Primary amenorrhea in adolescents: a case-based narrative review to diagnostic evaluation

Background Primary amenorrhea (PA) in adolescents is a heterogeneous and complex clinical condition requiring a structured and age-appropriate diagnostic approach. Despite available guidelines, the evaluation of adolescent girls with PA represents a challenge in clinical practice, often resulting in delayed diagnoses and unnecessary investigations. Objective To provide a narrative, case-based review of the diagnostic evaluation of PA in adolescents, emphasizing practical clinical reasoning and a physiology-based approach to diagnosis and management. Methods This narrative review will be structured around real-world clinical scenarios representing the main etiological categories of PA. Each case will serve as a framework to discuss diagnostic strategies, whit a particular focus on clinical assessment, hormonal tests, imaging investigations, genetic testing, and fertility implications, with particular attention to adolescent-specific considerations. Results The narrative review highlights key diagnostic pathways, common pitfalls, and decision-making strategies, integrating current evidence with clinical experience. Practical diagnostic algorithms and concise take-home messages will be provided to support clinicians in everyday practice. Emphasis is placed on the interpretation of key clinical and laboratory findings to localize the underlying defect within the hypothalamic–pituitary–gonadal axis. Practical diagnostic algorithms and concise take-home messages are provided to support clinicians in everyday practice. Conclusion A case-based narrative approach may facilitate a clearer understanding of the biological heterogeneity and diagnostic complexity of PA in adolescents. The application of a structured, physiology-based framework can support timely diagnosis, guide appropriate investigations, and promote patient-centered multidisciplinary care.