Get Out! Understanding Proper Estrogen Detoxification through Phases 1, 2 and 3 to Reduce Risk

Estrogen detoxification is taught as phase 1, 2 and 3 but should be addressed in the reverse order. Phases 1 and 2 occur in the liver and are known as estrogen metabolism. Once water soluble, estrogen must leave the cell and enter phase 3 detoxification. A healthy metabolism shunts estrogen into 2-OH and then through methylation via COMT into 2-methoxy for proper disposal from the body. Unfortunately, if the pathway turns towards the more carcinogenic 4-OH or does not go through methylation, those estrogens go on to form a quinone that can result in DNA damage and increased cancer risk through unstable adduct formation. Certain enzymes, such as Quinone Reductase and Glutathione-S-Transferase, help prevent or reverse quinone formation and can be optimized with specific evidence based dietary changes and natural products. The ability to get from inside the cell out into the blood or bile into phase 3 is sometimes known colloquially as phase “2.5.” This phase can be hindered by inflammation but upregulated with Nrf2 activation. Lastly, it important to evaluate the gut as the microbiome has a huge influence on glucuronidation via b-glucuronidase and the resulting clearance or reactivation of estrogen into the system (known as phase 3). The purpose of this lecture is to help estrogen GET OUT and review estrogen metabolism from start to finish, including the genetics involved, the microbiome’s influence and discuss various treatment options to improve both phase 1, 2 and 3 detox to help reduce estrogen dominance and estrogen-based cancer risk in both men and women. Case examples will be included.