title: Anti-Müllerian Hormone in Female Adolescent Cancer Patients Before, During, and After Completion of Therapy: A Pilot Feasibility Study.
abstract: OBJECTIVE
  Alkylating agents are implicated in premature ovarian insufficiency. To optimize counseling regarding future ovarian function in survivors of adolescent cancer, we describe anti-Müllerian hormone (AMH) levels in female adolescents at diagnosis, during, and shortly after completion of chemotherapy. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This was a prospective single-institution study. Participants were a mixed population of newly diagnosed postmenarchal female adolescents with malignancy. AMH was performed at diagnosis (T1), 6 months from diagnosis (T2), at end of therapy or 12 months [T3, whichever came first], 1 year after the end of therapy or 24 months from diagnosis [T4, whichever came first], and 18 months from the time of diagnosis (T5). All patients had baseline pelvic ultrasound examinations. Presence of menses and hot flashes were recorded at each time point.
  
  
  RESULTS
  Sixteen participants with a median age at diagnosis of 14.3 years (range 12-17 years) were followed for 18.2 months (range, 14-24 months). Oncology diagnoses included leukemia, lymphoma, and sarcoma. Ten patients (62.5%) received alkylating agents with a median cumulative dose of 3041 mg/m2(range, 2639-6478 mg/m2) of cyclophosphamide. Almost half (n = 7; 44%) experienced amenorrhea during treatment with resumption of menses in 6 of 7 patients (85%). Fifteen of 16 (94%) participants showed a decline in mean AMH levels by 6 months (T2) from diagnosis (15.8 IU/mL at T1 vs 6.5 IU/mL at T2; P = .003) and 12 of 15 (80%) showed at least some recovery of AMH (mean AMH at T4 = 13.2 IU/mL compared with 6.5 IU/mL at T2; P = .02). There was no difference in the mean decline nor recovery of AMH in those who did, vs did not receive cyclophosphamide.
  
  
  CONCLUSIONS
  To our knowledge, this is the largest series to date in adolescents showing that AMH is uniformly suppressed during cancer therapy and short-term recovery occurs in just more than half of the patients by 18-24 months. The contribution of short-term AMH measurements in predicting long-term ovarian function remains to be defined. Long-term follow-up with serial AMH levels is required to help predict those at risk for premature ovarian insufficiency.
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Electronic address: abha.gupta@sickkids.ca.
authors.forename: Abha A
authors.initials: AA
authors.lastname: Gupta
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: Lee Chong
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Deveault
authors.affiliation: Department of Radiology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Traubici
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Maloney
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Samantha
authors.initials: S
authors.lastname: Knight
authors.affiliation: Division of Urology, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Armando
authors.initials: A
authors.lastname: Lorenzo
authors.affiliation: Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Gynecology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Allen
mesh_terms: D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced; D054304:Anti-Mullerian Hormone / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D002648:Child; D003520:Cyclophosphamide / Q000009:adverse effects*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000517:prevention & control*; D011446:Prospective Studies; D017741:Survivors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D054304:Anti-Mullerian Hormone; D003520:Cyclophosphamide
keywords: Anti-Müllerian hormone; Cancer; Chemotherapy; Fertility preservation