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American Journal of Epidemiology Advance Access published online on September 21, 2005
American Journal of Epidemiology, doi:10.1093/aje/kwi286
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American Journal of Epidemiology Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.
Received October 13, 2004
Accepted June 1, 2005

ORIGINAL CONTRIBUTIONS

The Association of Endogenous Sex Steroids and Sex Steroid Binding Proteins with Mammographic Density: Results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study

Gail A. Greendale 1*, Shana L. Palla 2, Giske Ursin 3, Gail A. Laughlin 4, Carolyn Crandall 5, Malcolm C. Pike 3, and Beth A. Reboussin 2

1 Division of Geriatrics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA
2 Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC
3 Department of Preventive Medicine/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA
4 Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA
5 Division of General Internal Medicine and Health Sciences Research, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA

* To whom correspondence should be addressed.
Gail A. Greendale, E-mail: ggreenda{at}mednet.ucla.edu


  Abstract

Mammographic density is an independent risk factor for breast cancer. In postmenopausal women, higher levels of endogenous sex steroids are associated with an increased risk of breast cancer. Limited prior data suggest that endogenous sex steroids either are not associated (total estradiol and progesterone) or are negatively associated (free estradiol) with higher mammographic density. To analyze the associations between endogenous sex steroids and mammographic density, the authors conducted a 1998-2005 cross-sectional analysis of baseline clinical trial data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial for US women who had not used hormone therapy for at least 3.1 months prior to baseline. In models adjusted for age, body mass index, parity, prior use of hormone therapy, time since last use of hormone therapy, and the interaction between prior hormone therapy use and time since last hormone therapy use, higher levels of estrone ({beta} = 0.0013, p = 0.014), estradiol ({beta} = 0.0009, p = 0.009), and bioavailable estradiol ({beta} = 0.0021, p = 0.018) were statistically significantly related to greater mammographic density. (Beta coefficients express the increment in mammographic density per-unit increment (pg/ml) of each hormone.) These results suggest that some sex steroids may increase the risk of breast cancer by stimulating breast epithelial or stromal proliferation, which appears on a mammogram as higher density.

Keywords: breast neoplasms; mammography; menopause; receptors, steroid; risk factors.
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