BACKGROUND

The diagnosis of central precocious puberty (CPP) relies on a gonadotropin releasing hormone stimulation test to assess the activation of the hypothalamic-pituitary-gonadal axis; this is costly and painful. Bile acids (BAs) have emerged as pivotal signaling molecules in the reproductive system. This study aimed to identify circulating BA profile signatures and explored if they may serve as biomarkers for CPP diagnosis in girls.

METHODS

We enrolled 431 girls, including 241 in the training cohort and 190 in the validation cohort. Participants were divided into four groups based on their body mass index Z-score and whether they were diagnosed with CPP. Ultra-performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs.

RESULTS

There were 18 individual BAs that were statistically different between CPP and non-CPP counterparts. The majority of these BAs (14/18) correlated significantly with sex-related hormones (P < 0.05). In girls with normal weight (NW), a logistic regression model combining chenodeoxycholic acid, tauroα-muricholic acid, and 6-ketolithocholic acid achieved an area under the receiver operating characteristic curve (AUC) of 0.885. For girls who were overweight/obese (OB), hyocholic acid and taurohyocholic acid enhanced the diagnostic efficiency of basal luteinizing and follicle stimulating hormones to an AUC value 0.914. In validation cohort, 75.34% NW girls and 84.09% OB girls were accurately classified.

CONCLUSIONS

Serum BA profiles of CPP girls showed significant changes that were associated with serum sex-related hormone levels. BA profiles could be potential biomarkers in CPP diagnosis and screening.