Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's health initiative randomized trial

Anne McTiernan, Christopher F. Martin, Jennifer D. Peck, Aaron K. Aragaki, Rowan T. Chlebowski, Etta D. Pisano, C. Y. Wang, Robert L. Brunner, Karen C. Johnson, Jo Ann E. Manson, Cora E. Lewis, Jane Morley Kotchen, Barbara S. Hulka, Barbara Alving, Jacques Rossouw, Linda Pottern, Ross Prentice, Garnet Anderson, Andrea LaCroix, Ruth E. PattersonSally Shumaker, Pentti Rautaharju, Evan Stein, Steven Cummings, John Himes, Bruce Psaty, Sylvia Wassertheil-Smoller, Jennifer Hays, Annlouise R. Assaf, Lawrence Phillips, Shirley Beresford, Judith Hsia, Cheryl Ritenbaugh, Bette Caan, Barbara V. Howard, Linda Van Horn, Henry Black, Marcia L. Stefanick, Dorothy Lane, Rebecca Jackson, Cora Beth Lewis, Tamsen Bassford, Jean Wactawski-Wende, John Robbins, Allan Hubbell, Howard Judd, Robert D. Langer, Margery Gass, Marian Limacher, David Curb, Robert Wallace, Judith Ockene, Norman Lasse, Mary Jo O'Sullivan, Karen Margolis, Robert Brunner, Gerardo Heiss, Lewis Kuller, Karen C. Johnson, Robert Brzyski, Gloria Sarto, Denise Bonds

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224 Scopus citations


Background: Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density. Methods: In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models. Results: Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P<.001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P<.001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P<.001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density. Conclusions: Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.

Original languageEnglish
Pages (from-to)1366-1376
Number of pages11
JournalJournal of the National Cancer Institute
Issue number18
StatePublished - Sep 2005


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