title: Low Anti-Müllerian Hormone in Pediatric Cancer Survivors in the Early Years after Gonadotoxic Therapy.
abstract: OBJECTIVE
  To obtain anti-Müllerian hormone (AMH) levels in female childhood cancer survivors and determine the association of therapeutic exposures with diminished ovarian reserve (DOR).
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Forty-nine survivors (mean age = 14.9 years, SD = 3.3 years; mean time without therapy = 7.5 years, SD = 3.6 years) who received alkylator/heavy metal chemotherapy, and/or radiation exposure to the ovaries with 2 or more years without therapy were recruited.
  
  
  METHODS
  None.
  
  
  METHODS
  AMH, follicle stimulating hormone (FSH) levels (random), and therapeutic characteristics such as cyclophosphamide equivalent dose (CED), heavy metal exposure, and bilateral ovarian radiation exposure were determined for each subject. DOR was defined as a low AMH (less than the fifth percentile for age-matched controls), and premature ovarian insufficiency as an FSH greater than 40 IU/L with AMH less than the fifth percentile.
  
  
  RESULTS
  Fourteen subjects (28.6%) had DOR, and 5 (10.2%) had premature ovarian insufficiency. Those with a low AMH were more likely exposed to a higher CED (P = .001) and/or bilateral ovarian radiation exposure (P = .048). In the multivariate model of DOR adjusted for age at diagnosis, DOR was associated with bilateral radiation (odds ratio = 39.9; 95% confidence interval 2.1-759.7; P = .04). There was a nonsignificant trend with increasing odds of low AMH with increased CED.
  
  
  CONCLUSIONS
  DOR, defined by an AMH less than the fifth percentile, was observed in more than one-quarter of pediatric cancer survivors exposed to gonadotoxic cancer therapy and was significantly associated with bilateral ovarian irradiation. Identifying risk factors for low AMH prompts AMH and FSH surveillance in the early years after cancer therapy and, if needed, early referral to a reproductive specialist.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia. Electronic address: selchur@emory.edu.
authors.forename: Swati V
authors.initials: SV
authors.lastname: Elchuri
authors.affiliation: Division of Endocrinology and Metabolism, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; Division of Hematology/Oncology/BMT and Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Briana C
authors.initials: BC
authors.lastname: Patterson
authors.affiliation: Division of Endocrinology and Metabolism, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Milton
authors.initials: M
authors.lastname: Brown
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Atlanta, Georgia.
authors.forename: Carrie
authors.initials: C
authors.lastname: Bedient
authors.affiliation: Division of Hematology/Oncology/BMT and Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Record
authors.affiliation: Division of Hematology/Oncology/BMT and Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Karen
authors.initials: K
authors.lastname: Wasilewski-Masker
authors.affiliation: Division of Hematology/Oncology/BMT and Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Mertens
authors.affiliation: Division of Endocrinology and Metabolism, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; Division of Hematology/Oncology/BMT and Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Lillian R
authors.initials: LR
authors.lastname: Meacham
mesh_terms: D000293:Adolescent; D054304:Anti-Mullerian Hormone / Q000097:blood*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D003520:Cyclophosphamide / Q000009:adverse effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D019216:Metals, Heavy / Q000009:adverse effects; D009369:Neoplasms / Q000628:therapy*; D010053:Ovary / Q000187:drug effects / Q000528:radiation effects; D016649:Primary Ovarian Insufficiency / Q000097:blood* / Q000209:etiology; D011832:Radiation Injuries / Q000097:blood* / Q000209:etiology; D017741:Survivors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019216:Metals, Heavy; D054304:Anti-Mullerian Hormone; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone
keywords: AMH; Anti-Müllerian hormone; Cancer survivor; Gonadotoxic; Ovarian reserve; Premature ovarian failure