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Association of obstructive sleep apnea risk factors with nocturnal enuresis in postmenopausal women

Koo P, McCool FD, Hale L, Stone K, Eaton CB

Menopause 2016; 23: 175-82

Commented by Prof. Donald L. Bliwise:
Although sleep apnea is now well-recognized as a risk factor for nocturia (possibly by increasing levels of atrial natriuretic peptide [ANP], whose release may suppress the release of vasopressin), much less is known about the relationship between obstructive sleep apnea (OSA) and enuresis in adults. This study, derived from participants in the observational arm of the Women Health Initiative, a very large (> 161,000) United States epidemiologic study, attempts to address this gap in the literature. Compared to nocturia, vastly less is known about the prevalence and correlates of nocturnal enuresis in adults. Although OSA was not measured physiologically, the study reported that many proxies for it, including higher Body Mass Index, hypertension, reported snoring, worse sleep quality, greater sleep fragmentation and higher levels of daytime sleepiness were related to enuresis, both individually and as a combined measure (an OSA “score”). One notable aspect of the study was that data on nocturnal enuresis were collected in the context of questions regarding both urge incontinence and stress incontinence. In other words, conditions in which women experienced urinary leakage were presented in check list format, which included many different situations. As described in the paper, of women who experienced nocturnal enuresis, 64% also experienced urge incontinence and 56% also experienced stress incontinence, suggesting substantial overlap among these symptoms. However, in sensitivity analyses, the authors reported that elimination of such cases resulted in only small changes in the relative magnitude of the associations between OSA symptoms and nocturnal enuresis.

Although increased urine production accompanying OSA via accompanying ANP release represents a likely mechanism underlying the associations observed here, the pathophysiological substrates for the findings remain uncertain. Other possible explanations remain. OSA is characterized by what has been termed “negative pressure breathing,” in which negative intrathoracic pressure, introduced by diaphragmatic effort against a closed glottis, induces increased sympathetic tone. Indeed, the release of ANP from the myocardium in OSA is often considered to be secondary to such action. However, the multiple effects of such mechanical forces should not be overlooked. For example, one wonders what effect such negative pressures (essentially representing a Muller maneuver) might not have on detrusor activity and subsequently, on urine leakage. In 2004, we reported that among nursing home patients with urinary incontinence, wetness episodes (record with a closed direct current switch placed within a diaper) often occurred nearly simultaneously (i.e., within seconds) with apneic episodes. There is no reason to think that similar mechanisms could not be operating in fully ambulatory women who experience similar effects of negative pressure breathing during sleep, particularly in the context of a full bladder. This is an area that deserves more attention.

Abstract
 

Objective: The prevalence of obstructive sleep apnea (OSA) in women increases significantly after menopause. However, identifying at-risk women is difficult because they tend to underreport symptoms and their complaints may differ from those traditionally associated with OSA. We investigated whether OSA risk factors are associated with the presence of a "nontraditional" complaint, such as nocturnal enuresis, in postmenopausal women. Methods: A cross-sectional study of postmenopausal women aged 50 to 79 years who participated in the Women's Health Initiative Observational Study and clinical trials (1993-2005) at 40 clinical centers in the United States was performed. Multiple variable logistic regression analysis was used to determine the association of OSA risk factors with nocturnal enuresis. Results: A cohort of 2,789 women (1.7%) reported having nocturnal enuresis. Obesity (odds ratio [OR], 2.29; 95% CI, 2.00-2.62), snoring (OR, 2.01; 95% CI, 1.74-2.32), poor sleep quality (OR, 1.70; 95% CI, 1.52-1.91), sleep fragmentation (OR, 2.44; 95% CI, 2.14-2.79), daytime sleepiness (OR, 1.50; 95% CI, 1.33-1.68), and hypertension (OR, 1.13; 95% CI, 1.01-1.26) were associated with nocturnal enuresis. Each additional OSA risk factor in a predefined OSA score significantly increased the odds of having nocturnal enuresis in a dose-response fashion (OR of 1.38, 2.00, 2.80, 3.87, 5.10, and 7.02 for scores of 1-6, respectively) compared with no risk factors. Conclusions: OSA risk factors are associated with nocturnal enuresis in postmenopausal women. Mechanisms relating nocturnal enuresis to OSA may include apnea-associated changes in intrathoracic pressure, leading to increased urine output. Questioning at-risk postmenopausal women presenting with nocturnal enuresis about other OSA risk factors should be considered. © 2015 by The North American Menopause Society.

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