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Arch Intern Med. 2006 Aug 14-28;166(15):1578-84.

Association of new-onset breast discomfort with an increase in mammographic density during hormone therapy.

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Divisions of General Internal Medicine, The David Geffen School of Medicine at UCLA, University of California-Los Angeles, 911 Broxton Avenue, Los Angeles, CA 90024, USA.

Erratum in

  • Arch Intern Med. 2006 Nov 13;166(20):2176.



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.


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).


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 (beta = .033, P<.001). The association between incident breast discomfort and increased percent breast density was similar in all active treatment arms.


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

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