2-OH-E1
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.
What does it mean if your 2-OH-E1 result is too high?
- 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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What does it mean if your 2-OH-E1 result is too low?
What Does Low 2-OH-E1 Mean?
2-Hydroxyestrone (2-OH-E1) is a protective estrogen metabolite produced during Phase I liver detoxification. It is considered less estrogenic and helps neutralize excess estrogen. If 2-OH-E1 is low, it may indicate inefficient estrogen metabolism, which can contribute to estrogen dominance and an increased risk of estrogen-related symptoms or conditions.
Potential Causes of Low 2-OH-E1
- Impaired Phase I Liver Detoxification – The conversion of estrone (E1) into 2-OH-E1 depends on CYP1A1 and CYP1B1 enzymes. Low activity of these enzymes can reduce 2-OH-E1 levels.
- Poor Dietary Support – Low intake of cruciferous vegetables (such as broccoli, Brussels sprouts, and kale) can lead to decreased production of 2-OH-E1.
- Chronic Inflammation & Oxidative Stress – These can suppress Phase I detoxification, reducing 2-OH-E1 levels.
- Poor Methylation (Phase II Detox Impairment) – Once 2-OH-E1 is produced, it must be methylated into 2-Methoxy-E1 for elimination. Poor methylation can disrupt this process.
- Excess Estrogen or Estrogen Dominance – If estrogen metabolism is skewed toward the more potent estrogen metabolites (such as 16α-OH-E1 or 4-OH-E1), it may result in low 2-OH-E1 levels relative to total estrogen metabolism.
Symptoms Associated with Low 2-OH-E1
- Increased estrogenic effects (bloating, PMS, breast tenderness, mood swings)
- Heavy or prolonged menstrual cycles
- Increased risk of hormone-related conditions (fibroids, endometriosis, estrogen-positive breast cancer)
- Difficulty losing weight, particularly in hips and thighs
- Increased risk of DNA damage due to a shift toward pro-inflammatory estrogen metabolites
How to Increase 2-OH-E1 Levels
Your healthcare provider can work with you to improve 2-OH-E1 production through diet, lifestyle changes, and targeted supplements.
1. Increase Cruciferous Vegetables
Cruciferous vegetables like broccoli, cauliflower, kale, and Brussels sprouts contain indole-3-carbinol (I3C), which supports the conversion of estrogens into 2-OH-E1.
2. Consider I3C or DIM Supplementation
- I3C (Indole-3-Carbinol) is naturally found in cruciferous vegetables and is converted in the body into diindolylmethane (DIM).
- DIM (Diindolylmethane) helps shift estrogen metabolism toward 2-OH-E1, promoting a more favorable estrogen balance.
- Some health professionals recommend DIM supplements, while others prefer I3C or a combination of both to support Phase I estrogen detoxification.
3. Support Liver Detoxification
- Reduce alcohol, processed foods, and environmental toxins that impair estrogen detoxification.
- Ensure adequate intake of B vitamins (B6, B12, folate), magnesium, and methyl donors (SAMe, betaine) to support Phase II detox and methylation of 2-OH-E1 into 2-Methoxy-E1 for proper elimination.
- Increase antioxidants (vitamin C, glutathione, NAC) to help combat oxidative stress and improve detox pathways.
4. Manage Insulin and Blood Sugar Levels
- High insulin levels can increase aromatase activity, leading to higher estrogen levels and a shift toward less favorable estrogen metabolites.
- Focus on a low-glycemic, anti-inflammatory diet to maintain stable blood sugar and reduce insulin resistance.
5. Reduce Inflammation & Xenoestrogen Exposure
- Avoid plastics, pesticides, and endocrine disruptors that can increase estrogen load.
- Manage chronic inflammation through omega-3-rich foods (fatty fish, flaxseeds), turmeric, and polyphenols to support estrogen metabolism.
Final Thoughts
Low 2-Hydroxyestrone (2-OH-E1) on a DUTCH test may indicate inefficient estrogen metabolism, increasing the risk of estrogen dominance and hormone-related conditions. By incorporating cruciferous vegetables, liver-supportive nutrients, and targeted supplementation with DIM or I3C, you can enhance 2-OH-E1 production and support a healthier estrogen balance.
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