Anti-Mullerian Hormone Is a Marker of Gonadotoxicity in Pre- and Postpubertal Girls Treated for Cancer: A Prospective Study

Context: Cytotoxic treatment may accelerate depletion of the primordial follicle pool, leading to impaired fertility and premature menopause. Assessment of ovarian damage in prepubertal girls is not currently possible, but Anti-Mullerian Hormone (AMH) is a useful marker of ovarian reserve in adults. Objective: The objective of the study was to prospectively evaluate AMH measurement in children as a marker of ovarian toxicity during cancer treatment. Design and Setting: This was a prospective, longitudinal study at a University Hospital. Patients: Twenty-two females (17 prepubertal), median age 4.4 yr (range 0.3-15 yr), were recruited before treatment for cancer. Main Outcome Measures: AMH, inhibin B, and FSH at diagnosis, after each chemotherapy course and during follow-up, were measured. Risk of gonadotoxicity was classified as low/medium (n = 13) or high (n = 9) based on chemotherapy agent, cumulative dose, and radiotherapy involving the ovaries. Results: Pretreatment AMH was detectable across the age range studied. AMH decreased progressively during chemotherapy (P < 0.0001) in both prepubertal and pubertal girls, becoming undetectable in 50% of patients, with recovery in the low/medium risk groups after completion of treatment. In the high-risk group, AMH became undetectable in all patients and showed no recovery. Inhibin B was undetectable in most patients before treatment and, with FSH, showed no clear relationship to treatment. Conclusion: AMH is detectable in girls of all ages and falls rapidly during cancer treatment in both prepubertal and pubertal girls. Both the fall during treatment and recovery thereafter varied with risk of gonadotoxicity. AMHis therefore a clinically useful marker of damage to the ovarian reserve in girls receiving treatment for cancer. (J Clin Endocrinol Metab 97: 2059-2067, 2012)