Abnormal timing of menarche in survivors of central nervous system tumors

Armstrong, Gregory T.; Whitton, John; Gajjar, Amar; Kun, Larry E.; Chow, Eric J.; Stovall, Marilyn; Leisenring, Wendy M.; Robison, Leslie L.; Sklar, Charles A.

doi:10.1002/cncr.24294

Cited by 68 publications

(44 citation statements)

References 34 publications

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“…In contrast to the report by Armstrong et al [4], who noted a markedly increased risk of premature menarche among patients who had CNS tumors and a very young age at diagnosis, a similar trend was not observed in the present group of patients. This might have been due to the smaller numbers of patients with CNS tumors in our study.…”

Section: Discussioncontrasting

confidence: 56%

“…In the framework of the Childhood Cancer Survivor Study in the United States, age at menarche among brain tumor patients and among former patients with acute lymphoblastic leukemia (ALL) was investigated [4,6]. An increased risk was observed among brain tumor patients both for early (<10 years) and late (>16 years) age at menarche.…”

Section: Introductionmentioning

confidence: 99%

“…For pediatric oncology patients, a significant proportion of the side effects are endocrinological. For example, the development of puberty or, among girls, the onset of menarche may be shifted to an earlier or later time point or may not occur [3,4,5,6]. …”

Section: Introductionmentioning

confidence: 99%

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Age at Menarche in Childhood Cancer Survivors: Results of a Nationwide Survey in Germany

Wessel

Balcerek²,

Reinmuth³

et al. 2012

Horm Res Paediatr

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Background/Aims: With rising cure rates of childhood cancer, side effects of treatment are attracting increasing interest. The present analysis evaluates the influence of tumor localization, radiotherapy and chemotherapy on the age of menarche. Methods: 4,689 former pediatric oncology patients, diagnosed 1980–2004, were contacted in collaboration with the German Childhood Cancer Registry. Results: 1,036 out of 1,461 female participants reported their age at menarche and had an oncological diagnosis before menarche. The median age at menarche was 13 years, compared to 12.8 years in the German general population. A significant delay of menarche was seen in patients with pituitary radiation doses of ≧30 Gy (mean 13.6 years, SD 2.2) compared to <30 Gy (mean 12.5 years, SD 1.4, p = 0.05). Patients with additional spinal radiation were even older at menarche (mean 14.4 years, SD 2.5). Pelvic and pelvic-near radiation significantly delayed onset of menarche (mean 14.0 years, SD 1.9 and mean 14.3, SD 2.6, respectively, p < 0.001). Only some chemotherapeutic agents (carboplatin/cisplatin, etoposide) were associated with a menarcheal delay of <1 year. Conclusion: Overall, female childhood cancer survivors showed a normal menarcheal age. Pituitary radiation dosage of ≧30 Gy, spinal and pelvic radiotherapy were associated with a moderate delay in the occurrence of menarche.

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Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

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Age at Menarche in Childhood Cancer Survivors: Results of a Nationwide Survey in Germany

Wessel

Balcerek²,

Reinmuth³

et al. 2012

Horm Res Paediatr

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“…CRT dose > 50 Gy, CSI, and diagnosis of CNS tumor at older age (> 10 years) conferred an increased risk of late menarche [36]. Exposure to alkylating agents was not associated with an increased risk of altered timing of menarche [36]. Delayed pubertal development occurred in 11.8% of our cohort and was not clearly associated with either age at treatment or specific therapeutic exposures.…”

Section: Discussionmentioning

confidence: 99%

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

DeWire

Green

Sklar

et al. 2014

Pediatric Blood & Cancer

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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 1–2 and FSH >15 mIU/ml, or Tanner stage 3–5, 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 to 10.8 years). The cumulative incidence of pubertal onset was 75.6% by age 13 years. Precocious puberty was observed in 11.1% and delayed puberty in 11.8%. The cumulative incidence of primary ovarian insufficiency 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 primary ovarian insufficiency, a subset of whom will recover function over time. Further refinement of therapies is needed in order to reduce late ovarian insufficiency.

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“…Female CNS survivors who received RT are also at increased risk for abnormal timing of menarche 26. A population of 235 survivors diagnosed and treated prior to menarche had higher rates than siblings of both early onset of menarche (before 10 years of age, 11.9% vs. 1%, OR 14.1, 95% CI 7.0-30.9) and delayed menarche (10.6% vs. 1.9%, OR 6.6, 95% CI 3.4-11.4).…”

Section: Chronic Medical Conditionsmentioning

confidence: 99%

Long-term survivors of childhood central nervous system malignancies: The experience of the Childhood Cancer Survivor Study

Armstrong

2010

European Journal of Paediatric Neurology

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139

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In the last four decades, advances in neurosurgical technique, delivery of radiation therapy (RT), supportive care, and use of chemotherapy have improved 5-year survival for children with central nervous system (CNS) malignancies. Currently, in the United States 74% of children will become 5-year survivors of their primary CNS malignancy. This improved outcome has resulted in a new and growing population of childhood cancer survivors. Surgery, RT and chemotherapy, while essential components of primary treatment for most childhood CNS malignancies, have also been associated with risk of long-term morbidity and late mortality. The Childhood Cancer Survivor Study, a retrospective cohort of over 14,000 survivors of childhood cancer diagnosed between 1970 and 1986, has been an important resource for quantification of associations between these therapeutic modalities and risk of long-term adverse health and quality of life outcomes. CNS malignancy survivors are at significant risk for late mortality, development of second neoplasms, as well as increased risk for multiple endocrinopathies and adverse neurologic health conditions. Importantly, the CCSS has identified a number of dose-response relationships between RT and development of subsequent malignant neoplasms of the central nervous system, abnormal timing of menarche and neurocognitive function. Ongoing study of childhood cancer survivors is needed to establish longterm risks and evaluate impact of newer techniques such as conformal RT or proton beam delivery that limit RT exposure and may reduce long-term effects.

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Abnormal timing of menarche in survivors of central nervous system tumors

Cited by 68 publications

References 34 publications

Age at Menarche in Childhood Cancer Survivors: Results of a Nationwide Survey in Germany

Age at Menarche in Childhood Cancer Survivors: Results of a Nationwide Survey in Germany

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

Long-term survivors of childhood central nervous system malignancies: The experience of the Childhood Cancer Survivor Study

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