Abstract
<title>Abstract</title> <p>Background Primary amenorrhea is a complex clinical manifestation with diverse genetic, anatomical, and endocrinologic etiologies. This case series is reported to illustrate the novelty of contrasting four distinct pathophysiological nodes—outflow tract obstruction, receptor resistance, and gonadal failure—within a single clinical framework, emphasizing how a systematic diagnostic approach can navigate overlapping phenotypes to identify specific underlying pathologies. Case Presentation: This series describes four adolescent patients presenting with a failure of menarche. Patient 1 (46,XX) demonstrated normal secondary sexual characteristics but Müllerian agenesis with ectopic ovaries and absent uterus. Patient 2 (46,XY) presented with a female phenotype, well-developed breasts, and sparse pubic hair, diagnosed as complete androgen insensitivity syndrome (CAIS), with an MRI showing intraabdominal gonads. Patient 3 exhibited cyclic pelvic pain and a functional uterus with an obstructed outflow tract due to vaginal atresia, and a hypoplastic uterus. Patient 4 displayed short stature and sexual infantilism with elevated FSH, diagnosed as Turner syndrome (45,X). The diagnostic evaluation was carried out through a combination of karyotyping, hormonal profiling (FSH, LH, estradiol), and pelvic imaging (ultrasound/MRI) to localize the defects. Interventions included non-surgical oophoropexy with vaginoplasty for patient 1, hormonal therapy and laparoscopic gonadectomy for patient 2, surgical reconstruction to relieve the obstruction in patient 3, and pubertal induction with hormone replacement therapy (HRT) for patient 4. Outcomes centered on restoring anatomical function, achieving pain relief, and initiating long-term metabolic and psychological support. Conclusions This case series puts into evidence that a structured diagnostic approach based on the assessment of secondary sexual characteristics and pelvic anatomy is essential for accurate localization of the defect. Timely identification allows for etiology-specific interventions—such as HRT for bone protection in Turner syndrome or surgical drainage for obstructive defects—while addressing the profound psychosexual impact and future fertility options, including uterus transplantation or surrogacy, for these patients.</p>