When the Uterus is Not Visualized on Ultrasonography in Adolescents and Young Adults with Primary Amenorrhea: Diagnostic Pitfalls and Clinical Implications

Uterine nonvisualization on ultrasonography in adolescents and young adults (AYAs) presenting with primary amenorrhea is frequently interpreted as Müllerian agenesis. However, in hypoestrogenic conditions or during the prepubertal period, the uterus may be small or difficult to detect on imaging, potentially leading to diagnostic uncertainty and misclassification. This study aimed to evaluate the diagnostic outcomes and clinical implications of uterine nonvisualization in AYAs with primary amenorrhea.

We retrospectively reviewed AYAs aged 13-20 years evaluated for primary amenorrhea at a tertiary referral Pediatric and Adolescent Gynecology clinic between January 2021 and December 2025. AYAs with confirmed uterine nonvisualization on ultrasonography comprised the study cohort. Clinical findings, hormonal profiles, imaging studies, and longitudinal follow-up records were reviewed.

Eighteen AYAs were included in the final cohort. Final diagnoses were Müllerian agenesis (n = 9), hypogonadotropic hypogonadism (n = 4), premature ovarian insufficiency (n = 4), and obstructed hemivagina with ipsilateral renal anomaly (OHVIRA) syndrome (n = 1). In AYAs with hypoestrogenic conditions, magnetic resonance imaging initially failed to demonstrate the uterus or suggested Müllerian agenesis; however, follow-up imaging demonstrated progressive uterine development after hormonal treatment. More than half of the AYAs with Müllerian agenesis had associated renal anomalies, and one individual fulfilled the criteria for MURCS association. In the OHVIRA case, uterine nonvisualization during early pubertal development contributed to diagnostic uncertainty, and the correct diagnosis became apparent during follow-up.

Uterine nonvisualization on ultrasonography in AYAs with primary amenorrhea may reflect developmental or hormonal factors rather than true uterine absence. Accurate interpretation requires a stepwise diagnostic approach integrating pubertal assessment, hormonal evaluation, physical examination, and imaging findings. Uterine nonvisualization should be regarded as a finding requiring further evaluation rather than definitive evidence of Müllerian agenesis.