Sex hormone-related factors and the risk of PIRA in women with multiple sclerosis

Background: Sex-related differences affect multiple sclerosis (MS), but the impact of sex hormones on disease progression remains unclear. We investigated whether sex hormone-related factors influence progression independent of relapse activity (PIRA) in women with MS over a long-term follow-up. Methods: The study analysed 1210 female MS patients from the San Raffaele MS Center using data from an environmental survey (2019-2023). PIRA was defined as 12-week confirmed disability progression independent of recent relapses (<30 days). Cox proportional-hazard models (adjusted for confounding factors) were used to assess the effect of hormone-related factors on PIRA risk. Results: Patients who used oral contraceptives before MS diagnosis had a 26% lower risk of PIRA and a delayed median time to the first PIRA event (9.94 vs 7.5 years; HR=0.74; 95% CI 0.61 to 0.89; p=0.0018). Conversely, menopause at diagnosis (HR=1.82; 95% CI 1.24 to 2.67; p=0.0022) and pregnancy before diagnosis (HR=1.22; 95% CI 1.006 to 1.47; p=0.043) were associated with a shorter time to PIRA. No significant differences were found with abortion, menstrual irregularity or fertility therapy. Conclusions: This study suggests that early oral contraceptives may delay future disability progression, supporting the importance of sex hormones in MS and prompting further prospective investigations on oral contraceptives to slow disease progression.