The quality of sleep is greatly impacted by hours of undisturbed sleep (HUS). Waking up during the initial hours of sleep has a profound negative effect because the most restorative part of sleep happens early in the night.(1) Studies have shown that sleep deprivation in humans suppresses the renin-angiotensin-aldosterone system at night, resulting in decreased sodium reabsorption in the kidneys.(2) Additionally, Tyagi et al. reported that antidiuretic hormone and aldosterone peak during sleep, followed by a steady rise in atrial natriuretic peptide during basal conditions and angiotensin II peaks during sleep loss; thus, hormonal regulatory mechanisms for salt-water balance are profoundly affected by sleep and posture in healthy older adults.(3) Considering these reports, the chronotherapy in our study may have reduced the NUV by promoting the renin-angiotensin-aldosterone system. We investigated whether HUS and nocturnal urine volume could be enhanced by regular sleep habits at an appropriate bedtime.

The study adopted an open-label, multicentre, quasi-randomized, crossover design with alternate 4-week intervention and non-intervention periods and a 2-week washout period. Participants were alternately assigned to sequences A (non-intervention period → washout period → intervention period) and B (intervention period → washout period → non-intervention period) in the order of entry.(figure 1) The participants wore an Actiwatch Spectrum® in the first and last week. During the non-intervention period, they went to bed at their usual bedtime. During the intervention period, a personalized bedtime was determined by the data obtained from the Actiwatch in the first week, and participants went to bed at the determined time in the remaining 3 weeks. The participants were asked to follow certain instructions: 1) go to bed within 15 minutes of a specified bedtime as consistently as possible; 2) turn off the TV and any lights; 3) do not operate devices that emit light in bed, such as smartphones; and 4) avoid naps as much as possible. A frequency-volume chart spanning at least 3 days was administered before and after the intervention and non-intervention periods. The Pittsburgh sleep quality index (PSQI), overactive bladder symptom score (OABSS), and international prostate symptom score (IPSS) were assessed before and after both periods.
The outcomes were measured using a two-way repeated-measures analysis of variance, and the treatment, sequence, and period effects were tested. Significance tests were based on two-sided α = 0.05 (two-sided 95% confidence intervals [CIs]). Correlations were tested using Spearman’s rank test. Statistical analyses were performed using SPSS version 28.0 (IBM Corp., Armonk, NY, USA). 
Variations in HUS, nocturnal urinary volume (NUV), and NUV per hour (NUV/h) up to the HUS point were examined.

The changes in NUV were significantly different (4.4 ml vs. -105.6 ml, p=0.041), and the changes in nocturnal bladder capacity were also different but not significant (9.0 ml vs. 20.6 ml, p=0.53). The changes in the mid-wake duration and sleep-onset latency showed almost no differences. The changes in hours of undisturbed sleep (HUS) were 62.8±72.0 mins during the intervention period in contrast to 12.7±58.7 mins during the non-intervention period, which was a significant difference (p=0.008). Furthermore, the changes in NUV/h during HUS were significantly decreased in the interventional period compared with those in the non-interventional period (-28.4 ml/h vs. -0.17 ml/h, p=0.044). The least-square mean change in nocturnal urinary frequency within-participant difference was -0.889 (-1.30 to -0.482) times (p<0.001).In each questionnaire, changes in sleep quality evaluated using the PSQI were significantly different (1.2 vs. -2.4, p = 0.022).(Figure 2)

The chronotherapy in our study may have reduced the NUV, especially in NUV per hour during HUS by promoting the renin-angiotensin-aldosterone system, so prolonged HUS. Because of these changes, nocturia and sleep quality were  improved significantly.

Behavioral therapy with chronotherapy can improve reduce NUV, especially in NUV/h during HUS, and prolong HUS.

Kobelt G, Borgström F, Mattiasson A. Productivity, vitality and utility in a group of healthy professionally active individuals with nocturia. BJU Int. 2003;91(3):190-195.
Kamperis K, Hagstroem S, Radvanska E, Rittig S, Djurhuus JC. Excess diuresis and natriuresis during acute sleep deprivation in healthy adults. American Journal of Physiology-Renal Physiology. 2010;299(2):F404-F411.
Tyagi S, Resnick NM, Clarkson BD, et al. Impact of sleep on chronobiology of micturition among healthy older adults. Am J Physiol Renal Physiol. 2023;325(4):F407-f417.