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Carolyn J. Crandall, MD, MS; Arun Karlamangla, MD, PhD; Mei-Hua Huang, DrPH; Giske Ursin, PhD; Min Guan, MS; Gail A. Greendale, MD

Arch Intern Med. 2006;166:1578-1584.

Background  Postmenopausal use of estrogen and progestin therapy increases breast density and breast discomfort. Whether this increase in breast density is heralded by new-onset breast discomfort is unknown.

Methods  We used data from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study, which retrieved and examined baseline and 12-month mammograms for 594 (67.9%) of 875 women aged 45 to 64 years enrolled in the randomized controlled trial. Treatments included placebo, 0.625 mg/d of conjugated equine estrogens, 0.625 mg/d of conjugated equine estrogens and medroxyprogesterone acetate (10 mg/d for 12 d/mo or 2.5 mg/d continuously), or 0.625 mg/d of conjugated equine estrogens and 200 mg/d of micronized progestin for 12 d/mo. Breast density (the percent of the breast composed of dense tissue) was calculated from digitized mammograms obtained at baseline and at 12-month follow-up. Breast discomfort was ascertained at baseline and at follow-up using standardized self-report questionnaires. In bivariate analysis, and then in multivariable linear regression models, we assessed the association between change in percent breast density from baseline to 12-month follow-up and new-onset breast discomfort in participants who had no breast discomfort at baseline (N = 533).

Results  After adjustment for age, treatment assignment (placebo, conjugated equine estrogens, or progestin-containing regimen), and other potential confounders, women with new-onset breast discomfort had a 3.9% increase in percent breast density compared with a 0.6% increase in percent breast density among women without new-onset breast discomfort ( = .033, P<.001). The association between incident breast discomfort and increased percent breast density was similar in all active treatment arms.

Conclusion  In postmenopausal women randomly assigned to menopausal hormone therapy vs placebo, new-onset breast discomfort is associated with increased mammographic density.

Author Affiliations: Divisions of General Internal Medicine (Dr Crandall) and Geriatrics (Drs Karlamangla, Huang, and Greendale), The David Geffen School of Medicine at UCLA, and Department of Biostatistics (Ms Guan), University of California, Los Angeles; Department of Preventive Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; and Department of Nutrition, University of Oslo, Oslo, Norway (Dr Ursin).

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