Sex effect on disease characteristics in patients with narcolepsy type 1

Study objectives Narcolepsy type 1 (NT1) is a rare sleep disorder caused by orexin/hypocretin (Hcrt-1) deficiency, equally prevalent in women and men. Sex differences have been reported in animal models, particularly regarding cataplexy. Whether these differences can be transposed to humans remains unclear. We studied the sex effect on the characteristics of the disease in a large population of patients with NT1 in drug-free conditions. Methods Six hundred and seventy-three drug-free NT1 patients (221 children under the age of 18 years, 297 women/girls), all Hcrt-1-deficient, were evaluated at baseline in two European Experts Centers. Clinical characteristics, cerebrospinal fluid Hcrt-1 levels, nocturnal polysomnography (PSG), and multiple sleep latency tests (MSLT) were compared between sexes. Results were adjusted for several potential confounding factors (center, age, body mass index, drug status). Results A younger age of NT1 onset was more frequent in men/boys than in women/girls. In adults, women had a lower body mass index, slept longer, with a higher sleep efficiency, more stage 3, less wakefulness after sleep onset, and sleep apnea. In children, girls reported more hallucinations, disrupted nocturnal sleep, and higher Narcolepsy Severity Scale scores, without differences for PSG/MSLT features. Conclusions Few differences were observed between men/boys and women/girls with NT1 on age at onset, nocturnal sleep, and hallucinations, without differences related to the severity of daytime sleepiness and cataplexy. Future longitudinal studies could investigate possible sex-specificities such as hormonal status conditions, treatment response, and disease course.