title: Mechanisms of sex difference: a historical perspective.
abstract: OBJECTIVE
  The history of the discovery of mechanisms contributing to sex difference helps to better appreciate gender factors in a variety of disease states. The objective of this article is to illustrate four mechanisms of sex differences in disease incidence: X-linkage (including inactivation, escape from inactivating, skewed inactivation), sex-specific exposure to disease-producing pathogens, fetal microchimerism, and iron depletion.
  
  
  METHODS
  This is a historic review.
  
  
  RESULTS
  An emphasis on sex difference led to the uncovering of four different mechanisms by which illness rates differ in men and women.
  
  
  CONCLUSIONS
  Research into many disease states can benefit from a focus on potential mechanisms that yield sex differences in illness susceptibility, progression, and outcome.
authors.affiliation: Centre for Addiction and Mental Health, Psychiatry, 250 College Street, Toronto, Ontario M5T 1R8, Canada. mary.seeman@utoronto.ca
authors.forename: Mary V
authors.initials: MV
authors.lastname: Seeman
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics / Q000266:history*; D046528:Chimerism; D004700:Endocrine System Diseases / Q000235:genetics / Q000266:history*; D005260:Female; D005783:Gender Identity; D049673:History, 20th Century; D006801:Humans; D007729:Kuru / Q000266:history; D008297:Male; D035583:Rare Diseases / Q000235:genetics / Q000266:history*; D015518:Rett Syndrome / Q000266:history; D012727:Sex Characteristics