title: Statistical testing of association between menstruation and migraine.
abstract: OBJECTIVE
  To repair and refine a previously proposed method for statistical analysis of association between migraine and menstruation.
  
  
  BACKGROUND
  Menstrually related migraine (MRM) affects about 20% of female migraineurs in the general population. The exact pathophysiological link from menstruation to migraine is hypothesized to be through fluctuations in female reproductive hormones, but the exact mechanisms remain unknown. Therefore, the main diagnostic criterion today is concurrency of migraine attacks with menstruation. Methods aiming to exclude spurious associations are wanted, so that further research into these mechanisms can be performed on a population with a true association.
  
  
  METHODS
  The statistical method is based on a simple two-parameter null model of MRM (which allows for simulation modeling), and Fisher's exact test (with mid-p correction) applied to standard 2 × 2 contingency tables derived from the patients' headache diaries. Our method is a corrected version of a previously published flawed framework. To our best knowledge, no other published methods for establishing a menstruation-migraine association by statistical means exist today.
  
  
  RESULTS
  The probabilistic methodology shows good performance when subjected to receiver operator characteristic curve analysis. Quick reference cutoff values for the clinical setting were tabulated for assessing association given a patient's headache history.
  
  
  CONCLUSIONS
  In this paper, we correct a proposed method for establishing association between menstruation and migraine by statistical methods. We conclude that the proposed standard of 3-cycle observations prior to setting an MRM diagnosis should be extended with at least one perimenstrual window to obtain sufficient information for statistical processing.
authors.affiliation: Health Services Research Center, Akershus University Hospital, Lørenskog, Akershus, Norway.
authors.forename: Mathias
authors.initials: M
authors.lastname: Barra
authors.forename: Fredrik A
authors.initials: FA
authors.lastname: Dahl
authors.forename: Kjersti G
authors.initials: KG
authors.lastname: Vetvik
mesh_terms: D003198:Computer Simulation; D005260:Female; D006801:Humans; D008598:Menstruation; D008599:Menstruation Disturbances / Q000150:complications* / Q000453:epidemiology; D008881:Migraine Disorders / Q000150:complications* / Q000453:epidemiology; D015233:Models, Statistical; D012372:ROC Curve
keywords: Fisher's exact mid-p; ROC curve analysis; classification; diagnostic criteria; menstrual migraine; statistical association