Delayed Puberty in Adolescents: Advances in Diagnosis, Classification, and Treatment Modalities

Delayed puberty (DP) in adolescents is an increasingly recognized clinical condition that poses physiological, psychosocial, and reproductive concerns. Defined by the absence of pubertal onset beyond established age thresholds, DP may arise from benign variants such as constitutional delay of growth and puberty (CDGP) or from pathological causes including hypogonadotropic hypogonadism (HH), hypergonadotropic hypogonadism, and chronic systemic diseases. This review synthesizes evidence published between February 2021 and July 2025 to evaluate recent advances in diagnosis, classification, and treatment. A structured search of PubMed, Scopus, Web of Science, and Google Scholar identified randomized trials, cohort studies, genetic investigations, biomarker analyses, and guideline updates. Findings highlight progress in hormonal assays, genetic sequencing, AMH/INHB biomarkers, neuroimaging, and predictive models that improve CDGP–HH differentiation. Advancements in classification frameworks, including phenotype–genotype integration, offer improved clinical decision-making. Treatment evolution includes optimized sex-steroid induction therapies, gonadotropin-based regimens, and emerging modalities such as kisspeptin analogues. Comparative analyses show varying therapeutic efficacy across etiologies. Despite progress, challenges remain regarding diagnostic heterogeneity, limited biomarker standardization, variable treatment protocols, and insufficient long-term outcome data. Future directions emphasize precision medicine, equitable access to diagnostics, and long-term monitoring strategies. This review consolidates current evidence to guide clinical practice and inform future research priorities.