Unveiling “Idiopathic” Nocturia: The Central Role of Sleep‐Induced Hypogonadism and ANP‐Mediated Hemodynamics

We read with great interest the Think Tank review by Song et al., which eloquently proposes targeting sleep quality, bladder water reabsorption, and circadian mechanisms as therapeutic avenues for idiopathic nocturia [1]. While the authors rightly emphasize the “Brain-Kidney-Bladder axis,” we suggest that two critical systemic mechanisms—often driven by occult Obstructive Sleep Apnea (OSA)—are frequently overlooked in these “idiopathic” cases: the central suppression of the Hypothalamic-Pituitary-Gonadal (HPG) axis and the hemodynamic “override” of aquaporin regulation by Atrial Natriuretic Peptide (ANP). First, regarding sleep quality and circadian mechanisms, the authors focus on the peripheral bladder clock. However, we propose that the central mechanism linking sleep fragmentation to endocrine failure is equally vital. As detailed in our hypothesis of “Sleep-Induced Hypogonadism,” chronic sleep fragmentation (a hallmark of both nocturia and OSA) disrupts the central circadian rhythmicity required for pulsatile GnRH secretion [2]. This suppression of the HPG axis leads to a decline in serum testosterone, creating a vicious cycle where androgen deficiency exacerbates metabolic syndrome and impairs bladder compliance, further perpetuating nocturia [2, 3]. Thus, restoring sleep continuity is fundamental to recovering endocrine homeostasis. Second, regarding bladder water reabsorption, the authors discuss aquaporins but do not fully address the hemodynamic drivers that disrupt their function. As we recently illustrated in Nature Reviews Urology, OSA generates significant negative intrathoracic pressure, mimicking volume overload and triggering the release of ANP from the heart [3, 4]. Crucially, this elevated ANP does not merely promote natriuresis; it can functionally override the antidiuretic effect of Antidiuretic Hormone (ADH) on aquaporins, leading to persistent water loss despite normal ADH levels [4]. This “ANP override” explains why targeting aquaporins or using desmopressin may fail if the underlying hemodynamic trigger (OSA) remains untreated. Screening for “Sleep-Induced Hypogonadism”: Evaluating serum testosterone, as correcting sleep architecture may reverse this central endocrine deficit [2, 3]. Assessing Hemodynamic Stress: Screening for OSA to identify ANP-driven polyuria that overrides physiological water conservation [4]. Po-Ting Lin: conceptualization, writing – original draft. Jau-Yuan Chen: conceptualization, writing – review and editing. Yu-Hsiang Lin: conceptualization, writing – review and editing. The authors received no specific funding for this work. The authors declare no conflicts of interest. This Letter to the Editor is based on previously published literature and does not involve any new data collected by the authors. All analyses and discussions are derived from publicly available sources, which are cited within the manuscript. Therefore, there are no data sets generated or analyzed during the current study.