Low Anti-Müllerian Hormone in Pediatric Cancer Survivors in the Early Years after Gonadotoxic Therapy

Abstract Study 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). Design Cross-sectional study. Setting Academic medical center. Participants 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. Interventions None. Main Outcome Measures 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. Conclusion 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.