Optimal Result: 2.5 - 6.5 ng/mg.

The biomarker 2-Methoxy-E1 is part of the phase 2 metabolism.

2-Methoxy-E1 is produced from 2-OH-E1 through the COMT enzyme. Anti-cancerogenic effects have been ascribed to 2-OH-E1 and particularly 2-Methoxy-E1.

2-Methoxy-E1 has shown antiproliferative effects in both hormone-dependent and hormone-independent breast cancer cells. These studies have shown that urinary 2-Methoxy-E1 levels were lower in breast cancer patients than controls.

As an example: The average woman usually turns her 2-OH-E1 with a value of 10 into 2-Methoxy-E1 with a value of 5. So it’s usually a 2:1 relationship. So look at your 2-OH-E1 value and your 2-Methoxy-E1 value and see if you have a 2:1 ratio.

The 2-Methoxy Estrogens are considered to be protective. Low levels are usually a reflection of overall low estrogens and may be improved with supplemental estrogen. Metabolized from 2-OH-E1. A comparison of 2-Methoxy-E1 with 2-OH-E1 allows insight into methylation pathways. If the 2-Methoxy-E1 value is at least 25% of 2-OH-E1 value, methylation is probably adequate. If <25% consider adding methyl donors.

Phase 2 metabolism (methylation):

After estrogens go through phase 1 detoxification, they move on to methylation which is part of phase 2 detoxification. Methylation, in essence, “neutralizes” the phase 1 metabolites and prepares them to be excreted out of the body instead of shuttling them back into circulation. Only 2-OH and 4-OH estrogens are methylated. 16-OH-E1 is not.

What does it mean if your 2-Methoxy-E1 result is too low?

Identify cause:

If 2-OH-E1 and 4-OH-E1 are high, then low 2-Methoxy-E1 is likely the result of poor methylation. Follow methylation treatment recommendations.

- Ensure adequate COMT function via methyl donors such as SAMe, B12, folic acid, and B6.

- Poor cancer protection

- Associated with preeclampsia

Possible reasons for poor conversion to 2-Methoxy-E1:

- Nutrient deficiency

- Genetic defects in methylation (MTHFR, COMT). These genes are involved in methylation.

If someone has poor methylation, they may be at higher risk for estrogen dominance and estrogenic cancers. 

- It is important to note that methylation is not the only phase II option for these hormones. Technically every estrogen measured in the DUTCH profile is a Phase 2 metabolite because they only exist in urine as phase 2 conjugates like glucuronides. For example, all of the estradiol in urine is in one of three different forms of estradiol-glucuronide.

- It is also important to note that methylation is an important detoxification step for catecholamines (like adrenaline) and other compounds. Compromised methylation can affect overall health in multiple ways and the methylation index on the DUTCH results can give insight into overall methylation efficiency.

- Poor methylation can be caused by nutrient deficiencies or genetic defects in enzymes (namely MTHFR and COMT). Magnesium and methyl donors (SAMe, B Vitamins, TMG, Choline, Folate, Methionine) are cofactors needed for methylation to work properly.

It’s important however not to rush to supplement with all of these or just one of the nutrients listed above but to do proper testing to assess whether the issue is elevated estrogen levels only, poor phase I, poor phase II or all of the above! Supporting the system only partly, or supporting only phase I when phase II may be sluggish, may only exacerbate your symptoms or not be nearly as effective.

Note: When levels of 2-OH-E1 and the methylated 2-Methoxy-E1 are very low (<0.5), ratios of the metabolites are more approximate as the individual values are somewhat less reproducible. 

What does it mean if your 2-Methoxy-E1 result is too high?

- Generally no treatment recommended

- Ensure adequate phase II detoxification

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