title: Decreased ovarian function is associated with obesity in very long-term female survivors of childhood cancer.
abstract: OBJECTIVE
  Obesity and gonadal dysfunction are known major side effects of treatment in adult childhood cancer survivors (CCS). In the general population, obesity has a negative influence on female fertility. We aimed to evaluate whether obesity and serum insulin are associated with decreased ovarian reserve markers in CCS.
  
  
  METHODS
  Retrospective single-center cohort study.
  
  
  METHODS
  Data of 191 female survivors of childhood cancer were analyzed. Median follow-up time was 18.8 (2.348.8) years. Outcome measures were serum anti-Müllerian hormone (AMH) and total follicle count (FC). Potential risk factors were: BMI; body composition measures, determined by dual-energy X-ray absorptiometry (total fat percentage, lean body mass, and visceral fat percentage); and fasting insulin.
  
  
  RESULTS
  Lower serum AMH was found in obese subjects (β (%) -49, P=0.007) and in subjects with fasting insulin in the highest tertile (β (%) -43, P=0.039). Total fat percentage tends to be associated with serum AMH (β (%) -2.1, P=0.06). Survivors in the highest tertile of insulin had significantly lower FC than survivors in the lowest tertile (β -6.3, P=0.013). BMI and other measures of body composition were not associated with FC. Correlation between serum AMH and antral follicle count (AFC) was ρ=0.32 (P=0.08).
  
  
  CONCLUSIONS
  Obesity and insulin resistance are associated with gonadal damage, as reflected by decreased AMH and reduced FC in adult survivors of childhood cancer. In contrast to its highly predictive value for AFC in the healthy female population, serum AMH does not seem to correlate as well with AFC in CCS.
authors.affiliation: Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children's Hospital, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands. w.vandorp@erasmusmc.nl
authors.forename: W
authors.initials: W
authors.lastname: van Dorp
authors.forename: K
authors.initials: K
authors.lastname: Blijdorp
authors.forename: J S E
authors.initials: JS
authors.lastname: Laven
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.forename: J A
authors.initials: JA
authors.lastname: Visser
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: S J C M M
authors.initials: SJ
authors.lastname: Neggers
authors.forename: M M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D054304:Anti-Mullerian Hormone / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D009369:Neoplasms / Q000097:blood / Q000503:physiopathology*; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D010053:Ovary / Q000503:physiopathology*; D012189:Retrospective Studies; D012307:Risk Factors; D017741:Survivors
chemical_list: D007328:Insulin; D054304:Anti-Mullerian Hormone