ASPO Abstracts
Androgens, Stress and Adiposity accelerate Puberty with Implications for Breast Cancer Risk
Category: Molecular Epidemiology & Environment
Conference Year: 2023
Abstract Body:
Purpose of the Study: The prevailing paradigm for breast cancer (BC) etiology focuses on endogenous estrogen exposure beginning at puberty to explain postmenopausal, but not premenopausal, BC risk. In contrast, androgens are associated with increased pre- and post-menopausal BC risk. We tested the hypothesis that elevated androgens, in addition to childhood adiposity and stress, accelerate pubertal development, an early life risk factor for BC. Methods: In the LEGACY Girls Study, we measured 36 steroid metabolites grouped as androgens (A), estrogens (E), progestogens (P) and glucocorticoids (G) in two urine specimens. The pre-puberty specimen was in 327 girls and the peri-puberty specimen, after the onset of breast development but before menarche, was in 115 of the 327 girls. Mothers/guardians assessed age at onset of breast development (thelarche) through the Pubertal Development Scale. Girls self-reported age at menarche. Study staff measured participants' body mass index (BMI) and administered questionnaires including the Internalizing Composite Scale (a parent proxy of child stress). We estimated hazard ratios and 95% confidence intervals for the association between steroid metabolites and age at thelarche and menarche using Weibull survival models, controlling for study site, race and ethnicity, and birthweight. Results: Higher levels of urinary A [1.3 (1.1-1.6)] and P [1.3 (1.1-1.6)] were associated with accelerated thelarche. Peri-pubertal levels of A [1.2 (1.1-1.2)], P [1.3 (1.1-1.4)], and G [1.1 (1.1-1.2)] were associated with accelerated menarche, adjusting for pre-pubertal levels and age at thelarche. Stress and BMI modified the associations with thelarche, but not menarche. The association of A with earlier thelarche was stronger among girls with BMI above the median [1.5 (1.0- 2.1)] and who also had internalizing stress above the median [2.0 (1.2-3.2)]. Conclusion: Our results confirm that androgens are associated with accelerated pubertal timing and that BMI and stress modify this association. Mechanisms underlying the puberty and BC association have previously focused on estrogens, menarche and BMI; our results suggest that androgens and stress impact the timing of thelarche with implications regarding the overall etiology of BC.
Keywords: hormones, puberty, breast cancer, stress