Pubertal development and primary ovarian insufficiency in female survivors of embryonal brain tumors following risk-adapted craniospinal irradiation and adjuvant chemotherapy

Pediatr Blood Cancer. 2015 Feb;62(2):329-334. doi: 10.1002/pbc.25274. Epub 2014 Oct 18.

Abstract

Background: Female survivors of central nervous system (CNS) tumors are at an increased risk for gonadal damage and variations in the timing of puberty following radiotherapy and alkylating agent-based chemotherapy.

Procedure: Clinical and laboratory data were obtained from 30 evaluable female patients with newly diagnosed embryonal CNS tumors treated on a prospective protocol (SJMB 96) at St. Jude Children's Research Hospital (SJCRH). Pubertal development was evaluated by Tanner staging. Primary ovarian insufficiency (POI) was determined by Tanner staging and FSH level. Females with Tanner stage I-II and FSH > 15 mIU/ml, or Tanner stage III-V, FSH > 25 mIU/ml and FSH greater than LH were defined to have ovarian insufficiency. Recovery of ovarian function was defined as normalization of FSH without therapeutic intervention.

Results: Median length of follow-up post completion of therapy was 7.2 years (4.0-10.8 years). The cumulative incidence of pubertal onset was 75.6% by the age of 13. Precocious puberty was observed in 11.1% and delayed puberty in 11.8%. The cumulative incidence of POI was 82.8%, though recovery was observed in 38.5%.

Conclusions: Treatment for primary CNS embryonal tumors may cause variations in the timing of pubertal development, impacting physical and psychosocial development. Female survivors are at risk for POI, a subset of whom will recover function over time. Further refinement of therapies is needed in order to reduce late ovarian insufficiency. Pediatr Blood Cancer 2015;62:329-334. © 2014 Wiley Periodicals, Inc.

Keywords: medulloblastoma; ovarian dysfunction; ovarian insufficiency; puberty.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Alkylating Agents / therapeutic use
  • Brain Neoplasms / radiotherapy*
  • Child
  • Child, Preschool
  • Craniospinal Irradiation / adverse effects*
  • Female
  • Follicle Stimulating Hormone / blood
  • Humans
  • Neoplasms, Germ Cell and Embryonal / radiotherapy*
  • Primary Ovarian Insufficiency / diagnosis*
  • Puberty, Delayed / diagnosis*
  • Puberty, Precocious / diagnosis*
  • Young Adult

Substances

  • Alkylating Agents
  • Follicle Stimulating Hormone