Three Types of Estrogen and their Cancer Implications Explained

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The three types of estrogen; estradiol, estrone, and estriol have different effects in the body especially relating to cancer.

Estrogens play a very important role in your body. Compounding pharmacists have informed us that it is essential for BioHRT (Bio Hormone Replacement Therapy) to include estradiol with estrogen, as well as pregnenolone and DHEA ingredients in BHRT for most menopausal women. This is important not just for beauty, health, and sexuality, but also for heart health, stroke prevention, cognition, and mental clarity.

All estrogens are not created equally. Whether it is the three types of estrogen we’ll discuss in this article or the many other types and their effects of the different estrogens in men as well as in women, there is much confusion regarding estrogens.

It would appear that the majority of people believe that there is only 1 important estrogen and for women, estrogen production stops after menopause or after a total hysterectomy.

The body never stops producing estrogens.  That applies to perimenopausal and postmenopausal women.  That applies to men and women.

Estrogens are produced by various tissues in the body. Most know that the ovaries are the primary production site of estrogens in cycling women.

But, did you know that the adrenal glands and fat cells produce estrogens as well?  In fact, beyond menopause and in men, abdominal and visceral fat is the primary site of estrogen production.

The three types of estrogen produced in the body are:

  • estradiol
  • estrone
  • estriol

These 3 estrogens, though similar, have very different estrogenic effects which have significant cancer implications.

Estriol (E3) is the weakest of the estrogens. Estriol dominates during pregnancy and is produced in very large amounts from the placenta during pregnancy. However, estriol production is not confined to the placenta during pregnancy.

Estriol is also produced from the liver in smaller amounts. Estriol’s activity is focused on hair, nails, skin, and the vaginal lining. Studies also suggest estriol has potential in breast cancer prevention secondary to its higher affinity for the beta estrogen receptors (ER-beta).

Estriol binds to the ER-beta in the breast to inhibit breast cell growth.  Estriol has a 3:1 higher affinity for ER-beta versus ER-alpha which promotes a more anti-inflammatory signal [1] [2].  It is important to remember that the ER-beta receptor regulates the ER-alpha receptor.  Thus, estriol’s affinity for ER-beta will counter any ER-alpha signaling. In contrast, estradiol and estrone will increase breast cell growth (cancer) because of their higher affinity for the alpha estrogen receptors (ER-alpha).

Estrone (E1) is the second most potent estrogen produced in the body.  In women, premenopausal estrone production predominantly comes from the adrenal glands and fat.

Estrone is produced predominately from fat cells beyond menopause. Overweight and obese women and men have high circulating estrone levels.  The enzyme aromatase, that converts DHEA into estrone, is upregulated in fat.

Dr. Nathan Goodyear Explains the 3 Main Types of Estrogen

Approximately 67% of adult Americans are either overweight or obese which translates to a lot of estrone production. Regardless of age and sex, excess abdominal fat will result in an increase in estrone production. The postmenopausal increase in estrone production has been implicated in breast tumors in animal studies.

In stark contrast to estriol, estrone has a 5:1 higher affinity for ER-alpha versus ER-beta in the breast and other tissues 23 24.  This ER-alpha preference will preferentially promote breast growth. Estrone increases inflammation due to its higher affinity for the ER-alpha receptors.

Estradiol is the most potent and dominant estrogen for a woman who is cycling. Estradiol is produced predominately from the ovaries and declines after menopause with the decline in ovarian function.

Estradiol is the main stimulus for the lining of the uterus during the first 2 weeks of a woman’s monthly cycle and is also involved in triggering ovulation. Estradiol has an equal affinity for ER-alpha and ER-beta alpha receptors 23 24.  However, estradiol has a very high affinity for the estrogen receptors which promote breast growth and inflammation.

 

 

[1] Zhu BT, Han GZ, Shim JY, Wen Y, Jiang XR. Quantitative structure-activity relationship of various endogenous estrogen metabolites for human estrogen receptor alpha and beta subtypes: Insights into the structural determinants favoring a differential subtype binding.

Endocrinology. 2006;147(9):4132–4150.

[2] Rich RL, Hoth LR, Geoghegan KF, et al. Kinetic analysis of estrogen receptor/ligand interactions. Proc Natl Acad Sci U S A.2002;99(13):8562–8567.

23 Zhu BT, Han GZ, Shim JY, Wen Y, Jiang XR. Quantitative structure-activity relationship of various endogenous estrogen metabolites for human estrogen receptor alpha and beta subtypes: Insights into the structural determinants favoring a differential subtype binding.

Endocrinology. 2006;147(9):4132–4150.

24 Rich RL, Hoth LR, Geoghegan KF, et al. Kinetic analysis of estrogen receptor/ligand interactions. Proc Natl Acad Sci U S A.2002;99(13):8562–8567.

 

 

This article is courtesy of An Oasis of Healing, an integrative medical and healing facility utilizing alternative cancer treatments that help patients and their families learn to re-establish health after having been diagnosed with cancer.

 

 

Dr. Nathan Goodyear is dedicated to disease prevention, disease resolution, and the Wellness Lifestyle through a solution-based, Integrative Medicine approach founded in science. Dr. Goodyear received his Bachelor of Arts from Louisiana Tech University and his Doctor of Medicine from LSU Health Sciences Center.

He is Board Certified in Obstetrics and Gynecology and served as the Chief Resident in Obstetrics and Gynecology at the University of Tennessee. Dr. Goodyear has practiced Integrative Medicine since 2006. Dr. Goodyear is a Fellow in Functional and Regenerative Medicine and served on the board of the American Functional Medicine Association. Dr. Goodyear is a published author, Man Boob Nation–an Integrative medicine approach to low Testosterone published in 2014, and Total Testosterone Transformation published in 2017

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