Estrogen is a sex hormone involved in many biological processes, including female and male reproduction, neuroendocrine, vascular, skeletal, and immune systems.
Estrogens are active compounds, and when their active role is done, they must be excreted from the body. But, this is not necessarily a simple process. First, the active compound must be converted to an inactive compound (typically water soluble) so that it can then be sent to the colon and kidneys to healthfully leave the body via feces and urine.
Estrogen is a hormone that both males and females make endogenously. However, estrogens and estrogen-like compounds are also found in the environment. For example, phytoestrogens are plant chemicals that mimic the structure of estrogen. Also, man-made chemicals such as polychlorinated biphenyls (PCBs), bisphenol A (BPA), and phthalates can also mimic estrogen when it comes into contact with our bodies.
Whether it is an endogenous estrogen that we make ourselves, a natural plant-derived phytoestrogen, or a man-made estrogen-mimicking chemical, they must be adequately metabolized to be excreted from the body. Functional medicine can help us better understand how estrogen is supposed to be metabolized and how to assist in the metabolism to have optimal healthy estrogen levels.
How is Estrogen Metabolized in the Body
Estrogen is mainly metabolized in the liver through a process called biotransformation. Biotransformation is the process of breaking down estrogens into metabolites that can be excreted from the body. This process is also sometimes referred to as detoxification.
Hydroxylation is the process occurring in the first phase of biotransformation in the liver with the use of the cytochrome P450 enzymes. By the end of this phase 1, there are three different possible estrogen metabolites: 2-hydroxy estrone (2-OH), 16-hydroxy estrone (16α-OH), and 4-hydroxy estrone (4-OH).
The amount of each metabolite that an individual's body produces is up to various genetic factors and the efficiency of the liver biotransformation pathways. Also, each metabolite has varying bioactive properties. For example, the 2-OH metabolite is the weakest metabolite of the three. Because of this "weakness," it has less estrogenic activity overall in the body and is considered the safest metabolite (some call this metabolite the "good" estrogen). 4-OH is a much stronger estrogen metabolite and has been shown to alter DNA, leading to potential tumor growth. 16α-OH has also been shown to have potential tumor initiation properties and specifically has been shown to be associated with breast cancer.
Post hydroxylation, these estrogen metabolites are further metabolized through the processes of methylation, glucuronidation, and sulfation. Methylation is important, but specifically for the 2-OH and 4-OH metabolites, because the methylation process will activate the beneficial properties of the 2-OH metabolite and decrease the harmful properties of the 4-OH metabolite.
While there is significantly less research on glucuronidation and sulfation, research suggests that these processes also play a role in the detoxification and biotransformation of estrogen.
Newer research has defined the gut microbiome's specific genes responsible for metabolizing estrogens as the estrobolome. However, we know that β-glucuronidase plays a role in glucuronidation and that microbes in our gut microbiome secrete it. This leads to the understanding that gut health, specifically a diverse microbiome, also plays a significant role in the overall metabolism of estrogen.
What Causes Estrogen Imbalance
An estrogen imbalance can be caused by a disruption anywhere within the known estrogen metabolic pathways.
An imbalance of other hormones, such as thyroid hormones, blood sugar regulation hormones, or other reproductive hormones, such as testosterone or progesterone, can contribute to an estrogen imbalance since there is a delicate balance required for hormonal homeostasis.
Poor liver function is also a possible cause of estrogen imbalance. This is because the liver is the location for most estrogen metabolism. So, if it isn't functioning optimally, the result could be an imbalance of estrogen and estrogen metabolites.
Dysbiosis of the gut microbiome can also be a cause of estrogen imbalance. The gut microbiome strongly influences the overall metabolism of estrogen. So, if the gut microbiome is disrupted or not diverse enough, an estrogen imbalance could occur.
Endocrine Disrupting Chemicals (EDCs) are also a potential cause of estrogen imbalance. Research shows that these EDCs can potentially interfere with the synthesis, action, and metabolism of all sex steroid hormones, particularly estrogen. EDCs are rampant in our environment and can be found in industrial chemicals, pesticides on food, plasticizers in our plastic, metals, pharmaceuticals, and chemicals in personal care products.
Estrogen Imbalance Signs & Symptoms
Common signs and symptoms of estrogen imbalances
- Bloating and digestive upset
- Low libido
- Irregular periods
- Tender, swollen, or fibrocystic breasts
- Weight gain
- Hot flashes
- Mood swings
- Polycystic ovarian syndrome (PCOS)
- Male hormonal issues: gynecomastia, male infertility, erectile dysfunction
How Do I Know if Estrogen is Being Properly Metabolized in My Body
Functional medicine can be beneficial in helping to uncover and diagnose the issues that may be going on in the process of estrogen metabolism.
A thorough hormone panel can be beneficial if hormonal imbalances are seemingly present. The Hormones Panel by Vibrant America tests 13 sex hormones and related biomarkers that can help distinguish whether estrogen is out of balance or if the hormone symptoms are caused by a different hormone imbalance.
The DUTCH Complete (Dried Urine Test) by Precision Analytical (DUTCH) is a beneficial test for estrogen metabolism. It looks at the specific estrogen metabolites in the urine and reports how much of each metabolite is present. Then based on those results, overall liver biotransformation can be inferred.
Looking at overall liver function via the Hepatic Function Panel by Vibrant America could also help determine whether liver dysfunction or liver "sluggishness" is going on.
Because the microbiome also plays such a significant role in overall estrogen metabolism, looking into the health of the microbiome would be a good idea. The GI360 Profile Test from Doctor's Data is excellent for this purpose. It is a comprehensive stool analysis that can help us examine the microbiome's abundance and diversity.
The ENVIROtox Complete Panel by Great Plains Laboratory provides a comprehensive look at the current toxic chemical burden someone might have, as well as any resulting oxidative stress, inflammation, and mitochondrial damage. This is a thorough look that would be helpful when trying to determine if EDCs are a causative issue going on.
How to Support Estrogen Metabolism & Detox
Hormone Balancing Diet
Gut health is an area that must be focused on. The microbiome's diversity impacts estrogen metabolism. So, ensuring a robust and diverse microbiome is essential. Probiotics have been shown to restore the gut microbiome. However, for those interested in a more food-based treatment, eating a low inflammatory high fiber diet consisting of fermented foods has been shown to also positively affect the diversity of the gut microbiome.
Supporting overall hormonal balance is a great way to ensure that estrogen is found at proper levels in the body. Using herbal medicine is a great way to ensure the balance of hormones, specifically estrogen. Glycyrrhiza glabra, also commonly known as licorice, is an herb that has alterative properties. This means that when estrogen levels are too high, it can inhibit estrogen action, and when estrogens are too low, it can help increase estrogen production.
Calcium-d-glucarate supplementation can also help support the excretion of excess estrogen since it inhibits beta-glucuronidase and allows more estrogen to leave the body in the stool.
Liver health is also essential for ensuring proper estrogen metabolism since most estrogen metabolism occurs within the liver. Milk thistle, resveratrol, coffee, and green tea all have evidence to be beneficial in assisting with liver function.
Because EDCs can cause estrogen imbalance, reducing xenoestrogens, estrogen-specific EDCs, is an important part of a functional medicine treatment plan. Xenoestrogens can be found in synthetic hormones (i.e., in birth control pills), personal care products (i.e., parabens), pesticides (i.e., in our food supply - particularly food that is not grown organically), and plastics (i.e., BPA). Simple actions would include:
- Consuming more organic food.
- Moving away from plastics.
- Choosing glass or stainless steel.
- Using chemical-free personal care products.
Estrogen metabolism and detoxification is an important process consisting of several steps that must all be functioning properly to efficiently excrete estrogen metabolites and ensure a balance of estrogen in relation to all other hormones.
Phases 1 and 2 of liver biotransformation are the first step, followed by further processing and excreting in the gut. If liver and gut health is suboptimal, then estrogen cannot be adequately processed, leaving an excess of estrogen or estrogen metabolites.
With the help of functional medicine, optimal estrogen metabolism and detoxification can be identified and supported to ensure healthy levels of this vital hormone.