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Fig. 2: Estrogen circulation pathways. Estrogens are locally produced in several tissues (mainly ovaries but also adrenal glands and adipose tissue). They circulate in the bloodstream, reaching several target organs such as the liver and kidney. Once reaching the liver, they undergo conjugation by glucuronidation or sulfonation reactions. Moreover, conjugated estrogens are converted into water-soluble molecules and can subsequently be excreted in bile, urine, and feces (Kwa et al., 2016). Some fractions of conjugated estrogens can be subjected to deconjugation by gut microbes in the intestine and be reabsorbed through the portal vein into the liver (Kwa et al., 2016; Rose, 1993).[ATTACH=full]13316[/ATTACH]