Menopause Not Found to Accelerate Disability Progression in MS

Menopause does not appear to be a major driver of clinical worsening in women with multiple sclerosis (MS), according to new findings from a longitudinal cohort study. The analysis, which followed nearly 1,000 women with relapse‑onset MS, found no statistically significant increase in risk of confirmed disability progression or conversion to secondary progressive MS associated with the menopausal transition.

Menopause represents a major biological inflection point during midlife, and many women living with MS will traverse this hormonal transition. Yet whether menopause meaningfully alters disease trajectory has remained unclear. The new study sought to clarify that by using registry data from the MSBase network augmented with retrospective women’s health surveys.

The investigators analyzed data on 987 women with relapse‑onset MS (583 premenopausal and 404 postmenopausal). All participants had at least three Expanded Disability Status Scale (EDSS) measurements, and had recorded their menopausal status. Median age at menopause was 48.5 years. The team used Cox proportional hazards models, treating menopause as a time‑varying covariate, and adjusted for confounders including age at MS onset, baseline disease duration, baseline EDSS, relapse history, and disease‑modifying therapy exposure.

Their primary outcome was time to 6‑month confirmed disability progression (CDP); the secondary outcome was time to secondary progressive MS (SPMS). In both crude and adjusted models, menopause was not associated with a higher risk of either outcome (adjusted hazard ratio for CDP: 0.95, 95% CI 0.70–1.29; P = 0.70; for SPMS: HR 1.00, 95% CI 0.60–1.67; P = 1.00). A secondary “inflection point” analysis of longitudinal EDSS trajectories similarly did not reveal menopause as a point of accelerated worsening after adjustment.

These results suggest that reproductive aging—while physiologically consequential—may not be the main catalyst for disability accrual in MS among women at midlife. The authors caution that menopause might exert only an additive effect to general somatic aging, rather than a dominant influence on MS progression.

Still, a few caveats deserve attention. The study cohort was drawn from 8 Australian neuroimmunology centers and derived from the MSBase Registry; while MSBase is a large, international dataset, the sample here represents a selected subpopulation with detailed women’s health information. The reliance on EDSS as the measure of disability may miss subtle changes in cognition, upper limb function, or non‑ambulatory features. And the observational design cannot exclude residual confounding, such as unmeasured hormonal factors or lifestyle changes around midlife.

Interestingly, emerging work in the MS field hints at potential effects of menopause on biomarkers of neuronal injury (e.g., increased serum neurofilament light), which may precede or complement overt disability transitions. 

Additionally, prior analyses in MS have noted that hormone fluctuations shape relapse risk (e.g. during pregnancy or postpartum), so the absence of a strong menopause effect in this study helps refine our understanding of how sex hormones and aging intersect in MS.

For neurologists and women with MS, these findings offer some reassurance: menopause alone may not herald a surge in disability accrual. That said, clinicians should continue to monitor midlife patients carefully, considering age, comorbidities, and overall health. The study authors point to the need for more granular measures of neurological change (beyond EDSS), prospective hormone assays, and potentially interventional trials assessing hormone therapy’s role in MS outcomes.

As the MS field continues to embrace precision neurology, understanding how sex‑specific transitions (menopause, pregnancy, aging) interact with disease mechanisms will remain an important frontier. This new study nudges the field away from simplistic assumptions about menopause as a “trigger” for worsening, and toward a more nuanced view of midlife in women with MS.