Chronological ageing and ovarian reserve in MS: insights from anti-Müllerian hormone and disability progression

Accelerated biological ageing has been proposed as a key mechanism influencing disease progression in multiple sclerosis. Anti-Müllerian hormone (AMH), a marker of ovarian reserve, may reflect biological ageing in women and could be associated with disability progression. We aim to evaluate the prognostic implications of AMH levels measured at the first demyelinating event (FDE) suggestive of multiple sclerosis (MS).

This retrospective study analysed prospectively collected data from three Spanish neuroimmunology centres (since 1994). It included 365 females aged 20-45 years with serum AMH measured within 2 years of onset. According to AMH tertiles (n, median ng/mL (range)), participants were classified as follows: high (n=121; 4.6 (3.2-17.4)), medium (n=122; 2.1 (1.3-3.2)) and low (n=121; 0.6 (0.01-1.3)). A total of 145 healthy females served as controls. Age-adjusted multivariable linear regression models assessed associations between AMH and baseline clinical, radiological and serum biomarkers. Cox regression models evaluated the risk of Expanded Disability Status Scale 3.0, second relapse, progression independent of relapse activity and relapse-associated worsening.

At FDE, median (range) age was 32.9 (22.2-44.9) years, follow-up 6.5 years (0.01-29.4) and AMH 2.2 (0.01-17.4); 68% received disease-modifying treatment. AMH levels did not differ between patients and controls and were inversely correlated with chronological age (β -1.21 (95% CI -1.42 to -1.00), p<0.001). After adjustment for chronological age, AMH showed no independent association with clinical, radiological or biomarker measures, or long-term outcomes.

AMH levels at the time of an FDE suggestive of MS were not associated with baseline activity or long-term outcomes related to relapses or disability. Our findings suggest that the apparent associations between AMH and disease characteristics are largely driven by chronological age, supporting the concept that ovarian reserve primarily reflects biological ageing rather than an independent determinant of MS progression.