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

BACKGROUND. Because patients with germ cell tumors expect an additional lif e span of around 50 years after successful treatment, attention is now focu sed on potential long term toxicity. Limited data are available on Leydig c ell function in long term survivors. METHODS, The authors measured testosterone, sex hormone binding-globulin (S HBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) leve ls in 244 patients with germ cell tumors. Patients were divided into three groups: Group I had received no chemotherapy (n = 58 patients), Group 2 had received cumulative doses of cisplatin less than or equal to 400 mg/m(2) ( n = 117 patients), and Group 3 had received cumulative doses of cisplatin > 400 mg/m(2) (n = 69 patients). The median times from chemotherapy were 74 months and 75 months in Groups 2 and 3, respectively. RESULTS. Subnormal testosterone levels (<10 nmol/L) were found in 5%, 11%, and 20% in Groups 1, 2, and 3, respectively (Group 1 vs. Group 3; P = 0.02) . The mean testosterone level and the testosterone/SHBG ratio did not diffe r significantly between Groups I and 2; however, they did differ between Gr oups 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 signif icant inverse correlation between the testosterone/SHBG ratio and LH (corre lation coefficient [r] = -0.25; P = 0.0002). A significant positive correla tion was found for LH and FSH (r = 0.78; P < 0.0001), indicating a strong a ssociation 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 cau se a significant and persistent impairment of Leydig cell function. More da ta are needed regarding the clinical relevance of moderate testosterone def iciency. Further research is necessary to determine whether some patients m ay benefit from testosterone replacement. <(c)> 2001 American Cancer Societ y.