Sex- and gender-related differences in narcolepsy and idiopathic hypersomnia: a narrative review

Sex- and gender-related differences are increasingly recognised across central disorders of hypersomnolence, although evidence varies between narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia. Literature suggests females experience longer diagnostic delays in narcolepsy and are more frequently diagnosed with idiopathic hypersomnia. Females also report greater subjective sleepiness, poorer quality of life and higher rates of psychiatric comorbidity, whereas males may experience greater impacts on personal relationships and higher rates of suicidality. Preclinical studies demonstrate sex-specific differences in the orexin system, stress responses, energy metabolism and neuroendocrine regulation, providing plausible mechanisms for clinical heterogeneity; however, human evidence remains limited and inconsistent. Sex-related differences in objective sleep testing and treatment response have been reported, although few studies were designed to evaluate these outcomes. Women face additional management challenges related to pregnancy, contraception and medication safety as reproductive safety data remain limited for many wake-promoting and anti-cataplectic therapies. Overall, substantial evidence gaps remain, particularly for narcolepsy type 2 and idiopathic hypersomnia. Future prospective, sex-stratified studies and objective biomarkers capable of identifying biologically meaningful disease subtypes are needed to improve diagnosis, refine disease classification and support personalised management.