The relationship between physical activity and 2-hydroxyestrone, 16alpha-hydroxyestrone, and the 2/16 ratio in premenopausal women (United States)

Cancer Causes Control. 2005 May;16(4):455-61. doi: 10.1007/s10552-004-6256-6.


Objectives: Estrogen is metabolized in the body through two mutually exclusive pathways yielding metabolites with different biological activities: the low estrogenic 2-hydroxyestrone (2-OHE1) and the highly estrogenic 16alpha-hydroxyestrone (16alpha-OHE1). The ratio of these metabolites (2/16) may be predictive of risk for developing breast cancer. Early evidence has demonstrated that exercise may alter estrogen metabolism to favor the weak estrogen, 2-OHE1.

Methods: Seventy-seven eumenorrheic females completed physical activity logs for two weeks prior to providing a luteal phase urine sample. Concentrations of 2-OHE1 and 16alpha-OHE1 were measured and the 2/16 ratio computed. Hierarchical regression, controlling for age and body mass index (BMI), was used to determine relationships between estrogen metabolites and daily physical activity.

Results: Regression analyses indicated significant positive relationships between physical activity and 2-OHE1 and the 2/16 ratio (p < 0.05) that appears to be independent of BMI. 16alpha-OHE1 was not significantly related to physical activity.

Conclusion: These results indicate that physical activity may modulate estrogen metabolism to favor the weak estrogen, 2-OHE1, thus producing a higher 2/16 ratio. This alteration in estrogen metabolism may represent one of the mechanisms by which increased physical activity reduces breast cancer risk.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Body Mass Index
  • Breast Neoplasms / prevention & control*
  • Exercise
  • Female
  • Humans
  • Hydroxyestrones / metabolism*
  • Hydroxyestrones / urine
  • Middle Aged
  • Physical Fitness / physiology*
  • Predictive Value of Tests
  • Premenopause / metabolism*
  • Premenopause / physiology
  • Prospective Studies
  • Regression Analysis
  • Risk Assessment
  • Sampling Studies
  • Statistics, Nonparametric
  • Urinalysis


  • Biomarkers
  • Hydroxyestrones