Optimal Result: 0 - 0.04 µg/g.

Other names: 4-Methoxy Estrone, 4-Methoxyestrone, 4-ME1, 4-ME-E1

Healthy Phase II metabolism methylates 2-hydroxy (2-OH) estrogens to the more cancer-protective 2-methoxy (2-MeO) forms, and neutralizes the potentially carcinogenic 4-OH estrogens to their 4-MeO forms.

Neutralized version of carcinogenic 4-OH-E1 (via methylation in Phase II)

4-OHE1 is less likely to oxidize to carcinogenic compounds if neutralized by COMT. COMT catalyses the shift of a methyl group from the co-enzyme S-adenosyl-L-methionine (SAMe) to one hydroxyl group of the catechols with Mg2+ acting as a co-factor.

COMT uses SAMe as its methyl donor; therefore, maintaining SAMe availability will encourage COMT activity

– Methionine (especially important if low homocysteine)

– Magnesium

– B2, B6, B12

– Folic acid (also as folinic acid, 5-formyl THF, or 5-methyl THF)

– TMG (betaine)


4-Methoxyestrone (4-ME1) is an endogenous, naturally occurring methoxylated catechol estrogen and metabolite of estrone that is formed by catechol O-methyltransferase via the intermediate 4-hydroxyestrone. It has estrogenic activity similarly to estrone and 4-hydroxyestrone. Estrone is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized from cholesterol and secreted mainly from the gonads, though they can also be formed from adrenal androgens in adipose tissue. Relative to estradiol, both estrone and estriol have far weaker activity as estrogens. Estrone can be converted into estradiol and serves mainly as a precursor or metabolic intermediate of estradio.

What does it mean if your 4-MeO Estrone result is too low?

- Low levels of the methoxy-estrogens in the presence of normal or high hydroxylated estrogens usually indicates poor methylation.

- Low levels may be associated with an increased breast cancer risk.

What does it mean if your 4-MeO Estrone result is too high?

Elevated methoxy-estrogens, particularly the 4-methoxy-estrogens (4-MeO-E2 and 4-MeO-E1) are beneficial if the 4-hydroxylated precursors are also high.

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