Association between low testosterone and brain atrophy in men multiple sclerosis. (S38.006)

OBJECTIVE: To determine the association between testosterone levels and brain atrophy in men with multiple sclerosis (MS). BACKGROUND: In men with MS, low testosterone levels are associated with greater disease severity. Given the neuroprotective effects of testosterone noted in animal models, we hypothesized that low testosterone would be associated with brain atrophy in relapsing remitting MS (RRMS). DESIGN/METHODS: Thirty-eight male patients, aged 18-65 years, with RRMS or clinically-isolated syndrome and first symptoms < 10 years prior were selected from a longitudinal clinical study. We measured testosterone in stored morning blood samples. We calculated brain parenchymal fraction (BPF), a surrogate of whole brain atrophy, using expert manual correction of an automated template driven segmentation. RESULTS: The patients had a mean (SD) age of 40.3 (10.0) years, EDSS of 0.99 (0.94) and disease duration of 4.6 (2.2) years. Mean total testosterone levels were 375 ng/dL (SD= 153; range= 49-672 ng/dL); 31.6[percnt] men were hypogonadal (<288 ng/dL). Testosterone levels were not correlated with vitamin D, smoking status or MS treatment. There was no significant age-adjusted correlation between testosterone levels and BPF (partial Pearson’s correlation r=0.252; p=0.132). However, when we classified testosterone levels into clinically meaningful categories (<288, 289-600, and above 600 ng/dL), we detected a marginally significant association with BPF (p=0.052 for three group comparison). The estimated group difference between the highest and lowest testosterone levels was 0.042, with lower testosterone levels associated with worse atrophy ( p=0.050 for group comparison after Bonferroni correction). We will present analyses, including longitudinal, from a larger cohort, at the Conference. CONCLUSIONS: This exploratory study suggests that low testosterone levels may be associated with brain atrophy in early MS. A potential neuroprotective role for testosterone warrants further investigation. STUDY SUPPORTED BY: NMSS, American Brain Foundation. Disclosure: Dr. Bove has nothing to disclose. Dr. Healy has received research support from Merck Serono. Dr. Egorova has nothing to disclose. Dr. Glanz has received research support from Merck Serono. Dr. Bakshi has received personal compensation for activities with Biogen Idec, Novartis, Sanofi/Genzyme, and Teva Neuroscience as a consultant. Dr. De Jager has received personal compensation for activities with Teva Neuroscience and Biogen Idec. Dr. De Jager has received research support from Biogen Idec and Sanofi/Genzyme. Dr. Miller has nothing to disclose. Dr. Guttman has stock and/or stock options in Novartis, Roche, GlaxoSmithKline, Alnylam, Cocrystal Pharma, Arrowhead Research, Sangamo BioSciences, Inc., and Protalix Biotherapeutics. Dr. Chitnis has received personal compensation for activities with Biogen Idec and Alexion. Dr. Chitnis has received research support from Merck Serono and Novartis.