This original study addresses a major unmet need in nocturia management by evaluating whether add-on Gosha-jinki-gan improves hours of undisturbed sleep (HUS) and nocturia-related parameters in patients with persistent nocturia despite desmopressin. Although desmopressin reduces nocturnal urine production, many patients continue to experience nocturia. We hypothesised that a dual-mechanism approach targeting both nocturnal polyuria and bladder-related mechanisms would improve sleep continuity, as reflected by HUS, which has emerged as a clinically meaningful endpoint associated with patient satisfaction and quality of life.

This retrospective observational study included men aged ≥60 years with nocturnal polyuria, defined according to ICS terminology as nocturnal polyuria index (NPi) ≥33%, who had persistent nocturia (≥2 nocturnal voids) or HUS ≤3 hours despite desmopressin. Forty consecutive patients were analysed. Add-on Gosha-jinki-gan (7.5 g/day) was initiated while concomitant lower urinary tract symptom (LUTS) medications were continued unchanged.
Outcomes were assessed using 3-day bladder diaries at baseline, immediately before add-on therapy, and at 4 weeks. Primary outcomes were nocturnal voiding frequency, nocturnal urine volume, NPi, and HUS. Secondary outcomes included International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Athens Insomnia Scale, and Patient Global Impression of Improvement (PGI-I).
Ethical approval was obtained from an institutional ethics committee (approval number: 2025-04).

The mean age was 78.9 years. Before desmopressin treatment, the mean voided volume was low (109.9 mL), suggesting reduced functional bladder capacity.
Nocturnal voiding frequency decreased from 3.96 to 3.38 episodes/night after desmopressin and further decreased to 2.60 after add-on therapy. Nocturnal urine volume and NPi also showed significant reductions after add-on therapy.
Mean HUS increased from 116 minutes at baseline to 186 minutes at 4 weeks, exceeding the clinically meaningful 3-hour threshold. Sleep quality significantly improved as assessed by the Athens Insomnia Scale.
IPSS total score and quality of life index significantly improved. PGI-I showed that 57.8% of patients reported “much improved” or better, while no patients reported worsening of symptoms.
No serious adverse events were observed, and the treatment continuation rate was 92.5%, indicating good short-term tolerability in this elderly population.

These findings highlight the multifactorial nature of nocturia and limitations of single-mechanism therapy. Persistent nocturia despite desmopressin indicates that nocturnal polyuria alone does not fully explain symptoms.
The low baseline voided volume suggests that patients with persistent nocturia despite desmopressin represent a phenotype characterised by reduced functional bladder capacity. In this phenotype, even modest nocturnal urine production may exceed bladder capacity, leading to early awakening and fragmented sleep.
Gosha-jinki-gan may modulate afferent C-fiber activity and central inhibitory pathways without impairing detrusor contractility, thereby complementing the effect of desmopressin. The improvement in both nocturnal urine volume and voiding frequency supports a synergistic effect of dual-mechanism therapy.
Importantly, prolongation of HUS reflects restoration of sleep continuity and represents a clinically meaningful outcome beyond reduction in nocturnal voiding frequency. These findings support a mechanism-based, stepwise treatment strategy for persistent nocturia.
Furthermore, the observed improvements in both objective bladder diary parameters and patient-reported outcomes suggest that targeting both urine production and bladder-related sensory mechanisms may provide a more comprehensive therapeutic approach. This integrated strategy may be particularly relevant in older patients, in whom multiple pathophysiological factors often coexist and contribute to treatment resistance.

Add-on Gosha-jinki-gan improves nocturia-related parameters and prolongs hours of undisturbed sleep in patients with persistent nocturia despite desmopressin. Achieving HUS ≥3 hours represents a clinically meaningful therapeutic goal.
This study addresses a clear unmet clinical need by demonstrating, for the first time, that a dual-mechanism, add-on strategy can restore clinically meaningful sleep continuity (HUS ≥3 hours) in patients with residual nocturia after desmopressin.

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