estrogen metabolism: the good the bad and the ugly

Estrogen is very important for all women and men. A lot of people don’t realize that estrogen doesn’t exist as a singular molecule; there are different versions of estrogen. As you’ll see, there are good estrogens, bad estrogens, and downright ugly estrogens.

What is Estrogen?

Estrogen is a steroid hormone, originating from cholesterol (specifically LDL-C). It’s produced in the ovaries and adrenal glands of women, and the testicles and adrenal glands of men. The production of estrogen is a multi-step process, as depicted below.

schematic diagram showing the metabolism of cholesterol into various hormones including progesterone, cortisol, testosterone, and estrogen

Three Forms of Estrogen

Estrogen isn’t as simple as the diagram above shows. In fact, there are various forms of estrogen, each having unique properties in health and disease.

The three forms of estrogen are: estrone, estradiol and estriol [1].

  • Estrone (E1): is the dominant estrogen in post-menopausal women
  • Estradiol (E2): is the most biologically active estrogen. In pre-menopausal women, this estrogen is the most dominant estrogen
  • Estriol (E3): is the major estrogen found in pregnant women
schematic diagram showing the 3 forms of the hormone estrogen: estrone, estradiol, estriol

Estrogen Metabolism

Estradiol and estrone are metabolised in the liver by 3 competitive pathways [1], where they are converted to various ‘metabolites’ of estrogen. The scientific terms are 2-hydroxyestrone, 4-hydroxyesterone, 2-hydroxyestradiol, 4-hydroxyestradiol and 16a-hydroxyestrone.

These estrogens are simply referred to as the 2-hydroxy-Estrogens, 4-hydroxy-Estrogens and 16-hydroxyestrogens. The chemical abbreviation of hydroxy is OH.

So, the remainder of this article will refer to them as:

  • 2-OH-Estrogens
  • 4-OH-Estrogens
  • 16-OH-Estrogens

As you’ll soon learn, 2-OH is good, 4-OH is bad, and 16-OH is ugly.

diagram explaining estrogen hormone metabolism showing the different forms of estrone, the good and the bad ones.
diagram explaining estrogen hormone metabolism showing the different metabolites of estradiol, including the good and bad ones

Estrogen: The Good, The Bad and The Ugly

It's clear estrogen can be transformed to form various metabolites.

The most significant part of estrogen metabolism is some are good for health and others are quite bad for health.

Click here to learn more about what makes a hormone good or bad.

In a nutshell:

  • 2-hydroxy-estrogens are good
    • There is evidence these types of estrogen inhibit certain cancers [1]
    • They’re good because they have lower binding affinity at estrogen receptors, high rate of clearance and reduced hormonal potency [2] [3]
  • 4-hydroxy-estrogens are bad
    • These possess carcinogenic potential due to their ability to cause DNA damage [1]
    • They also increase oxidation and inflammation, which explains why they relate to PMS, cancers, menstrual cramps, headaches and more [1] [4]
    • This metabolite is 4 times more active in breast cancer cells than the good 2-hydroxy-estrogen type; the ratio of 2-OH to 4-OH is used to screen for breast cancer and objectivity risk [1]
  • 16-hydroxy-estrogens are ugly [1]
    • These ones are potential tumor initiators [1]
    • They promote unscheduled DNA synthesis and growth, which are bad things when it comes to cancer [1]
    • Plays an important role in breast cancer induction [1]

Testing for Estrogens

Since estrogen is implicated is a wide range of conditions, testing is often necessary. I use specific urine tests which analyzes for the breakdown between the various estrogen metabolites mentioned here.

If you’re curious, talk to your naturopath about whether testing is necessary or indicated.

Summary

Estrogen is not a single molecule – there are various forms, each having different implications for overall health. There are many ways we can investigate and treat for estrogen metabolism issues. Talk to your naturopath today!

References

Interested in learning more?

Read on in our series of articles on Hormone Health!

About the Author - Dr. Johann de Chickera

Dr. Johann de Chickera is a naturopath at Absolute Health and Wellness in Paris Ontario

Dr. Johann is a licensed naturopathic doctor and co-owner of Absolute Health and Wellness. He completed his 4-year degree at the Canadian College of Naturopathic Medicine (CCNM). His clinical focus lies in chronic disease, such as those related to the Gastrointestinal, Endocrine, and Immune Systems.

His approach to medicine relies on working with the patient to come up with a feasible, multi-factorial approach that addresses all complaints at once. He employs a strong background in diagnostic medicine and human physiology and pathology to diagnose and treat. His treatment involve a combination of nutritional counselling, botanical medicine, eastern medicine (acupuncture), nutraceutical supplementation and hands on physical medicine.

To book in please call us at (519) 442-2206 or click here.

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