title: Age at menarche and risk of asthma: systematic review and meta-analysis.
abstract: BACKGROUND
  Several studies have suggested a relationship between the age at menarche and risk of asthma development.
  
  
  OBJECTIVE
  To conduct a systematic review and meta-analysis of the relationship between the age at menarche and the risk of asthma.
  
  
  METHODS
  This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). A pre specified literature search strategy was used to identify studies of potential relevance and independent reviews were carried out by two authors. Raw data was pooled using the software package RevMan to calculate summary odds ratios. The risk of publication bias was assessed graphically by using a funnel plot and the robustness of the overall estimate obtained was assessed by using sensitivity analyses.
  
  
  RESULTS
  The searches identified 61 potentially relevant articles of which seven articles, with a total of 22,859 subjects, matched the inclusion criteria for the meta-analysis. Pooling of the seven studies showed that girls with early menarche (<12 years) had an increased risk of asthma relative to girls with late menarche; random effects odds ratio = 1.37 (1.15-1.64), (p = 0.0005). Substantial heterogeneity was revealed (I(2) = 55%). Sensitivity analysis showed that the risk estimate was not markedly changed when excluding any of the studies. The funnel plot did not indicate publication bias.
  
  
  CONCLUSIONS
  Early menarche appears to be associated with increased risk of asthma. Hormonal, immunological, genetic and environmental factors may act in a developmental context to explain this relationship. Future studies are warranted to further determine the mechanisms responsible for this observation.
authors.affiliation: Department of Respiratory Medicine, Bispebjerg Hospital , Copenhagen , Denmark .
authors.forename: Sofie
authors.initials: S
authors.lastname: Lieberoth
authors.forename: Elisabeth Juul
authors.initials: EJ
authors.lastname: Gade
authors.forename: Jesper
authors.initials: J
authors.lastname: Brok
authors.forename: Vibeke
authors.initials: V
authors.lastname: Backer
authors.forename: Simon Francis
authors.initials: SF
authors.lastname: Thomsen
mesh_terms: D000367:Age Factors; D001249:Asthma / Q000453:epidemiology*; D015992:Body Mass Index; D002648:Child; D005260:Female; D006801:Humans; D008572:Menarche; D016017:Odds Ratio; D012307:Risk Factors
keywords: Asthma; Menarche; Meta-analysis; Systematic review; epidemiology