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January 16, 2018; 90 (3) Article

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

Jennifer S. Graves, Roland G. Henry, Bruce A.C. Cree, Geralyn Lambert-Messerlian, Ruth M. Greenblatt, Emmanuelle Waubant, Marcelle I. Cedars, Alyssa Zhu, University of California, San Francisco MS-EPIC Team,, Peter Bacchetti, Stephen L. Hauser, Jorge R. Oksenberg
First published December 22, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004843
Jennifer S. Graves
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.
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Roland G. Henry
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.
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Bruce A.C. Cree
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.
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Geralyn Lambert-Messerlian
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.
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Ruth M. Greenblatt
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.
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Emmanuelle Waubant
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.
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Marcelle I. Cedars
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.
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Alyssa Zhu
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.
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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.
Peter Bacchetti
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.
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Stephen L. Hauser
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.
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Jorge R. Oksenberg
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.
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Citation
Ovarian aging is associated with gray matter volume and disability in women with MS
Jennifer S. Graves, Roland G. Henry, Bruce A.C. Cree, Geralyn Lambert-Messerlian, Ruth M. Greenblatt, Emmanuelle Waubant, Marcelle I. Cedars, Alyssa Zhu, University of California, San Francisco MS-EPIC Team,, Peter Bacchetti, Stephen L. Hauser, Jorge R. Oksenberg
Neurology Jan 2018, 90 (3) e254-e260; DOI: 10.1212/WNL.0000000000004843

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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.

Glossary

AMH=
anti-Müllerian hormone;
BMI=
body mass index;
CI=
confidence interval;
DMT=
disease-modifying therapy;
EDSS=
Expanded Disability Status Scale;
FSH=
follicular stimulating hormone;
GM=
gray matter;
MS=
multiple sclerosis;
MSFC=
MS Functional Composite;
PPMS=
primary progressive multiple sclerosis;
RA=
rheumatoid arthritis;
SPMS=
secondary progressive multiple sclerosis

Footnotes

  • Coinvestigators are listed at links.lww.com/WNL/A126.

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received February 28, 2017.
  • Accepted in final form October 2, 2017.
  • Copyright © 2017 American Academy of Neurology
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