Noncytotoxic-Related Primary Ovarian Insufficiency in Adolescents: Multicenter Case Series and Review

Study objective: Primary ovarian insufficiency (POI) in adolescents not due to cytotoxic therapy has not been well studied. Causes of POI have been described in adults, but adolescents might represent a unique subset necessitating a targeted approach to diagnosis, workup, and treatment. We sought to better characterize adolescent POI through a descriptive multicenter study.

Design: Case series of patients with POI.

Setting: Six tertiary care institutions.

Participants: Patients presenting from 2007 to 2014 aged 13-21 years diagnosed with noncytotoxic POI, with exclusions for those who received gonadotoxic therapy, with 46XY gonadal dysgenesis, or lack of evidence of hypergonadotropic hypogonadism on chart review.

Interventions: Review and data extraction of records identified according to International Classification of Diseases Ninth or Tenth Revision codes.

Main outcome measures: Data were analyzed for signs and symptoms, workup, and treatments. Complete workup was on the basis of American College of Obstetricians and Gynecologists guidelines. Characteristics of patients with POI who presented with delayed puberty/primary amenorrhea vs secondary amenorrhea were compared.

Results: One hundred thirty-five records were identified. Those who had received cytotoxic therapy (n = 52), 46XY gonadal dysgenesis (n = 7), or on review did not have POI (n = 19) were excluded. Of 57 remaining cases, 16 were 45X, 2 had galactosemia, and 4 had X-chromosome abnormalities. Most did not undergo full etiologic evaluation. Girls diagnosed after primary amenorrhea/delayed puberty were less symptomatic and more likely to receive an estrogen patch than those diagnosed after secondary amenorrhea.

Conclusion: Noncytotoxic POI in adolescents is an uncommon condition with, to our knowledge, only 64 cases in 6 institutions over 7 years. These patients might not undergo complete etiological workup. Aside from 45X, the most common etiologies were X-chromosome abnormalities or galactosemia.