Structural sex differences at disease onset in multiple sclerosis patients

Background: Male sex is associated with worsening disability and a more rapid progression of multiple sclerosis (MS). This study analysed structural sex differences in magnetic resonance images of the brain, comparing women whose disease started before and after the menopause with a control group of men. Methods: This was a case control study in which female patients whose MS started before (Group 1) and after (Group 2) the menopause were included. The control group was matched by age, disease duration, Expanded Disability Status Scale and disease-modifying treatment. Patients were analysed according to demographic and clinical variables, as well as in terms of radiological measurements at disease onset and during the first 12 months of follow-up. These measurements included normalised total brain volume (NTBV), normalised cortical volume (NCV), normalised white matter volume, left and right hippocampus, the thalamus, brain stem volume, lesion load and percentage brain volume change. A linear regression model was used to analyse the data. Results: A total of 97 patients were included: 53 in Group 1 (27 females) and 44 in Group 2 (22 females). In Group 1, we observed a reduction in brain volume in males compared with females at disease onset in NTBV (p = 0.01), NCV (p = 0.001) and brain stem volume (p = 0.01). We did not observe differences in Group 2 at disease onset in the brain volumes analysed. Conclusion: We observed structural sex differences in brain volume at disease onset in the pre-menopausal group. However, no structural differences were observed at disease onset between the sexes after the menopause had started.