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Title: $Accelerated Worsening in Serum Neurofilament Light Chain Levels and Multiple Sclerosis Functional Composite in Women with MS after Menopause (S9.009)
Abstract: <h3>Objective:</h3> To evaluate the effect of menopause on functional outcomes and disease biomarkers in a longitudinal cohort of women with multiple sclerosis (MS). <h3>Background:</h3> 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. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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). <h3>Conclusions:</h3> Menopause may lead to increased neuronal injury and functional decline in people with MS, as found for the first time in continuous, objective measures. <b>Disclosure:</b> Ms. Silverman has nothing to disclose. Alan Bostrom has nothing to disclose. Prof. Lazar has nothing to disclose. Refujia Gomez has nothing to disclose. Adam Santaniello has nothing to disclose. Mr. Renschen has nothing to disclose. Ms. Harms has nothing to disclose. Ms. Cooper has nothing to disclose. Robin R. Lincoln has nothing to disclose. Mr. Poole has nothing to disclose. Dr. Henry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MEDDAY. Dr. Henry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Henry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Henry has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi/Genzyme. Jorge Oksenberg has nothing to disclose. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Atara. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Therini. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. Dr. Cree has received publishing royalties from a publication relating to health care. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jansen. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Roche Genentech. The institution of Dr. Bove has received research support from Novartis.