Dr. Weeks’ Comment: It is official: the FDA has classified estrogen as a carcinogen.
Being a father of lovely daughters and wildly in love with my bride of 25 years, I took umbrage at this classification but it is true: estrogens are proliferative and must be carefully assessed and managed. We offer the Estronex test described below.
Men, you must pay attention also because prostate cancer also is driven by estrogens.
Are you at risk?
You, or someone you know, make estrogen and it gets metabolized. It starts with the conversion of estradiol to estrone, and then undergoes hydroxylation at C2, C4 or C16. Each metabolite has a different physiologic effect; 2-hydroxyestrone (2-OHE1) has very little estrogenic activity, while 16-hydroxyestrone (16-OHE1) is known as an estrogen-like compound. This estrogen-like effect is thought to increase proliferation of breast epithelial cells, which can lead to cancer. There is sound evidence that breast cancer risk can be modulated by looking at estrogen metabolites, specifically the ratio of 2-hydroyestrogens as compared to 16-hydroxyestrone in urine, the 2/16 ratio.
Now you should have two questions for me, the first being “Are urinary estrogens representative of breast tissue level?”
In a recent (2010) study, Taioli et.al looked for a correlation in the level of estrogens and estrogen metabolites between breast tissue and urine in women with primary breast cancer. Not all estrogens and metabolites correlated, though they found the pattern of the 2/16 ratio showed a correspondence between urine and breast tissue, and supported the use of the ratio in urine as a surrogate for tissue levels. Other studies have looked at a correlation between breast tissue and plasma, and found that plasma levels are generally much lower. Interestingly, the sum of all the metabolites measured in tissue correlated with BMI.
So if urine estrogen metabolites, specifically the 2/16 ratio, correlate to what is in breast tissue, the next question you should ask is: “Does the breast tissue level of estrogen metabolites, specifically the 2/16 ratio, correlate with cancer risk?” For the answer to that question I turned to a study that looked at the same estrogen metabolites in breast tissue from breast cancer patients and controls. In a 2002 study by Castagnetta et.al, breast tissue from breast cancer patients was found to have statistically significant, higher levels of 2-hydroxyestrodial and 16-hydroxyestone. Breast tissue from controls was found to have a higher 2/16 ratio.
The 2/16 ratio found in breast tissue is related to risk of breast cancer. Urinary 2/16 ratio is an adjunct measure of the breast tissue’s 2/16 ratio.
If you or your patients have a low 2/16 ratio, hope is not lost…below is a chart of several factors that have been found to increase the ratio as well as factors that can cause the ratio to be low:
|To increase 2;16 ratio
||Cause of low ratios
Additionally, you should think of race, genetics, detoxification abilities, and laboratory technique when evaluating a 2/16 ratio. Race is an independent predictor. In studies of mixed race, white women were found to have significantly higher mean 2/16 ratios. SNPs (single nucleotide polymorphisms), in the enzymes that breakdown estrogens, can also have an impact on the level of metabolites. The 2-OHE1 (E2) is catalyzed by the activating enzymes CYP1A1, and 16-hydroxyestrone by CYP3A4 and CYP2E. It’s also important to remember that these estrogens are inactivated by conjugating reactions, such as glucuronidation and sulfation, and methylation via the COMT enzyme. As far as laboratory technique, RIA and ELISA are routinely used for measuring estrogen metabolites due to efficiency and low cost. However in a recent study LC-MS/MS was found to be more accurate, with a higher correlation coefficient and lower coefficients of variation, than ELISA and RIA. The widely used RIA and ELISA measures may be problematic, especially at low estrogen metabolite levels.
The 2/16 ratio can identify a possible risk of breast cancer, and the number can be modulated by lifestyle and supplement factors.