Open Access Research article

No sex-specific difference in disease trajectory in multiple sclerosis patients before and after age 50

Riley Bove12, Alexander Musallam1, Brian C Healy123, Maria Houtchens12, Bonnie I Glanz1, Samia Khoury12, Charles R Guttmann12, Philip L De Jager124 and Tanuja Chitnis12*

Author Affiliations

1 Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women’s Hospital, Brookline 02445, MA, USA

2 Harvard Medical School, Boston 02115, MA, USA

3 Massachusetts General Hospital Biostatistics Center, Boston 02114, MA, USA

4 Center for Neurologic Disease, Harvard Medical School, 77 Avenue Louis Pasteur, NRB168, Boston 02115, MA, USA

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BMC Neurology 2013, 13:73  doi:10.1186/1471-2377-13-73

Published: 3 July 2013



The disease course in multiple sclerosis (MS) is influenced by many factors, including age, sex, and sex hormones. Little is known about sex-specific changes in disease course around age 50, which may represent a key biological transition period for reproductive aging.


Male and female subjects with no prior chemotherapy exposure were selected from a prospective MS cohort to form groups representing the years before (38–46 years, N=351) and after (54–62 years, N=200)age 50. Primary analysis assessed for interaction between effects of sex and age on clinical (Expanded Disability Status Scale, EDSS; relapse rate) and radiologic (T2 lesion volume, T2LV; brain parenchymal fraction, BPF) outcomes. Secondarily, we explored patient-reported outcomes (PROs).


As expected, there were age- and sex- related changes with male and older cohorts showing worse disease severity (EDSS), brain atrophy (BPF), and more progressive course.

There was no interaction between age and sex on cross-sectional adjusted clinical (EDSS, relapse rate) or radiologic (BPF, T2LV) measures, or on 2-year trajectories of decline.

There was a significant interaction between age and sex for a physical functioning PRO (SF-36): the older female cohort reported lower physical functioning than men (p=0.002). There were no differences in depression (Center for Epidemiological Study – Depression, CES-D) or fatigue (Modified Fatigue Impact Scale, MFIS) scores.


There was no interaction between age and sex suggestive of an effect of reproductive aging on clinical or radiologic progression. Prospective analyses across the menopausal transition are needed.

Demyelinating disease; Multiple sclerosis; Natural history studies; MRI; Disease progression; Menopause; Gender