Narcolepsy in the postpartum period: current evidence and future directions

Narcolepsy is a chronic sleep–wake disorder characterized by hypocretin (HCRT) deficiency, most commonly resulting from immune-mediated mechanisms targeting HCRT-producing neurons in the lateral hypothalamus. Although narcolepsy affects men and women at similar rates, increasing evidence suggests that female reproductive transitions influence disease expression and clinical burden. The postpartum period is characterized by abrupt endocrine changes, immune reactivation, neuroimmune remodeling, and profound behavioral adaptations, all of which intersect with biological pathways implicated in HCRT regulation. Clinical observations further suggest that this period may exacerbate pre-existing symptoms of narcolepsy and, in some cases, coincide with its first clinical manifestation. This mini review summarizes current evidence linking postpartum physiology and narcolepsy, with particular emphasis on neuroendocrine and immune mechanisms involving the HCRT system. We review clinical studies describing postpartum symptom exacerbation and postpartum-onset narcolepsy, discuss the biological plausibility of the postpartum period as a window of vulnerability, and examine the current landscape of preclinical models, highlighting the absence of experimental paradigms specifically designed to investigate pregnancy or the postpartum period. The relevance of the postpartum period extends beyond its clinical implications, offering an opportunity to investigate how reproductive physiology interacts with HCRT signaling and contributes to narcolepsy pathophysiology. This perspective may inform both the development of targeted research strategies and the clinical management of women with narcolepsy.