Girls with high hormonal steroids, BMI and stress reach puberty early

Lauren Houghton; ying wei; Stephan Wudy; Michaela hartmann; Frank stanczyk; Julia Knight; Irene andrulis; Angela Bradbury; Lisa Schwartz; Saundra Buys; Mary Daly; Esther John; Wendy Chung; regina santella; Russell Romeo; Terry Mary Beth

doi:10.1530/endoabs.110.P991

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Endocrine Abstracts (2025) 110 P991 | DOI: 10.1530/endoabs.110.P991

ECEESPE2025 Poster Presentations Reproductive and Developmental Endocrinology (93 abstracts)

Girls with high hormonal steroids, BMI and stress reach puberty early

Lauren Houghton ¹ , ying wei ¹ , Stephan Wudy ² , Michaela hartmann ² , Frank stanczyk ³ , Julia Knight ⁴ , Irene andrulis ⁴ , Angela Bradbury ⁵ , Lisa Schwartz ⁵ , Saundra Buys ⁶ , Mary Daly ⁷ , Esther John ⁸ , Wendy Chung ⁹ , regina santella ¹ , Russell Romeo ¹⁰ & Mary Beth Terry ¹

Author affiliations

¹Columbia University, New York, United States; ²Justus Liebig University, Giessen, Germany; ³Keck School of Medicine, Los Angeles, United States; ⁴Lunenfeld-Tanenbaum Research Institute, Toronto, Canada; ⁵University of Pennsylvania, Philadelphia, United States; ⁶University of Utah, Utah, United States; ⁷Fox Chase Cancer Center, Philadelphia, United States; ⁸Stanford University, Stanford, United States; ⁹Boston Children’s Hospital, Boston, United States; ¹⁰Barnard University, New York, United States

JOINT1739

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.

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 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 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. We also used 12 principal components of pre-pubertal steroid metabolite data as predictors in Weibull models.

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. There were 12 primary principal components that explained 95% of the variation in the steroid metabolites and 3 of these were significantly associated with earlier age at thelarche including scores either high glucocorticoids, or high in androgen and progesterone metabolites and low levels of glucocorticoid metabolites, or high progesterone metabolites, specifically high 17a-hydroxypregnanolone, pregnenediol, but low 11-oxo-androsterone.

Conclusion: Elevated metabolites of glucocorticoids, androgens and progesterone are associated with accelerated pubertal onset, and BMI and stress modify this association. Previous studies focus on estrogens, menarche and BMI; our results suggest that androgens and stress impact age at thelarche with implications for our understanding of pubertal development.