OR15-06 Steroids, stress and body mass index interact to accelerate female pubertal development

Abstract Disclosure: L.C. Houghton: None. Y. Wei: None. S.A. Wudy: None. M. Hartmann: None. F.Z. Stanczyk: None. J. Knight: None. I. Andrulis: None. A. Bradbury: None. L. Schwartz: None. S. Buys: None. M. Daly: None. E. John: None. W. Chung: None. R. Santella: None. R.D. Romeo: None. M. Terry: None. Background: There are ongoing concerns about declining age of puberty in females and what is driving the decline. We aimed to identify patterns in the hormonal steroid metabolome associated with accelerated pubertal development in girls, and to determine if this association was modified by body mass index (BMI), markers of stress, and breast cancer family history. We hypothesized that higher androgens and glucocorticoids are associated with accelerated pubertal timing, and this acceleration would be further increased in girls with elevated BMI and stress. We further hypothesized that the stress response changes during the pubertal window. Methods: In the LEGACY Girls Study, we measured 36 metabolites of glucocorticoids, androgens, progesterone, and estrogens in two urine specimens collected before (pre, n=327) and during puberty (pubertal, n=115). Parents assessed the age at onset of breast development (thelarche) through the Pubertal Development Scale. Girls aged ≥10 years self-reported age at menarche. Study staff measured participants’ height and weight and administered questionnaires including the Internalizing Composite Scale (a parent proxy of child stress). We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between a doubling in steroid metabolites (μg/mL per mg of creatinine) and age at thelarche, pubarche and menarche using Weibull survival models, testing for interactions with stress BMI z-scores, and family history using cross-product terms. Results: Higher pre-pubertal levels of urinary metabolites of glucocorticoids (HR=1.9, 95% CI 1.5-2.5), androgens (HR=3.9, 95%CI 2.7-5.6) and progesterone (HR=6.7, 95%CI 4.1-10.9) were associated with accelerated thelarche. Higher pre-pubertal (HR=0.2, 95%CI 0.1-0.5) and pubertal (HR=0.4, 95%CI 0.2-0.9) levels of estrogen metabolites were associated with delayed menarche. Higher levels of pubertal androgen (HR=0.3, 95%CI 0.1-0.8) and progesterone (HR=0.2, 95%CI 0.07-0.7) metabolites were associated with longer pubertal tempo. Girls with high glucocorticoid metabolites, BMI (≥15.6 kg/m2) and stress (≥ 46) reached thelarche 7 months earlier than girls with low glucocorticoid metabolites, BMI (<15.6 kg/m2) and stress (<46). There were no interactions with family history. Conclusion: Elevated metabolites of glucocorticoids, androgens and progesterone are associated with accelerated pubertal onset, and BMI and stress modify this association. Previous studies have focused on estrogens, menarche and BMI; our results suggest that androgens and stress impact the timing of thelarche with implications for our understanding of pubertal development. Presentation: Sunday, July 13, 2025