Overactive Bladder as a Bioenergetic Disorder: A Sex-Convergent Mitochondrial-Oxidative Framework

Overactive bladder (OAB) is an urgency-based symptom syndrome that increases with aging in both sexes, but its explanations remain fragmented around benign prostatic hyperplasia/bladder outlet obstruction in men, menopause/estrogen loss in women, and metabolic, sleep-related, or neurogenic mechanisms. We examine whether these diverse associations can be organized within a sex-convergent mitochondrial-oxidative framework while distinguishing OAB from urodynamic detrusor overactivity (DO) and broader lower urinary tract dysfunction (LUTD).

This hypothesis-generating Debate article was informed by a targeted narrative search of PubMed/MEDLINE and citation chaining through August 2026. We prioritized direct human lower urinary tract studies, validated symptom or urodynamic phenotypes, causal animal models, and bladder intervention studies; evidence extrapolated from non-bladder tissues was treated as indirect.

Evidence supports mitochondrial-oxidative injury in selected bladder ischemia, obstruction, diabetes, aging, and sex-hormone-deprivation models, with limited human associations. Diverse upstream exposures may converge on candidate detrusor-urothelial dysfunction, but direct comparative male-female evidence is lacking. Sleep-circadian/endocrine disruption is the most speculative arm; autonomic dysregulation is considered a parallel, potentially interacting route rather than a consequence of mitochondrial dysfunction. Existing OAB treatments may also alter afferent, smooth-muscle, or neural signaling. The framework therefore generates testable predictions rather than asserting a universal lesion.

Age-related OAB may be usefully examined through a bioenergetic framework that integrates detrusor, urothelial, vascular, metabolic, hormonal, and neural influences. Mitochondrial-oxidative dysfunction should currently be regarded as a candidate contributor rather than a universal final pathway, requiring direct bladder-level and sex-comparative validation.