Sex differences in healthcare use before the first multiple sclerosis-related demyelinating event

While the multiple sclerosis (MS) prodrome may be prolonged, healthcare use by sex >5 years pre-onset remains underexplored. We examined healthcare use up to 29 years pre-MS onset, stratified by sex. Using administrative data from Ontario, Canada (1991-2020), we compared annual physician visit rates by diagnostic chapter between MS and matched non-MS cohorts, stratified by sex. Quasi Poisson models estimated rate ratios (RRs) with 95% confidence intervals (CI). Included were 35,018 MS and 136,007 matched non-MS individuals (mean onset age ∼43 years; standard deviation ∼14 years; ∼69% female in both cohorts). Sex differences were observed for nervous system-related visits; males exhibited higher RRs from 10 years pre-onset ('year -10'), peaking in year -1 for both sexes (RRs: males=28.60;95%CI:24.10-34.00, females=13.60;95%CI:12.56-14.70). This was followed by mental disorders, being higher for males from year -4, peaking in year -1 (RRs: males=2.98;95%CI:2.73-3.25; females=2.09;95%CI:1.99-2.21), then ill-defined signs/symptoms and injury-related visits from year -3 to -1 (e.g., ill-defined signs/symptoms, RRs range: males=1.85-4.26 and females=1.67-3.27). Additionally, males had higher RRs in the 1-2 years pre-onset for respiratory, genitourinary, musculoskeletal, circulatory, digestive, and infection-related visits. Sex differences in healthcare use were evident up to 10 years pre-MS onset across multiple diagnostic chapters. Findings suggest that prodromal MS patterns differ by sex, potentially reflecting differences in symptom presentation, health-seeking behaviour, or diagnostic recognition before MS onset.