Genetic, neuropeptidergic, and cardiometabolic interplay in female central precocious puberty

Central precocious puberty (CPP) results from premature reactivation of the hypothalamic–pituitary–gonadal axis and is increasingly recognized as a systemic condition linked to cardiometabolic health. Genetic mutations, particularly in imprinted genes such as MKRN3 and DLK1 , are major monogenic causes of familial CPP, while rare activating variants in KISS1 and KISS1R highlight the pivotal role of kisspeptin signaling. Neuropeptides, including kisspeptin and neurokinin B, are central to pubertal regulation. Advances in clinical assessment, biochemical markers, pelvic ultrasound, and genetic testing have improved diagnostic precision, though differentiating CPP from benign variants remains challenging. Gonadotropin-releasing hormone analogs remain the gold standard for halting progression and optimizing adult height, while novel neuropeptide modulators show promise. Beyond growth outcomes, accumulating evidence indicates significant cardiometabolic sequelae, underscoring the importance of early, precision-guided intervention. Integrating genomic, neuropeptidergic, and metabolic insights can refine diagnosis, guide therapy, and potentially mitigate lifelong cardiovascular risk in affected females.