A healthy result should fall into the range 0 - 0.3 ng/mg.
4-OH-E1 is referred to as the “bad” estrogen, along with 16-OH-E1.
- It is a minor pathway of estrogen metabolism.
- It may also enhance cancer development.
- It may directly damage DNA by causing breaks in the molecular strands of DNA.
Human breast cancer tissue produces much higher levels of 4-OH-E1 than 2-OH-E1, while normal breast tissue produces approximately equal amounts of the two metabolites. Women taking hormone therapy with a polymorphism in CYP1B1 had twice the risk of developing breast cancer compared to other HRT users.
Furthermore, the 4-Hydroxyestrones have the ability to convert to metabolites that react with DNA and cause mutations that can be carcinogenic. It is also present in greater quantities in patients deficient in methionine and folic acid. Women who have uterine fibroids also may have increased levels of 4-Hydroxyestrones.
- Spink BC, Fasco MJ, Gierthy JF, Spink DC. 12-O-tetradecanoylphorbol-13-acetate upregulates the Ah receptor and differentially alters CYP1B1 and CYP1A1 expression in MCF-7 breast cancer cells. J Cell Biochem. Sep 1 1998;70(3):289- 296.
- Hayes CL, Spink DC, Spink BC, Cao JQ, Walker NJ, Sutter TR. 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc Natl Acad Sci USA. Sep 3 1996;93(18):9776-9781.
- Yang L, Gaikwad NW, Meza J, et al. Novel biomarkers for risk of prostate cancer: results from a case-control study. Prostate. Jan 1 2009;69(1):41-48.
- Castagnetta LA, Granata OM, Traina A, et al. Tissue content of hydroxyestrogens in relation to survival of breast cancer patients. Clin Cancer Res. Oct 2002;8(10):3146-3155.
Generally no treatment recommended
- Improve methylation by adding cofactors (B12, folate) or methyl donors (betaine, dimethyl glycine)
- Consider genetic testing for COMT and CYP1B1 activity, particularly if positive family history
- Reduce stress: COMT is involved in the metabolism of epinephrine, reducing availability for estrogen metabolism
- Increase inhibitors of CYP1B1 (Grapefruit, Ginseng)
- Avoidance of CYP1B1 inducers (Polycyclic aromatic hydrocarbons)
Evaluate methylation activity:
- Serum Homocysteine
- Serum B12 or methylation
- Urinary FIGLU
- Urinary xanthurenate
Other potential protective factors:
- Glutathione (reduction of estrogen quinones)
- Resveratrol (prevents estrogen quinone formation)
- Selenium, zinc, magnesium
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