The Role of Estrogen in Insulin Resistance A Review of Clinical and Preclinical Data

Insulin resistance results when peripheral tissues, including adipose, skeletal muscle, and liver, do not respond appropriately to insulin, causing the ineffective uptake of glucose. This represents a risk factor for the development of type 2 diabetes mellitus. Along with abdominal obesity, hypertension, high levels of triglycerides, and low levels of high-density lipoproteins, insulin resistance is a component of a condition known as the metabolic syndrome, which significantly increases the risk of developing cardiometabolic disorders. Accumulating evidence shows that biological sex has a major influence in the development of cardiometabolic disturbances, with females being more protected than males. This protection appears to be driven by female sex hormones (estrogens), as it tends to disappear with the onset of menopause but can be re-established with hormone replacement therapy. This review evaluates current knowledge on the protective role of estrogens in the relevant pathways associated with insulin resistance. The importance of increasing our understanding of sex as a biological variable in cardiometabolic research to promote the development of more effective preventative strategies is emphasized. (Am J Pathol 2021, 191: 1490e1498; https://doi.org/10.1016/j.ajpath.2021.05.011)

Automated summary

Insulin resistance is associated with metabolic syndrome, impacting the development of type 2 diabetes and cardiometabolic disorders. Females are more protected than males, with estrogen playing a key role in this protection.