Investigation Of Sex Differences In The Association Between Multiple Sclerosis Disease Severity And Hormonal Markers Of Vitamin D, Obesity, And Testosterone. (S24.003)

OBJECTIVE: To integrate the relative contributions of vitamin D, obesity markers and gonadal steroids in sex-specific hormonal profiles of disease severity in multiple sclerosis (MS). BACKGROUND: Recent investigations of MS have suggested a stronger association of hormonal pathways (vitamin D and obesity) with MS risk in women. METHODS: Morning blood samples drawn more than 30 days from glucocorticoid administration from adults with onset of RRMS or CIS in prior 10 years were selected from our Center’s CLIMB longitudinal cohort. Samples were analyzed for levels of 25-hydroxyvitamin D (25(OH)VitD), androgens (testosterone, free testosterone, androgen index), and obesity biomarkers (leptin and adipocyte-fatty acid binding protein (a-FABP)). Body mass index (BMI, kg/m2) was obtained from records. Expanded Disease Severity Scale (EDSS) was collected every six months. For each hormonal measure, association with EDSS, as well as sex by hormone interaction on EDSS, were assessed using a proportional odds model. To find a subset of predictors most associated with EDSS, a step-wise backward elimination approach was utilized in men and women separately. All models controlled for age, disease duration and disease type. RESULTS: This cohort of 173 subjects (55% women, 88% RRMS) had mean age of 39.3 years and mean EDSS of 1. Consistent with prior studies, higher EDSS was associated with lower 25(OH)VitD levels (p=0.003), lower testosterone levels (p=0.0134), and higher adiposity markers (p-value leptin=0.0006, a-FABP=0.0005, and BMI=0.0345). There was no significant sex by hormone interaction for any of the measures. When we used backward elimination, 25(OH)VitD (p=0.0054) and a-FABP (p=0.0204) were retained in the female model; only testosterone was retained in the males (p=0.0062). CONCLUSION: We did not observe a significant interaction between sex and 25(OH)vitD on EDSS. However, while 25(OH)VitD and a-FABP showed a strong association in women, only testosterone was retained in a final stepwise model in men. Study supported by: ABF/NMSS. Disclosure: Dr. Bove has nothing to disclose. Dr. Musallam has nothing to disclose. Dr. Healy has received research support from Merck Serono. Dr. Soltany has nothing to disclose. Dr. Kivisakk has received research support from Merck Serono. Dr. Glanz has received research support from Merck Serono. Dr. De Jager has received personal compensation for activities with Merck Serono, Teva Neuroscience, and Biogen Idec. Dr. De Jager has received research support from Biogen Idec. Dr. Miller has nothing to disclose. Dr. Chitnis has received personal compensation for activities with Biogen Idec, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., EMD Serono, and Teva Neuroscience as a consultant. Dr. Chitnis has received research support from Merck & Co., Inc.