The impact of chemotherapy on Leydig cell function in long term survivors of germ cell tumors

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Abstract
BACKGROUND Because patients with germ cell tumors expect an additional life span of around 50 years after successful treatment, attention is now focused on potential long term toxicity. Limited data are available on Leydig cell function in long term survivors. METHODS The authors measured testosterone, sex hormone binding‐globulin (SHBG), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) levels in 244 patients with germ cell tumors. Patients were divided into three groups: Group 1 had received no chemotherapy (n = 58 patients), Group 2 had received cumulative doses of cisplatin ≤ 400 mg/m2 (n = 117 patients), and Group 3 had received cumulative doses of cisplatin > 400 mg/m2 (n = 69 patients). The median times from chemotherapy were 74 months and 75 months in Groups 2 and 3, respectively. RESULTS Subnormal testosterone levels (P = 0.02). The mean testosterone level and the testosterone/SHBG ratio did not differ significantly between Groups 1 and 2; however, they did differ between Groups 1 and 3 (testosterone: 17.0 nmol/L vs. 14.9 nmol/L, respectively; P = 0.02; testosterone/SHBG ratio: 0.70 vs. 0.59; P < 0.05). There was a significant inverse correlation between the testosterone/SHBG ratio and LH (correlation coefficient [r] = −0.25; P = 0.0002). A significant positive correlation was found for LH and FSH (r = 0.78; P < 0.0001), indicating a strong association between Leydig cell dysfunction and germinal epithelial damage. CONCLUSIONS Standard doses of cisplatin‐based chemotherapy do not lead to a significant deterioration of Leydig cell function in long term survivors of germ cell tumors. In contrast, high cumulative doses of chemotherapy cause a significant and persistent impairment of Leydig cell function. More data are needed regarding the clinical relevance of moderate testosterone deficiency. Further research is necessary to determine whether some patients may benefit from testosterone replacement. Cancer 2001;91:1297–303. © 2001 American Cancer Society.

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