Steroidomic Changes in the Cerebrospinal Fluid of Women with Multiple Sclerosis

Multiple sclerosis (MS) is a long-term disease, causing inflammation and damage to the nervous system. This study evaluated steroidomic alterations related to MS in 57 female MS patients during the follicular phase and 17 during the luteal phase, as well as in age- and phase-matched controls. The data showed 1) Unconjugated and conjugated steroids were strongly linked between the blood and CSF. 2) MS patients have lower levels of unconjugated steroids compared to controls. However, unchanged levels of conjugated steroids indicate increased activity of steroid sulfotransferase. 3) MS patients have reduced functioning of steroid 11β-hydroxylase (CYP11B1). Problems with cortisol biosynthesis, linked to weakened functioning of both CYP11B1 and 17α-hydroxylase/17,20-lyase, are connected to more severe cases of MS. 4) Reduced levels of 5α/β-steroids and protective GABAergic 3α-hydroxy-5α/β-steroids in MS patients might be linked to the pathophysiology of MS. 5) Higher AKR1C3 function in MS could cause inflammation, as this enzyme catalyzes the synthesis of both steroids and prostaglandins. 6) Lower pregnenolone levels in MS patients might weaken neuroprotection, while higher pregnenolone sulfate levels could support cognitive function. 7) Lower levels of protective pregnenolone, DHEA, and androstenediol were associated with worse MS, suggesting these steroids may help shield against the disease.