The estrogen metabolites 4-OH-E1 and 16-OH-E1 are known as the riskier estrogen metabolites.
Estrogen is metabolized (primarily by the liver) down three phase I pathways.
The 2-OH pathway is considered the safest because of the anti-cancer properties of 2-OH metabolites.
Conversely, the 4-OH pathway is considered the most genotoxic as its metabolites can create reactive products that damage DNA.
The third pathway, 16-OH creates the most estrogenic of the metabolites (although still considerably less estrogenic than estradiol).
When evaluating phase I metabolism, it may be important to look at the ratios of the three metabolites to see which pathways are preferred relative to one another. It may also be important to compare these metabolites to the levels of the parent hormones (E1, E2). If the ratios of the three metabolites are favorable but overall levels of metabolites are much lower than E1 and E2, this may imply sluggish phase I clearance of estrogens, which can contribute to high levels of E1 and E2.
When a person is high in 4 and 16 but low in 2, two things might be considered:
- They are at greater risk of female cancers (such as breast cancer)
- They are likely not methylating well (or don’t have the necessary minerals/nutrients necessary for proper methylation).
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