Estradiol metabolism during oral and transdermal estradiol replacement therapy in postmenopausal women

Horm Metab Res. 1998 Sep;30(9):598-600. doi: 10.1055/s-2007-978940.


The metabolism of estradiol was investigated in postmenopausal women after 4 weeks' treatment with oral or transdermal unopposed estradiol. The urinary excretion of the metabolites was examined. With both administration routes, 2-hydroxyestrone, the main A-ring metabolite, and 16alpha-hydroxyestrone, the main D-ring metabolite, were excreted in higher amounts than estradiol and estrone. The ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone remained the same for both administration routes. It has been suggested that dominance of D-ring metabolism, i.e. increase of 16alpha-hydroxyestrone production, is associated with an increased risk of breast cancer. The present study indicates that neither oral nor transdermal estradiol substitution shift this ratio to a higher level of possible risk. Oral estradiol substitution, however, in our study leads to higher metabolite concentrations which may be regarded as hazardous for women with diseases favoring D-ring metabolism.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Estradiol / administration & dosage*
  • Estradiol / pharmacokinetics*
  • Estradiol / urine
  • Estrone / urine
  • Female
  • Hormone Replacement Therapy*
  • Humans
  • Hydroxyestrones / urine
  • Middle Aged
  • Postmenopause
  • Radioimmunoassay


  • Hydroxyestrones
  • 16-hydroxyestrone
  • Estrone
  • Estradiol
  • 2-hydroxyestrone