Adolescent Endogenous Sex Hormones and Breast Density in Early Adulthood

During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer. METHODS: Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25–29 years who participated in the Dietary Intervention Study in Children from 1988–1997 and had sex hormones and sex hormone binding globulin (SHBG) measured in serum collected on 1–4 occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV. RESULTS: Dehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all Ptrend ≤ 0.03) but not when measured in postmenarche samples (all Ptrend ≥ 0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7% to 22.1% and from 14.1% to 24.3%, respectively. Estrogens, progesterone, androstenedione, and testosterone were not associated with %DBV pre- or post-menarche (all Ptrend ≥ 0.16). CONCLUSIONS: Our results suggest that higher DHEAS and SHBG levels during adolescence, particularly before the onset of menarche, are associated with higher%DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown.