Hypothesis / aims of study
Nocturia is the most bothersome lower urinary tract symptom (LUTS) in aging men with benign prostatic obstruction (BPO), frequently persisting despite alpha-1 adrenergic antagonist therapy. We hypothesized that add-on prolonged-release melatonin 2 mg would reduce nocturia and prolong the First Uninterrupted Sleep Period (FUSP) ,defined as time from sleep onset to first nocturia compared with placebo. We report preliminary results from the first 20 participants of an ongoing trial.
Study design, materials and methods
This is an ongoing randomized, double-blind, placebo-controlled, crossover trial. Men with LUTS/BPO on stable alpha-1 adrenergic antagonist with nocturia ≥2 on a 3-day bladder diary were eligible. Exclusion criteria included use of sleep-promoting medications, anticholinergics, or beta-3 agonists. To detect a 0.3 nocturia episode/night difference (90% power, p < 0.05, 20% dropout), the target sample is 48 patients. Participants were randomized 1:1 by computer-generated sequence to prolonged-release melatonin 2 mg or placebo once nightly for 4 weeks, followed by a 2-week washout, then crossover. [ Figure1 ] Participants, investigators, and data analyzer were blinded. Secondary outcomes included FUSP, IPSS, OABSS, ICIQ-Nocturia, ICIQ-NQoL, and nocturnal polyuria index (NPi), assessed by bladder diary and questionnaires at the end of each treatment period. Adverse events were monitored. Within-participant comparisons used the Wilcoxon signed-rank test; results are reported as median [IQR] and median paired difference between melatonin and placebo.
Results
Twenty men were enrolled (Group A, melatonin-first: n = 10; Group B, placebo-first: n = 10); Two withdrew from the melatonin-first group due to restlessness. Baseline characteristics: mean age 72.2±7.6 years; BMI 24.1±3.1 kg/m²; prostate volume 49.4±17.0 mL; Qmax 14.0±4.7 mL/s; post-void residual 58.6±35.8 mL. Except for FUSP (p=0.044), baseline parameters were comparable between sequence groups; this imbalance is inherently accounted for by the crossover design.
For the primary outcome, nocturia episodes did not differ significantly: melatonin 2.0 [1.5–4.0] vs placebo 3.0 [2.0–3.6] episodes/night; median paired difference −0.5 [−1.0 to −0.2]; p=0.096.
Melatonin significantly prolonged FUSP by median of 60 minutes [187.5 vs 142.5 min; difference +60.0 (16.7 to 137.5); p = 0.003] Statistically significant improvements were observed in OABSS (p=0.002), IPSS storage subscore (p=0.005), IPSS total (p=0.009), ICIQ-Nocturia (p=0.003), and ICIQ-NQoL (p=0.002). IPSS voiding subscore, IPSS QoL, and NPi did not differ. No serious adverse events occurred. [Table 1] No serious adverse events occurred.
Interpretation of results
While the reduction in nocturia episodes was not statistically significant, the median decrease of 0.5 highlights a trend toward clinical impact. However the significant 60-minute prolongation of FUSP and improvements of storage symptoms and QoL questionnaires (IPSS, OABSS, ICIQ), while showing no effect on voiding symptoms or nocturnal urine volume. This pattern supports a mechanism mediated primarily through circadian and sleep-quality modulation rather than lower urinary tract pharmacology. These preliminary findings should be interpreted with caution given the small sample size.