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Increasing evidence supports the observation that multiple sclerosis (MS) has a preclinical period, with various prodromal signs and symptoms more frequently represented in patients with confirmed MS many years later. Considering the apparent gender differences in the incidence and clinical course of MS, it remains unclear whether it could be reflected in prodromal symptom features. This study aimed to compare a broad spectrum of prodromal signs and symptoms between males and females in the 7-year period before the definite diagnosis of MS. Data came from the central register of the national payer of services, financed under the public healthcare system in Poland. They covered a 7-year period of patient health record claims, from 2009 to 2016. The following groups of symptoms were significant with women: musculoskeletal (p < 0.001), ophthalmic (p < 0.001), laryngological (p < 0.001), digestive system (p < 0.001), urinary tract (p < 0.001), mental (p < 0.001), cardiovascular (p < 0.001), complaints and headaches (p < 0.001). There was also a weak correlation with head injuries (p = 0.03) while dermatological and reproductive system complaints did not appear to be significant (p < 0.05). For males, the following groups of symptoms were significant: musculoskeletal (p < 0.001), ophthalmic (p < 0.001), laryngological (p = 0.007), cardiovascular system symptoms (p < 0.001), and headaches (p < 0.001). Interestingly, reproductive system problems were overrepresented in the male population (p = 0.008). There was no significant correlation with MS risk for dermatological, digestive, urinary, and mental complaints. Similarly, head injuries were not significant. Our results shed more light on well-known differences in the epidemiological and clinical characteristics between sexes in multiple sclerosis, and show differences in prodromal complaints before MS onset.

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