical characteristics. Estimates with relative standard errors greater than 30% were identified as statistically unreliable. Multivariable logistic regression
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models were constructed using variables from the bivariate analyses that demonstrated statistically significant associations with nocturia (p ⬍0.1). Due to collinearity between BMI and waist circumference, the final multivariable model included waist circumference as a covariate. POR and 95% CIs were reported from the multivariable models with the level of statistical significance set at p ⬍0.05.
RESULTS Of the 7,274 men 20 years old or older in the NHANES 2005–2006 and 2007–2008 samples 5,297 completed the household interview (72.8%). Of these men 5,081 completed physical examinations for a response rate of 69.8%. Of these 5,081 men 638 were missing data on the nocturia question. Men who were missing nocturia data were not significantly different on age (p ⫽ 0.27) or survey cycle (p ⫽ 0.70), but were more likely to be nonHispanic black (13.6% vs 10.8%, p ⫽ 0.03) and less likely to have a high school education (9.8% vs 12.4%, p ⫽ 0.03). After eliminating these 638 cases our final analytic data set was comprised of 4,659 men. A total of 3,098 men were 40 years old or older and answered prostate condition questions. Overall 21.1% of the sample (95% CI 19.3, 23.0) experienced nocturia occurring 2 or more times at night and 7.8% (95% CI 6.7, 9.0) of these men had nocturia 3 or more times a night. A third of the sample (33.1%; 95% CI 30.6, 35.7) had nocturia 1 time per night. Based on age adjusted United States population counts from the NHANES, this represents more than 38 million men with nocturia occurring 2 or more times nightly. The prevalence of nocturia occurring 2 or more times nightly increased from 8.2% (95% CI 6.6, 10.2) in men 20 to 34 years old, to 55.8% (95% CI 51.3, 60.2) in those 75 years old or older. The figure depicts the linear progression in the prevalence of nocturia with age (p ⬍0.001). Factors significantly associated with nocturia in all men in the multivariable analysis (4,163) were a
Prevalence of nocturia occurring 1, 2, or 3 or more times per night among United States men, National Health and Nutrition Examination Survey, 2005–2006 and 2007–2008.
10-year age increment (POR 1.5; 95% CI 1.5, 1.6), nonHispanic black race/ethnicity (POR 2.0; 95% CI 1.6, 2.7), poor/fair self-rated health (POR 1.5; 95% CI 1.2, 1.9), major depression (POR 2.5; 95% CI 1.5, 3.9), hypertension (POR 1.4; 95% CI 1.0, 1.9) and arthritis (POR 1.3; 95% CI 1.0, 1.7). Men with more than a high school education and a better income status were less likely to report nocturia. Among men 40 years old or older (2,689) who were asked about prostate conditions, significant associated factors for nocturia also included the presence of BPE (POR 1.4; 95% CI 1.1, 1.8) and having prostate cancer (POR 1.6; 95% CI 1.0, 2.4). Education was no longer a significant factor when BPE and prostate cancer were included in the multivariable model. Having a self-reported history of stroke, cardiovascular disease, diabetes, chronic lung disease and a waist circumference at or above the 75th percentile were statistically significant factors for nocturia in the bivariate analysis, but were not significant in multivariable analyses.
DISCUSSION This analysis presents nationally representative, population based prevalence estimates and risk factors for nocturia in men 20 years old or older in the United States. The data indicate that nocturia occurring 2 or more times nightly is present in 1 of every 5 men. Other population based studies of nocturia in men concluded that between 10.3% and 25.2% of men have nocturia 2 or more times per night.4,9 –11 This variability in reported prevalence may be influenced by the age and ethnic diversity of the sampled population or the specificity of the question used to assess for the presence of nocturia. Our study, using 2 cycles of NHANES data, is unique in its use of a previously validated question to assess nocturia frequency that is common to those used in clinical practice, and in its use of a sample population of men that has geographic and economic diversity, and includes representative percentages of ethnic minorities in the United States. By 2050 more than a sixth of men in the United States will be 65 years old or older. Our results for older men reveal that more than half experience a frequency of nightly nocturia that is likely to be clinically significant. Consistent with other studies of nocturia in men and women, age was a significant independent risk factor even after adjustment for chronic diseases and multimorbidity associated with advancing age.9,13,18 Because nocturia may be a risk factor for other significant comorbid conditions (poor sleep, falls, depression), it is important to assess for the presence of frequent nocturia, particularly in older men. We found that nonHispanic black race/ethnicity was associated with nocturia on multivariable analysis, which is consistent with results from other
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epidemiological studies of nocturia that have included representative percentages of minorities.9,13 While socioeconomic factors could explain some of these differences, the increased risk among nonHispanic black men persisted after controlling for measures of education and income, as found in another study.19 The presence or absence of certain comorbid diseases was controlled for in the multivariable analysis. However, there may be other unmeasured conditions that could impact this difference such as the presence of obstructive sleep apnea. In addition, the severity of included conditions, particularly hypertension and diabetes, could affect the development of nocturia, and was not assessed in this analysis. Nocturia may result from conditions which lead to small volume voids (such as overactive bladder, BPE, urinary tract infections or inflammatory bladder conditions), excessive nighttime urine output (such as congestive heart failure, poorly controlled diabetes mellitus, nocturnal polyuria from loss of diurnal rhythm of arginine vasopressin, partial central vasopressin deficiency or peripheral edema) and/or sleep disorders (such as obstructive sleep apnea or periodic limb movement disorder). Furthermore, multiple causes for nocturia may coexist in an individual and further research is needed on all potential causes.2 Consistent with the pathophysiological basis for nocturia, we found that hypertension was associated with nocturia in the entire NHANES population of men. When controlling for waist circumference or BMI, diabetes was not associated with nocturia. The association with arthritis has not been reported consistently in previous studies of nocturia, although arthritis has been associated with increased severity of LUTS20 and incontinence.21 Among men 40 years old or older, self-report of BPE was associated with nocturia. It is interesting to note that we found an association of nocturia with a prior history of prostate cancer. Treatments for prostate cancer, such as prostatectomy and radiation, may increase LUTS in men. It is unclear if prostate cancer treatments increase nocturia specifically, or other symptoms such as urgency and frequency. The NHANES data did not contain sufficient numbers of men with prostate cancer to evaluate individual prostate cancer treatments, which definitely vary in impact on LUTS.
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Other studies have revealed that depression as well as poor self-rated health are independent risk factors for other LUTS in women and in men.4,6 Poor self-rated health is often a marker for mortality in older adults.22 Although causal associations between nocturia and poor self-rated health are not known, poor self-rated health and nocturia have been linked to mortality.12,22 Nocturia may lead to poor sleep and could be linked with depression. However, depression may also interfere with sleep quality and contribute to increased nocturia.23 Our study has some limitations. While the presence of nocturia was assessed using a validated question, the response depended upon self-report and did not include information that might be gained from a patient completed frequency volume chart that would allow insight into the etiology of nocturia.2 Using a definition of clinically significant nocturia occurring 2 or more times nightly we can directly compare population based prevalence estimates of nocturia in men in the United States to those of men in other countries. However, using a conservative definition may underestimate the prevalence of nocturia given the equal proportion of men with mild nocturia compared to those with more frequent nocturia. The variable BPE has several potential limitations including physician impression of symptoms, results of digital rectal examination (recognized to be of limited reliability and validity) or a patient’s own impression. As with most prevalence studies the NHANES sampled only the noninstitutionalized population. Lastly these cross-sectional data do not allow for the assessment of causality.
CONCLUSIONS Frequent nocturia affects a substantial proportion of men in the United States and prevalence increases with age. Risk factors associated with nocturia include advanced age, nonHispanic black race/ethnicity, major depression, fair/poor self-rated health, hypertension, and (among men 40 years old or older) BPE and prostate cancer. Identification of men who may have an increased risk of nocturia and providing treatment has important implications for improvement in quality of life.
REFERENCES 1. Van Kerrebroeck P, Abrams P, Chaikin D et al: The standardization of terminology in nocturia: report from the standardization subcommittee of the International Continence Society. BJU Int 2002; 90: 11. 2. DuBeau CE, Yalla SV and Resnick NM: Implications of the most bothersome prostatism symp-
tom for clinical care and outcomes research. J Am Geriatr Soc 1995; 43: 985. 3. Abrams P, Chapple C, Khoury S et al: Evaluation and treatment of lower urinary tract symptoms in older men. J Urol 2009; 181: 1779.
4. Coyne KS, Zhou Z, Bhattacharyya SK et al: The prevalence of nocturia and its effect on healthrelated quality of life and sleep in a community sample in the USA. BJU Int 2003; 92: 948. 5. Foley DJ, Vitiello MV, Bliwise DL et al: Frequent napping is associated with excessive daytime
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sleepiness, depression, pain, and nocturia in older adults: findings from the National Sleep Foundation ‘2003 Sleep in America’ Poll. Am J Geriatr Psychiatry 2007; 15: 344. 6. Kupelian V, Rosen RC, Link CL et al: Association of urological symptoms and chronic illness in men and women: contributions of symptom severity and duration–results from the BACH Survey. J Urol 2009; 181: 694. 7. Parsons JK, Mougey J, Lambert L et al: Lower urinary tract symptoms increase the risk of falls in older men. BJU Int 2009; 104: 63. 8. Tikkinen KA, Johnson TM 2nd, Tammela TL et al: Nocturia frequency, bother, and quality of life: how often is too often? A population-based study in Finland. Eur Urol 2010; 57: 488. 9. Fitzgerald MP, Litman HJ, Link CL et al: The association of nocturia with cardiac disease, diabetes, body mass index, age and diuretic use: results from the BACH survey. J Urol 2007; 177: 1385. 10. Tikkinen KA, Tammela TL, Huhtala H et al: Is nocturia equally common among men and women? A population based study in Finland. J Urol 2006; 175: 596. 11. Lee YS, Lee KS, Jung JH et al: Prevalence of overactive bladder, urinary incontinence, and
lower urinary tract symptoms: results of Korean EPIC study. World J Urol 2009; Epub ahead of print. 12. Bing MH, Moller LA, Jennum P et al: Nocturia and associated morbidity in a Danish population of men and women aged 60-80 years. BJU Int 2008; 102: 808. 13. Burgio KL, Johnson TM 2nd, Goode PS et al: Prevalence and correlates of nocturia in community-dwelling older adults. J Am Geriatr Soc 2010; 58: 861. 14. Barry MJ, Fowler FJ Jr, O’Leary MP et al: The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. J Urol 1992; 148: 1549. 15. Weiss CO, Boyd CM, Yu Q et al: Patterns of prevalent major chronic disease among older adults in the United States. JAMA 2007; 298: 1160.
Nhanes/SurveyDesign/SampleDesign/intro.htm. Accessed July 7, 2010. 18. Johnson TM 2nd, Sattin RW, Parmelee P et al: Evaluating potentially modifiable risk factors for prevalent and incident nocturia in older adults. J Am Geriatr Soc 2005; 53: 1011. 19. Kupelian V, Link CL, Hall SA et al: JB: Are racial/ethnic disparities in the prevalence of nocturia due to socioeconomic status? Results of the BACH survey. J Urol 2009; 181: 1756. 20. Seim A, Hoyo C, Ostbye T et al: The prevalence and correlates of urinary tract symptoms in Norwegian men: the HUNT study. BJU Int 2005; 96: 88. 21. Tennstedt SL, Link CL, Steers WD et al: Prevalence of and risk factors for urine leakage in a racially and ethnically diverse population of adults: the Boston Area Community Health (BACH) Survey. Am J Epidemiol 2008; 167: 390.
16. Kroenke K, Spitzer RL and Williams JB: The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16: 606.
22. Strawbridge WJ and Wallhagen MI: Self-rated health and mortality over three decades: results from a time-dependent covariate analysis. Res Aging 1999; 21: 402.
17. National Center for Health Statistics, Centers for Disease Control and Prevention: Continuous NHANES Web Tutorial on Sampling Design. Available at http://www.cdc.gov/nchs/tutorials/
23. Hakkinen JT, Shiri R, Koskimaki J et al: Depressive symptoms increase the incidence of nocturia: Tampere Aging Male Urologic Study (TAMUS). J Urol 2008; 179: 1897.