Impaired testicular function after an ifosfamide-containing regimen for pediatric osteosarcoma: a case series and review of the literature.

To assess testicular function after standard dose ifosfamide, we evaluated 6 young adult osteosarcoma survivors (median age at diagnosis, 16.5 y; median follow-up, 4 y) treated with ifosfamide (median dose, 45.5 g/m) as part of a chemotherapy regimen (adriamycin/cisplatin/methotrexate/ifosfamide/± muramyl-tripeptide-phosphatidyl-ethanolamine). Four of 6 survivors (67%) had abnormal semen analysis (2 oligospermic, 2 azoospermic). Of those, 1/4 had reduced testicular volume, and 2/3 elevated FSH levels. All reported adequate sexual function, 6/6 had normal testosterone levels, but 4/6 had elevated LH levels. Ifosfamide exposure in the context of this regimen was associated with a high likelihood of impaired spermatogenesis and Leydig cell insufficiency.

'Idiopathic' partial androgen insensitivity syndrome in 28 newborn and infant males: impact of prenatal exposure to environmental endocrine disruptor chemicals?

OBJECTIVE: 46,XY disorders of sex differentiation (46,XY DSD) can be due to a testis determination defect, an androgen biosynthesis defect, or androgen resistance (complete or partial androgen insensitivity syndrome (PAIS), or 5α reductase deficiency). We aimed to evaluate the impact of a prenatal contamination by environmental xenoestrogens in 'idiopathic' PAIS-like phenotype. SUBJECTS: We investigated 28 newborn/infant males with 46,XY DSD, normal androgen production, and no androgen receptor or steroid-5αR type II enzyme (SRD5A2) gene mutations. METHODS: To exclude other genetic defects, we sequenced the steroidogenic factor 1 (SF1) and mastermind-like domain-containing 1 (MAMLD1) genes, which were recently found to be associated with the PAIS-like phenotype. Parents were interviewed about their environmental/occupational exposure to endocrine disrupting chemicals (EDCs) before/during the patients' fetal life. Total estrogenic bioactivity of patient serum was analyzed by ultrasensitive bioassay. RESULTS: All the patients had normal SF1 sequence and one patient showed a double polymorphism of MAMLD1. Eleven (39.3%) of the 28 patients had reported parental fetal exposure to EDCs. The mean estrogenic bioactivity in these 11 patients with fetal EDC exposure (6.65 ± 8.07 pg/ml) versus 17 cases without contamination (1.27 ± 0.34 pg/ml) and controls (1.06 ± 0.44 pg/ml; P<0.05) was elevated. CONCLUSIONS: Our results indicate that the 'idiopathic' PAIS-like phenotype may in some cases be related to EDC contamination during fetal life.