title: Obesity independently influences gonadal function in very long-term adult male survivors of childhood cancer.
abstract: OBJECTIVE
  Although obesity is associated with gonadal dysfunction in the general population, gonadotoxic treatment might diminish the impact of obesity in childhood cancer survivors (CCS). The aim was to evaluate whether altered body composition is associated with gonadal dysfunction in male CCS, independent of gonadotoxic cancer treatment.
  
  
  METHODS
  Three hundred fifty-one male CCS were included. Median age at diagnosis was 5.9 years (0-17.8) and median age at follow-up 25.6 years (18.0-45.8). Total and non-SHBG-bound testosterone, sex hormone-binding globulin, inhibin B, and follicle-stimulating hormone (FSH) were studied. Potential determinants were BMI, waist circumference, waist-hip ratio, and body composition measures (dual energy X-ray absorptiometry).
  
  
  RESULTS
  Non-SHBG-bound testosterone was significantly decreased in survivors with BMI ≥ 30 kg/m(2) (adjusted mean 9.1 nmol/L vs. 10.2 nmol/L, P = 0.015), high fat percentage (10.0 vs. 11.2, P = 0.004), and high waist circumference (>102 cm) (9.0 vs. 11.0, P = 0.020). Survivors with high fat percentage (≥25%) had significantly lower inhibin B/FSH ratios (inhibin B/FSH ratio: β -34%, P = 0.041).
  
  
  CONCLUSIONS
  Obesity is associated with gonadal dysfunction in male CCS, independent of the irreversible effect of previous cancer treatment. Randomized controlled trials are required to evaluate whether weight normalization could improve gonadal function, especially in obese survivors with potential other mechanisms than lifestyle causing their obesity.
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Medicine - Section Endocrinology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Blijdorp
authors.forename: Wendy
authors.initials: W
authors.lastname: van Dorp
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.forename: Saskia M F
authors.initials: SM
authors.lastname: Pluijm
authors.forename: Aart Jan
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
authors.forename: Sebastian J C M M
authors.initials: SJ
authors.lastname: Neggers
mesh_terms: D000293:Adolescent; D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007223:Infant; D007265:Inhibins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D009765:Obesity / Q000150:complications*; D012189:Retrospective Studies; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D017741:Survivors; D013737:Testis / Q000503:physiopathology*; D013739:Testosterone / Q000097:blood; D055105:Waist Circumference; D049629:Waist-Hip Ratio; D055815:Young Adult
chemical_list: D012738:Sex Hormone-Binding Globulin; C422364:inhibin B; D013739:Testosterone; D007265:Inhibins; D005640:Follicle Stimulating Hormone