Ovarian age is associated with gray matter volume and disability in women with MS independent of chronological age and disease duration

Jennifer S. Graves M.D., Ph.D., University of California at San Francisco

Newswise — Background: Women with MS tend to have more benign initial course than men, but often transition to secondary progressive disease near menopause. It is not known if ovarian decline contributes to accumulation of disability in women with MS.

Objectives: To determine if ovarian decline as measured by levels of anti-Mullerian hormone (AMH) is associated with clinical disability or brain atrophy in women with MS.Methods: Women with MS and healthy controls were included from a longitudinal research cohort with up to 10 years of clinical and MRI follow-up. AMH levels were measured in batch using a highly sensitive ELISA (pico AMH, Ansh labs) on plasma samples from baseline, year 3, year 5 and years 8-10 time-points. Logistic, linear and mixed model regression techniques were employed, with adjustments for age, disease duration, smoking, race, ethnicity, vitamin D level, disease modifying therapy (DMT), birth control, and hormone replacement therapy as appropriate.

Results: In models controlling for age, AMH levels were similar (1.01 fold difference;95%CI=0.72,1.41;p=0.97) in women with MS (n=412,mean age 42.6) and healthy controls (n=180,mean age 44). In a multivariable model of women with MS, including rigorous adjustments for age and disease duration, ovarian reserve (per 2 fold decrease in AMH pg/ml) was associated with total normalized gray matter volume (β=-3.29 mm3;95%CI=-6.57,-0.01;p=0.049) and multiple sclerosis functional composite (MSFC) z-scores (β=-0.060,95%CI=-0.12,-0.004;p=0.036) at baseline. After adjustment for age, white matter volumes were also associated with AMH levels (β=-2.64 mm3;95%CI=-5.25,-0.03;p=0.047) at baseline, but the association did not remain statistically significant after additional adjustments (β=-1.49 mm3; 95%CI=-3.95,0.98;p=0.24). Having undetectable levels of AMH (28% of subjects) was associated with 0.60-point higher expanded disability status scale (EDSS) score (95% CI 0.03,1.17, p=0.039). In a multivariable random-intercept-random-slope model using all observations over time, two fold decrease in AMH(pg/ml) was associated with 1.85 mm3decrease in gray matter volume over the follow-up period (95%CI=-3.77,0.08;p=0.060). Longitudinal analyses of clinical outcomes are in progress.

Conclusion: There is no reduction in follicular reserve in women with MS, implying normal fertility compared to healthy women. On the other hand, AMH was associated with total gray matter volume and disability in MS patients independent of chronological age and disease duration.

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