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 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 < or = 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 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.
Gerl
A
A
Department of Internal Medicine III (Hematology/Medical Oncology), Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Mühlbayer
D
D
Hansmann
G
G
Mraz
W
W
Hiddemann
W
W
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D018237:Germinoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007985:Leydig Cells / Q000187:drug effects / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D013739:Testosterone / Q000097:blood
D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002945:Cisplatin