Associations of daily 17 β-estradiol and progesterone with mammographic density in premenopausal women . The Norwegian EBBA-I Study

Purpose: To investigate the associations between daily salivary 17β-estradiol and progesterone concentrations and percent mammographic density among premenopausal women enrolled in the Norwegian Energy Balance and Breast cancer Aspects (EBBA)-I Study and followed over the course of an entire menstrual cycle. Methods: Among 202 healthy women, aged 25-35 years, daily salivary 17β-estradiol and progesterone concentrations were measured. Computer-assisted breast density readings (MADENA) were obtained from digitized mammograms taken between day 7 and 12 of the menstrual cycle. Multivariable linear and logistic regression models examined the associations between ovarian hormones and percent mammographic density. Results: Compared with women having a low percent mammographic density (< 28.5%), women with a high percent mammographic density (≥ 28.5%) had 25% higher daily 17β-estradiol concentrations (P = 0.007), and 31% higher daily progesterone concentrations (P = 0.010) across the entire menstrual cycle. Compared with women in the first quartile of overall average daily progesterone concentrations, the odds of high percent mammographic density (≥ 28.5%) increased among women in higher progesterone quartiles (Q4 vs. Q1: Odds Ratio 3.70, 95% Confidence interval 1.35-10.11, Ptrend = 0.011). These associations were even stronger among nulliparous women with an interaction between parity and average daily progesterone in the luteal phase (P = 0.017). We also observed strong associations between serum concentrations of ovarian hormones and percent mammographic density. Conclusion: Daily 17β-estradiol and progesterone were strongly associated with percent mammographic density in premenopausal women, and could in part explain the association of breast density with increased breast cancer risk.