Immunometabolic profiling in menopausal women with multiple sclerosis: the role of adipokines and hormone therapy.

Background: Menopausal changes in adipose tissue distribution and adipokine profiles may influence immune activity in multiple sclerosis (MS). We investigated relationships between adipokines, inflammation and disease severity in menopausal women with MS and evaluated changes in adipokines during menopausal hormone therapy (MHT). Methods: 16 menopausal women with MS (participants with MS, PwMS) and 15 age-matched healthy controls were assessed for the associations of adipokines with inflammatory markers, and clinical, radiological and fluid biomarkers of MS severity. Adipokine levels were monitored over 1 year of oral MHT in baseline-controlled design. Results: In PwMS, body mass index and leptin-to-adiponectin ratio correlated with circulating high-sensitivity C reactive protein (hs-CRP), tumour necrosis factor (TNF)-α and interleukin-6 (ρ=0.51-0.66, p<0.05). The associations with hs-CRP and TNF-α were independent of age, disease duration, follicle-stimulating hormone and vitamin D. Serum vitamin D inversely correlated with hs-CRP, TNF-α and interferon-γ (ρ=-0.64-0.65, p<0.01). Adipsin showed strong correlation with neurofilament light chain (ρ=0.72, p=0.002) and decreased during MHT (3 months: p=0.007; 12 months: p=0.04). Conclusions: Adipokine imbalance and lower vitamin D levels were associated with systemic inflammation in PwMS. Adipsin emerged as a promising biomarker, with potential relevance for disease monitoring and therapeutic modulation via hormonal pathways. These findings support further exploration of multibiomarker profiling to guide personalised care in menopausal MS.