Mammographic Density and Circulating Sex Hormones: a Cross-Sectional Study in Postmenopausal Korean Women

Mammographic density (MD) is a strong independent risk factor for breast cancer. It has been suggested that breast cancer is related to the exposure to circulating sex hormones. However, relations between MD and hormones have been inconsistent. In addition, such relations are mainly evaluated in Western populations. Therefore, we conducted a cross-sectional study in 396 cancer-free postmenopausal Korean women who had never used hormone replacement therapy. We assayed estradiol, testosterone, and sex hormone-binding globulin (SHBG) levels. We then calculated free testosterone (cFT) levels. Total and dense areas of digital mammogram were measured using a computer-assisted thresholding method, and non-dense area and percent dense area were calculated. Linear mixed model was used for analyses. Estradiol and testosterone levels were not associated with any MD measures after adjusting for reproductive factors and body mass index. However, cFT was persistently associated with non-dense area even after adjusting for covariates, with non-dense area increased by 3.5% per 1 standard deviation increase of cFT. SHBG showed an inverse association with non-dense area, although it showed a positive association with dense area and percent dense area regardless of adjustment for covariates. Non-dense area was decreased by 5.6% while percent dense area was increased by 13.4% per 1 standard deviation increase of SHBG. These findings suggest that SHBG might be related with breast cancer risk, probably through its association with breast density.