Primary Amenorrhea in Females with Emphasis on Genetic Causes, Cytogenetic Evaluation and Clinical Management

Primary amenorrhea is an important gynecological and endocrine disorder characterized by the absence of menarche by the age of 15 years in females with normal secondary sexual characteristics or by 13 years in the absence of secondary sexual development. Although endocrine, anatomical, nutritional, and systemic disorders contribute to its etiology, genetic abnormalities represent a significant proportion of cases, particularly those involving chromosomal abnormalities, disorders of sex development (DSDs), and mutations affecting gonadal differentiation and reproductive hormone regulation. Advances in cytogenetics and molecular genetics have considerably improved the diagnosis and classification of genetic causes of primary amenorrhea through conventional karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and next-generation sequencing (NGS). Early identification of the underlying genetic abnormalities facilitates appropriate clinical management, hormonal therapy, fertility counseling, and psychological support while reducing long-term complications such as osteoporosis, cardiovascular disease, and infertility. This review discusses the epidemiology, genetic mechanisms, cytogenetic evaluation, diagnostic approaches, clinical management, recent advances, and future perspectives in the management of primary amenorrhea with special emphasis on chromosomal disorders and molecular diagnostics.