Neutral effect of ultra-low-dose continuous combined estradiol and norethisterone acetate on mammographic breast density

Climacteric. 2007 Jun;10(3):249-56. doi: 10.1080/13697130701385805.


Objective: To compare the effects of two different ultra-low doses of continuous combined hormone therapy and placebo on mammographic breast density in postmenopausal women.

Methods: A subpopulation of 255 postmenopausal women from the CHOICE trial were randomly assigned to 0.5 mg 17beta-estradiol (E2) + 0.25 mg norethisterone acetate (NETA), 0.5 mg E2 + 0.1 mg NETA, or placebo. Women using hormone replacement therapy (HRT) up to 2 months prior to the study were excluded; 154 women fulfilled the inclusion criteria. Mammograms were performed at baseline and after 6 months. Breast density was evaluated by visual classification scales and a computer-assisted digitized technique.

Results: No significant differences were detected between the active treatment groups and the placebo group in the digitized quantification. The mean baseline values for density around 20% were unchanged after 6 months. Also, visual classifications showed no increase in breast density in any study group.

Conclusion: In contrast to currently available bleed-free regimens, the new ultra-low-dose combination of 0.5 mg E2 and 0.1 mg NETA seems to have very little or even a neutral effect on the breast. Both digitized quantification and visual assessment of breast density were unchanged after 6 months. Larger prospective studies should be performed to confirm this new finding.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast / drug effects*
  • Breast / pathology
  • Double-Blind Method
  • Drug Administration Schedule
  • Estradiol / administration & dosage
  • Estradiol / pharmacology*
  • Estrogen Replacement Therapy*
  • Female
  • Humans
  • Mammography
  • Middle Aged
  • Norethindrone / administration & dosage
  • Norethindrone / analogs & derivatives*
  • Norethindrone / pharmacology
  • Norethindrone Acetate
  • Postmenopause
  • Sweden
  • Treatment Outcome


  • Estradiol
  • Norethindrone Acetate
  • Norethindrone