The Phenomenon of the Switching of Estrogen Effects and Joker Function of Glucose: Similarities and Relation to Age‐Associated Pathology and Approaches to Correction

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Abstract
Estrogens and glucose are characterized by a myriad of functions that can be reduced to a small number of principal actions. In aging there is a simultaneous increase in the prevalence of diseases connected with estrogen deficiency as well as with estrogenic excess and associated with the phenomenon of the switching of estrogen effects (PSEE). Estrogens possess hormonal and genotoxic properties. An increase in genotoxic effect (isolated or combined with a decrease in hormonal effect) can influence the course of age‐associated diseases that, contrary to the situation with adaptive hypersensitivity to estrogens, may become less favorable or more aggressive. Inductors of PSEE include smoking, irradiation, and aging. Yet with “glycemic load” and the endocrine effect of glucose (the stimulation of insulin secretion), reactive oxygen species are formed in multiple sites, including adipose tissue. The ratio between hormonal and genotoxic effects reflects a “joke” function of glucose and can be conditioned by endogenous (perhaps including genetic) and exogenous factors. The shift in this glucose‐associated ratio may selectively encourage some chronic non‐communicable diseases. Several groups of treatments can be distinguished including alleviators of PSEE and insulin resistance syndrome (biguanides, glitazones, statins, modifiers of adipocytokines secretion, etc.) as well as other compounds aimed to optimally orchestrate the balance between endocrine and DNA‐damaging effects of estrogens and glucose.