A healthy result should fall into the range 0.3 - 2 ng/mg.
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.
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.
The 2:16alpha-Hydroxyestrone ratio appears from the literature to be an important gauge of estrogen metabolism. In general, the higher the ratio, the less association there is with estrogen-dependent diseases such as breast cancer and lupus, and the more likely the person has a beneficial hormone metabolism. A 2:16alpha-hydroxyestrone ratio in serum greater than 0.4 is generally thought to be beneficial. There are numerous modifiers of this value, most of which induce changes in the level of 2-OHE1. 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-OHE1 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-OHE1 levels. Therefore, follow-up testing after treatment is strongly suggested. There may be an increased likelihood of osteoporosis with excessive 2-OHE1 production. It is important to note that the ideal upper limit of 2-OHE1 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.
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