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The 2/16 Ratio – Urinary 2/16a Estrogen Metabolites

OVERVIEW:

Urinary 2/16a Estrogen Metabolite Ratio:

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.

CLINICAL SIGNIFICANCE:

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: this test is only available as part of a comprehensive 24-hr urine hormone test

BENEFITS:

  • Convenient UPS Next Day Air pickup and return shipping
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  • Call (425) 271-8689 to Order Collection Kits

Learn More About 24 Hour Urine Hormone Tests

  1. Bradlow HL, Sepkovic DW, Telang NT, Osborne MP. Indole-3-carbinol: A novel approach to breast cancer prevention. Ann NY Acad Sci 1995; 768:180-200.
  2. Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-Hydroxyestrone: the ‘good’ estrogen. J Endocrinol 1996:150:Suppl S259-S265.
  3. Zumoff B. Hormonal profiles in women with breast cancer. Obstet Gyn Clin North America 1994;21:751-772.
  4. Bradlow HL, Telang NT, Sepkovic DW, et al. 2-Hydroxyestrone: the ‘good’ estrogen. J. Endocrinol 1996;150S:259-265.
  5. Kabat GC, Chang CJ, Sparano JA et al. Urinary estrogen metabolites and breast cancer: a case controlled study. Cancer Epidemiol Biomarkers Prev 1997;6(7):505-509.
  6. Ursin G, London S, Stanczyk F, et al. Urinary 2-hydroxyestrone ratio and risk of breast cancer in postmenopausal women. J Natl Cancer Institute 1999 June;91(12):1067-1072.
  7. Ho GH, Luo XW, Ji CY, et al. Urinary 2/16 alpha-hydroxyestrone ratio: correlation with serum insulin-like growth factor binding protein-3 and a potential biomarker of breast cancer risk. Ann Acad Med Singapore 1998;27:294-299.
  8. Fleisher M, Sepkovic D, Bradlow HL, et al. Estrogen metabolite ratios as biomarkers of hormonally related breast cancer risk. Conference abstract in Clin Chem 1996;42(6): S261.
  9. Coker A, Crane M, Sticca R, Sepkovic D. Re: Ethnic differences in estrogen metabolism in healthywomen. J Natl Cancer Institute Jan 1997;89(1):89.
  10. Meilahn E, De Stavola B, Allen DS, et al. Do urinary oestrogen metabolites predict breast cancer? Guernsey III cohort follow-up. Brit J Cancer 1998;78(9):1250-1255.
  11. Haggans C, Hutchins A, Olson B, et al. Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women. Nutrition and Cancer 1999;33(2):188-195.
  12. Lu LJ, Cree M, Josyula S, Nagamani M, Grady JJ, Anderson KE. Increased urinary excretion of 2-hydroxyestrone but not 16alpha-hydroxyestrone in premenopausal women during a soyadiet containing isoflavones. Cancer Res 2000 60:1299-1305.