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Associations among Circulating Sex Hormones, Insulin-Like Growth Factor, Lipids, and Mammographic Density in Postmenopausal Women

¹ Center for Health Studies, Group Health Cooperative; ² Cancer Prevention Program, Fred Hutchinson Cancer Research Center; and ³ Department of Epidemiology, School of Public Health and Community Medicine and ⁴ Department of Medicine, School of Medicine, University of Washington, Seattle, Washington; ⁵ Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; ⁶ School of Medicine, University of Southern California, Los Angeles, California; and ⁷ Department of Epidemiology and Public Health, School of Medicine, Yale University, New Haven, Connecticut

Requests for reprints: Anne McTiernan, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109-1024. Phone: 206-667-7979; Fax: 206-667-7850. E-mail: amctiern{at}fhcrc.org

Objective: Hormone therapy use has been positively associated with mammographic density in several studies. However, few studies have examined the association between endogenous hormone levels and mammographic density. Therefore, we evaluated the relationship of endogenous sex hormones, insulin-like growth factor (IGF), and lipids with mammographic density in 88 overweight, postmenopausal women not taking hormone therapy.

Methods: Percent density and dense area were evaluated as continuous measures using a computer-assisted program. We used multiple linear regression to evaluate the associations of sex hormones, IGF, and cholesterol with mammographic density, adjusting for confounders, including adiposity. We evaluated stratification by history of hormone therapy use (former versus never) and hormone therapy latency (<5 versus 5 years).

Results: Among former hormone therapy users, mammographic density was inversely associated with circulating levels of estrone (P = 0.01), estradiol (P = 0.003), free estradiol (P = 0.004), testosterone (P = 0.04), free testosterone (P = 0.02), androstenedione (P < 0.001), dehydroepiandrosterone (P = 0.01), and the ratio of IGF-I to its binding protein (IGF-I/IGFBP-3; P = 0.04). We found similar associations when we limited the analyses to women who had used hormone therapy within the past 5 years. We also noted positive associations of mammographic density with total cholesterol (P = 0.03) and low-density lipoprotein (P = 0.03) among former hormone therapy users. No associations were noted among women who had never used hormone therapy.

Conclusions: These results suggest that there is an inverse relationship between endogenous sex hormones and mammographic density in postmenopausal women among former users of hormone therapy. This is not consistent with the hormone therapy literature and should be confirmed in larger studies.

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