Estrogen Metabolites Profile

What this laboratory test evaluates

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.

Additional test information

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.

Collection and processing

• Sample type: Urine
• Fasting: No
• Estimated laboratory processing: Results should arrive 5 to 7 days after the lab receives samples.

How Sunridge uses laboratory information

Sunridge considers the medical question, symptoms, history, medications, prior results, and whether the finding could change care before recommending testing. A laboratory result is not interpreted in isolation and does not establish a diagnosis by itself.

Before requesting this test

Availability, collection requirements, eligibility, and processing estimates can change. Sunridge reviews each request and, when appropriate, creates the order through Fullscript. Follow the current instructions supplied with the approved order.