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. 32:T41d,Testosterone, discovered during the endocrine gold rush of the 1930s, was the first hormone chemically synthesized for replacement therapy. In both men and women, testosterone functions directly through the androgen receptor (AR) and indirectly as a prohormone, converted by aromatase into 17β-oestradiol (oestradiol), which activates the oestrogen receptors ERα and ERβ. Testosterone is also metabolized to dihydrotestosterone-a potent, non-aromatizable AR agonist-through steroid 5α-reductases. Testosterone and its metabolites signal through AR- and ER-mediated genomic and rapid non-genomic actions. Long recognized for its role as a sex hormone, mounting evidence underscores the importance of testosterone in the regulation of systemic metabolism in both male and female organisms. Here, we highlight key milestones in the history of testosterone's discovery and therapeutic applications. Additionally, we synthesize the current understanding of testosterone as a key messenger promoting metabolic homeostasis in preclinical models and humans.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Androgen: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Androgen (modality). 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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