title: Age at Menarche and Risk of Multiple Sclerosis: A Prospective Cohort Study Based on the Danish National Birth Cohort.
abstract: Few studies have addressed the possible association between age at menarche and multiple sclerosis (MS), and results are conflicting. We studied this issue in a large prospective cohort study. The study cohort comprised 77,330 women included in the Danish National Birth Cohort (1996-2002). Information on menarcheal age was ascertained at the first interview, which took place in the 16th week of pregnancy. Women were followed for MS from the first interview to December 31, 2011. Associations between age at menarche and risk of MS were evaluated with hazard ratios and 95% confidence intervals using Cox proportional hazards regression models. Overall, 226 women developed MS during an average follow-up period of 11.7 years. Age at menarche among women with MS was generally lower than that among women without MS (Wilcoxon rank-sum test; P = 0.002). We observed an inverse association between age at menarche and MS risk. For each 1-year increase in age at menarche, risk of MS was reduced by 13% (hazard ratio = 0.87, 95% confidence interval: 0.79, 0.96). Early age at menarche appears to be associated with an increased risk of MS. The mechanisms behind this association remain to be established.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Nete Munk
authors.initials: NM
authors.lastname: Nielsen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Harpsøe
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Simonsen
authors.affiliation: Institute of Regional Health Research, University of Southern Denmark, DK-5000, Odense, Denmark.|Focused Research Unit in Neurology, Hospital of Southern Jutland, DK-6200, Aabenraa, Denmark.
authors.forename: Egon
authors.initials: E
authors.lastname: Stenager
authors.affiliation: The Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark/Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Melinda
authors.initials: M
authors.lastname: Magyari
authors.affiliation: The Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark/Department of Clinical Epidemiology, Clinical Institute, University of Aarhus, Aarhus, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Koch-Henriksen
authors.affiliation: Department of Clinical Epidemiology (formerly Institute of Preventive Medicine), Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.|Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Baker
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.|Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjalgrim
authors.affiliation: Department of Biometry and Population Genetics, IFZ Research Centre for Biosystems, Land Use and Nutrition, Justus Liebig University GiessenGiessen, Germany.
authors.forename: Morten
authors.initials: M
authors.lastname: Frisch
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Bager
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008572:Menarche; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000209:etiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D055815:Young Adult
keywords: Danish National Birth Cohort; cohort studies; menarcheal age; multiple sclerosis