Nocturia, defined as waking to void during the main sleep period, is a highly prevalent and bothersome lower urinary tract symptom (LUTS) associated with impaired sleep and reduced quality of life. Its prevalence increases markedly after menopause, largely driven by nocturnal polyuria (NP) resulting from disrupted circadian regulation of renal sodium and water handling. Estrogen deficiency may impair antidiuretic hormone (ADH) and renin–angiotensin–aldosterone system (RAAS) activity, though evidence remains inconsistent. Systemic hormone therapy (HT) can reduce nocturnal urine output, while exercise improves metabolic health and may influence circadian renal function. However, their combined effect has not been investigated.
This randomized controlled trial (OPERATE - hOrmone replacement Exercise tRaining And posTmenopauzE) aims to compare the effects of combined exercise and systemic hormone therapy (Ex+HT) with Exercise alone (Ex) or HT alone on nocturnal urine production, circadian renal function, LUTS, and sleep quality in postmenopausal women.

This single-center, prospective, randomized trial includes postmenopausal women aged 45–65 years (0–10 years postmenopause) with moderate-to-severe vasomotor symptoms, BMI 20–30 kg/m², and a clinical indication for HT. Participants are randomized (1:1:1) into: (A) Exercise + HT (Ex+HT), (B) Exercise only (Ex), or (C) HT only (HT). Exercise involves 12 weeks of supervised combined resistance–endurance training (3×/week). HT consists of transdermal estrogen replacement (1.53 mg/dose, twice daily). Assessments are conducted at baseline and after 12 weeks.
Primary outcomes include nocturnal urine volume, nocturia episodes, maximal voided volume, ICIQ-FLUTS subscales, and PSQI sleep scores. Circadian renal function is evaluated using separated day–night urine collections and 24 h frequency–volume charts. 
Based on an expected 200 mL difference in nocturnal volume, sample size of 24 participants per group is required. Data were analyzed using the Shapiro–Wilk test for normality, Wilcoxon signed-rank test (within-group) and Kruskal-Wallis test (between-group).

Interim analysis included 36 participants. Within-group analyses are shown in Figure 1. After 12 weeks of intervention, PSQI scores significantly improved in both Ex+HT and HT groups and ICIQ-FLUTS voiding score decreased in the Ex group. On Frequency-Volume Chart (FVC), daytime frequency decreased and an increased diuresis and diuresis rate was reported in the Ex+HT group. No differences in daytime or nighttime maximal voided volume (MVV) was shown. No intervention resulted in a decreased nighttime diuresis or diuresis rate, and no changes in Nocturnal Polyuria index (NPi) or nocturnal urine production (NUP) was reported.

Preliminary evidence suggests that combined systemic hormone therapy and exercise or systemic hormone therapy alone offers additive benefits on subjective sleep quality based on questionnaire data. Median NPi and NUP failed to show nocturnal polyuria across all groups, both pre- and post-intervention. No intervention (A, B or C) demonstrated an improvement in circadian rhythm of diuresis, overall symptomatic bladder complaints or greater bladder capacity based on 24-hour FVC.

Given the small interim sample size, results must be interpreted with caution and between-group comparisons remain limited in statistical power. Generalizability of these results is limited.

Hormone therapy either combined with supervised exercise or provided as intervention alone may beneficially subjective sleep quality. Further recruitment will clarify effects on subjective LUTS, nocturnal urine output and solute clearances.

Continence 19S (2026) 102748
DOI: 10.1016/j.cont.2026.102748