Estrogen Metabolism – why it’s so crucial to keep the balance!



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Estrogen Metabolism – why it’s so crucial to keep the balance!

Hormones are chemical substances that act as messengers to control the functioning of the body’s organs. Most hormones are proteins consisting of amino acid chains while some hormones are steroids, made of fatty cholesterol-produced substances. Dietary fat is required for the production of all hormones-from growth hormone to sex hormones.

Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, thymus, thyroid, adrenal glands, and pancreas. In addition, men produce hormones in their testes and women produce them in their ovaries. Hormones travel in your bloodstream to tissues or organs. They work slowly, over time, and affect many different processes, including:

  • Growth and development
  • Metabolism – how your body gets energy from the foods you eat
  • Sexual function and reproduction
  • Mood

Liver’s role in hormone regulation

The liver acts as a hormone processor (regulating some hormone levels and guiding various hormones to accomplish their function in certain areas).  It also breaks down or metabolizes the hormones once they have done their work in the body. Liver function has a critical effect on hormones and hormones will affect the liver.

Functions of the liver

  • Bile production, which is stored in the gallbladder and released when required for the digestion of fats
  • Regulates blood sugar levels and involved in the metabolism of proteins and fats
  • Stores vitamins A, D, K B12 and folate
  • Creates blood clotting factors
  • Detoxification of metabolic waste, drugs, alcohol and chemicals
  • Sex hormone regulation and elimination of excess hormones

Symptoms of liver dysfunction

  • Poor fat metabolism and digestive problems
  • Blood sugar problems
    Immune dysfunction
  • Hormonal imbalance  *
    • Intolerance to the contraceptive pill or to hormone replacement therapy (side effects)
    • Menopausal symptoms may be more severe (hot flashes)
    • Premenstrual syndrome may be more intense

When the body experiences a hormone excess (whether produced by the body or introduced by hormone therapy), the liver may not be able to process the hormone(s) as quickly or efficiently, causing a hormone imbalance.  Hormones are powerful; it takes only a tiny amount to cause big changes in cells or even your whole body. That is why too much or too little of a certain hormone can be serious.

Hormone Metabolism

The female sex hormone estrogen is tied to sexual health, and bone density, so maintaining healthy levels is crucial. Estrogen and another hormone, progesterone, are also involved in pregnancy and the regulation of the menstrual cycle. Estrogen is a big culprit in many cases as it promotes cellular growth in the breast tissues and reproductive organs. Excess estrogen causes the body to build up fat for a pregnancy and slows metabolism. Thus, estrogen dominance produces fat on the belly and hips and sugar cravings, despite exercise and dieting.

It is important to consider how estrogens are metabolized and the effects of that metabolism. Estrogens break down into estrogen metabolites that have varying levels of estrogenic activity, and the stronger the estrogenic effect, the greater the risk of developing estrogen-related cancer. Risk factors that result in the breasts being exposed to more estrogen for longer periods of time are: onset of menstruation before age 9, having a first child after the age of 30, having no or few children and experiencing menopause after age 55.

The liver metabolizes hormones and other substances using two primary phases known as the Phase 1 and Phase 2 pathways.

During Phase 1, some hormones or substances are metabolized directly, but often they are converted into intermediate forms, which are then further metabolized in Phase 2.  Phase 1 pathway is the main metabolic pathway for the estrogen hormones.

Cumulatively, these two phases of biological transformation are how the liver provides the body with nutrients and supports the excretion of excess or toxic substances in the urine, liver bile, perspiration and exhaled air. The pathways depend on a large number of nutrients, including enzymes and amino acids, and their availability (or lack thereof) seems to have a significant influence on the metabolic outcome.

In premenopausal women, the ovaries produce estrogen, primarily estradiol, most of which the body converts to estrone, and eventually estriol. The liver then metabolizes the remaining estradiol and converted estrone, breaking it down further, and excreting the excess from the body.  Some researchers now believe that the liver’s ability to metabolize estrone is the key to understanding estrogen-related cancer risk. During Phase 1 metabolism, estrone is converted into various metabolites (2-hydroxyestone, a very weak estrogen, and 16-alpha-hyroxyestrone, a very potent estrogen). If the conversion process favors the stronger form(s) rather than the weaker form(s) of estrogen metabolites, then tissue that has an abundance of estrogen receptors, such as the breasts and uterus, may be more vulnerable to excessive estrogen activity, potentially leading to the formation of fibroids or the stimulation of estrogen-sensitive cancers.

Phase 1 processing can be affected by many factors, including extreme overload, the effects of alcohol or drugs, a lack of nutrients, or interference from other substances. For example, grapefruit juice can slow down the enzymes in Phase 1, potentially altering hormone balance. And, many prescription drugs are metabolized in Phase 1, which can also interfere with the liver’s ability to handle the estrogen hormones.

Free Radicals

Each reaction in the Phase 1 pathway produces an intermediate form called a free radical. These can be very damaging to body tissues if they are not quickly neutralized by antioxidants. The intermediate forms produced in Phase 1 are in a highly reactive state until they are fully converted in Phase 2.

During Phase 2, a process known as conjugation begins, in which nutrients (amino acids) are combined with hormones and other substances, to convert them to water-soluble compounds that can be excreted efficiently in the urine or stool.

Of the various types of conjugation that may occur in Phase 2, the following are two of the most relevant to hormone metabolism:

Methylation:  aka methyl metabolism, is the process in which small parts of molecules (methyl groups), are passed from one molecule to another.  Once estrogens are methylated, they can be easily excreted.

Sulfation: is the process in which sulfur groups are added to estrogen or other molecules which allows for easy excretion.


Indole-3-carbinol (I3C): phytonutrient derived from cruciferous vegetables (Broccoli, cauliflower, cabbage), stimulates enzymes that promote the metabolism of estrogens into milder forms, potentially reducing the risk of estrogen-dependent cancers

S-adenylmethionine (SAMe): a rich source of methyl groups and sulfur (also improve bile flow, which is necessary for the removal of fat-soluble toxins and excess estrogens)

Glutathione: sulfur containing molecule added to estrogen for easy excretion.  Also a powerful antioxidant that inhibits formation of/protects against cellular damage from free radicals in phase 1 hormone metabolism.  Levels can deplete when the diet lacks essential nutrients and amino acids (fresh fruits, vegetables, fish and meats) that are required to synthesize it.

N-acetyl cysteine (NAC): sulfur containing amino acid and a building block for glutathione.


  • Eat plenty of fruits and vegetables (apples, onion, grapes, cabbage, broccoli, avocado, asparagus)
  • Drink green tea
  • Limit grapefruits and grapefruit juice which can slow down the enzymes activity and interferes with estrogen metabolism, potentially altering hormone balance
  • Adequate intake of vitamins B6 (whole grains and legumes) and B12 (primarily found in animal products) and folic acid (such as from green leafy vegetables) which support methyl metabolism
  • Adequate amounts of foods containing sulfur should be in the diet, including egg yolks, animal protein, garlic, onions and brussels sprouts
  • Avoiding overeating and heavy alcohol use
  • Dietary phytoestrogens such as soy foods modulate estrogen receptors (miso, tofu, soy milk)
  • Flax seeds contain phytochemicals that appear to lower the risk of breast cancer and hinder the action of excess estrogen in the body (grind flax seeds to optimize benefits)
  • Avoid all processed and refined foods, refined sugars, fatty foods, fried foods, junk foods, coffee, tea and soft drinks
  • Avoid all dairy products that are not certified organic – dairy foods contain high levels of antibiotics, steroids and artificial growth hormones
  • Limit chicken, turkey and eggs that are not free range/organic, as these often contain artificial growth hormones, antibiotics and steroids that increase the liver’s workload
  • Drink 8 glasses of water daily

Michelle Kramer B.Sc. Nutrition & Food Science

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