Timing of menarche among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study

Pediatr Blood Cancer. 2008 Apr;50(4):854-8. doi: 10.1002/pbc.21316.


Background: The objective of this study was to determine risk factors associated with abnormal timing of menarche among survivors of childhood acute lymphoblastic leukemia (ALL).

Procedure: Self-reported age of menarche was determined among 949 female ALL survivors participating in the Childhood Cancer Survivor Study (CCSS), a cohort of 5-year survivors of common pediatric cancers diagnosed from 1970 to 1986, and compared with 1,128 siblings.

Results: The majority of survivors (92%) and siblings (97%) reported menarche between the ages of 10 and 16. Survivors treated with chemotherapy alone, including those exposed to alkylating agents, experienced menarche at a similar rate to siblings. However, compared to chemotherapy alone, cranial radiotherapy was associated with early menarche (age < 10; OR 6.2, 95% CI 2.1, 18.5) while craniospinal radiotherapy was associated with both early (OR 8.6, 95% CI 1.9, 38.6) and late (age > 16; OR 4.8, 95% CI 1.4, 16.7) menarche. There were no differences in effect between <20 and >/=20 Gy radiotherapy doses. In multivariable analysis, younger age at diagnosis was an independent risk factor for early menarche.

Conclusions: Few female childhood ALL survivors experienced menarche outside of the normal range. Alkylating agent exposure was not associated with abnormal timing. However, those exposed to cranial and craniospinal radiotherapy, especially at a young age, should be monitored closely for abnormal timing of menarche.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Age of Onset
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Child
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Menarche / drug effects*
  • Menarche / radiation effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Radiotherapy / adverse effects*
  • Radiotherapy / methods
  • Risk Factors
  • Survivors
  • Time


  • Antineoplastic Agents, Alkylating