4-OH-E1 : 2-OH-E1 is a ratio that compares how much estrone (E1) your body routes down the 4-hydroxylation pathway (to 4-hydroxyestrone) versus the 2-hydroxylation pathway (to 2-hydroxyestrone). It’s a distribution metric, not a raw estrogen level. On this urine panel, values are typically normalized to creatinine so hydration has less effect.
Why it matters
Both 4-OH-E1 and 2-OH-E1 are catechol estrogens made by Phase I enzymes. The 2-OH route generally produces less estrogenic metabolites, while the 4-OH route forms reactive catechols that your body normally neutralizes via COMT-mediated methylation into methoxy estrogens. The ratio helps show your routing preference between these two pathways. It does not diagnose disease or predict cancer risk by itself; it’s one piece of your estrogen-metabolism picture and should be interpreted with 4-methoxy/2-methoxy partners, overall estrogen output, cycle timing, symptoms, and clinical history.
How to interpret (use your lab’s reference range)
Lower ratio (relatively more 2-OH than 4-OH): Often a comfortable pattern when 2-methoxy levels indicate good methylation. Still interpret with total estrogen production and symptoms.
Balanced ratio: Suggests a typical split between the 4-OH and 2-OH routes. Confirm that methoxy metabolites are adequate (showing COMT is working) and review the rest of the panel (4-OH %, 2-OH %, 16-OH %, total estrogen output).
Elevated ratio (relatively more 4-OH versus 2-OH): Indicates a shift toward 4-hydroxylation. On its own this does not equal high risk, but it’s a cue to check 4-methoxy-E1, 2-methoxy-E1, overall methylation support, oxidative stress, and modifiable factors (see below).
What can influence this ratio
Diet & lifestyle: Lower intake of cruciferous vegetables, high alcohol use, tobacco smoke, and habitual intake of charred foods can shift Phase I patterns; inadequate fiber, poor sleep, and high stress may impair downstream clearance.
Methylation capacity (COMT) & Phase II pathways: Adequate folate, B12, B6, magnesium, choline/betaine, phytonutrient diversity, and hydration support conversion to methoxy estrogens and excretion.
Medications/supplements: Enzyme inducers/inhibitors (some anticonvulsants, PPIs, botanicals like St. John’s wort) and hormonal contraception/HRT change metabolism.
Cycle timing & collection: Aim for consistent timing (many labs prefer early follicular) and first-morning urine; creatinine correction helps but extreme dilution/concentration can still nudge near-cutoff results.
What to do next (actionable plan)
Confirm properly if results are unexpected: repeat with first-morning urine, consistent cycle timing, and limited alcohol for 24–48 hours before the test.
Review partners: Look at 4-OH %, 2-OH %, 16-OH %, and especially 4-methoxy-E1 and 2-methoxy-E1 to ensure catechols are being methylated.
Food-first balance: Emphasize cruciferous vegetables (broccoli, kale, cabbage), broad plant diversity, and 25–35 g/day fiber; maintain hydration; prioritize sleep and stress management.
Consider clinician-guided supplements only if indicated: Compounds like I3C/DIM can alter Phase I routing, and methylation nutrients may support Phase II—but these should be personalized and re-tested, not self-prescribed.
Medication & exposure review: Discuss drugs/botanicals that affect liver enzymes; minimize smoking and excessive alcohol.
Key takeaways
The 4-OH-E1 : 2-OH-E1 ratio shows routing between two estrogen pathways; it isn’t a diagnosis or risk score.
Elevated ratios signal a relative shift toward 4-hydroxylation and call for a check of methoxy partners and modifiable factors.
Aim for balanced pathways and healthy downstream methylation, guided by your clinician and your symptoms.
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A high 4-OH-E1 : 2-OH-E1 ratio means your estrogen metabolism is relatively more routed to 4-hydroxylation than to 2-hydroxylation. This does not diagnose disease or equal high risk, but it’s a cue to confirm that your body is methylating these catechols efficiently (making 4-methoxy-E1 and 2-methoxy-E1) and to address modifiable factors.
Why it can be elevated
Phase I enzyme balance favoring the 4-OH route.
Lower methylation support (COMT) or low methoxy metabolites.
Alcohol, smoking, low cruciferous vegetable intake, low fiber, poor sleep, and high stress.
Medications/botanicals that induce or inhibit liver enzymes; hormonal contraception/HRT can reshape patterns.
Collection/cycle timing differences or very dilute urine (even with creatinine correction).
What to do next (practical plan)
Confirm correctly: Repeat with first-morning urine, consistent cycle timing, and minimal alcohol for 24–48 hours before testing.
Assess partners: Check 4-methoxy-E1 and 2-methoxy-E1 to ensure catechols are being neutralized; review 4-OH %, 2-OH %, 16-OH % for the whole pattern.
Food-first strategies: Increase cruciferous vegetables and overall plant diversity; target 25–35 g/day fiber; hydrate; prioritize sleep and stress care; moderate alcohol.
Targeted support (clinician-guided): Consider whether I3C/DIM or methylation nutrients (folate, B12, B6, magnesium; choline/betaine from foods) are appropriate; re-test rather than guessing.
Review meds & exposures: Discuss drugs/botanicals that alter CYP/COMT activity; reduce smoke exposure.
Key takeaways
A high ratio = relative shift toward 4-OH; it’s a routing clue, not a diagnosis.
Focus on methylation adequacy (methoxy metabolites) and modifiable habits to rebalance pathways.
Work with your clinician and re-test to confirm improvement over time.
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I have been using Healthmatters.io since 2021. I travel all over the world and use different doctors and health facilities. This site has allowed me to consolidate all my various test results over 14 years in one place. And every doctor that I show this to has been impressed. Because with any health professional I talk to, I can pull up historical results in seconds. It is invaluable. Even going back to the same doctor, they usually do not have the historical results from their facility in a graph format. That has been very helpful.
Karin
Advanced Plan Member since 2020
What fantastic service and great, easy-to-follow layouts! I love your website; it makes it so helpful to see patterns in my health data. It's truly a pleasure to use. I only wish the NHS was as organized and quick as Healthmatters.io. You've set a new standard for health tracking!
Paul
Healthmatters Pro Member since 2024
As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
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4-Methoxyestradiol (Pre-menopausal), 4-Methoxyestrone (male), 4-Methoxyestrone (Post-menopausal), 4-Methoxyestrone (Pre-menopausal), 4-OH-E1 % (male), 4-OH-E1 % (Post-menopausal), 4-OH-E1 % (Pre-menopausal), 4-OH-E1:2-OH-E1 (male), 4-OH-E1:2-OH-E1 (Post-menopausal), 4-OH-E1:2-OH-E1 (Pre-menopausal), 5-pregnenetriol (male), 5-pregnenetriol (Post-menopausal), 5-pregnenetriol (Pre-menopausal), 5a-Androstanediol (male), 5a-Androstanediol (Post-menopausal), 5a-Androstanediol (Pre-menopausal), 5a-Dihydrotestosterone (male), 5a-Dihydrotestosterone (Post-menopausal), 5a-Dihydrotestosterone (Pre-menopausal), 5A-PD:5B-PD (male), 5A-PD:5B-PD (Post-menopausal), 5A-PD:5B-PD (Pre-menopausal), 5a-Pregnanediol (male), 5a-Pregnanediol (Post-menopausal), 5a-Pregnanediol (Pre-menopausal), 5a-Tetrahydrocorticosterone, 5a-Tetrahydrocorticosterone (Pre-menopausal), 5a-Tetrahydrocortisol (male), 5a-Tetrahydrocortisol (Post-menopausal), 5a-Tetrahydrocortisol (Pre-menopausal), 5A-THF+5B-THF/THE (male), 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/ Etiocholanolone (5b) (Pre-menopausal), Androsterone (male), Androsterone (Post-menopausal), Androsterone (Pre-menopausal), Corticosterone, Corticosterone (Pre-menopausal), Cortisol Bedtime, Cortisol Bedtime (Pre-menopausal), Cortisol Dinnertime, Cortisol Dinnertime (Pre-menopausal), Cortisol Waking, Cortisol Waking (Pre-menopausal), Cortisol Waking+2hrs, Cortisol Waking+2hrs (Pre-menopausal), Cortisol/Cortisone, Cortisol/Cortisone (Pre-menopausal), Cortisol/day, Cortisol/day (Pre-menopausal), Cortisone Bedtime, Cortisone Bedtime (Pre-menopausal), Cortisone Dinnertime, Cortisone Dinnertime (Pre-menopausal), Cortisone Waking, Cortisone Waking (Pre-menopausal), Cortisone Waking+2hrs, Cortisone Waking+2hrs (Pre-menopausal), Cortisone/day, Cortisone/day (Pre-menopausal), Creatinine Bedtime (male), Creatinine Bedtime (Post-menopausal), Creatinine Bedtime (Pre-menopausal), Creatinine Dinnertime (male), Creatinine Dinnertime (Post-menopausal), Creatinine Dinnertime (Pre-menopausal), 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