2-Methoxyestrone

- Generally no treatment recommended

- Ensure adequate phase II detoxification

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. 

The 2-Methoxy Estrogens are considered to be protective.

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.