Accelerated Worsening in Serum Neurofilament Light Chain Levels and Multiple Sclerosis Functional Composite in Women with MS after Menopause
Hannah Silverman1, Alan Bostrom2, Ann Lazar3, Refujia Gomez1, Adam Santaniello1, Adam Renschen1, Meagan Harms1, Tiffany Cooper1, Robin Lincoln1, Shane Poole1, Roland Henry1, Jorge Oksenberg1, Stephen Hauser1, Bruce A. C. Cree1, Riley Bove1
1Weill Institute for Neurosciences, 2Division of Oral Epidemiology, Department of Preventive & Restorative Dental Sciences, 3Division of Oral Epidemiology, Department of Preventive & Restorative Dental Sciences; Division of Biostatistics, Department of Epidemiology and Biostatistics, University of California, San Francisco

To evaluate the effect of menopause on functional outcomes and disease biomarkers in a longitudinal cohort of women with multiple sclerosis (MS).

Hormonal changes, e.g. puberty and pregnancy, influence the onset and course of MS. After menopause, a worsening of disease trajectory measured on the clinician-rated Expanded Disability Status Scale (EDSS) was reported in some studies; however, the effects of menopause on other more objective measures of functional status and biomarkers of disease activity are unknown.
A cohort of 186 cis-women with MS who had undergone menopause was identified from a longitudinally followed sample at UCSF. Prospectively collected outcome measures included a performance-based measure of function (MS Functional Composite, MSFC) and serum neurofilament light chain (sNFL), a paraclinical marker of neuronal injury. Outcomes were analyzed using linear mixed effects models adjusted for age and MS duration, with a change in the slope at the time of menopause.

Median MS duration was 15 years (IQR=13) and median EDSS was 3 (IQR=2) at study entry. Median age at natural menopause was 52 years (IQR=5); 23% participants used any systemic menopausal hormone therapy. Menopause reflected an inflection point in MSFC worsening (slope difference 0.074 (95% CI: 0.015, 0.134), p=0.014), as well as in accumulation of serum NFL (slope difference -0.851 (95% CI: -1.546, -0.156), p=0.017).

Menopause may lead to increased neuronal injury and functional decline in people with MS, as found for the first time in continuous, objective measures.