Abstract 1362: Dyslipidemia, excess weight and high mammographic density are associated with high levels of daily estrogen and progesterone. .
Authors: Flote Vidar G. , Frydenberg Hanne , Ursin Giske , Iversen Anita , Fagerland Morten W. , Ellison Peter T. , Wist Erik A. , Egeland Thore , Furberg Anne-Sofie , Thune Inger 
Published: August 2014

Background: Dyslipidemia, excess weight, and high mammographic density have independently been associated with breast cancer development. However, little is known regarding the combined effect of dyslipidemia, excess weight and mammographic density on cyclic variation in estrogen and progesterone.

Material and Methods: 202 premenopausal women (25-35 years) participated in the Norwegian EBBA-I study including clinical examinations, and fasting blood sampling. Computer-assisted percent mammographic density (Madena) was obtained from digitized mammograms taken at day 7-12 of menstrual cycle. Daily saliva samples were collected across an entire menstrual cycle, and concentrations of 17β-estradiol and progesterone were measured at the Reproductive Ecology Laboratory, Harvard University, USA. Uni and multivariable linear and logistic regression models were used to study the combined association of high-density lipoprotein cholesterol (HDL-C), body mass index (BMI) and mammographic density with daily concentrations of 17β-estradiol and progesterone.

Results: Among women with mean age of 30.7 years, mean percent mammographic density 29.8 %, mean BMI 24.4 kg/m2, mean total cholesterol 4.45 mmol/l, and mean HDL-C 1.54 mmol/l, we observed overall mean salivary 17β-estradiol 16.2 pmol/l and progesterone 129.3 pmol/l. We used median split and women characterized by lower than median HDL-C (≤ 1.51 mmol/l), higher than median BMI (&gt; 23.6 kg/m2), and higher than median percent mammographic density (&gt; 28.5 %) (unfavorable profile), had higher concentrations of both 17β-estradiol (p = 0.005) and progesterone (p = 0.016) across the entire menstrual cycle, compared with women characterized by higher HDL-C(&gt; 1.51 mmol/l), lower BMI (≤ 23.6 kg/m2) and lower percent mammographic density (≤ 28.5 %) (favorable profile). Comparing the profiles, women with an unfavorable profile had 46 % higher overall mean 17β-estradiol (17β-estradiol; 22.2 versus 15.9 pmol/l) and 48% higher overall mean progesterone (progesterone; 187.5 versus 126.1pmol/l). These factors also showed strong associations with differences in AUC (area under curve) of these sex steroid hormones across the entire menstrual cycle, reflecting cumulative exposure. Women characterized by unfavorable profile had 48 % higher AUC estradiol compared with women having favorable profile (AUCe, 387, 95 % confidence interval (CI) 244 - 531 versus 262, 95% CI 244 - 281). Furthermore, women with unfavorable profile had 47 % higher AUC progesterone than women with favorable profile (AUCp, 1929, 95 % CI 1125 - 2733 versus 1309, 95% CI 1211 -1408).

Conclusion: A combination of low HDL-C, excess weight, and high percent mammographic density, was strongly associated with higher daily levels of 17β-estradiol and progesterone, and could in part explain the association of these factors with increased risk of breast cancer development.

Citation Format: Vidar G. Flote, Hanne Frydenberg, Giske Ursin, Anita Iversen, Morten W. Fagerland, Peter T. Ellison, Erik A. Wist, Thore Egeland, Anne-Sofie Furberg, Inger Thune. Dyslipidemia, excess weight and high mammographic density are associated with high levels of daily estrogen and progesterone. . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1362. doi:10.1158/1538-7445.AM2013-1362