Higher prepubertal urinary metabolites of glucocorticoids, androgens, and progesterone tend to speed up pubertal onset in girls, especially in those with high BMI and stress, a study has found.
“These findings have clear implications for paediatric clinical practice as well as public health strategies to prevent breast cancer,” the investigators said.
A total of 327 girls aged 5 to 13 years at baseline were selected from the LEGACY Girls Study, a longitudinal cohort followed for 6 years. The investigators measured 36 steroid metabolites of glucocorticoids, androgens, progesterone, and oestrogens in two urine samples collected before and during puberty.
Parents reported the age when breast development began (thelarche), which had a high correlation in the subset with clinically assessed Tanner. Participants had their height and weight measured and completed questionnaires, including the Internalizing Composite Scale, a parental proxy of child stress.
The investigators estimated hazard ratios (HRs) to assess 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.
Elevated metabolites of glucocorticoids (hazard ratio [HR], 1.9, 95 percent confidence interval [CI], 1.5‒2.5), androgens (HR, 3.9, 95 percent CI, 2.7‒5.6), and progesterone (HR, 6.7, 95 percent CI, 4.1‒10.9) significantly correlated with accelerated thelarche. [J Clin Endocrinol Metab 2026;111:2456-2465]
Notably, thelarche occurred 7 months earlier in girls with increased glucocorticoid metabolites combined with high BMI and stress than in those with low measures in said parameters.
Breast cancer
“The LEGACY cohort, which is enriched with participants that have a family history of breast cancer, allows the opportunity to assess whether pubertal hormone patterns may be harbingers of breast cancer risk,” the investigators said.
“We did not observe an interaction with breast cancer family history, but this means that, irrespective of breast cancer family history, similar mechanisms drive pubertal development,” they added.
These findings suggest that girls with and without a family history of breast cancer can benefit from lifestyle interventions, including physical activity, that help reduce or moderate BMI, stress, or hormones. [J Clin Endocrinol Metab 2023;108:e1603-e1613]
Androgens and glucocorticoids contribute to early pubertal timing, and a previous nested case-control study using the same urinary assay showed that these metabolite groupings are associated with a more than twofold increase in the odds of breast cancer development. [Cancer Epidemiol Biomarkers Prev 2021;30:89‐96]
“Therefore, these hormones and the phenotypes captured by the steroid metabolome principal components may serve as biomarkers of potential breast cancer risk,” the investigators said.
“Without any current population-based breast cancer screening for adults aged <40 years and with rates of early-onset breast cancer rising more than in other age groups, there is great potential for longitudinal hormonal biomarker tracking to be a screening modality,” they added. [JAMA 2013;309:800‐805; JNCI Cancer Spectr 2019;3:pkz038]
In paediatric practice, precocious puberty refers to breast development or pubic hair growth before 8 years of age in girls, which is potentially driven by underlying endocrine pathology, according to the investigators, noting how screening for early puberty after age 8 years but before 10 may indicate girls at risk for subsequent menstrual and breast health risks.
“Stress-reducing interventions may be effective interventions to offer during this time,” they said.