Estrogen dominance is often framed as “too much estrogen,” but the deeper issue is almost always poor estrogen clearance, not overproduction. The body may be making a normal amount of estrogen—yet struggling to process and excrete it through the liver, bile, and gut.
When Phase I and Phase II detoxification pathways become unbalanced—especially glucuronidation (UGTs) and sulfation (SULTs)—estrogens linger longer, recirculate through the gut, and bind receptors more aggressively. This creates the classic symptom patterns: heavy cycles, PMS, breast tenderness, migraines, mid-cycle irritability, and luteal phase instability.
This article explains the biochemistry behind estrogen dominance through an advanced but readable lens.
1. Estrogen Detox Is a Liver-Centric Process
Once estrogens are produced (primarily estradiol/E2 and estrone/E1), they undergo three essential stages in the liver:
- Phase I (CYP450 hydroxylation) → creates 2-OH, 4-OH, and 16-OH metabolites
- Phase II (conjugation) → adds molecules to make estrogens water-soluble
- Biliary excretion + gut elimination → final removal from the body
Estrogen dominance happens when conjugation and bile flow cannot keep up with incoming estrogen metabolites.
The two Phase II pathways most responsible are:
- Glucuronidation (UGT1A and UGT2B families)
- Sulfation (SULT1A1, SULT1E1)
Methylation helps too—but glucuronidation and sulfation do the heavy lifting. These two pathways can sometimes hand estrogens back and forth.
2. Glucuronidation (UGTs): The Main Exit Route for Estrogen
Glucuronidation attaches glucuronic acid to estrogen metabolites, forming estrogen-glucuronides, which can leave the body through bile or urine. Urine is the primary route, but I often see an issue with bile.
Key enzymes:
- UGT1A1, UGT1A3, UGT1A9
- UGT2B7, UGT2B15, UGT2B17
When glucuronidation slows, estrogen metabolites accumulate. This is one of the most common biochemical roots of estrogen dominance.
What blocks UGT activity?
- Excess inflammation (TNF-α, IL-6)
- Environmental toxicants (PCBs, BPA, phthalates)
- Liver congestion or sluggish bile flow
- Micronutrient deficiencies
- High beta-glucuronidase from dysbiosis
- Mitochondrial redox imbalance
Clinical note:
Pretty neat thing from a common household vegetable, artichoke extract has demonstrated supportive effects on bile flow which relieves pressure on hepatic conjugation pathways, offering indirect support for UGT function and conjugation.
3. Sulfation (SULTs): The Underrated Estrogen Metabolism Pathway
Sulfation attaches a sulfate group to estrogen, forming estrogen sulfates, which are less biologically active and easier to excrete. L-cysteine is the key amino acid here.
Key enzymes:
- SULT1A1 – broad sulfation, handles many estrogens
- SULT1E1 – highly specific for estradiol
These enzymes depend on the molecule PAPS (3′-phosphoadenosine-5′-phosphosulfate)—the universal sulfur donor.
If PAPS is low, sulfation stalls.
Why sulfation becomes overloaded:
- Low sulfur pool
- Poor mitochondrial ATP availability
- Impaired cysteine recycling
- High estrogen load
- Chronic gut/immune stress
Why L-cysteine supports sulfation better than NAC
N-acetylcysteine has become very popular and is probably the most researched cysteine out there. But it must be enzymatically cleaved into cysteine before entering the sulfate cycle, and under oxidative stress, that conversion becomes limited.
L-cysteine bypasses that bottleneck, directly replenishing the sulfur pool required to generate PAPS. As always this is not intended as a recommendation, just informative.
This is especially relevant in:
- Estrogen dominance with sulfur deficiency patterns
- Poor sulfation genetics (SULT polymorphisms)
- Chronic chemical exposure
- Mold or VOC-driven pathways
4. Beta-Glucuronidase: The Gut Enzyme That Reverses Estrogen Detox
Even if the liver glucuronidates estrogen successfully, it must be excreted via bile into the gut.
But certain bacteria produce beta-glucuronidase, an enzyme that deconjugates estrogen, freeing it to be reabsorbed back into circulation. This is not bad per se, just needs to be kept within a specific amount.
This enterohepatic recirculation amplifies estrogen dominance.
Factors that elevate beta-glucuronidase:
- Dysbiosis
- High Clostridia species
- LPS-driven inflammation
- Low dietary fiber
- High toxin load
What can be done?
What is going on with the gut needs to be addressed. Dysbiosis, diet, etc. can have a negative impact on all of this. Hence, a multifactorial approach is needed. There are many great herbs that can help here like melia. It has been shown that calcium D-glucarate can help by lowering beta-glucuronidase activity. Bitter herbs can also help.
5. Bile Flow: The Forgotten Estrogen Highway
Without adequate bile flow, estrogen conjugates can’t leave the liver. Estrogen dominance often reflects bile stasis rather than hormone imbalance.
What impairs bile flow?
- Low-fat diets
- Low-choline intake
- Mold exposure
- Estrogen dominance, yes it can be a vicious cycle.
- Sluggish gallbladder
- Aldehyde toxicity
- Ammonia toxicity
- Mitochondrial dysfunction
- Chronic inflammation
Artichoke extract is one of the most researched bitter herbs for supporting healthy bile flow.
6. Mitochondria and Estrogen Detox: Redox Determines Conjugation Capacity
Phase II conjugation is ATP-dependent.
Sulfation requires ATP to synthesize PAPS.
Glucuronidation requires UDP-glucuronic acid, produced through energy-dependent carbohydrate metabolism.
Under mitochondrial stress (infection, toxins, redox imbalance, excessive exercise, chronic stress), these pathways suffer.
This explains why estrogen dominance patterns often accompany:
- Chronic fatigue
- High oxidative stress
- Viral reactivation patterns
- Mold toxicity
- Gut LPS signaling
Hopefully you are beginning to see how complicated the picture can get and the increasing need for a multifactorial approach.
7. Applied Kinesiology: Identifying Which Pathway Is Jammed
AK is uniquely positioned to help determine whether a patient’s estrogen overload is due to:
- UGT1A/UGT2B overload
- SULT insufficiency
- Poor bile flow
- Elevated beta-glucuronidase
- Mitochondrial redox issues
- Dysbiosis-driven recirculation
- Gallbladder stress
- Choline deficiency patterns
You can distinguish between glucuronidation vs. sulfation issues through targeted challenges, nutrient signaling, or organ-specific reflexes. This allows individualized, tolerable support—critical for patients who don’t respond well to broad detox protocols. That is why I always state that AK is like a fine tuner. Helps you figure out which pathway and why.
Conclusion
Estrogen dominance is rarely an issue of overproduction. It is typically a problem of impaired clearance, driven by bottlenecks in glucuronidation, sulfation, bile flow, and gut recirculation. These pathways reflect the health of the liver, mitochondria, and gut—not simply the ovaries.
Applied Kinesiology helps clinicians distinguish which specific detox pathway is congested, guiding supportive, individualized care that respects the body’s natural physiology.
Bibliography
- Gebhardt R. Anticholestatic activity of flavonoids from artichoke (Cynara scolymus L.) and of their metabolites. Med Sci Monit. 2001 May;7 Suppl 1:316-20. PMID: 12211745. https://pubmed.ncbi.nlm.nih.gov/12211745/
- Kirchhoff R, Beckers C, Kirchhoff GM, Trinczek-Gärtner H, Petrowicz O, Reimann HJ. Increase in choleresis by means of artichoke extract. Phytomedicine. 1994 Sep;1(2):107-15. doi: 10.1016/S0944-7113(11)80027-9. PMID: 23195882. https://pubmed.ncbi.nlm.nih.gov/23195882/
- Ben Salem M, Affes H, Ksouda K, Dhouibi R, Sahnoun Z, Hammami S, Zeghal KM. Pharmacological Studies of Artichoke Leaf Extract and Their Health Benefits. Plant Foods Hum Nutr. 2015 Dec;70(4):441-53. doi: 10.1007/s11130-015-0503-8. PMID: 26310198. https://pubmed.ncbi.nlm.nih.gov/26310198/
- Hu S, Ding Q, Zhang W, Kang M, Ma J, Zhao L. Gut microbial beta-glucuronidase: a vital regulator in female estrogen metabolism. Gut Microbes. 2023 Jan-Dec;15(1):2236749. doi: 10.1080/19490976.2023.2236749. PMID: 37559394; PMCID: PMC10416750. https://pubmed.ncbi.nlm.nih.gov/37559394/
- Samantha M. Ervin, Hao Li, Lauren Lim, Lee R. Roberts, Xue Liang, Sridhar Mani, Matthew R. Redinbo, Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens, Journal of Biological Chemistry, Volume 294, Issue 49, 2019, Pages 18586-18599, ISSN 0021-9258, https://doi.org/10.1074/jbc.RA119.010950. https://www.sciencedirect.com/science/article/pii/S0021925820304130
- Ning L, Hong, J. Gut microbial β-Glucuronidase: A key regulator of endobiotic homeostasis. Cell Host Microbe. 2024. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128%2824%2900179-3
- Jacociunas LV, Dihl RR, Lehmann M, de Barros Falcão Ferraz A, Richter MF, da Silva J, de Andrade HH. Effects of artichoke (Cynara scolymus) leaf and bloom head extracts on chemically induced DNA lesions in Drosophila melanogaster. Genet Mol Biol. 2014 Mar;37(1):90-104. doi: 10.1590/s1415-47572014000100015. Epub 2013 Feb 28. PMID: 24688296; PMCID: PMC3958332. https://pmc.ncbi.nlm.nih.gov/articles/PMC3958332/
- Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA. The Regulation of Steroid Action by Sulfation and Desulfation. Endocr Rev. 2015 Oct;36(5):526-63. doi: 10.1210/er.2015-1036. Epub 2015 Jul 27. PMID: 26213785; PMCID: PMC4591525. https://pmc.ncbi.nlm.nih.gov/articles/PMC4591525/
- Austin W. Hansen, Kallidaikurichi V. Venkatachalam, Sulfur-Element containing metabolic pathways in human health and crosstalk with the microbiome, Biochemistry and Biophysics Reports, Volume 35, 2023, 101529, ISSN 2405-5808, https://www.sciencedirect.com/science/article/pii/S2405580823001103