Hormone Replacement Therapy and Disability Progression in Women with Multiple Sclerosis
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Evidence on menopausal hormone replacement therapy (HRT) and disability progression in women with multiple sclerosis (MS) is limited, particularly in the era of high-efficacy disease-modifying therapy. We estimated the association between systemic HRT and sustained disability progression and recurring relapses in a contemporary national cohort.
Methods
In a nationwide Swedish registry-based cohort, we followed women with MS aged 40 to 60 years entering from 2006 through 2024, with follow-up through 2025, under a new-user design. Systemic HRT was modeled as time-varying current use and quarterly oral-equivalent dose categories. Outcomes were sustained Expanded Disability Status Scale (EDSS) 4.0, sustained EDSS 6.0, and recurring relapses. Cox models adjusted for baseline covariates and time-varying age and disease-modifying therapy (DMT) class.
Results
Among 7,623 women, 1,192 (15.6%) initiated HRT. Current HRT use was associated with a lower hazard of sustained EDSS 4.0 (adjusted hazard ratio [aHR] 0.70, 95% confidence interval [CI] 0.51 to 0.96) but not sustained EDSS 6.0 (aHR 0.80, 95% CI 0.55 to 1.16) or recurring relapses (aHR 1.00, 95% CI 0.74 to 1.36). Dose categories showed no consistent gradient. Raising the cohort-entry age floor to 50 years gave a consistent EDSS 4.0 estimate (aHR 0.62, 95% CI 0.40 to 0.95).
Conclusions
HRT was not associated with increased relapse risk or severe disability progression. The lower hazard of sustained EDSS 4.0 was not mirrored at EDSS 6.0 and showed no dose gradient. Given menopausal status was unmeasured, replication in cohorts with verified menopausal status is required for clear clinical interpretation.
