Study design, materials and methods
A multi-centre, cross-sectional study was undertaken, involving data collection from consenting women aged 40 or over who were attending tertiary hospital continence clinics. Women who were pregnant or had end stage renal disease, bladder cancer, previous pelvic radiotherapy, an indwelling catheter or dementia requiring supervision were excluded from the study. Data was collected using a 3-day bladder diary and a study questionnaire capturing hormone status and use of known modifying agents. Clinically relevant nocturia and Nocturnal polyuria (NP) were defined as ≥ two voids and ≥33% of 24 hour urine during the main sleep period respectively (1). Nocturnal bladder capacity index (NBCi) >1.3 was considered reflective of compromised bladder storage (2).
Ethics approval was obtained. Participant data was entered into the statistical database SPPS Version 25. Descriptive statistics were used to describe the study sample overall, and by age and nocturia severity. Frequency of item endorsement on the study questionnaire was evaluated and items checked for association with nocturia severity and clinical parameters from the bladder diary. In order to assess contribution of hormonal status on nocturia parameters a binary logistic regression model was created with n≥ 2 as the dependent variable.
Results
Data sets from 158 women with a mean age of 64.3 (SD 12.1) years were analysed. From bladder diary data 85% of women voided at least once per night; 49% had clinically-relevant nocturia. There was a moderate positive and significant correlation between self-report and bladder diary evidence of nocturia severity (r=0.64, p<0.001). Overall 16% of women were pre or peri menopausal.
Nocturia severity was significantly and positively correlated with night diuresis rate (p<0.001), NUV (p<0.001) and Vitamin D supplementation (p=0.017) but not with hormone depletion symptoms at night, consumption of phytoestrogen foods, oestrogen replacement, prolapse or self-reporting as “overweight”. Reporting ≥150 minutes of physical exercise per week approached a significant association with reduced nocturia severity. There were two independent predictors of nocturia severity, Vitamin D supplementation (OR 2.33, p=0.026) and age (OR 1.04, p=0.038). After adjustment for age the significant association with nocturia ≥ 2 remained (95% CI 1.1-4.9, p=0.03).
Nocturnal urine volume (NUV): Women voiding twice or more per night produced 167.5mL more urine than those with less severe nocturia (p<0.001). NP was observed in 78% of participants with clinically relevant nocturia (p<0.001) and 29% of women who voided less than twice at night (p=0.002). Median NUV was significantly higher in women reporting use of vitamin D than in women not supplementing (635 vs 500mL, p=0.047).
Bladder storage: There was no difference between maximum voided volume day vs night (p=0.398). Overall participants with more severe nocturia demonstrated a significantly higher NBCi than those with mild nocturia (1.25 vs 0.4, p<0.001). NBCi was significantly higher in women reporting daytime flushes and sweating (p=0.004), but lower when respondents either used probiotics (p=0.045) or participated in 150 minutes of physical activity each week (p=0.036).
Hormonal factors: Hormone depletion symptoms during the day or at night were reported by 28% and 30% of women respectively; no association with time since last menses was found. Neither NUV nor NBCi were associated with time since last menstrual period. Table 1 reports the significant relationship between hormone-specific variables endorsed by ≥20% of participants and nocturia severity, bladder-diary derived NUV and bladder capacity.
The logistic regression model for nocturnal polyuria index >33% was significant (chi squared =35.82, p<0.001). There were two independently significant predictors: age increased the odds of having and NPi>33% by 7% (OR 1.07, p<0.001), while exercise was protective (OR 0.22, p=0.001). The logistic regression model for nocturia index > 2.0 was significant (chi squared =30.52, p<0.001). Four predictor variables were identified: : i) Age – OR 1.06, p=0.001) ii) self-report of use of hormone replacement therapy - OR 0.18, p=0.049 iii) 150 minutes of exercise per week – OR 0.29, p=0.002 and iv) flushes or sweating during the day – OR 2.97, p=0.014). While the logistic regression model for nocturnal bladder capacity index (NBCi) was not significant (chi squared = 8.77, p=0.187), women reporting flushes or sweating during the day were 2.8 times more likely to have an NBCi>1.3 (p=0.187).
Interpretation of results
In women > 40 years clinically-relevant nocturia is mixed, driven by both i) increased overnight urine volume and diuresis rate and ii) reduced maximum voided volumes both day and night. Future work to elucidate mechanism of Vitamin D on NUV and to test addition of >150 mins exercise and urogenital oestrogen to current therapy is warranted.