Mammographic breast density during hormone replacement therapy: effects of continuous combination, unopposed transdermal and low-potency estrogen regimens

Climacteric. 2001 Mar;4(1):42-8.


Objective: The aim of this study was to evaluate the impact of different hormone replacement therapy (HRT) regimens on mammographic breast density.

Study design: Mammographic density was recorded in women participating in a population-based screening program. At first mammogram, all women were non-users of HRT, and thereafter reported continuous use of the same HRT regimen. The study population comprised 158 women: a total of 52 women were using continuous combined HRT (conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 5 mg); 51 women were using low-dose oral estrogen alone (estriol 2 mg daily); and 55 women were using unopposed transdermal estrogen given as a patch (estradiol 50 micrograms/24 h). Films were coded and analyzed for mammographic density by an independent radiologist blinded to treatments. Mammographic density was classified according to Wolfe.

Results: An increase in mammographic density was much more common among women taking continuous combined HRT (40%) than for those using oral low-dose estrogen (6%) and transdermal (2%) treatment. The increase in density was already apparent at the first visit after starting HRT. During long-term follow-up, there was very little change in mammographic status.

Conclusion: HRT regimens were shown to have different effects on the normal breast. There is an urgent need to clarify the biological nature and significance of a change in mammographic density during treatment and, in particular, its relation to symptoms and breast cancer risk.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Adult
  • Analysis of Variance
  • Drug Therapy, Combination
  • Estriol / administration & dosage*
  • Estriol / adverse effects*
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogen Replacement Therapy / methods*
  • Estrogens, Conjugated (USP) / administration & dosage*
  • Estrogens, Conjugated (USP) / adverse effects*
  • Female
  • Fibrocystic Breast Disease / chemically induced*
  • Fibrocystic Breast Disease / classification
  • Fibrocystic Breast Disease / diagnostic imaging*
  • Follow-Up Studies
  • Humans
  • Mammography*
  • Medroxyprogesterone Acetate / administration & dosage*
  • Medroxyprogesterone Acetate / adverse effects*
  • Middle Aged
  • Progesterone Congeners / administration & dosage*
  • Progesterone Congeners / adverse effects*
  • Single-Blind Method


  • Estrogens, Conjugated (USP)
  • Progesterone Congeners
  • Medroxyprogesterone Acetate
  • Estriol