A pilot study of urinary estrogen metabolites (16alpha-OHE1 and 2-OHE1) in postmenopausal women with and without breast cancer

Environ Health Perspect. 1997 Apr;105 Suppl 3(Suppl 3):601-5. doi: 10.1289/ehp.97105s3601.


The two main pathways for metabolizing estrogen are via 16alpha-hydroxylation and 2-hydroxylation. The 16alpha-hydroxy metabolites are biologically active; the 2-hydroxy metabolites are not. It is suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16alpha-hydroxy pathway may be at significantly elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxy pathway. In particular, it is suggested that the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alpha-hydroxyestrone (16alpha-OHE1) is an index of reduced breast cancer risk. This pilot study compared this ratio in postmenopausal women diagnosed with breast cancer to those of healthy controls. Urinary concentrations of estrone (E1), 17beta-estradiol (E2) and estriol (E3) were also quantified. White women who were subjects in a previous breast cancer case-control study at our institution were eligible for inclusion. All participants provided a sample of their first morning urine. The results from the first 25 cases and 23 controls are presented here. The ratio of 2-OHE1 to 16alpha-OHE1 was 12% lower in the cases (p=0.58). However, urinary E1 was 30% higher (p=0.10), E2 was 58% higher (p=0.07), E3 was 15% higher (p=0.48), and the sum of E1, E2, and E3 was 22% higher (p=0.16) in the cases. These preliminary results do not support the hypothesis that the ratio of the two hydroxylation metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for breast cancer or that it is a better predictor of breast cancer risk than levels of E1, E2 and E3 measured in urine.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / etiology
  • Breast Neoplasms / urine*
  • Case-Control Studies
  • Estradiol / urine
  • Estriol / urine
  • Estrone / urine
  • Female
  • Humans
  • Hydroxyestrones / urine*
  • Menopause
  • Middle Aged
  • Neoplasms, Hormone-Dependent / etiology
  • Neoplasms, Hormone-Dependent / urine*
  • Pilot Projects
  • Risk Factors
  • Steroid 16-alpha-Hydroxylase


  • Hydroxyestrones
  • 16-hydroxyestrone
  • Estrone
  • Estradiol
  • Steroid 16-alpha-Hydroxylase
  • Estriol
  • 2-hydroxyestrone