Abstract
Introduction: Persistent lower urinary tract symptoms (LUTSs) in young adults following childhood primary nocturnal enuresis (PNE) refractory to desmopressin represent an undercharacterized condition at the pediatric-adult care interface. No prior study has compared pharmacotherapy options in this specific population. Methods: We performed a retrospective, single-center, hypothesis-generating comparative cohort study at a tertiary urology center (January 2017–September 2025). Male adults aged 18–35 years with documented childhood PNE based on International Children’s Continence Society (ICCS) criteria, desmopressin treatment failure, and persistent storage-phase LUTSs were included. Patients received mirabegron 25–50 mg daily (group A, n = 33) or anticholinergic therapy (group B, n = 32). The primary outcome was categorical treatment response (complete ≥75%, partial 50–74%, minimal 25–49%, failure <25%). Secondary outcomes included nocturia, urgency, micturition frequency, incontinence episodes, International Prostate Symptom Score (IPSS), quality of life, and adverse events. Analyses used independent t tests, chi-square/Fisher exact tests, paired t tests, and analysis of covariance. Results: Baseline characteristics were comparable between groups. Childhood nonmonosymptomatic enuresis phenotype was prevalent in 86.2% of patients, with reduced functional bladder capacity documented in 86.2%. Mirabegron achieved higher overall clinical benefit (≥50% improvement) than anticholinergics (78.8% vs. 56.3%, p = 0.042) and higher complete response rates (24.2% vs. 6.3%, p = 0.044). Symptom reductions consistently favored mirabegron: nocturia 51% vs. 38% (p = 0.031), urgency 48% vs. 36% (p = 0.024), micturition frequency 37% vs. 26% (p = 0.018), and quality of life improvement 58% vs. 38% (p = 0.009). Safety profiles were comparable with no serious adverse events and similar treatment persistence (90.9% vs. 87.5%, p = 0.642). Conclusion: Pending prospective confirmation, mirabegron provides superior efficacy with comparable safety versus anticholinergic therapy in male adults with persistent LUTS after desmopressin-refractory childhood PNE, supporting β3-adrenergic agonist therapy as a promising option for this underserved transitional population.
Plain Language Summary
Primary nocturnal enuresis – commonly known as bedwetting – is a prevalent voiding disorder in children that typically resolves spontaneously during adolescence. Nevertheless, a subset of affected individuals continues to experience persistent symptoms into young adulthood, including increased urinary frequency, urgency (a sudden, compelling need to urinate), and nocturnal voiding (waking at night to urinate). Desmopressin, the established first-line pharmacological treatment, acts by reducing overnight urine production. Its efficacy is limited in patients who also present with daytime bladder storage symptoms, and no consensus exists on optimal management when desmopressin treatment fails. This retrospective cohort study enrolled 65 young men (aged 18–35 years) with persistent bladder symptoms following childhood bedwetting that had not responded to desmopressin. Patients received either mirabegron – a medication that promotes bladder relaxation during the urine storage phase – or anticholinergic agents, a class of drugs that suppress involuntary bladder contractions. Both are established pharmacological treatments for overactive bladder, a condition characterized by urinary urgency, increased voiding frequency, and sometimes involuntary urine leakage. At 3 months, mirabegron demonstrated superior clinical response compared with anticholinergic therapy (79% vs. 56% of patients achieving meaningful improvement), with greater reductions in nocturnal voiding episodes and urgency, and more pronounced improvements in health-related quality of life. Both treatments were safe and well tolerated, with no serious adverse events and comparable treatment persistence in either group. These findings indicate that mirabegron may represent a more effective pharmacological option for this patient population. Prospective randomized trials are warranted to confirm these preliminary results.
