Estrogen Detoxification
Intro
When speaking about any type of hormone imbalance, most people focus on and want to learn about hormone detoxification. However, it’s very important to understand the whole life cycle of the hormone - how & why it’s made, how & why it’s used, symptoms of hormone imbalance, how the hormone is detoxified/metabolized and where, and how & where hormone metabolites are eliminated out of the body. Last week, I spoke about one of the avenues which estrogen is eliminated out of the body after it is detoxified/metabolized, and how the gut and gut bacteria play a role estrogen imbalance. In this week’s post, you will learn about how hormone detoxification pathways can play a role in the development of relative estrogen dominance.
Metabolism or detoxification?
Metabolism is defined as the biochemical cellular processes that transform compounds that produce or consume energy and detoxification is defined as the “reduction of toxic property of a substance by chemical changes” in the body, which produces a “less-poisonous” compound or a compound that is easier to eliminate out of the body. So, cellular detoxification is a form of cellular metabolism, and I will be interchanging between the saying “detoxification” and “metabolism” throughout this post.
Estrogen is detoxified via various enzymes, and detoxification can be classed in different stages - Phase I and Phase II.
Phase I detoxification usually transforms estrogen from a fat-soluble molecule to a water-soluble molecule that is unstable.
Phase II detoxification usually transforms this unstable molecule into a more-stable compound that is also easier to eliminate out of the body.
enzymes involved in Phase I estrogen detoxification are:
Cytochrome enzymes
enzymes involved in Phase II estrogen detoxification are:
Catechol-O-Methyltransferase (COMT)
Glucuronidase
Sulfotransferase
& more
Where does estrogen metabolism take place?
Lots of integrative practitioners seem to focus solely on the liver for estrogen metabolism. But in truth, estrogen metabolism takes place in:
Oxidation via cytochrome: Breast tissue, uterus, brain, and liver.
Methylation via COMT: Kidney and breast tissue.
Glucuronidation via glucuronidase: Liver, biliary epithelium, kidney, gut, prostate, ovary, and breast tissues
Sulfonation via sulfotransferase: Liver, small intestine, kidney, placenta, uterus, adrenal gland, and breast tissues. And, the highest level of sulfonation is completed in the liver
And, from a quantitative perspective, sulfonation and glucuronidation are not major metabolism pathways for estrogen detoxification.
Suboptimal Enzyme function = Suboptimal detox
Proper function of estrogen detoxification enzymes are necessary to support healthy levels of estrogen in the system. However, when enzymes are functioning sub-optimally, this can lead to relative estrogen dominance where there are higher levels of unopposed estrogens in the system. There are 2 factors that can cause suboptimal enzymes function:
Genetic mutations: Literature reveals that genetic mutations in genes for COMT and glucuronidase can lead to reduced enzyme function. Literature also suggests that genetic mutations for COMT and cytochrome could potentially lead to higher levels of disease-causing estrogen metabolites.
Nutrient deficiencies: Cytochrome enzymes have heme centers, which need iron to function properly. If there is insufficient iron, it could potentially cause suboptimal cytochrome function. Methylation detoxification completed by MTHFR and COMT need folate, B12, and magnesium to function properly. When MTHFR and COMT are not functioning properly, an inflammatory protein called homocysteine increases and can be measured. And, literature reveals that B12 and folate deficiency increase homocysteine levels. Magnesium is an important mineral needed for optimal COMT function, and literature suggests that calcium and iron can block magnesium from entering COMT.
Elimination Of Estrogen metabolites
After undergoing transformations of metabolism and detoxification, estrogen metabolites are prepared to be safely eliminated out of the body. Depending on the location of metabolism, the route of elimination will differ.
Methylated metabolites: Primarily eliminated out of the body via urine.
Glucuronides: Can be eliminated out of the body via bile and urine, but a majority appears to be eliminated out via bile.
Sulfonated metabolites: Animal models indicate that sulfonate metabolites can be elimination out via bile.
Takeaways + Summary
Estrogen metabolism/detoxification undergoes various routes through various enzymes, and it’s important to understand that these processes happen in other organs outside of the liver. Contrary to what many functional providers believe, it is important to support those organs to help optimize healthy estrogen detoxification and elimination - rather than just focusing solely on liver detoxification pathways and bile/gut excretion. Additionally, the organs, nutrients, and genetic mutations that one needs support with are all bio-individual and will differ from person to person.
So, I hope that this blog post is illuminating and empowers you to have healthy conversation with your trusted doctor to see what is worth your while you if you are experiencing symptoms of relative estrogen dominance and are looking for methods to support optimal levels of estrogen.
Key takeaways from this blog post:
Estrogen undergoes 2 levels of metabolism for detoxification to transform estrogen and safely eliminate it out of the body.
Estrogen metabolism can happen in the liver, the kidneys, breast tissue, and more.
Sulfonation and glucuronidation are not major detoxification pathways for estrogen from a quantitive perspective, and it could be suggested that methylation is a major route of metabolism.
Estrogen metabolites can be eliminated out of the body through urine and bile.
Supporting healthy estrogen metabolism means understanding the bio-individuality of a person since optimizing organ function, nutrient deficient, and genetic mutations can differ from person to person.
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