This test measures the ratio of 2-hydroxy (E1-Estrone +E2-Estradiol + E3-Estriol) to 16 alpha-hydroxyestrone (2/16 ratio) in a random urine sample. Considerable evidence indicates that this ratio is relevant as a risk factor for estrogen-sensitive diseases including breast and cervical cancers, osteoporosis, and recurrent respiratory papillomatosis. Diet, dietary supplementation, and certain drugs have been shown to change the 2/16 ratio. “Favorable” alteration of the ratio has been shown to be associated with lowered recurrence of specific estrogen-sensitive diseases, and may decrease risk for development of certain estrogen-sensitive cancers.
Several theories of breast carcinogenesis involve altered metabolism of estrone. Bradlow has proposed that increased levels of 16a-hydroxyestrone (16a-OHE1), a potent agonist of estrogen action, are linked to increased risk for breast cancer.1 By contrast, increased levels of 2-hydroxy(E1+E2+E3), an antagonist of estrogen action, may be associated with decreased risk for breast cancer.2
Zumoff has summarized some of the animal and human epidemiological data supporting a role for 16a-OHE1 in carcinogenesis.3 There is considerable evidence to support the notion that 2-hydroxy(E1+E2+E3) exerts anti-carcinogenic action 2,4 at least in in vitro studies.
The relationship of the urinary estrogen metabolite ratio 2/16 to breast cancer in humans has been explored in both retrospective 5-9 and prospective studies.10 On balance, the retrospective studies support a lowering of the 2/16 ratio in postmenopausal women with breast cancer, with decreased 2-hydroxy(E1+E2+E3) and increased 16a-OHE1 contributing to the lowered ratio. Of course any interpretation of this finding must consider that the altered ratio could possibly be a result of the disease, not a cause of it. A recent prospective study, however, found a 15% reduction in the baseline 2/16 ratio in postmenopausal women who went on to develop breast cancer up to 19 years after sampling. Furthermore, dietary interventions known to influence the risk of breast cancer such as consumption of flaxseed and soy also raise the 2/16 ratio significantly.11,12
Although many additional human studies are in progress, at the present time there appears to be a reasonable body of evidence indicating that the urinary 2/16 ratio is a useful test for clinicians who wish to assess the risk for estrogen-sensitive diseases including breast cancer in their postmenopausal patients. This ratio can also be useful for monitoring dietary and pharmaceutical interventions intended to reduce risk for development of breast cancer and other estrogen-dependent disorders.
Please Note: The 2/16α Estrogen Metabolite Ratio only comes in the Comprehensive Plus with Hgh, Comprehensive Plus, and Estrogen Profiles.