title: Neuroprotective effects of testosterone treatment in men with multiple sclerosis.
abstract: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. While current medication reduces relapses and inflammatory activity, it has only a modest effect on long-term disability and gray matter atrophy. Here, we have characterized the potential neuroprotective effects of testosterone on cerebral gray matter in a pilot clinical trial. Ten men with relapsing-remitting MS were included in this open-label phase II trial. Subjects were observed without treatment for 6 months, followed by testosterone treatment for another 12 months. Focal gray matter loss as a marker for neurodegeneration was assessed using voxel-based morphometry. During the non-treatment phase, significant voxel-wise gray matter decreases were widespread (p≤ 0.05 corrected). However, during testosterone treatment, gray matter loss was no longer evident. In fact, a significant gray matter increase in the right frontal cortex was observed (p≤ 0.05 corrected). These observations support the potential of testosterone treatment to stall (and perhaps even reverse) neurodegeneration associated with MS. Furthermore, they warrant the investigation of testosterone's neuroprotective effects in larger, placebo controlled MS trials as well as in other neurodegenerative diseases. This is the first report of gray matter increase as the result of treatment in MS.
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA ; Brain Mapping Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Kurth
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA ; Brain Mapping Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Luders
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA ; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Sicotte
authors.affiliation: Department of Psychiatry, Jena University Hospital, Jena, Germany ; Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gaser
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Giesser
authors.affiliation: Department of Medicine, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute, Torrance, CA, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Swerdloff
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Montag
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Rhonda R
authors.initials: RR
authors.lastname: Voskuhl
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA ; Brain Mapping Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Mackenzie-Graham
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D066128:Gray Matter / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D013739:Testosterone / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D013739:Testosterone