Estrogen Metabolism Testing

There is no single test that accurately predicts breast cancer risk. However, several tests are available that may be of interest in breast cancer. For example, saliva hormone testing provides evidence of a common pattern of hormone imbalance in breast cancer patients. Other tests may have predictive value for breast cancer risk, including the tumor marker Ca 15-3 and the Estrogen Metabolism Ratio.

What is the Estrogen Metabolism Ratio?

The Estrogen Metabolism Ratio looks at how estrogens are broken down by the body. Two of the metabolites of estrogen are 16-alpha-hydroxyestrone (16OHE1) and 2-hydroxyestrone (2OHE1). A proper balance between these two metabolites is important to maintaining good health 16-alpha-hydroxyestrone (16OHE1) is a more potent estrogen and may therefore promote growth of hormone dependent cancers like breast cancer. Conversely, there is some evidence that the weaker major urinary metabolite of estrogen, 2-hydroxyestrone (2OHE1),
alpha-hydroxyestrone may give an indication of breast cancer risk. Studies suggest that an Estrogen Metabolism Ratio (EMR) of greater than 2.0 is associated with decreased breast cancer risk in both pre- and post-menopausal women.

Research

Several retrospective case-control studies have demonstrated that the EMR is lower in both pre and postmenopausal women diagnosed with breast cancer, compared to disease-free, age matched controls. A lower EMR is most often associated with decreased urinary excretion of 2OHE1, the principal urinary estrogen metabolite.

Several prospective case-control studies have examined the relationship between EMR and future risk of breast cancer. Estrogen Metabolism Ratios were measured in frozen urine specimens obtained at the inception of a large observational study of women on the Isle of Guernsey. The findings were as follows:

Postmenapausal Women

After more than 16 years of follow-up,a baseline EMR of greater than 2.1 resulted in a 30% decrease in the risk of breast cancer in post-menopausal women compared to those whose EMR was less than 1.4 at baseline.

Pre-Menapausal Women

Again after 16 years of follow-up,a baseline EMR of greater than 2.4 resulted in a 30% decrease in the risk of breast cancer in pre-menopausal women compared to those whose EMR was less than 1.8 at baseline. A study by Muti confirmed Meilahn‘s findings for pre-menopausal women. The aforementioned studies suggest that maintaining a minimum EMR of between 2.0 and 2.4 through premenopause and into postmenopause may modestly reduce the risk of breast cancer.

Men

Although research in this area is very preliminary, the Estrogen Metabolism Ratio may also help identify men at risk of prostate cancer.

Raising the Estrogen Metabolism Ratio

It is important to note that no interventional trials have prospectively examined the effect of raising a low EMR. Therefore, even though the natural products listed in Table 1 help increase the EMR (primarily through increased excretion of 2-hydroxyestrone relative to 16-6-hydroxyestrone), to date there is no proof that increasing the ratio in adult women now reduces their risk of breast cancer later. 

Monitoring the Estrogen Metabolism Ratio

Treatment decisions should be based on an assessment of the Ratio, rather than on the concentrations of the component urinary estrogens (2-OHE and 16-OHE1). In any given patient, across-time comparison of the concentrations of the component estrogens is not recommended. For pre-menopausal women, the absolute amount of estrogens excreted can vary widely throughout the menstrual cycle, and from patient to patient. The assay itself so has certain limitations. For example, sample dilution is necessary in some cases. Dilution has little impact on the Ratio, but increases the apparent concentrations of the individual estrogens. Also, the concentration of estrogens in the specimen is a function of the hydration status of the patient, whereas the EMR is not sensitive to this factor. Apparent estrogen concentrations can also vary somewhat across different kit lot numbers, whereas the EMR is more stable across time. Again, clinical decisions should be made on the ratio, not the absolute levels of the component estrogens.