Estrogen Metabolites Profile
Doctor's Data
Sample type: Urine
Requires fasting: No
At home test
Details
The Estrogen Metabolites Profile provides a detailed insight into estrone, estradiol, estriol, metabolism, as well as the efficiency of COMT (methylation activity). This non-invasive test requires only 4 or 5 separate urine collections. Because the breakdown of hormones relies so heavily on processes within the liver, this test can also elucidate areas of interest as it pertains to conjugation of each metabolite. Additionally, testing urinary hormone metabolites can contribute to further understanding of endogenous hormone secretion, supplemental hormone utilization, enzyme activity, oxidative stress, and insight into whether your body is safely metabolizing hormones.
This profile is a consideration for baseline or follow up testing for patients with concerns that are particular to estrogens and/or monitoring for harmful metabolites due to the influence of HRT/BHRT.
- 16-Hydroxyestrone
- Estradiol, Urine
- Estrone, Urine
- 4-hydroxysterone (4-oh-e1)
- 2-methoxyestrone (2-m-e1)
- 4-methoxyestrone (4-m-e1)
- 2-hydroxyestradiol (2-oh-e2)
- 4-hydroxyestradiol (4-oh-e2)
- 2-methoxyestradiol (2-m-e2)
- 4-methoxyestradiol (4-m-e2)
- Creatinine/day
- 2-hydroxyesterone (2-oh-e1)
Estimated days for results: Results should arrive 5 to 7 days after the lab receives samples.
Evaluation of the estrogen metabolism pathway relies on understanding several key steps of metabolism: the amount of parent estrogens, hydroxylation of E1 and E2, methylation of hydroxy estrogens, and the function of key enzymes.
Unconjugated Estrogens: Unconjugated estrogens are the main steroid hormones estrone (E1), estradiol (E2), and estriol (E3). In females, these hormones are primarily produced in and excreted from the ovaries, with a smaller percentage coming from the adrenal glands and conversion in peripheral tissues. In males, adrenal and peripheral production is primary, with a small amount produced in the testes. The amount of unconjugated estrogens is important as this will determine the starting pool for further metabolism.
Hydroxylation of Estrogens: Phase I metabolism is essentially the addition of a reactive hydroxyl group to the 2 and 4 positions of estrone and estradiol and the 16 position of estrone. These estrogens make up what is known as the catechol estrogens. 2-OH E1 and 2-OH E2 are the primary metabolites of the estrogens and are thought to be “safe” due to their low potencies, association with cell differentiation, high clearance rate, and anti-cancer properties compared to the 4-OH pathway metabolites. The 4-OH pathway implies higher risk as these metabolites can generate a large amount of free radical and DNA damage compared to the 2-OH pathway. 16-OH E1 is considered the most “estrogenic” of the metabolites as it has also been shown to play a role in genotoxic reactions. However, once hydroxylated to estriol, it is rendered a non-proliferative / protective estrogen. The ratio of 2OHE1 to 16a-OHE1 can provide a marker for breast health and cancer risk with a lower 2OHE1 to 16a-OHE1 ratio shown to correlate with higher cancer risk in post-menopausal women.
When evaluating phase 1 metabolism, comparison of the percentages of 2, 4, and 16 hydroxy metabolites may elucidate which pathways are preferred. Understanding this can be helpful in choosing the appropriate treatments.
Methylation of Hydroxy Estrogens: Phase II detoxification of 2-OH and 4-OH metabolites via Catechol-o-Methyl Transferase (COMT) creates 2-M E1/E2 and 4-M E1/E2. Methyl metabolites are harmless and, in this form, can be rapidly excreted in the urine. If methylation pathways are inadequate due to low levels of COMT or cofactors necessary for methylation, the 2-OH and 4-OH metabolites can travel down a more metabolically dangerous pathway leading to oxidation and the potential for the formation of highly reactive quinones. Estrogen quinones, especially the 4-quinone of E1 and E2, are highly reactive and can bind to DNA to form adducts that can lead to permanent mutations in DNA.
The ratio of 4-M E1/E2 to 4-OH E1 / 2 and 2-M E1/E2 to 2-OH E1/E2 can help determine if adequate methylation of catechol estrogens is occurring. The higher the ratio, the higher the likelihood of metabolizing toward the less harmful pathway of methylation and therefore less reactive quinone formation. Even if 4-OH metabolites are elevated, adequate methylation means these metabolites are being detoxified rendering them less harmful.
Unconjugated Estrogens: Unconjugated estrogens are the main steroid hormones estrone (E1), estradiol (E2), and estriol (E3). In females, these hormones are primarily produced in and excreted from the ovaries, with a smaller percentage coming from the adrenal glands and conversion in peripheral tissues. In males, adrenal and peripheral production is primary, with a small amount produced in the testes. The amount of unconjugated estrogens is important as this will determine the starting pool for further metabolism.
Hydroxylation of Estrogens: Phase I metabolism is essentially the addition of a reactive hydroxyl group to the 2 and 4 positions of estrone and estradiol and the 16 position of estrone. These estrogens make up what is known as the catechol estrogens. 2-OH E1 and 2-OH E2 are the primary metabolites of the estrogens and are thought to be “safe” due to their low potencies, association with cell differentiation, high clearance rate, and anti-cancer properties compared to the 4-OH pathway metabolites. The 4-OH pathway implies higher risk as these metabolites can generate a large amount of free radical and DNA damage compared to the 2-OH pathway. 16-OH E1 is considered the most “estrogenic” of the metabolites as it has also been shown to play a role in genotoxic reactions. However, once hydroxylated to estriol, it is rendered a non-proliferative / protective estrogen. The ratio of 2OHE1 to 16a-OHE1 can provide a marker for breast health and cancer risk with a lower 2OHE1 to 16a-OHE1 ratio shown to correlate with higher cancer risk in post-menopausal women.
When evaluating phase 1 metabolism, comparison of the percentages of 2, 4, and 16 hydroxy metabolites may elucidate which pathways are preferred. Understanding this can be helpful in choosing the appropriate treatments.
Methylation of Hydroxy Estrogens: Phase II detoxification of 2-OH and 4-OH metabolites via Catechol-o-Methyl Transferase (COMT) creates 2-M E1/E2 and 4-M E1/E2. Methyl metabolites are harmless and, in this form, can be rapidly excreted in the urine. If methylation pathways are inadequate due to low levels of COMT or cofactors necessary for methylation, the 2-OH and 4-OH metabolites can travel down a more metabolically dangerous pathway leading to oxidation and the potential for the formation of highly reactive quinones. Estrogen quinones, especially the 4-quinone of E1 and E2, are highly reactive and can bind to DNA to form adducts that can lead to permanent mutations in DNA.
The ratio of 4-M E1/E2 to 4-OH E1 / 2 and 2-M E1/E2 to 2-OH E1/E2 can help determine if adequate methylation of catechol estrogens is occurring. The higher the ratio, the higher the likelihood of metabolizing toward the less harmful pathway of methylation and therefore less reactive quinone formation. Even if 4-OH metabolites are elevated, adequate methylation means these metabolites are being detoxified rendering them less harmful.
5–7 business days
- Add-on: Comprehensive Neurotransmitter Profile
- Add-on: DNA Oxidative Damage Assay
- Add-on: NeuroBasic Profile
- Add-on: Urine Amino Acids
BEFORE YOU START: Please read all of the instructions in the sample collection kit carefully.
Collect urine on days that are determined by you and your provider. We recommend that you adhere to your most common sleep schedule and collect your urine samples as close as possible to the times specified on page 5 of the instructions included in the sample collection kit. Shift workers should adapt the collection times in accordance with sleep schedule.
Never discontinue prescription medications without first consulting your provider. Please do not send any medications with your kit.
Collection Schedule Summary
Please follow instructions included in sample collection kit.
Day 1 Collection
#1 Dinnertime: collect within 1-2 hours prior to eating dinner
#2 Bedtime: collect within 1 hour prior to sleep
Mid Sleep
Midsleep: collect only if you wake to urinate while sleeping
Day 2 Collection
#3 Waking: collect within 10 mins of waking
#4 Post-waking: collect after 2-4 hours
What days of the month should I collect?
- Men, post-menopausal women, and those testing only corticoids: collect any day.
- Women with menstrual cycles: begin the collection between days 19 and 23 of a 28-day cycle, counting the first day of your period as day 1.
- If cycles are irregular, contact your provider for clarity about the timing of your collection.
Recommendations for women and men on hormones
- 72 hours prior and during collection: Discontinue oral and sublingual hormones.
- 72 hours prior and during collection: Do not use hormones vaginally, as this may directly contaminate the urine.
- Other hormones such as topical creams and gels, injectables, and patches can be used on your regular schedule.
- Do not skip doses of oral birth control pills unless instructed by your healthcare provider.
A baseline hormone level may require supplement usage to stop for a longer period of time. Call your provider with questions.
Additional Recommendations
- Cortisol/glucocorticoid supplementation: Consult with your health care provider if you are taking glucocorticoids. Certain medications such as asthma inhalers and hydrocortisone contain cortisol. To evaluate natural cortisol production, it is recommended to stop cortisol containing products 5 days prior to sample collection.
- 24 hours prior and during collection: avoid alcohol, caffeine, tobacco or nicotine-containing products and strenuous exercise.
- 24 hours prior and during collection: for best results, minimize fluid intake (between 4-8 cups/1-2L).
The intent of this collection method is to create a urine test that closely represents a 24-hour collection. With this in mind, we want you to include as much urine as possible that is produced throughout a day and night. During the time period that urine is being collected it is important to collect urine from a full bladder as much as possible. It is more important to get a good representation of urine than it is to collect at a precise time.
State restrictions:
Patient can't order this test if they are located in Hawaii, Puerto Rico, New Jersey, New York, or Rhode Island
