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The combination of elevated stress, higher BMI, and increased levels of glucocorticoids may accelerate puberty onset in girls, according to new research involving more than 300 participants.

Thelarche — the onset of breast development — is one of the earliest signs of puberty and typically occurs 2-4 years before menarche, making it an important clinical marker, said Lauren C. Houghton, PhD, assistant professor of epidemiology at the Columbia University Mailman School of Public Health in New York, and colleagues. 

Although many studies have documented a trend toward earlier puberty onset, the underlying drivers remain unclear. 

“Previous work has been siloed into disciplines that focus on stress as a driver of early puberty or those that consider BMI,” Houghton told Medscape Medical News. “Showing that drivers include both stress and BMI, and that hormones beyond those we typically think of as female hormones are the mechanism, is a new contribution.”

The study was published in The Journal of Clinical Endocrinology & Metabolism.

Contributors to Thelarche 

Researchers reviewed data from the LEGACY Girls Study, a longitudinal cohort with 6 years of follow-up. The analysis included 327 girls (mean age, 8.1 years; 74% White) aged 5-13 years who were prepubertal at enrollment and provided urine samples before and after puberty onset.

The investigators measured 36 steroid metabolites of glucocorticoids, androgens, progesterone, and estrogens in pre- and post-pubertal samples. Thelarche was determined by parent reports and, in some cases, Tanner staging. Stress was assessed using the Internalizing Composite Scale, completed by mothers or guardians. 

Hazard ratios (HRs) were estimated to evaluate associations between steroid metabolites and pubertal development, accounting for BMI and stress. 

Doubling of glucocorticoid, androgen, and progesterone levels from pre- to post-puberty was significantly associated with younger age at thelarche (HRs: 1.9, 3.9, and 6.7, respectively). In contrast, doubling of estrogen levels was linked to a later onset (HR, 0.3). 

When BMI and stress were included in the analysis, girls with higher prepubertal glucocorticoids, higher BMI, and greater stress reached thelarche an average of 7.2 months earlier than their peers with lower levels of these variables. 

Clinical Implications

The authors noted several limitations, including potential measurement variability in hormone assays, incomplete metabolite profiling, and a predominantly White study population, which may limit generalizability.

However, they suggest that, although precocious puberty may result from underlying endocrine conditions, screening for early puberty between the ages of 8 and 10 years could help identify girls at increased risk for menstrual and breast health concerns, with possible implications for future breast cancer screening.

“These findings were exciting, as they confirmed my long-held hypothesis that elevated adrenal hormones, activated by stress and metabolized in adipose tissue, accelerate breast development,” Houghton said.

Houghton developed this hypothesis based on prior research involving first-generation Bangladeshi child migrants to the United Kingdom, who exhibited higher androgen levels and earlier puberty onset than their British peers.

Expert Perspective

Cassandra C. Brady, MD, associate professor of clinical pediatrics, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, Tennessee, said the findings align with existing knowledge but add important mechanistic insight. 

“Endocrinologists are aware that higher BMI can lead to early puberty, but the correlations to urinary metabolites and stress in this study provide a pathophysiologic explanation,” said Brady, who was not involved in the study. 

From a clinical standpoint, the study reinforces the importance of promoting healthy weight and stress management in youth.

“This needs to start in the home and with general pediatricians,” Brady told Medscape Medical News, noting that early-life exposures may contribute to both pediatric and adult comorbidities. 

The study was funded by grants from the National Cancer Institute and the Breast Cancer Research Foundation. Disclosure information for the authors is available in the original publication. Brady reported no relevant financial conflicts of interest.