Menopause found to shape initial symptoms and comorbidities in multiple sclerosis

New research presented today at the 41^st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2025) reveals that menopause may significantly influence how multiple sclerosis (MS) first presents in women, as well as the types of associated health conditions they experience. These novel findings could pave the way for more targeted, personalised treatment strategies for women tailored to their life stage.

While female sex is known to affect MS progression, the impact of menopause on initial symptom patterns remains largely underexplored. To investigate this, Yasemin Şimşek and her team analyzed data from 864 MS patients, drawn from a larger cohort of 4,191 individuals, including 298 premenopausal women, 300 postmenopausal women, and 265 age-matched men.

The analysis revealed distinct differences in where MS symptoms first appeared. The optic nerve was more frequently the site of initial symptoms in premenopausal women (21.8%) compared to postmenopausal women (15%) and men (11.7%). In contrast, the spinal cord was the first site affected in 44% of postmenopausal women and 48.3% of men, compared with 27.5% of premenopausal women.

These differences likely reflect the biological effects of hormonal changes. Hormonal status, immune system modulation and neuroprotective mechanisms likely influence how lesions develop and where symptoms first appear. Younger premenopausal women may have more robust inflammatory responses, leading to certain symptom patterns, whereas older individuals, both men and postmenopausal women, may experience more insidious and progressive symptom onset due to neurodegenerative processes.”

Yasemin Şimşek, lead author

The analysis also demonstrated striking differences in comorbidity burden. Only 15.1% of premenopausal women had comorbid conditions, compared with 41% of postmenopausal women and 36.6% of men. Among postmenopausal women, cardiovascular disease (including hypertension, arrhythmia, and coronary artery disease) was the most frequent comorbidity, affecting 24.7%. Endocrine and metabolic disorders such as type 2 diabetes, hypothyroidism and dyslipidaemia were also frequent in postmenopausal women, seen in 10.3%. In contrast, psychiatric comorbidities such as depression and anxiety were more common in premenopausal women than in postmenopausal women.

Overall, men had a comorbidity profile resembling that of postmenopausal women, particularly with respect to cardiovascular risk.

“The lower prevalence of cardiovascular and metabolic disorders in premenopausal women can be partly attributed to the protective effects of estrogen and younger biological age,” Şimşek noted. “Meanwhile, psychiatric comorbidities may be more frequent in this group due to higher psychosocial stress, earlier disease onset and possible hormonal influences on mood regulation.”

Mortality patterns further underlined these differences. During the study period, deaths occurred in 15 men and 9 postmenopausal women, while no deaths were reported among premenopausal women.

“These findings have important implications for clinical care,” Şimşek said. “Men and postmenopausal women may benefit from strategies targeting neurodegeneration and disability prevention, whereas premenopausal women may require closer monitoring of relapse activity and optimisation of disease-modifying therapies.”