Nocturia, or the act to pass urine during the main sleeping period, is a common urological symptom in the elderly population. Today, little is known about nocturia in postmenopausal women. However, due to the lack of endogenous produced estrogen in these women, an increased prevalence of nocturia is expected in this population. 

Equally for the global population, a multifactorial etiology for nocturia in postmenopausal women is expected, as the effect of impaired estrogen production can probably be seen through different mechanisms. Firstly, the depletion of estrogen leads to a higher incidence of nocturnal hot flushes and thus an increased risk of sleep fragmentation. Secondly, lack of estrogen leads to a lower excretion of anti-diuretic hormone (ADH) and thus an impaired nocturnal water reabsorption, resulting in a higher nighttime urine production. Moreover, impaired estrogen production will lead to atrophy of estrogen receptors, which are present in the urethra and bladder trigonum, and will therefore induce a higher incidence of lower urinary tract symptoms (LUTS). Lastly, the incidence of obstructive sleep apnea syndrome (OSAS) is higher in postmenopausal women compared to premenopausal women.

Multiple studies have shown that nocturia has severe consequences on overall health, as nocturia is an independent risk factor for depressive symptoms, a reduced productivity and increases the risk on falls and fractures. Moreover, it has been found that nocturia patients had 23% increase in the risk on all-cause mortality. A further specification of the incidence, origin and impact of nocturia in postmenopausal women, is important as it may guide the professional to an optimal assessment and treatment of nocturia. 

The aim of this study is threefold: to observe the prevalence of nocturia in the Belgian postmenopausal population, to report the bother of nocturia in this population and to define risk factors for developing nocturia as a postmenopausal women.

All patients in this prospective observational trial were recruited when consulting the menopause clinic between March 2015 and June 2019. Exclusion criteria were: thyroid dysfunction, the use of antihypertensive agents, history of psychiatric or neurological disorders and a history of alcohol or drug addiction.

Women were asked to complete the ICI questionnaire on nocturia (ICIQ-N). Nocturia was defined as ≥ 2 nocturnal voids. Bother linked with nocturia was reported on a VAS-scale, with ‘0’ defined as having no bother and ‘10’ as having high bother. Moreover, women were asked to fulfill the ‘Targeting the individual’s Aetiology of Nocturia to Guide Outcomes’ (TANGO) screening tool to observe underlying risk factors (comorbidities, sleep characteristics, LUTS  and self-reported health status) for nocturia. At last, baseline characteristics including age, weight, height and waist circumference, were collected.  

Descriptive statistics are presented as median(s) (interquartile range). Differences in bother between different nocturnal frequencies were assessed using the non-parametric Mann-Whitney U test for continuous variables. Categorical variables of the TANGO were compared between ‘no nocturnal voids’, ‘1 nocturnal void’ and ‘≥ 2 nocturnal voids’  in 2 x 2  assessment using the non-parametric Chi-square test. To identify independent predictors for nocturia, a univariate and multivariate logistic regression analysis with calculation of the adjusted odds ratio was performed. This study was approved by the institution’s ethical board.

This study recruited 191 postmenopausal women with a median age of 52 (47– 56) years. The overall median weight and height was 67 (60 – 74) kg and 165 (162 - 169) cm respectively, which corresponds with a median Body Mass Index of 23.9 (21.4– 27.5) kg/m2. The median waist circumference was 89 (84 – 96) cm. 

Nocturia was reported in 23.6% (45/191) of the post-menopausal women. Twenty-nine percent (55/191) of the women slept through the night without waking up to void. One nocturnal void was seen in 47.6% (91/191) of the postmenopausal women, 18.3% (35/191) reported 2 nocturnal voids and 5.2% (10/191) reported more than two nocturnal voids. Obviously, patients who did not void during the night, reported no bother linked with nocturia. A significant difference (p <0.001) in bother linked with nocturnal voiding was seen between women who had to get up once and women who voided two or more times during the night (1/10 (IQR 0/10 - 5/10) and 5.5/10 (IQR 3/10 – 7/10) respectively). 

No differences among prevalence of comorbidities (intake of diuretics, presence of lower limb edema, orthostatic hypotension or diabetes) were found between women with a different number of nocturnal voids. Moreover, no different responses on the statements: ‘My sleep quality is bad’ and ‘I report my health as bad’ were reported between patients with a different nocturnal frequency. Lastly, although no differences in daytime incontinence and sleep apnea signs were reported between the aforementioned groups, a trend towards a higher prevalence of sleep apnea signs could be visualized in women with a higher nocturnal frequency. Figure 1 shows significant differences in onset and maintain insomnia, awaking in the first 3 hours of the night and daytime urgency compared between women without nocturia; with 1 and with ≥ 2 nocturnal voids. 

Univariate logistic regression showed that waist circumference could be identified as an independent risk factor for developing nocturia (OR 1.04; 95% CI: 1.01 – 1.08). Secondly, a significant association between nocturia and urgency could be observed (OR 3.7; CI: 1.76 – 7.8). Different models of multivariate analyses with potential confounders were tested as shown in table 1.

The prevalence of nocturnal voiding in postmenopausal women is high. Approximately half of women in this cohort had to get up once at night to void, and 23% of this cohort report two or more nighttime voids. Equal to previous literature, getting up twice at night goes along with a significant increase in bother linked with nocturia. 

After analysis of the TANGO screening tool, different underlying causes for nocturia can be suggested. Daytime urgency symptoms increased significantly with each nocturia episode, suggesting an underlying overactive bladder syndrome in patients with a high nocturnal frequency.  Moreover, a non-significant trend towards a higher incidence of sleep apnea signs could be seen in women with two or more nighttime voids. Both of the aforementioned causes can be linked with an impaired secretion of estrogen during menopause. Subsequently, a significant increased risk of insomnia (both onset and maintained) linked with an increase of nighttime frequency is found. This finding seems logical, however it could be that this association is the other way around, as insomnia can induce an early night toilet visit. Lastly, the proportion of women who awakes during the first 3 hours of sleep increases linear with increase in nocturnal frequency. This early nighttime voiding can be due to a high fluid intake in the evening, impaired secretion of ADH resulting in an increased water diuresis overnight or a combination of one of both aforementioned causes in combination with a low bladder capacity. Unfortunately, information about bladder capacity, overnight diuresis and timing of voids was not available. Further research including frequency volume charts, fluid assessment and sleep observation is necessary.

In this cohort of postmenopausal women, the prevalence of nocturia was reported as 23%. A significant increase in bother was seen, linked with nocturnal frequency. Waist circumference and daytime urgency could be determined as potential risk factors for developing nocturia in the postmenopausal population. Different underlying causes of nocturia in the postmenopausal women were suggested, however more research is necessary.