- Email: [email protected]
Urgency Is an Independent Factor for Sleep Disturbance in Men with Obstructive Sleep Apnea
Prostatic Diseases and Male Voiding Dysfunction Urgency Is an Independent Factor for Sleep Disturbance in Men with Obstructive Sleep Apnea Akira Tsujimura, Tetsuya Takao, Yasushi Miyagawa, Keisuke Yamamoto, Shinichiro Fukuhara, Jiro Nakayama, Hiroshi Kiuchi, Nakamori Suganuma, Tadashi Nakamura, Takayuki Kumano-go, Yoshiro Sugita, Norio Nonomura, and Akihiko Okuyama OBJECTIVES
METHODS
RESULTS
CONCLUSIONS
The relationship between overactive bladder (OAB) symptoms, other than nocturia, and sleep, has not been fully evaluated, although a close relationship between nocturia and sleep disturbance has been reported. In the present study, we evaluated the relationship between OAB symptoms and several polysomnography (PSG) parameters in middle-age men with sleep disturbance, especially to clarify whether urgency as the hallmark symptom of an OAB is independently associated with sleep quality. A total of 32 men ⬎40 years of age (mean age 58.0 ⫾ 12.6), who had been diagnosed with obstructive sleep apnea syndrome by PSG, were included in the present study. Their OAB symptoms were evaluated using the OAB symptom score (OABSS) before PSG. The relationship between the OABSS and several parameters, such as sleeping time, sleeping efficiency, sleep latency, percentage of rapid eye movement during sleeping time, and apnea/hypopnea index obtained from PSG, was evaluated. Multivariate analysis showed that only sleeping efficiency was an influencing factor on the total OABSS. Of the 4 subscores of OABSS, including frequency, nocturia, urgency, and urgency incontinence, multivariate analysis showed that the subscores of nocturia and urgency were independent influencing factors on sleeping efficiency. Nocturia correlated negatively with sleeping efficiency (Pearson’s correlation 0.533, P ⬍.01), and urgency also correlated negatively with sleeping efficiency (Pearson’s correlation 0.492, P ⬍.01). We found that urgency and nocturia were factors that independently affected sleep or were affected by sleep quality, although only the association of nocturia with sleep disturbance has been the focus of previous studies. UROLOGY 76: 967–970, 2010. © 2010 Elsevier Inc.
O
veractive bladder (OAB) is defined as a symptom syndrome characterized by urgency, with or without urgency incontinence, and usually characterized by frequency and nocturia in the absence of confirmed infection or other obvious pathologic features.1 OAB is a common, bothersome condition that compromises the quality of life of those affected.2 In an epidemiologic survey in Japan that included a modified King’s Health Questionnaire, the quality of life of sleep and vitality were compromised in 37% of the respondents with OAB symptoms.3 Many studies have shown that From the Departments of Urology, Psychiatry, and Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan Reprint requests: Akira Tsujimura, M.D., Ph.D., Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: [email protected] Submitted: November 26, 2009, received (with revisions): January 27, 2010
© 2010 Elsevier Inc. All Rights Reserved
nocturia, which has been considered among OAB symptoms, is associated with sleep disturbances such as obstructive sleep apnea syndrome (OSAS). It is easily recognized that frequent waking for several urinations at night would segmentalize the sleep period and affect one’s sleep adversely as a result, although patients with sleep disturbance and nocturia are often uncertain whether the nocturia is the cause of their sleep disturbance or whether the sleep disturbance leads to nocturia. Nocturia has been reported to be the most common (71%), followed by a disturbing light or noise (38%), among the causes for sleep disturbance reported in a study of elderly people.4 The relationship between OAB symptoms and sleep, other than nocturia, has not been fully evaluated. With respect to the evaluation of sleep quality, polysomnography (PSG) during the night is thought to be the 0090-4295/10/$34.00 doi:10.1016/j.urology.2010.01.070
967
most reliable method at present. PSG is a multiparametric test used in the study of sleep and as a diagnostic tool in sleep medicine.5 It is a comprehensive recording of the biophysiologic changes that occur during sleep, and it monitors many body functions, including the brain, eye movements, muscle activity, skeletal muscle activation, and heart rhythm during sleep to diagnose, or rule out, many types of sleep disorders, including OSAS. A few studies have reported the relation between OAB and PSG parameters. In the present study, we evaluated the relationship between the symptom score from a specific questionnaire for OAB and several PSG parameters in middle-age men with sleep disturbance to clarify, in particular, whether urgency, as the hallmark symptom of OAB, is independently associated with sleep quality.
MATERIAL AND METHODS Participants A total of 32 men aged ⱖ40 years (mean age 58.0 ⫾ 12.6 years), who had visited our special clinic for sleep at Osaka University Hospital with complaints of sleep disturbance and were diagnosed with OSAS by PSG, were included in the present study. No patient had taken medication for lower urinary tract symptoms caused by benign prostatic hypertrophy, OAB, or other etiologies. Their OAB symptoms, including urgency, were evaluated using the overactive bladder symptom score (OABSS). This is a single-symptom score derived from 4 questions that express the OAB symptoms collectively and is useful as a brief assessment tool for symptom severity and annoyance,6,7 It assesses frequency, nocturia, urgency, and urgency incontinence.
Table 1. Patient characteristics Characteristic
Value
Patients (n) Age (y) PSG factors SPT (min) SE (%) SL (min) %REM (%) AHI (events/h)
32 58.0 ⫾ 12.6 474.3 ⫾ 114.3 71.7 ⫾ 16.9 54.1 ⫾ 47.5 16.1 ⫾ 6.9 26.3 ⫾ 17.5
SPT, sleeping time; SE, sleep efficiency; SL, sleep latency; %REM, percentage of rapid eye movement during sleeping time; AHI, apnea/hypopnea index.
Table 2. Factors with influence on OABSS on multivariate analysis Factor
Regression Coefficient
t
P Value
0.004 ⫺0.070 ⫺0.002 ⫺0.022 0.036
0.996 ⫺0.069 ⫺0.204 ⫺0.243 1.226
NS ⬍.05 NS NS NS
SPT (min) SE (%) SL (min) %REM (%) AHI (events/h)
OABSS, overactive bladder symptom score; NS, nonsignificant; other abbreviations as in Table 1.
including awake time in bed), sleep latency in minutes, percentage of rapid eye movement during sleeping time, and AHI, were evaluated. PSG scoring was performed by experienced accredited sleep technologists. The patient characteristics regarding PSG are listed in Table 1.
Statistical Analysis Polysomnography All patients underwent full-night PSG at the Sleep Medical Center of the Osaka University Hospital. The overnight recordings were performed with the “lights out” generally at 10 PM and continued for 7-9 hours, using an Alice 5 Diagnostic Sleep System (Respironics, Murrysville, PA). The sleep stage was determined using standardized definitions, and arousals were scored according to American Sleep Disorders Association guidelines. The following variables were monitored: central and occipital electroencephalograms, right and left electro-oculograms, electromyogram, and electrocardiogram. Airflow was monitored using a nasal pressure transducer. Respiratory movements were assessed by thoracic and abdominal inductance plethysmography. Snoring was evaluated with a piezoelectric sensor. Oxygen saturation during sleep was measured continuously using a pulse oximeter. Leg movements were recorded by left and right anterior tibial electromyograms. Apnea was defined as complete airflow cessation for ⱖ10 seconds, with oxygen desaturation of ⱖ3% and/or associated with arousal. Hypopnea was defined as a reduction in the amplitude of airflow or thoracoabdominal wall movement ⬎50% of the baseline measurement for ⬎10 seconds with accompanying oxygen desaturation of ⱖ3% and/or associated with arousal. The apnea/ hypopnea index (AHI) was calculated as the total number of apnea and hypopnea episodes per hour of sleep. OSAS was defined as an AHI with a frequency of ⬎5 events/h. The 5 parameters, including sleeping time in minutes, sleeping efficiency (the proportion of sleeping time to total sleeping time, 968
The factors influencing the total OABSS were investigated using the 5 PSG parameters by multivariate analysis. After detection of the factors with an influence on the total OABSS, these were investigated further by multivariate analysis to determine which of the OABSS subscores, such as frequency, nocturia, urgency, and urgency incontinence, affected a specific factor. Pearson’s correlation coefficient was also investigated in the relationship between the subscores of OABSS and the PSG parameter, when the relationship was shown to be significant on multivariate analysis. P ⬍.05 was considered statistically significant.
RESULTS The multivariate analysis showed that only sleeping efficiency was an influencing factor on the total OABSS (Table 2). This close relationship between sleeping efficiency and total OABSS is shown in Figure 1 (Pearson’s correlation 0.595; P ⬍.01). Of the 4 subscores of the OABSS, the multivariate analysis showed that the subscores of nocturia and urgency were independent influencing factors on sleeping efficiency (Table 3). Nocturia correlated negatively with sleeping efficiency (Pearson’s correlation 0.533, P ⬍.01; Fig. 2A). Urgency also correlated negatively with sleeping efficiency (Pearson’s correlation 0.492, P ⬍.01; Fig. 2B). UROLOGY 76 (4), 2010
Figure 1. Relationship between OABSS and sleep efficiency. Table 3. Factors with influence on sleep efficiency on multivariate analysis Variable Frequency Nocturia Urgency Urgency incontinence
Regression Coefficient
t
P Value
⫺5.919 ⫺7.031 ⫺7.137 8.541
⫺1.005 ⫺2.514 ⫺2.177 1.042
NS ⬍.05 ⬍.05 NS
NS, not significant.
Figure 2. Relationship between (A) nocturia and (B) urgency and sleep efficiency.
COMMENT Sleep disturbances increase with age and lead to daytime fatigue, a decreased ability to concentrate, impaired memory, and physical and mental disorders such as depression. Thus, good quality sleep is important for elderly people with UROLOGY 76 (4), 2010
respect to their quality of life. Nocturia might be one of the contributors to sleep disturbance owing to the segmentalized sleep it causes. Conversely, sleep disturbance could be one of the causes of nocturia, because the duration of sleep has been independently related to the number of nocturia episodes and nocturnal urine volume and the nighttime maximal voided volume.8 Several studies have been conducted with PSG, in which the AHI associated positively with nocturia in middle-age9 and elderly10 patients with OSAS. Nocturnal urination of ⬎3 episodes nightly has been reported to a significantly greater degree by patients with severe OSAS diagnosed using the AHI.11-13 With respect to the relationship between OAB and OSAS, the overall prevalence of OAB in male patients with OSAS has been recorded at 39%,14 much greater than the prevalence of 14% identified by an epidemiologic survey in Japan.3 It was also shown that the OABSS was significantly greater in the severe and moderate OSAS group than in the mild OSAS group.14 Another study in women alone showed that OSAS was present in 13 (81%) of 16 women with OAB compared with 4 (40%) of 10 normal women.15 However, the relationship between OAB symptoms, including urgency and sleep quality, on multivariate analysis has not been previously investigated in patients with OSAS. OAB has received increased attention among the aged population because the prevalence rates increase with age. For the diagnosis of OAB, urgency is essential according to the definition of the International Continence Society1 and is thought to be central in driving all other OAB symptoms, including frequency, nocturia, and urgency incontinence. It is also well known that urgency has a significant negative effect on health-related quality of life.16,17 In the present study, we found on multivariate analysis that urgency and nocturia are associated with sleeping efficiency (Table 3). We also found that the subscore of urgency in the OABSS correlated negatively with sleeping efficiency (Fig. 2B) similar to nocturia (Fig. 2A). It has been reported that more than one half of the OAB population experience urgency combined with ⱖ3 other lower urinary tract symptoms and that the most prevalent combination of OAB symptoms was urgency and nocturia in a large-scale study.18 However, the possibility that a significant difference in the relationship between urgency and sleeping efficiency is caused by a significant difference in the relationship between nocturia and sleeping efficiency has been disproved by our multivariate analysis. A previous study demonstrated similar results, with patients with severe OSAS complaining significantly more often about urgency compared with those with mild OSAS.14 Thus, we suggest that urgency is a factor that independently affects or is affected by sleep quality. The link between sleep and OAB symptoms is still obscure. Sleep disturbances such as OSAS have been demonstrated to cause erectile dysfunction,19,20 possibly by way of occult nerve dysfunction induced by hypoxia.21 969
Thus, in a mechanism similar to that of erectile dysfunction, the accommodation disturbance of the afferent nerve for urinary sensation might link urgency and sleep disturbances. The other possibility is that problems with central nervous system regulation of sleep and voiding might influence sleep quality and OAB. The hypothalamus, which sends afferent signals directly to the pontine micturition center,22 is usually associated with regulating sleep and arousal.23 Thus, continuous activation of the hypothalamus, which might induce urgency, might fail in its regulation of sleep and arousal. Additional studies are needed to elucidate the mechanism by which sleep disturbances can affect OAB, especially urgency. It was recently reported that patients with sleep disturbances and nocturia who were treated for sleep disturbance using continuous positive airway pressure therapy24,25 or medications such as naproxen and oxazepam26 demonstrated a significant decrease in the frequency of nocturnal urination. No doubt seems to exist that treatment of sleep disturbances can improve nocturia; however, it is still unclear whether such treatment can improve urgency. In contrast, it is logical to treat OAB symptoms such as urgency with anticholinergic medication. Controlled trials have shown that tolterodine27 and solifenacin28 reduced nocturnal urination in patients with OAB. To clarify this effect, we plan to study patients’ sleep quality before and after solifenacin treatment of OAB.
CONCLUSIONS Several factors evaluated by PSG were analyzed for their relationship with OAB symptoms. We found that urgency and nocturia are factors that independently affect, or are affected by, sleep quality, although only the association of nocturia with sleep disturbances has been the focus of previous studies. Because the relationship between sleep disturbances and OAB symptoms is complicated, additional studies are needed to elucidate the possibility that treatment such as anticholinergic medication can improve sleep disturbance and OAB. References 1. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-Committee of the International Continence Society. Neurourol Urodyn. 2002;21:167-178. 2. Abrams P, Kelleher CJ, Kerr LA, et al. Overactive bladder significantly affects quality of life. Am J Manag Care. 2000;6:S580-S590. 3. Homma Y, Yamaguchi O, Hayashi K. An epidemiological survey of overactive bladder symptoms in Japan. BJU Int. 2005;96:1314-1318. 4. Gentili A, Weiner DK, Kuchibhatil M, et al. Factors that disturb sleep in nursing home residents. Aging. 1997;9:207-213. 5. Vaughn BV, Giallanza P. Technical review of polysomnography. Chest. 2008;134:1310-1319. 6. Homma Y, Gotoh M. Symptom severity and patient perceptions in overactive bladder: how are they related? BJU Int. Epub 2009 March 10.
970
7. Homma Y, Yoshida M, Seki N, et al. Symptom assessment tool for overactive bladder syndrome— overactive bladder symptom score. Urology. 2006;68:318-323. 8. Udo Y, Nakao M, Honjo H, et al. Sleep duration is an independent factor in nocturia: analysis of bladder diaries. BJU Int. 2009;104: 75-79. 9. Hajduk IA, Strollo PJ Jr, Jasani RR, et al. Prevalence and predictors of nocturia in obstructive sleep apnea-hypopnea syndrome—a retrospective study. Sleep. 2003;26:61-64. 10. Umlauf MG, Chasens ER. Sleep disordered breathing and nocturnal polyuria: nocturia and enuresis. Sleep Med Rev. 2003;7:403-411. 11. Guilleminault C, Lin CM, Goncalves MA, et al.A prospective study of nocturia and the quality of life of elderly patients with obstructive sleep apnea or sleep onset insomnia. J Psychosom Res. 2004;56:511-515. 12. Kaynak H, Kaynak D, Oztura I. Does frequency of nocturnal urination reflect the severity of sleep-disordered breathing? J Sleep Res. 2004;13:173-176. 13. Moriyama Y, Miwa K, Tanaka H, et al. Nocturia in men less than 50 years of age may be associated with obstructive sleep apnea syndrome. Urology. 2008;71:1096-1098. 14. Kemmer H, Mathes AM, Dilk O, et al. Obstructive sleep apnea syndrome is associated with overactive bladder and urgency incontinence in men. Sleep. 2009;32:271-275. 15. Lowenstein L, Kenton K, Brubaker L, et al. The relationship between obstructive sleep apnea, nocturia, and daytime overactive bladder syndrome in women. Am J Obstet Gynecol. 2008;198:e591e595. 16. Coyne KS, Payne C, Bhattacharyya SK, et al. The impact of urinary urgency and frequency on health-related quality of life in overactive bladder: results from a national community survey. Value Health. 2004;7:455-463. 17. Tubaro A. Defining overactive bladder: epidemiology and burden of disease. Urology. 2004;64:2-6. 18. Irwin DE, Abrams P, Milsom I, et al. Understanding the elements of overactive bladder: questions raised by the EPIC study. BJU Int. 2008;101:1381-1387. 19. Hirshkowitz M, Karacan I, Arcasoy MO, et al. Prevalence of sleep apnea in men with erectile dysfunction. Urology. 1990;36:232-234. 20. Margel D, Cohen M, Livne PM, et al. Severe, but not mild, obstructive sleep apnea syndrome is associated with erectile dysfunction. Urology. 2004;63:545-549. 21. Fanfulla F, Malaguti S, Montagna T, et al. Erectile dysfunction in men with obstructive sleep apnea: an early sign of nerve involvement. Sleep. 2000;23:775-781. 22. Griffiths D, Tadic SD. Bladder control, urgency, and urge incontinence: evidence from functional brain imaging. Neurourol Urodyn. 2008;27:466-474. 23. Szymusiak R, McGinty D. Hypothalamic regulation of sleep and arousal. Ann NY Acad Sci. 2008;1129:275-286. 24. Fitzgerald MP, Mulligan M, Parthasarathy S. Nocturic frequency is related to severity of obstructive sleep apnea, improves with continuous positive airways treatment. Am J Obstet Gynecol. 2006;194: 1399-1403. 25. Margel D, Shochat T, Getzler O, et al. Continuous positive airway pressure reduces nocturia in patients with obstructive sleep apnea. Urology. 2006;67:974-977. 26. Kaye M. Nocturia: a blinded, randomized, parallel placebo-controlled self-study of the effect of 5 different sedatives and analgesics. Can Urol Assoc J. 2008;2:604-608. 27. Rackley R, Weiss JP, Rovner ES, et al. Nighttime dosing with tolterodine reduces overactive bladder-related nocturnal micturitions in patients with overactive bladder and nocturia. Urology. 2006;67:731-736. 28. Abrams P, Swift S. Solifenacin is effective for the treatment of OAB dry patients: a pooled analysis. Eur Urol. 2005;48:483-487.
UROLOGY 76 (4), 2010
METHODS
RESULTS
CONCLUSIONS
The relationship between overactive bladder (OAB) symptoms, other than nocturia, and sleep, has not been fully evaluated, although a close relationship between nocturia and sleep disturbance has been reported. In the present study, we evaluated the relationship between OAB symptoms and several polysomnography (PSG) parameters in middle-age men with sleep disturbance, especially to clarify whether urgency as the hallmark symptom of an OAB is independently associated with sleep quality. A total of 32 men ⬎40 years of age (mean age 58.0 ⫾ 12.6), who had been diagnosed with obstructive sleep apnea syndrome by PSG, were included in the present study. Their OAB symptoms were evaluated using the OAB symptom score (OABSS) before PSG. The relationship between the OABSS and several parameters, such as sleeping time, sleeping efficiency, sleep latency, percentage of rapid eye movement during sleeping time, and apnea/hypopnea index obtained from PSG, was evaluated. Multivariate analysis showed that only sleeping efficiency was an influencing factor on the total OABSS. Of the 4 subscores of OABSS, including frequency, nocturia, urgency, and urgency incontinence, multivariate analysis showed that the subscores of nocturia and urgency were independent influencing factors on sleeping efficiency. Nocturia correlated negatively with sleeping efficiency (Pearson’s correlation 0.533, P ⬍.01), and urgency also correlated negatively with sleeping efficiency (Pearson’s correlation 0.492, P ⬍.01). We found that urgency and nocturia were factors that independently affected sleep or were affected by sleep quality, although only the association of nocturia with sleep disturbance has been the focus of previous studies. UROLOGY 76: 967–970, 2010. © 2010 Elsevier Inc.
O
veractive bladder (OAB) is defined as a symptom syndrome characterized by urgency, with or without urgency incontinence, and usually characterized by frequency and nocturia in the absence of confirmed infection or other obvious pathologic features.1 OAB is a common, bothersome condition that compromises the quality of life of those affected.2 In an epidemiologic survey in Japan that included a modified King’s Health Questionnaire, the quality of life of sleep and vitality were compromised in 37% of the respondents with OAB symptoms.3 Many studies have shown that From the Departments of Urology, Psychiatry, and Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan Reprint requests: Akira Tsujimura, M.D., Ph.D., Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: [email protected] Submitted: November 26, 2009, received (with revisions): January 27, 2010
© 2010 Elsevier Inc. All Rights Reserved
nocturia, which has been considered among OAB symptoms, is associated with sleep disturbances such as obstructive sleep apnea syndrome (OSAS). It is easily recognized that frequent waking for several urinations at night would segmentalize the sleep period and affect one’s sleep adversely as a result, although patients with sleep disturbance and nocturia are often uncertain whether the nocturia is the cause of their sleep disturbance or whether the sleep disturbance leads to nocturia. Nocturia has been reported to be the most common (71%), followed by a disturbing light or noise (38%), among the causes for sleep disturbance reported in a study of elderly people.4 The relationship between OAB symptoms and sleep, other than nocturia, has not been fully evaluated. With respect to the evaluation of sleep quality, polysomnography (PSG) during the night is thought to be the 0090-4295/10/$34.00 doi:10.1016/j.urology.2010.01.070
967
most reliable method at present. PSG is a multiparametric test used in the study of sleep and as a diagnostic tool in sleep medicine.5 It is a comprehensive recording of the biophysiologic changes that occur during sleep, and it monitors many body functions, including the brain, eye movements, muscle activity, skeletal muscle activation, and heart rhythm during sleep to diagnose, or rule out, many types of sleep disorders, including OSAS. A few studies have reported the relation between OAB and PSG parameters. In the present study, we evaluated the relationship between the symptom score from a specific questionnaire for OAB and several PSG parameters in middle-age men with sleep disturbance to clarify, in particular, whether urgency, as the hallmark symptom of OAB, is independently associated with sleep quality.
MATERIAL AND METHODS Participants A total of 32 men aged ⱖ40 years (mean age 58.0 ⫾ 12.6 years), who had visited our special clinic for sleep at Osaka University Hospital with complaints of sleep disturbance and were diagnosed with OSAS by PSG, were included in the present study. No patient had taken medication for lower urinary tract symptoms caused by benign prostatic hypertrophy, OAB, or other etiologies. Their OAB symptoms, including urgency, were evaluated using the overactive bladder symptom score (OABSS). This is a single-symptom score derived from 4 questions that express the OAB symptoms collectively and is useful as a brief assessment tool for symptom severity and annoyance,6,7 It assesses frequency, nocturia, urgency, and urgency incontinence.
Table 1. Patient characteristics Characteristic
Value
Patients (n) Age (y) PSG factors SPT (min) SE (%) SL (min) %REM (%) AHI (events/h)
32 58.0 ⫾ 12.6 474.3 ⫾ 114.3 71.7 ⫾ 16.9 54.1 ⫾ 47.5 16.1 ⫾ 6.9 26.3 ⫾ 17.5
SPT, sleeping time; SE, sleep efficiency; SL, sleep latency; %REM, percentage of rapid eye movement during sleeping time; AHI, apnea/hypopnea index.
Table 2. Factors with influence on OABSS on multivariate analysis Factor
Regression Coefficient
t
P Value
0.004 ⫺0.070 ⫺0.002 ⫺0.022 0.036
0.996 ⫺0.069 ⫺0.204 ⫺0.243 1.226
NS ⬍.05 NS NS NS
SPT (min) SE (%) SL (min) %REM (%) AHI (events/h)
OABSS, overactive bladder symptom score; NS, nonsignificant; other abbreviations as in Table 1.
including awake time in bed), sleep latency in minutes, percentage of rapid eye movement during sleeping time, and AHI, were evaluated. PSG scoring was performed by experienced accredited sleep technologists. The patient characteristics regarding PSG are listed in Table 1.
Statistical Analysis Polysomnography All patients underwent full-night PSG at the Sleep Medical Center of the Osaka University Hospital. The overnight recordings were performed with the “lights out” generally at 10 PM and continued for 7-9 hours, using an Alice 5 Diagnostic Sleep System (Respironics, Murrysville, PA). The sleep stage was determined using standardized definitions, and arousals were scored according to American Sleep Disorders Association guidelines. The following variables were monitored: central and occipital electroencephalograms, right and left electro-oculograms, electromyogram, and electrocardiogram. Airflow was monitored using a nasal pressure transducer. Respiratory movements were assessed by thoracic and abdominal inductance plethysmography. Snoring was evaluated with a piezoelectric sensor. Oxygen saturation during sleep was measured continuously using a pulse oximeter. Leg movements were recorded by left and right anterior tibial electromyograms. Apnea was defined as complete airflow cessation for ⱖ10 seconds, with oxygen desaturation of ⱖ3% and/or associated with arousal. Hypopnea was defined as a reduction in the amplitude of airflow or thoracoabdominal wall movement ⬎50% of the baseline measurement for ⬎10 seconds with accompanying oxygen desaturation of ⱖ3% and/or associated with arousal. The apnea/ hypopnea index (AHI) was calculated as the total number of apnea and hypopnea episodes per hour of sleep. OSAS was defined as an AHI with a frequency of ⬎5 events/h. The 5 parameters, including sleeping time in minutes, sleeping efficiency (the proportion of sleeping time to total sleeping time, 968
The factors influencing the total OABSS were investigated using the 5 PSG parameters by multivariate analysis. After detection of the factors with an influence on the total OABSS, these were investigated further by multivariate analysis to determine which of the OABSS subscores, such as frequency, nocturia, urgency, and urgency incontinence, affected a specific factor. Pearson’s correlation coefficient was also investigated in the relationship between the subscores of OABSS and the PSG parameter, when the relationship was shown to be significant on multivariate analysis. P ⬍.05 was considered statistically significant.
RESULTS The multivariate analysis showed that only sleeping efficiency was an influencing factor on the total OABSS (Table 2). This close relationship between sleeping efficiency and total OABSS is shown in Figure 1 (Pearson’s correlation 0.595; P ⬍.01). Of the 4 subscores of the OABSS, the multivariate analysis showed that the subscores of nocturia and urgency were independent influencing factors on sleeping efficiency (Table 3). Nocturia correlated negatively with sleeping efficiency (Pearson’s correlation 0.533, P ⬍.01; Fig. 2A). Urgency also correlated negatively with sleeping efficiency (Pearson’s correlation 0.492, P ⬍.01; Fig. 2B). UROLOGY 76 (4), 2010
Figure 1. Relationship between OABSS and sleep efficiency. Table 3. Factors with influence on sleep efficiency on multivariate analysis Variable Frequency Nocturia Urgency Urgency incontinence
Regression Coefficient
t
P Value
⫺5.919 ⫺7.031 ⫺7.137 8.541
⫺1.005 ⫺2.514 ⫺2.177 1.042
NS ⬍.05 ⬍.05 NS
NS, not significant.
Figure 2. Relationship between (A) nocturia and (B) urgency and sleep efficiency.
COMMENT Sleep disturbances increase with age and lead to daytime fatigue, a decreased ability to concentrate, impaired memory, and physical and mental disorders such as depression. Thus, good quality sleep is important for elderly people with UROLOGY 76 (4), 2010
respect to their quality of life. Nocturia might be one of the contributors to sleep disturbance owing to the segmentalized sleep it causes. Conversely, sleep disturbance could be one of the causes of nocturia, because the duration of sleep has been independently related to the number of nocturia episodes and nocturnal urine volume and the nighttime maximal voided volume.8 Several studies have been conducted with PSG, in which the AHI associated positively with nocturia in middle-age9 and elderly10 patients with OSAS. Nocturnal urination of ⬎3 episodes nightly has been reported to a significantly greater degree by patients with severe OSAS diagnosed using the AHI.11-13 With respect to the relationship between OAB and OSAS, the overall prevalence of OAB in male patients with OSAS has been recorded at 39%,14 much greater than the prevalence of 14% identified by an epidemiologic survey in Japan.3 It was also shown that the OABSS was significantly greater in the severe and moderate OSAS group than in the mild OSAS group.14 Another study in women alone showed that OSAS was present in 13 (81%) of 16 women with OAB compared with 4 (40%) of 10 normal women.15 However, the relationship between OAB symptoms, including urgency and sleep quality, on multivariate analysis has not been previously investigated in patients with OSAS. OAB has received increased attention among the aged population because the prevalence rates increase with age. For the diagnosis of OAB, urgency is essential according to the definition of the International Continence Society1 and is thought to be central in driving all other OAB symptoms, including frequency, nocturia, and urgency incontinence. It is also well known that urgency has a significant negative effect on health-related quality of life.16,17 In the present study, we found on multivariate analysis that urgency and nocturia are associated with sleeping efficiency (Table 3). We also found that the subscore of urgency in the OABSS correlated negatively with sleeping efficiency (Fig. 2B) similar to nocturia (Fig. 2A). It has been reported that more than one half of the OAB population experience urgency combined with ⱖ3 other lower urinary tract symptoms and that the most prevalent combination of OAB symptoms was urgency and nocturia in a large-scale study.18 However, the possibility that a significant difference in the relationship between urgency and sleeping efficiency is caused by a significant difference in the relationship between nocturia and sleeping efficiency has been disproved by our multivariate analysis. A previous study demonstrated similar results, with patients with severe OSAS complaining significantly more often about urgency compared with those with mild OSAS.14 Thus, we suggest that urgency is a factor that independently affects or is affected by sleep quality. The link between sleep and OAB symptoms is still obscure. Sleep disturbances such as OSAS have been demonstrated to cause erectile dysfunction,19,20 possibly by way of occult nerve dysfunction induced by hypoxia.21 969
Thus, in a mechanism similar to that of erectile dysfunction, the accommodation disturbance of the afferent nerve for urinary sensation might link urgency and sleep disturbances. The other possibility is that problems with central nervous system regulation of sleep and voiding might influence sleep quality and OAB. The hypothalamus, which sends afferent signals directly to the pontine micturition center,22 is usually associated with regulating sleep and arousal.23 Thus, continuous activation of the hypothalamus, which might induce urgency, might fail in its regulation of sleep and arousal. Additional studies are needed to elucidate the mechanism by which sleep disturbances can affect OAB, especially urgency. It was recently reported that patients with sleep disturbances and nocturia who were treated for sleep disturbance using continuous positive airway pressure therapy24,25 or medications such as naproxen and oxazepam26 demonstrated a significant decrease in the frequency of nocturnal urination. No doubt seems to exist that treatment of sleep disturbances can improve nocturia; however, it is still unclear whether such treatment can improve urgency. In contrast, it is logical to treat OAB symptoms such as urgency with anticholinergic medication. Controlled trials have shown that tolterodine27 and solifenacin28 reduced nocturnal urination in patients with OAB. To clarify this effect, we plan to study patients’ sleep quality before and after solifenacin treatment of OAB.
CONCLUSIONS Several factors evaluated by PSG were analyzed for their relationship with OAB symptoms. We found that urgency and nocturia are factors that independently affect, or are affected by, sleep quality, although only the association of nocturia with sleep disturbances has been the focus of previous studies. Because the relationship between sleep disturbances and OAB symptoms is complicated, additional studies are needed to elucidate the possibility that treatment such as anticholinergic medication can improve sleep disturbance and OAB. References 1. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-Committee of the International Continence Society. Neurourol Urodyn. 2002;21:167-178. 2. Abrams P, Kelleher CJ, Kerr LA, et al. Overactive bladder significantly affects quality of life. Am J Manag Care. 2000;6:S580-S590. 3. Homma Y, Yamaguchi O, Hayashi K. An epidemiological survey of overactive bladder symptoms in Japan. BJU Int. 2005;96:1314-1318. 4. Gentili A, Weiner DK, Kuchibhatil M, et al. Factors that disturb sleep in nursing home residents. Aging. 1997;9:207-213. 5. Vaughn BV, Giallanza P. Technical review of polysomnography. Chest. 2008;134:1310-1319. 6. Homma Y, Gotoh M. Symptom severity and patient perceptions in overactive bladder: how are they related? BJU Int. Epub 2009 March 10.
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7. Homma Y, Yoshida M, Seki N, et al. Symptom assessment tool for overactive bladder syndrome— overactive bladder symptom score. Urology. 2006;68:318-323. 8. Udo Y, Nakao M, Honjo H, et al. Sleep duration is an independent factor in nocturia: analysis of bladder diaries. BJU Int. 2009;104: 75-79. 9. Hajduk IA, Strollo PJ Jr, Jasani RR, et al. Prevalence and predictors of nocturia in obstructive sleep apnea-hypopnea syndrome—a retrospective study. Sleep. 2003;26:61-64. 10. Umlauf MG, Chasens ER. Sleep disordered breathing and nocturnal polyuria: nocturia and enuresis. Sleep Med Rev. 2003;7:403-411. 11. Guilleminault C, Lin CM, Goncalves MA, et al.A prospective study of nocturia and the quality of life of elderly patients with obstructive sleep apnea or sleep onset insomnia. J Psychosom Res. 2004;56:511-515. 12. Kaynak H, Kaynak D, Oztura I. Does frequency of nocturnal urination reflect the severity of sleep-disordered breathing? J Sleep Res. 2004;13:173-176. 13. Moriyama Y, Miwa K, Tanaka H, et al. Nocturia in men less than 50 years of age may be associated with obstructive sleep apnea syndrome. Urology. 2008;71:1096-1098. 14. Kemmer H, Mathes AM, Dilk O, et al. Obstructive sleep apnea syndrome is associated with overactive bladder and urgency incontinence in men. Sleep. 2009;32:271-275. 15. Lowenstein L, Kenton K, Brubaker L, et al. The relationship between obstructive sleep apnea, nocturia, and daytime overactive bladder syndrome in women. Am J Obstet Gynecol. 2008;198:e591e595. 16. Coyne KS, Payne C, Bhattacharyya SK, et al. The impact of urinary urgency and frequency on health-related quality of life in overactive bladder: results from a national community survey. Value Health. 2004;7:455-463. 17. Tubaro A. Defining overactive bladder: epidemiology and burden of disease. Urology. 2004;64:2-6. 18. Irwin DE, Abrams P, Milsom I, et al. Understanding the elements of overactive bladder: questions raised by the EPIC study. BJU Int. 2008;101:1381-1387. 19. Hirshkowitz M, Karacan I, Arcasoy MO, et al. Prevalence of sleep apnea in men with erectile dysfunction. Urology. 1990;36:232-234. 20. Margel D, Cohen M, Livne PM, et al. Severe, but not mild, obstructive sleep apnea syndrome is associated with erectile dysfunction. Urology. 2004;63:545-549. 21. Fanfulla F, Malaguti S, Montagna T, et al. Erectile dysfunction in men with obstructive sleep apnea: an early sign of nerve involvement. Sleep. 2000;23:775-781. 22. Griffiths D, Tadic SD. Bladder control, urgency, and urge incontinence: evidence from functional brain imaging. Neurourol Urodyn. 2008;27:466-474. 23. Szymusiak R, McGinty D. Hypothalamic regulation of sleep and arousal. Ann NY Acad Sci. 2008;1129:275-286. 24. Fitzgerald MP, Mulligan M, Parthasarathy S. Nocturic frequency is related to severity of obstructive sleep apnea, improves with continuous positive airways treatment. Am J Obstet Gynecol. 2006;194: 1399-1403. 25. Margel D, Shochat T, Getzler O, et al. Continuous positive airway pressure reduces nocturia in patients with obstructive sleep apnea. Urology. 2006;67:974-977. 26. Kaye M. Nocturia: a blinded, randomized, parallel placebo-controlled self-study of the effect of 5 different sedatives and analgesics. Can Urol Assoc J. 2008;2:604-608. 27. Rackley R, Weiss JP, Rovner ES, et al. Nighttime dosing with tolterodine reduces overactive bladder-related nocturnal micturitions in patients with overactive bladder and nocturia. Urology. 2006;67:731-736. 28. Abrams P, Swift S. Solifenacin is effective for the treatment of OAB dry patients: a pooled analysis. Eur Urol. 2005;48:483-487.
UROLOGY 76 (4), 2010