Low testosterone is associated with disability in men with multiple sclerosis.
BACKGROUND
Gonadal steroids may modulate disease course in multiple sclerosis (MS).


OBJECTIVE
To assess the prevalence and clinical associations of hypogonadism in men with MS.


METHODS
Male patients, aged 18-65 years, with relapsing-remitting MS (RRMS) or clinically-isolated syndrome (CIS) and their first symptom < 10 years prior were selected from a longitudinal clinical study. We measured their hormones in stored morning blood samples, and collected their Expanded Disability Status Scale (EDSS) scores every 6 months and their Symbol Digit Modalities Test (SDMT) results annually.


RESULTS
Our analysis included 96 men with a mean age of 40 years, EDSS of 1.1 and disease duration of 4.6 years. Of these men, 39% were hypogonadal (total testosterone < 288 ng/dL); none showed compensatory elevations in luteinizing hormone. Their low testosterone levels and testosterone:estradiol ratios were negatively correlated with body mass index (BMI) and leptin, and showed no correlation with 25-hydroxy-vitamin D levels. In our primary cross-sectional analyses, there was a negative age-adjusted correlation between total testosterone and EDSS (p = 0.044). In the age-adjusted longitudinal analyses, higher baseline testosterone levels were associated with less decline in SDMT (p = 0.012).


CONCLUSIONS
Men with MS may experience hypogonadotropic hypogonadism. Low testosterone levels may be associated with worse clinical outcomes. A potential neuroprotective role for testosterone warrants further investigation.
Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Brookline, MA, USAHarvard Medical School, Boston, MA, USACenter for Neurologic Diseases, Harvard Medical School, Boston, MA, USA.
R
R
Bove
Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Brookline, MA, USA.
A
A
Musallam
Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Brookline, MA, USAHarvard Medical School, Boston, MA, USAMassachusetts General Hospital Biostatistics Center, Boston, MA, USA.
B C
BC
Healy
Harvard Medical School, Boston, MA, USA.
K
K
Raghavan
Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Brookline, MA, USAHarvard Medical School, Boston, MA, USA.
B I
BI
Glanz
Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Brookline, MA, USAHarvard Medical School, Boston, MA, USA.
R
R
Bakshi
Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Brookline, MA, USAHarvard Medical School, Boston, MA, USACenter for Neurologic Diseases, Harvard Medical School, Boston, MA, USA.
H
H
Weiner
Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Brookline, MA, USAHarvard Medical School, Boston, MA, USACenter for Neurologic Diseases, Harvard Medical School, Boston, MA, USA.
P L
PL
De Jager
Harvard Medical School, Boston, MA, USANeuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
K K
KK
Miller
Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Brookline, MA, USAHarvard Medical School, Boston, MA, USACenter for Neurologic Diseases, Harvard Medical School, Boston, MA, USA tchitnis@rics.bwh.harvard.edu.
T
T
Chitnis
D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D006233:Persons with Disabilities; D018450:Disease Progression; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood*; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
D013739:Testosterone
Body mass index; cognition; cognitive impairment; disability; hormones; hypogonadism; leptin; multiple sclerosis; testosterone