Endogenous Sex Hormone Levels and Mammographic Density among Postmenopausal Women
- 1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; 2Department of Epidemiology, Harvard School of Public Health; 3Harvard Center for Cancer Prevention, Boston, Massachusetts; and 4Cancer Genetics and Epidemiology Program, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia
- Requests for reprints:
Rulla M. Tamimi, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115. Phone: 617-525-0862. E-mail: rulla.tamimi{at}channing.harvard.edu.
Abstract
Background: Mammographic density is one of the strongest predictors of breast cancer risk. The mechanism by which breast density increases breast cancer risk is unclear although it has been hypothesized that breast density reflects cumulative exposure to estrogens.
Methods: To evaluate this hypothesis, we conducted a cross-sectional study among 520 postmenopausal women in the Nurses' Health Study that examined the relation between circulating sex hormones and mammographic density. Women were postmenopausal and not taking exogenous hormones at the time of blood collection and mammogram. Percent breast density was measured from digitized mammograms using a computer-assisted method. Circulating estrone, estradiol, androstenedione, testosterone, DHEA, DHEA sulfate, sex hormone–binding globulin, progesterone, and prolactin were measured in plasma.
Results: In contrast to the prior hypothesis, circulating estrogens were inversely related to percent mammographic density. The mean percent mammographic density was 25.6% among women in the lowest quartile of circulating estradiol compared with 14.4% among women in the highest quartile [Spearman correlation (r) = −0.22, P < 0.0001]. Circulating estrogens alone explained 1% to 5% of the variation of mammographic density. Body mass index was positively associated with circulating estradiol levels (r = 0.45, P < 0.0001) and inversely related to percent mammographic density (r = −0.51, P < 0.0001). After adjustment for body mass index, there was no association between estradiol and breast density (r = 0.01, P = 0.81). Likewise, there was no relation between the other sex hormones measured or prolactin and mammographic density after adjustment for body mass index.
Conclusion: These findings indicate that in postmenopausal women, mammographic density is independent of circulating sex hormone levels.
Footnotes
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Grant support: USPHS grants CA087969, CA049449, and CA075016; Specialized Programs of Research Excellence in Breast Cancer grant CA089393 from the National Cancer Institute, NIH, Department of Health and Human Services and Breast Cancer Research Fund; and American Cancer Society Cissy Hornung Clinical Research Professorship (G.A. Colditz).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted September 1, 2005.
- Received July 27, 2005.
- Revision received August 19, 2005.
