UROLOGICAL ONCOLOGY: TESTIS CANCER AND ADVANCES IN ONCOLOGICAL THERAPY The Metabolic Syndrome and Disturbances in Hormone Levels in Long-Term Survivors of Disseminated Testicular Cancer

Purpose: The metabolic syndrome may be an important risk factor for cardiovascular disease in long-term survivors of testicular cancer (TC). We investigated the associations between hormone levels and the metabolic syndrome in these men. Patients and Methods: We included TC patients cured by orchidectomy and cisplatinbased chemotherapy, stage I TC patients after orchidectomy only, and healthy men of comparable age. Presence of the metabolic syndrome was determined using guidelines from the National Cholesterol Education Program Adult Treatment Panel III. Thyroid-stimulating hormone, follicle-stimulating hormone (FSH), inhibin B, luteinizing hormone (LH), total testosterone, sex-hormone-binding globulin, free testosterone, estradiol, dehydroepiandrosterone sulfate, and insulin-like growth factor 1 were determined in blood. Cortisol metabolite excretion was measured in urine. Results: Eighty-six chemotherapy patients (median follow-up, 7 years) were compared with 44 stage I patients and 47 controls. LH and FSH were higher, and inhibin B and total and free testosterone were lower in chemotherapy patients than controls. Adrenal and thyroid hormone production were unaffected. Chemotherapy patients with the metabolic syndrome (n 22; 26%) had a higher body mass index (BMI) pretreatment, a larger BMI increase during follow-up, lower total testosterone, and higher urinary cortisol metabolite excretion than those patients without the metabolic syndrome. BMI and insulin were associated with the metabolic syndrome, while total testosterone and urinary cortisol metabolite excretion were associated with BMI. Conclusion: We found gonadal dysfunction, but normal adrenal and thyroid function. Through its association with BMI, testosterone may play a role in the development of the metabolic syndrome in long-term TC survivors. Editorial Comment: One of the potential long-term complications of chemotherapy for testicular cancer has been an increase in cardiovascular morbidity. Specifically, hypertension, dyslipidemia, obesity and insulin resistance are all components of the metabolic syndrome. Components of the metabolic syndrome have been reported as early as several years after chemotherapy. As noted in this article, gonadal dysfunction is also a common long-term complication of treatment, especially with chemotherapy. Low levels of testosterone and sex hormone binding globulin have been associated with obesity, dyslipidemia and insulin resistance. The authors investigated 86 patients with testis tumor a median of 7 years after chemotherapy, and compared them with 44 stage I patients and 47 controls. LH and FSH were increased, and testosterone was lower in the chemotherapy patients compared to controls, whereas adrenal function was unaffected. The authors noted that chemotherapy patients with the metabolic syndrome had a higher body mass index, and raised the question whether lower testosterone may be a contributing factor. The authors have surmised that testosterone supplementation may be useful in this subset of patients, a hypothesis that should be tested in randomized controlled trials.