Lexicon
Estrogen Metabolism (2/16-OH)
Also known as Estrogen metabolites, DUTCH test
Definition
The 2/16-OH concept refers to the balance between two oxidative estrogen metabolites, 2-hydroxyestrone and 16-alpha-hydroxyestrone, produced when the body metabolises parent estrogens. [1] These arise during estrogen metabolism, in which estrone (E1), estradiol (E2) and estriol (E3) undergo extensive phase I reactions including hydroxylation, oxidation and reduction, followed by phase II conjugation. [2]
How it works
2-hydroxyestrone (2-OHE1) has been most consistently characterised as anticarcinogenic: in experimental models, increasing 2-hydroxylation protected against tumors while decreasing it raised cancer risk. [3] By contrast, 16-alpha-hydroxyestrone is a mitogenic and cell-proliferative endogenous hormone, and a preponderance of 16-alpha-hydroxylated estrogens is regarded as an unfavourable sign in inflammatory tissue. [1] Estrogen 2- and 4-hydroxylases metabolise steroid estrogens to catechol estrogens, and enhanced 2-hydroxylation of the parent estrogens estrone and estradiol has been linked to reduced breast cancer risk. [4] [5]
Connected concepts
How it's measured
Early epidemiologic studies measured only 2-hydroxyestrone and 16-alpha-hydroxyestrone using direct enzyme immunoassays without purification steps, which had limited specificity, especially at the low concentrations characteristic of postmenopausal women. [5] A liquid chromatography-tandem mass spectrometry assay was later developed to measure concurrently all 15 estrogens and estrogen metabolites in serum and urine, as unconjugated and total concentrations, with high sensitivity and reproducibility. [5]
What levels mean
In the PLCO cohort, the serum ratio of 2-hydroxylation-pathway metabolites to parent estrogens was associated with a 28% reduction in breast cancer risk across extreme deciles after adjustment, and improved absolute risk estimates when added to a model already including unconjugated estradiol. [5] A relative shift toward 2-hydroxylation is viewed as favourable, consistent with the observation that urinary 2-hydroxyestrogen loss was about 10 times higher in healthy subjects than in patients with rheumatoid arthritis or systemic lupus erythematosus. [1] The clinical value of these ratios remains qualified, as earlier breast
Community knowledge
An unnamed hormones panel (Mastermind) noted that when estrogen is given exogenously, its hepatic metabolism into hydroxyestrone…
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- 1.Cutolo M, Sulli A, Straub RH. Estrogen metabolism and autoimmunity. Autoimmun Rev · 2012
- 2.Stanczyk FZ. Metabolism of endogenous and exogenous estrogens in women. J Steroid Biochem Mol Biol · 2024
- 3.Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-hydroxyestrone: the 'good' estrogen. J Endocrinol · 1996
- 4.Liehr JG. Genotoxic effects of estrogens. Mutat Res · 1990
- 5.Ziegler RG, Fuhrman BJ, Moore SC, Matthews CE. Epidemiologic studies of estrogen metabolism and breast cancer. Steroids · 2015
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