Ovarian aging is associated with gray matter volume and disability in women with MS.

Abstract

To determine if ovarian aging as measured by levels of anti-Müllerian hormone (AMH) is associated with pattern of multiple sclerosis (MS) progression in women. Women with MS and healthy controls were included from a longitudinal research cohort with up to 10 years follow-up. Plasma AMH levels were measured by ELISA for baseline and years 3, 5, and 8-10. Mixed effects logistic and linear regression models were employed, with adjustments for age, disease duration, and other covariables as appropriate. AMH levels were similar (0.98-fold difference, 95% confidence interval [CI] 0.69-1.37, <i>p</i> = 0.87) in women with MS (n = 412, mean age 42.6 years) and healthy controls (n = 180, mean age 44 years). In a multivariable model of women with MS, including adjustments for age, body mass index, and disease duration, 10-fold lower AMH level was associated with 0.43-higher Expanded Disability Status Scale (EDSS) score (95% CI 0.15-0.70, <i>p</i> = 0.003), 0.25-unit worse MS Functional Composite <i>z</i> score (95% CI -0.40 to -0.10, <i>p</i> = 0.0015), and 7.44 mm³ lower cortical gray matter volume (95% CI -14.6 to -0.30; <i>p</i> = 0.041) at baseline. In a multivariable random-intercept-random-slope model using all observations over time, 10-fold decrease in AMH was associated with a 0.27 increase in EDSS (95% CI 0.11-0.43, <i>p</i> = 0.006) and 5.48 mm³ (95% CI 11.3-0.33, <i>p</i> = 0.065) and 4.55 mm³ (95% CI 9.33-0.23, <i>p</i> = 0.062) decreases in total gray and cortical gray matter, respectively. As a marker of ovarian aging, lower AMH levels were associated with greater disability and gray matter loss in women with MS independent of chronological age and disease duration.