Decreased neurofilament light chain levels in estriol‐treated multiple sclerosis

Abstract

Estrogens have neuroprotective actions depending on estrogen type, dose, and timing in both preclinical models and in women during health and disease. Serum neurofilament light chain is a putative biomarker of neurodegeneration in multiple sclerosis, aging, and other neurodegenerative diseases. Here, oral treatment with an estrogen unique to pregnancy (estriol) using an 8 mg dose to induce a mid‐pregnancy blood estriol level reduced serum neurofilament light chain in nonpregnant MS women at mean age of 37 years. This is consistent with estriol‐mediated protection from neuro‐axonal injury and supports the use of serum neurofilament light chain as a biomarker in MS.

Estrogen receptor beta in astrocytes modulates cognitive function in mid-age female mice

“…Estriol treated MS women, compared to placebo treated, showed an improvement in performance on cognitive tests of processing speed, and better cognitive performance correlated with higher estriol blood levels 93 . Estriol treated MS women had less atrophy of subregions in cerebral cortex and also showed beneficial effects on other biomarkers of neurodegeneration 93 – 95 .…”

Hormonal Therapies in Multiple Sclerosis: a Review of Clinical Data

“…Due to many confounds, large randomized clinical trials are required to determine a true effect. To date, this has only been accomplished for combined oral contraceptives [ 8 ] and estriol [ 11 ]—both showing a modest effect on inflammatory activity when given as an add-on to first-line self-injectable DMTs, and the latter showing also potential neuroprotective effects. For the other indications, newer data in larger actively treated cohorts have not confirmed earlier concerns about fertility treatments and relapse activity, instead showing no elevated risk of relapses after diverse fertility treatments.…”

“…Furthermore, patients in the estriol group without enhancing lesions had less cortical gray matter atrophy than did those in the placebo group, suggesting a direct neuroprotective effect independent from anti-inflammatory effects. Taken together with the nFL data, this was interpreted as evidence of a protective effect of estriol from neuro-axonal injury [ 11 ]. While the authors postulated that this effect was mediated by remyelination induced by estrogen receptor beta ligand treatment, as previously shown in preclinical models, remyelination was not directly measured in the current trial.…”

“…There was a significant decrease in sNFL levels at 12 months for the Estriol + GA group ( t (109) = 4.10, p < 0.0001), while the Placebo + GA group did not change significantly ( t (109) = 0.41, p = 0.7). Further, the two treatment groups differed significantly in NfL at 12 months ( t (109) = − 2.15, p = 0.03), but not at 6 months ( t (109) = 0.51, p = 0.6) [ 11 ]. These levels were not adjusted for habitus, and it was not possible to distinguish possible effects of estriol on neuroprotection or neuroinflammation.…”

“… Estriol. In a post hoc analysis of the abovementioned trial of estriol as an add-on to glatiramer acetate [ 11 ], no difference in change in T2 lesion volumes was noted over time, but a reduction in cerebral cortex atrophy at 12 months was noted in the estriol group compared with the placebo group. Furthermore, patients in the estriol group without enhancing lesions had less cortical gray matter atrophy than did those in the placebo group, suggesting a direct neuroprotective effect independent from anti-inflammatory effects.…”