Östrogenmetaboliten: the pathway in the body

Östrogenmetaboliten is part of the pathway “Estrogen breakdown”. This page shows the whole pathway; the station of Östrogenmetaboliten is highlighted.

Where this laboratory value sits: 2-hydroxyestrone — phase I product. In the liver, enzymes of the cytochrome P450 family attach an OH group to the ring. CYP1A1 and CYP1A2 prefer position 2. The result is a catechol, a ring with two OH groups. Source 3

In brief

Estrogen metabolites are the conversion products of estradiol and estrone. Liver enzymes first attach OH groups, methylate them and add sugar or sulfate groups; in the gut, bacteria can undo that linkage again.

The pathway step by step

1. Estradiol → Estrone 17β-HSD type 2 · NAD⁺ 17β-hydroxysteroid dehydrogenases interconvert estradiol and estrone: type 2 forms estrone, type 1 forms estradiol. Further breakdown usually starts from estrone. Source 2
2. Estrone → 2-hydroxyestrone CYP1A1, CYP1A2 · NADPH In the liver, enzymes of the cytochrome P450 family attach an OH group to the ring. CYP1A1 and CYP1A2 prefer position 2. The result is a catechol, a ring with two OH groups. Source 3
3. Estrone → 4-hydroxyestrone CYP1B1 · NADPH CYP1B1 places the OH group at position 4. This is also a catechol; it is more easily oxidised further to reactive intermediates, which methylation in the next step intercepts. Source 3, 4
4. Estrone → 16α-hydroxyestrone CYP3A4 · NADPH CYP3A4 attaches the OH group at position 16, at the end of the second ring. Unlike the two catechols, this product still binds to the estrogen receptor. Source 4, 3
5. 2-hydroxyestrone → 2-methoxyestrone COMT · SAM, magnesium Catechol-O-methyltransferase (COMT) transfers a methyl group from SAM to one of the two OH groups. This makes the molecule unreactive and easier to excrete; COMT needs magnesium. Source 4
6. 4-hydroxyestrone → 4-methoxyestrone COMT · SAM, magnesium The same COMT also methylates the 4-form. Both routes thus end in a molecule that is not oxidised any further. Source 4
7. 2-methoxyestrone → Estrogen glucuronide UGT, SULT · UDP-glucuronic acid UGT enzymes attach a sugar residue, sulfotransferases a sulphate group. Only then are the breakdown products water-soluble enough to leave via urine and bile. Source 5
8. Glucuronide in the gut → Free estrogen β-glucuronidase Many gut bacteria produce the enzyme β-glucuronidase. It splits the sugar residue off again. The estrogen is then free and can pass back through the gut wall into the blood. Source 6, 7
9. Glucuronide in the gut → Out with the stool Whatever stays bound and is not reabsorbed leaves the body with the stool. Source 7

Cofactors in this pathway

• SAM (from methionine) — Donor of the methyl group that COMT attaches to the catechol estrogens Source 4, 9In the ORY catalogue as a laboratory value: Methionin
• Magnesium — Metal in the active site of COMT Source 9, 4In the ORY catalogue as a laboratory value: Magnesium
• NADPH — Electron donor of the cytochrome P450 enzymes that attach the OH groups Source 3, 8
• Iron — Central atom in the haem of aromatase and of the P450 enzymes of breakdown Source 8, 1In the ORY catalogue as a laboratory value: Eisen
• NAD⁺ — Hydrogen acceptor of 17β-HSD type 2, which converts estradiol into estrone Source 2In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• UDP-glucuronic acid — Provides the sugar group that the UGT enzymes attach Source 5
• PAPS (active sulfate) — Provides the sulfate group that the sulfotransferases attach Source 5

Sources

1. Simpson ER, Mahendroo MS et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994 · PubMed 8076586
2. Vihko P, Isomaa V et al. Structure and function of 17beta-hydroxysteroid dehydrogenase type 1 and type 2. Mol Cell Endocrinol 2001 · PubMed 11165013
3. Tsuchiya Y, Nakajima M et al. Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett 2005 · PubMed 16112414
4. Zhu BT, Conney AH. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis 1998 · PubMed 9472688
5. Raftogianis R, Creveling C et al. Estrogen metabolism by conjugation. J Natl Cancer Inst Monogr 2000 · PubMed 10963623
6. Ervin SM, Li H et al. Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. J Biol Chem 2019 · PubMed 31636122
7. Baker JM, Al-Nakkash L et al. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas 2017 · PubMed 28778332
8. Iyanagi T, Xia C, Kim JJ. NADPH-cytochrome P450 oxidoreductase: prototypic member of the diflavin reductase family. Arch Biochem Biophys 2012 · PubMed 22982532
9. Nissinen E, Männistö PT. Biochemistry and pharmacology of catechol-O-methyltransferase inhibitors. Int Rev Neurobiol 2010 · PubMed 21095460

Whole pathway: Estrogen breakdown

Related pathways

• Estradiol — estradiol
• DHEA — estradiol
• Testosterone — estradiol
• Dopamine, noradrenaline, adrenaline — Methionin, Magnesium
• Carnitine — Methionin, Eisen

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert approval pending
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