Mechanisms of sex difference: a historical perspective

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.

This is a historic review.

An emphasis on sex difference led to the uncovering of four different mechanisms by which illness rates differ in men and women.

Research into many disease states can benefit from a focus on potential mechanisms that yield sex differences in illness susceptibility, progression, and outcome.