Estrogen Metabolites
Is Testing Worthwhile?


In the Naturopathic community, testing estrogen metabolites has become almost commonplace.  However, if you ask your regular doctor about this testing, you may well be told that this testing is not proven to be reliable. 

We agree that more testing is needed but here is some information we have gathered to help you make a informed decision.  The testing is pricey because you have to pay out of pocket, but if you are considered at risk, it may be a worthwhile investment.

Estrogen 101

There are three main forms of naturally occurring estrogen in the body.  Estradiol is the most potent form of estrogen, estrone is next and estriol is the least potent form.  Estrogen and estrone can be converted back and forth into each other.  These two types of estrogen are the ones that are more commonly associated with breast cancer. 

Therefore, some people think it is better to have the lesser forms of potency in the blood.  It is the livers job to convert estradiol to estrone.  There are blood tests to see which types of estrogens are predominant in your body.  This test is often referred to as the 2/16 metabolite ratio test or estrogen metabolite testing.

You see, estradiol in the body seems to be metabolized in at least two distinct ways.  One end of an estrogen molecule has two carbon atoms; the other end has sixteen. Estrogen, which is metabolized through the two-carbon end seems to be innocuous, but a sixteen-carbon metabolite stimulates uncontrolled cell proliferation and allows groups of cells to grow without anchoring to a surface - two important factors needed for the development  of cancer.

Sixteen-carbon metabolites are also toxic to cellular DNA. Synthetic or xenoestrogens apparently block the 2-carbon pathway and promote 16-carbon metabolism.  (In contrast, natural plant xenoestrogens, like those occurring in broccoli, cabbage, and cauliflower, favor the two - carbon metabolite.)  Finally, xenoestrogens tend to stay in the body and remain active for a much longer time than natural estrogen, giving them the opportunity to do the body more harm.

More reent testing included the four-carbon pathway which is associated with the most toxic forms of estrogen.  Having a high ratio of E4 is now being thought to indicate an increased risk of breast cancer.

Why the Controversy?

Traditionally, your doctor will check for estrodiol, estrone or estriol levels if you are having heavy bleeding or some symptom of imbalance.  Testing the metabolites in this way is a newer test with some research saying it is helpful and other research saying it does not indicate risk in any way.

How good is the evidence?

We will certainly keep updating this page because the research is constant.  But as of February 2008, there are few long-term studies to prove this is prevention.  Prevention is notoriously hard to prove, but we do look forward to long-term studies.

What we have seen clinically is what other clinicians are reporting as well.  With a change in this ratio, the symptoms of estrogen in the body change.  For example, if the ratio of E$ is high or E16 is high and that ratio changes to a better balance of E2, the women have less breast pain, less hot flashes, easier periods, cooler thermograms, etc.

We have listed below several articles that will help you scout thru some of the evidence for yourself.  If you read something worthwhile or have an experience to share, please contact us.

Estrogen Metabolites

Estrogen and Breast Cancer Risk

Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16alpha-hydroxyestrone ratio in premenopausal and postmenopausal women.

Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer.

The classic 1997 study that is often sited.




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