2-hydroxyestrone and 16-hydroxyestrone are Phase I metabolites of Estrone (E1). Their ratio is of clinical significance in pre and peri-menopausal women. In post-menopausal women it does not have the same clinical significance. It is, however, hypothesized that the 2/16 ratio is important in menopausal women who are on hormone replacement therapy (HRT).
While traditional 2/16 ratio clinical utility may not be as robust as previously thought, a majority of findings indicate that metabolism of parent estrogens through 2-hydroxylation (independent of any relationship to 16α- OHE1) may be considered as a benign or even protective pathway. (Of note: one study found increased breast cancer risk with higher 2-OH levels, but only in a small subgroup of ER-/PR- cases.)
The clinical utility of the ratio of 2-hydroxyestrone (2-OHE1) to 16α-hydroxyestrone (16α-OHE1) – the 2/16 ratio or Estrogen Metabolite Ratio (EMR) – historically reported lower 2/16 ratio levels among breast cancer cases compared to controls (particularly in premenopausal women). Recent studies have been mixed: there appears to be no strong evidence in the literature that a higher urinary 2/16 ratio protects postmenopausal women from breast cancer, and only weak evidence of a protective effect in premenopausal women.
Men: Higher 2-OH (E1+E2)/16α –OH ratios in males have been associated with reduced risk of prostate cancer.
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