Jennifer S Graves1, Roland G Henry2, Bruce A C Cree2, Geralyn Lambert-Messerlian2, Ruth M Greenblatt2, Emmanuelle Waubant2, Marcelle I Cedars2, Alyssa Zhu2, Peter Bacchetti2, Stephen L Hauser2, Jorge R Oksenberg2. 1. From the Departments of Neurology (J.S.G., R.G.H., B.A.C.C., E.W., A.Z., S.L.H., J.R.O.), Pharmacology (R.M.G.), Obstetrics, Gynecology and Reproductive Sciences (M.I.C.), and Epidemiology and Biostatistics (P.B.), University of California, San Francisco; and Women and Infants Hospital and the Alpert Medical School at Brown University (G.L.-M.), Providence, RI. Jennifer.Graves@ucsf.edu. 2. From the Departments of Neurology (J.S.G., R.G.H., B.A.C.C., E.W., A.Z., S.L.H., J.R.O.), Pharmacology (R.M.G.), Obstetrics, Gynecology and Reproductive Sciences (M.I.C.), and Epidemiology and Biostatistics (P.B.), University of California, San Francisco; and Women and Infants Hospital and the Alpert Medical School at Brown University (G.L.-M.), Providence, RI.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: AMH levels were similar (0.98-fold difference, 95% confidence interval [CI] 0.69-1.37, p = 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, p = 0.003), 0.25-unit worse MS Functional Composite z score (95% CI -0.40 to -0.10, p = 0.0015), and 7.44 mm3 lower cortical gray matter volume (95% CI -14.6 to -0.30; p = 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, p = 0.006) and 5.48 mm3 (95% CI 11.3-0.33, p = 0.065) and 4.55 mm3 (95% CI 9.33-0.23, p = 0.062) decreases in total gray and cortical gray matter, respectively. CONCLUSION: 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.
OBJECTIVE: 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. METHODS: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. RESULTS:AMH levels were similar (0.98-fold difference, 95% confidence interval [CI] 0.69-1.37, p = 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, p = 0.003), 0.25-unit worse MS Functional Composite z score (95% CI -0.40 to -0.10, p = 0.0015), and 7.44 mm3 lower cortical gray matter volume (95% CI -14.6 to -0.30; p = 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, p = 0.006) and 5.48 mm3 (95% CI 11.3-0.33, p = 0.065) and 4.55 mm3 (95% CI 9.33-0.23, p = 0.062) decreases in total gray and cortical gray matter, respectively. CONCLUSION: 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.
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