Effect of cell cycle specificity of chemotherapeutic agents on the gonadal functions of a pediatric cancer population: role of anti-mullerian hormone (AMH)

Abstract

OBJECTIVE: The objectives of the study are to 1) determine whether AMH levels could be used to quantify gonadal damage inflicted by gonadotoxic chemotherapy and 2) to examine the effect of cell cycle specificity of the chemotherapeutic agents on the gonadal reserve as evidenced by the post-treatment AMH assay.DESIGN: Cohort study.MATERIALS AND METHODS: Baseline blood samples were obtained from 34 cancer patients (group I: 27 males and 7 females) and 10 normal controls (group II: 7 males and 3 females). Group I was composed of patients treated with chemotherapy for hematological, musculoskeletal and soft tissue cancers in 18,6 and 10 patients, respectively. Patients were followed until the completion of chemotherapy (range1-3 years). A second blood sample was collected at the completion of chemotherapy. AMH assay was completed using a commercially available kit.RESULTS: Using Spearman correlation, baseline AMH levels were significantly correlated with age of the study population (R=0.41, P=0.007). Patients and controls were comparable regarding their age at the initiation of chemotherapy. Baseline AMH levels were comparable between patients and controls irrespective of gender, age, pubertal status and type of malignancy (Boys7.83±4.75ng/ml vs 17.24±7.77 ng/ml; P=0.056) and (Girls 1.53±1.39 ng/ml vs 1.86±0.55 ng/ml; P=0.12)}. Post-chemotherapy AMH levels were not significantly different from baseline in boys (9.86±7.30 ng/ml vs 7.83±4.75 ng/ml, P=0.28). On the other side, post-chemotherapy AMH levels were significantly lower from baseline in girls (0.81±1.11 ng/ml vs 1.53±1.39 ng/ml, P=0.02). In boys and girls there was no significant reduction of post-chemotherapy AMH levels in subjects who received cell cycle specific chemotherapy. Similarly, there was no significant reduction of post-chemotherapy AMH levels in male subjects who received cell cycle non specific chemotherapy, P=0.06. On the contrary, girls who received cell cycle non specific chemotherapy showed significantly lower AMH levels compared to baseline (0.22 0.35 ng/ml vs 1.28 ±1.43 ng/ml; P=0.01).CONCLUSIONS: AMH assay is a sensitive marker for ovarian functions before and after puberty in patients at risk of gonadal damage secondary to chemotherapy. Ovarian reserve appears to be more sensitive to the insult of cell cycle non specific chemotherapeutic agents than the testicular reserve. AMH assay could be added to the initial work up of all patients undergoing chemotherapy to assess the damage to their reproductive potential. OBJECTIVE: The objectives of the study are to 1) determine whether AMH levels could be used to quantify gonadal damage inflicted by gonadotoxic chemotherapy and 2) to examine the effect of cell cycle specificity of the chemotherapeutic agents on the gonadal reserve as evidenced by the post-treatment AMH assay. DESIGN: Cohort study. MATERIALS AND METHODS: Baseline blood samples were obtained from 34 cancer patients (group I: 27 males and 7 females) and 10 normal controls (group II: 7 males and 3 females). Group I was composed of patients treated with chemotherapy for hematological, musculoskeletal and soft tissue cancers in 18,6 and 10 patients, respectively. Patients were followed until the completion of chemotherapy (range1-3 years). A second blood sample was collected at the completion of chemotherapy. AMH assay was completed using a commercially available kit. RESULTS: Using Spearman correlation, baseline AMH levels were significantly correlated with age of the study population (R=0.41, P=0.007). Patients and controls were comparable regarding their age at the initiation of chemotherapy. Baseline AMH levels were comparable between patients and controls irrespective of gender, age, pubertal status and type of malignancy (Boys7.83±4.75ng/ml vs 17.24±7.77 ng/ml; P=0.056) and (Girls 1.53±1.39 ng/ml vs 1.86±0.55 ng/ml; P=0.12)}. Post-chemotherapy AMH levels were not significantly different from baseline in boys (9.86±7.30 ng/ml vs 7.83±4.75 ng/ml, P=0.28). On the other side, post-chemotherapy AMH levels were significantly lower from baseline in girls (0.81±1.11 ng/ml vs 1.53±1.39 ng/ml, P=0.02). In boys and girls there was no significant reduction of post-chemotherapy AMH levels in subjects who received cell cycle specific chemotherapy. Similarly, there was no significant reduction of post-chemotherapy AMH levels in male subjects who received cell cycle non specific chemotherapy, P=0.06. On the contrary, girls who received cell cycle non specific chemotherapy showed significantly lower AMH levels compared to baseline (0.22 0.35 ng/ml vs 1.28 ±1.43 ng/ml; P=0.01). CONCLUSIONS: AMH assay is a sensitive marker for ovarian functions before and after puberty in patients at risk of gonadal damage secondary to chemotherapy. Ovarian reserve appears to be more sensitive to the insult of cell cycle non specific chemotherapeutic agents than the testicular reserve. AMH assay could be added to the initial work up of all patients undergoing chemotherapy to assess the damage to their reproductive potential.