Most consider 2-OH-E1 favorable - In women not on hormonereplacement therapy, 2-OH-E1 is considered a “good” estrogen because it is associated with reduced cancer growth.
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). 16-OH-E1 has been shown to encourage tumor development.
2-Hydroxyestrone is an endogenous biomarker and major urinary metabolite of estrone and estradiol. Along with 16α-Hydroxyestrone, 2-Hydroxyestrone is used as an indicator for increased risk of breast cancer.
This metabolite of Estrone is considered protective. A comparison with 2-Methoxyestrone, its Phase II liver metabolite, may help with assessing adequacy of methylation processes.
There are numerous modifiers of this value, most of which induce changes in the level of 2-OH-E1. These include intake of indole-3-carbinols from cruciferous vegetables, flaxseed, soy, omega-3 fatty acids, and vigorous exercise. All are shown to improve the levels of 2-OH-E1 in most individuals. It is to be emphasized that some individuals in clinical studies have exhibited a paradoxical response to treatments that would typically raise the 2-OH-E1 levels. Therefore, follow-up testing after treatment is strongly suggested. There may be an increased likelihood of osteoporosis with excessive 2-OH-E1 production. It is important to note that the ideal upper limit of 2-OH-E1 is not apparent from the existing literature.
Attention to bone loss processes in the urine is perhaps warranted in individuals with a very high 2:16alpha-hydroxyestrone ratio.
If low your health professional can work with you to address this in a few different ways, such as:
- Cruciferous vegetables like broccoli contain I3C
- I3C (=Indole-3-carbinol) gets metabolized to DIM
- DIM (=diindolylmethane) increases the conversion of estrogen to 2-OH-Estrogens
- Some health care professionals promote DIM, some I3C, and some providers promote a combination to help estrogens move down the 2-OH pathway.
- High levels of the “good estrogen” are typically considered beneficial; however, when coupled with a low 2-Methoxy-E1, it may indicate poor methylation activity.
- If both 2-OH-E1 and 16-OH-E1 are high, then total estrogen load may be high. Consider methods to better clear the estrogens from the body or HRT dosing may need revision if only 2-OH-E1 is very high.
- In post-menopausal women on hormone-replacement therapy, a very high 2-OH-E1 can result from high doses of estradiol. Thus, elevated levels of 2-OH-E1 are associated with increased cancer risk. The prescribing doctor should be consulted about dosing when such very high 2-OH-E1 are found.
The 2 pathway is the most favourable and we want to see it used more. It excretes estradiol and estrone. Estrone is converted into 2-Hydroxyestrone (2-OH-E1) as part of Phase 1 detox which is known as hydroxylation. 2-OH-E1 is a ‘good’ estrogen because it doesn’t stimulate cell growth. When it is methylated into the 2-Methoxy-E1 in Phase 2 it becomes cancer protective. Enough exercise, cruciferous veggies like broccoli, and specific supplements can raise 2-OH-E1 levels.
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