Many discussions concerning estrogen relate to its quantitative measurement, in other words the amount of estrogen one has. Pre-pubescence is the time when children have small amounts of estrogen. Puberty signifies a surge of estrogen that defines sexual characteristics and the onset of a woman’s childbearing years. Perimenopause and menopause are the times when estrogen begins to wane and becomes very minimal, respectively. While so much emphasis is placed on the amount more attention should be paid to how the body is metabolizing this estrogen. In this article we will discuss the forms of estrogen, the phases of estrogen metabolism and its relevance to overall health.
Three forms of estrogen
In women, most of the estrogen is produced by the ovaries. The adrenal glands, adipose (fat), skin, liver and brain also produce small amounts of estrogen in varying quantities throughout a woman’s lifespan.
The three forms of estrogen are:
- Estradiol (E2): the strongest form of estrogen, most abundant during childbearing years.
- Estrone (E1): a weaker form of estrogen, the most abundant form during the menopausal years. Estrone can convert into estradiol and, similarly, estradiol can convert to estrone.
- Estriol (E3): is also a weaker estrogen and is the most abundant form of estrogen during pregnancy.
These three forms of estrogen are metabolized, or broken down, into smaller molecules known as metabolites by enzymes in the liver in three distinct phases.
Phases of estrogen metabolism
Phase I
Phase 1 estrogen metabolism utilizes a water molecule to break down the estrogen into smaller components. This breakdown can use three different pathways. One of these pathways is more optimal for the body while the others can make the body more vulnerable to DNA damage if not detoxified appropriately.
The 2-OH-E1 pathway is the preferred enzyme pathway as it produces a weaker estrogen metabolite that binds to estrogen receptors. These pathways protect against cancerous cellular growth, cardiovascular and neurodegenerative diseases.1
The 4-OH-E1 pathway is more harmful to the body as the metabolite can break down further into a compound called quinone. Quinones can interact with and cause damage to the DNA in the breast and prostate tissue, for example, increasing the risk of cancer.
The 16-OH-E1 pathway has a mixed effect on the body, with elements of both protection and harm. It is a more potent form of estrogen than the 2-OH-E1 pathway and elevations of 16-OH-E1 have been linked with breast, endometrial cancer and cardiovascular and mother metabolic diseases. The benefit of elevated 16-OH-E1 is its effect on bone, as it stimulates bone growth, protecting against osteoporosis.
Phase 2
In phase two estrogen metabolism, the phase 1 metabolites are either methylated, or have a methyl group attached to them, or are conjugated using enzymes.
Phase 3
This is the phase when estrogen metabolism occurs. In other words, in Phase 3 the Phase 2 end-products are excreted in feces or in urine.
Tests for Estrogen Metabolism
There is a test known as DUTCH which stands for Dried Urine Test for Comprehensive Hormones. The test provides an individual’s quantity of sex hormones and adrenal hormones and their metabolites, melatonin and six organic acids using dried urine samples. It is collected over a fourteen-hour window providing a snapshot of what the hormones are doing over a large portion of the day. Hormones are released in pulses throughout the day rather than one or two releases in a twenty-four-hour period. Therefore, this extended testing period provides a broader, more accurate understanding of hormone production and metabolism.
Knowing which pathway your body favors is very important, given the health implications. The test allows a practitioner to tailor a specific supplemental and lifestyle plan to assist your body in utilizing the more protective pathways and supporting your individualized needs.
This test can be used at any time of life and amongst males and females. We have highlighted solely estrogen metabolism in this article. However, the test also provides information on testosterone, progesterone, cortisol levels and their metabolites. The results of a DUTCH test allow a more comprehensive picture of how all these hormones are being produced and broken down, giving a more focused view of how this may affect an individual’s health symptoms.
For more information on whether this test is appropriate for you, please consult a practitioner with expertise in women’s health.
Dr. Stacey Guggino, ND, LAc, graduated from the National College of Natural Medicine in Portland, Oregon with a Doctorate in Naturopathy and a master’s degree in Oriental Medicine. For the past 12 years, she has specialized in treating pain and sports injuries with acupuncture and prolotherapy. Dr. Guggino has also studied and practiced aesthetic medicine for 11 years.
Sources
- Ercole Cavalieri, Dhubajyoti Chakravarti, Joseph Guttenplan, Elizabeth Hart, James Ingle, Ryszard Jankowiak, Paola Muti, Eleanor Rogan, Jose Russo, Richard Santen, Thomas Sutter, Catechol estrogen quinones as initiators of breast and other human cancers: Implications for biomarkers of susceptibility and cancer prevention. Biochimica et Biophysica Acta (BBA) – Reviews on Cancer, Volume 1766, Issue 1,1 2006, Pages 63-78.
