Menopause not a risk factor for disability progression in multiple sclerosis

Menopause is not the main driver of worsening disability in older women with multiple sclerosis (MS), as shown in a retrospective study.

The primary outcome of 6-month confirmed disability progression was reported in 56.4 percent of women in the postmenopausal cohort and in 31.7 percent of those in the premenopausal cohort, with menopause not being a significant risk factor for disability progression (adjusted hazard ratio [aHR], 0.95, 95 percent confidence interval [CI], 0.70–1.29; p=0.70). [JAMA Neurol 2025;doi:10.1001/jamaneurol.2025.3538]

Similarly, menopause was not a significant contributor to the risk of secondary progressive MS, which occurred in 24.3 percent and 7.7 percent of women in the postmenopausal and premenopausal cohorts, respectively (aHR, 1.00, 95 percent CI, 0.60–1.67; p=1.00).

Factors positively associated with disability progression included older age at MS onset, longer baseline disease duration, and increased baseline Expanded Disability Status Scale (EDSS). Conversely, exposure to high-efficacy disease-modifying therapy was protective.

Secondary progressive MS was associated with longer disease duration and higher baseline EDSS.

Sensitivity analysis comparing the time to disability milestones for women whose menopause occurred at <45 vs ≥45 years, performed to isolate the impact of menopause from ageing, yielded consistent findings.

The authors acknowledged the possibility that reproductive ageing is an interactive factor in the risk of disability progression but noted that the magnitude of its effect was not sufficiently large to be detected above other important contributing factors, such as age, disease duration, and exposure to high-efficacy disease-modifying therapies.

“This study has important implications for women with MS, along with the clinicians that care for them. It provides reassurance that menopause does not significantly alter the risk of disability progression,” the authors said.

Menopause is particularly challenging for many women with MS, with common symptoms experienced during this transition (eg, vasomotor symptoms, cognitive symptoms, mood disturbance, and urinary dysfunction) potentially compounding the pre-existing MS-related symptoms they are already dealing with, the authors pointed out. [Front Neurol 2021;12:554375]

“Women with MS can benefit from the wholistic management of menopausal symptoms with lifestyle measures, such as exercise and maintaining a healthy diet, as well as pharmacological measures, such as menopausal hormone therapy and nonhormone-based medications to improve symptom burden and quality of life,” they added. [Front Neurol 2021;12:554375; Mult Scler Relat Disord 2022;61:103747]

The analysis included 583 premenopausal women (median age at MS onset 29.2 years) and 404 postmenopausal women (median age at MS onset 37.3 years, median age at menopause 48.5 years).  The median observation period was 7 years.

In a linked editorial, Drs Jennifer Graves from the University of California San Diego in San Diego, California, US, and Mar Tintoré from the University of Vic - Central University of Catalonia in Vic, Catalonia, Spain, noted that the impact of the entire reproductive ageing process on disease progression and in cohorts inclusive of women in all the MS continuum, including those with progressive onset, cannot be ruled out just yet. [JAMA Neurol 2025;doi:10.1001/jamaneurol.2025.2419]

“Beyond the impact on disability progression in MS, there remains a call to action to further study the health impacts of the menopausal transition, which even if not limited to direct effects on MS pathology, impact women living with the disease,” according to Graves and Tintoré.

They emphasized the need to use more sensitive measures than the standard EDSS to accurately assess key symptoms such as cognition, sleep, and bladder function in future studies.