Objective: Our purpose was to investigate the effects of various hormone replacement regimens on mammographic breast density. Study Design: Mammographic density was recorded in women participating in a population-based screening program. All women were nonusers of hormone replacement therapy at first mammogram and thereafter reported continuous use of the same treatment: estrogen alone (n = 50) or estrogen in cyclic (n = 75) or continuous (n = 50) combination with progestogen. Mammographic density was quantified according to the Wolfe classification. Results: An increase in mammographic density was much more common among women receiving continuous combination hormone replacement therapy (52%) than among those receiving cyclic (13%) and estrogen-only (18%) treatment. The increase in density was apparent already at first visit after the start of hormone replacement therapy. There was little change in mammographic status during long-term follow-up. Conclusion: Regimens of hormone replacement therapy were shown to have different effects on the normal breast. There is an urgent need to clarify the biologic nature and significance of a change in mammographic density during treatment and, in particular, its relation to symptoms and breast cancer risk. (Am J Obstet Gynecol 1999;181:348-52.).

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

JAMA. 2001;285(2):171-176. doi: 10.1001/jama.285.2.171

Changes in Breast Density Associated With Initiation, Discontinuation, and Continuing Use of Hormone Replacement Therapy

Abstract

Context  Initiation of hormone replacement therapy (HRT) has been shown to increase breast density. Evidence exists that increased breast density decreases mammographic sensitivity. The effects on breast density of discontinuing and continuing HRT have not been studied systematically.

Objective  To examine the effects of initiation, discontinuation, and continued use of HRT on breast density in postmenopausal women.

Design, Setting, and Participants  Observational cohort study of 5212 naturally postmenopausal women aged 40 to 96 years and enrolled in a large health maintenance organization in western Washington State who had 2 screening mammograms between 1996 and 1998.

Main Outcome Measures  Breast density, assessed using the clinical radiologists' BI-RADS 4-point scale, compared among women who did not use HRT before either mammogram (nonusers); who used HRT before the first but not before the second mammogram (discontinuers); who used HRT before the second but not before the first mammogram (initiators); and who used HRT prior to both mammograms (continuing users).

Results  Relative to nonusers, women who initiated HRT were more likely to show increases in breast density (relative risk [RR], 2.57; 95% confidence interval [CI], 2.12-3.08), while women who discontinued HRT use were more likely to show decreases in density (RR, 1.81; 95% CI, 1.06-2.98) and women who continued to use HRT were more likely to show both increases in density (RR, 1.33; 95% CI, 1.13-1.55) and sustained high density (RR, 1.45; 95% CI, 1.33-1.58).

Conclusions  These results indicate that breast density changes associated with HRT are dynamic, increasing with initiation, and decreasing with discontinuation.