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.)
2-OH (E1 + E2)/16-a- OH E1
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