title: Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort.
abstract: Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited.
  
  
  
  To describe the prevalence of POI, its risk factors, and associated long-term adverse health outcomes.
  
  
  
  Cross-sectional.
  
  
  
  The St. Jude Lifetime Cohort Study, an established cohort in a tertiary care center.
  
  
  
  Nine hundred twenty-one participants (median age, 31.7 years) were evaluated at a median of 24.0 years after cancer diagnosis.
  
  
  
  POI was defined by persistent amenorrhea combined with a follicle-stimulating hormone level >30 IU/L before age 40. Multivariable Cox regression was used to study associations between demographic or treatment-related risk factors and POI. Multivariable logistic regression was used to study associations between POI and markers for cardiovascular disease, bone mineral density (BMD), and frailty. Exposure to alkylating agents was quantified using the validated cyclophosphamide equivalent dose (CED).
  
  
  
  The prevalence of POI was 10.9%. Independent risk factors for POI included ovarian radiotherapy at any dose and CED ≥8000 mg/m2. Patients with a body mass index ≥30 kg/m2 at the time of the St. Jude Lifetime Cohort assessment were less likely to have a diagnosis of POI. Low BMD and frailty were independently associated with POI.
  
  
  
  High-dose alkylating agents and ovarian radiotherapy at any dose are associated with POI. Patients at the highest risk should be offered fertility preservation whenever feasible. POI contributes to poor general health outcomes in childhood cancer survivors; further studies are needed to investigate the role of sex hormone replacement in improving such outcomes.
authors.affiliation: Department of Pediatric Medicine-Endocrinology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.|Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Wassim
authors.initials: W
authors.lastname: Chemaitilly
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Krasin
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Brooke
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Wilson
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.|Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.affiliation: Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: James L
authors.initials: JL
authors.lastname: Klosky
authors.affiliation: Department of Pediatric Medicine-Endocrinology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Nicole
authors.initials: N
authors.lastname: Barnes
authors.affiliation: Department of Pediatric Medicine-Endocrinology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Clark
authors.affiliation: Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Farr
authors.affiliation: Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Israel
authors.initials: I
authors.lastname: Fernandez-Pineda
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Bishop
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Monika
authors.initials: M
authors.lastname: Metzger
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.affiliation: Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.|Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.|Department of Radiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163.
authors.forename: Sue C
authors.initials: SC
authors.lastname: Kaste
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Ness
authors.affiliation: Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Deo Kumar
authors.initials: DK
authors.lastname: Srivastava
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.|Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hudson
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000628:therapy*; D010024:Osteoporosis / Q000453:epidemiology / Q000209:etiology; D010053:Ovary / Q000528:radiation effects; D010298:Parity; D015995:Prevalence; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology / Q000209:etiology*; D011829:Radiation Dosage; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D017741:Survivors; D013714:Tennessee / Q000453:epidemiology; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating