2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T740,Estrogens underlie puberty in girls, but the steroid metabolome may also regulate pubertal timing in response to elevated stress and increasing body mass index (BMI). Our objective was to identify steroid metabolome patterns linked to accelerated puberty and test whether BMI and stress markers modify this relationship. From the LEGACY Girls Study, a longitudinal cohort followed for 6 years, we selected 327 girls aged 5 to 13 years at baseline to measure 36 steroid metabolites of glucocorticoids, androgens, progesterone, and estrogens in 2 urine samples collected before and during puberty. Parents reported the age at onset of breast development (thelarche), which had a high correlation in the subset with clinically assessed Tanner. Study staff measured height and weight and administered questionnaires, including the Internalizing Composite Scale, a parental proxy of child stress. We estimated hazard ratios (HRs) for the association between doubled steroid metabolites and ages at thelarche, pubarche, and menarche using Weibull survival models, testing interactions with stress and BMI z-scores. Accelerated thelarche was associated with higher prepubertal 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). Girls with high glucocorticoid metabolites combined with high BMI and stress reached thelarche 7 months earlier than their counterparts with low measures in these parameters. 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 as well, explaining secular declines in pubertal timing.31:Ta50,Abstract Context Estrogens underlie puberty in girls, but the steroid metabolome may also regulate pubertal timing in response to elevated stress and increasing body mass index (BMI). Objective Our objective was to identify steroid metabolome patterns linked to accelerated puberty and test whether BMI and stress markers modify this relationship. Methods From the LEGACY Girls Study, a longitudinal cohort followed for 6 years, we selected 327 girls aged 5 to 13 years at baseline to measure 36 steroid metabolites of glucocorticoids, androgens, progesterone, and estrogens in 2 urine samples collected before and during puberty. Parents reported the age at onset of breast development (thelarche), which had a high correlation in the subset with clinically assessed Tanner. Study staff measured height and weight and administered questionnaires, including the Internalizing Composite Scale, a parental proxy of child stress. We estimated hazard ratios (HRs) for the association between doubled steroid metabolites and ages at thelarche, pubarche, and menarche using Weibull survival models, testing interactions with stress and BMI z-scores. Results Accelerated thelarche was associated with higher prepubertal 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). Girls with high glucocorticoid metabolites combined with high BMI and stress reached thelarche 7 months earlier than their counterparts with low measures in these parameters. 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 as well, explaining secular declines in pubertal timing. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Early Pubertal Development: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Early Pubertal Development (condition). Clinician-written summaries and actionable practice insights. 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Girls with high glucocorticoid metabolites combined with high BMI and stress reached thelarche 7 months earlier than their counterparts with low measures in these parameters.","abstract":"$30","keywords":["BMI","breast cancer","puberty","steroid","stress"],"pubmed_id":"41955216","conclusions":"Elevated metabolites of glucocorticoids, androgens, and progesterone are associated with accelerated pubertal onset, and BMI and stress modify this association. 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Development","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"condition","value":"Precocious Puberty","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"modality","value":"Androgen","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"modality","value":"Glucocorticoid","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"modality","value":"Progesterone","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"sample_size","value":"n=327","value_numeric":327},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"study_design","value":"Prospective Longitudinal Cohort Study","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"warning","value":"No brand or generic drug names are applicable here; this is an observational etiologic study, not an intervention trial.","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"warning","value":"The 'impact_flag' of practice_changing is applied cautiously — the findings are novel and hypothesis-generating, but clinical translation of urinary steroid metabolomics is not yet standard of care.","value_numeric":null},{"paper_doi":"10.1210/clinem/dgag086","tag_type":"warning","value":"Thelarche onset was parent-reported for most participants; clinician-assessed Tanner staging was only available in a subset — the correlation was described as 'high' but the exact validation subset size is not reported in the abstract.","value_numeric":null}],"summaries":{"what_studied":"A longitudinal cohort study (LEGACY Girls Study, 6-year follow-up) examined how prepubertal urinary steroid metabolites (glucocorticoids, androgens, progesterone, estrogens) interact with BMI z-scores and internalizing stress scores to affect timing of thelarche, pubarche, and menarche in 327 girls aged 5–13 at baseline.","key_result":"Higher prepubertal glucocorticoid metabolites (HR 1.9, 95% CI 1.5–2.5), androgen metabolites (HR 3.9, 95% CI 2.7–5.6), and progesterone metabolites (HR 6.7, 95% CI 4.1–10.9) each independently predicted earlier thelarche. Girls with high glucocorticoids, high BMI, and high stress reached thelarche **7 months earlier** than peers with low levels across all three measures.","limitations":"Thelarche onset was primarily parent-reported (not clinician-assessed for the full cohort), introducing potential recall or observation bias. The study is observational, limiting causal inference. The sample was drawn from a single longitudinal cohort, which may limit generalizability.","practice_takeaway":"Clinicians evaluating early puberty in girls should consider not just BMI and estrogen status, but also stress burden and androgen/glucocorticoid activity — especially in girls with high BMI and signs of chronic stress, who may reach breast development 7 months earlier. Screening for psychosocial stress may be a practical early intervention target."}}],"initialOffset":1,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Early Pubertal Development"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Early Pubertal Development"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Early Pubertal Development"}}}]]

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