Gonadal function of patients treated with cisplatin based chemotherapy for germ cell cancer.
OBJECTIVE
The cure rate of patients with germ cell cancer of the testis has considerably improved since the introduction of cisplatin based chemotherapy. Because these patients are in their reproductive years and because some of them will be infertile after treatment, the effects of cytotoxic treatment on gonadal function are investigated by hormonal evaluations.


METHODS
In a transversal trial, luteinizing hormone, follicle-stimulating hormone and testosterone were determined radioimmunologically in serum samples of 232 patients with germ cell tumors after unilateral orchiectomy (patient age 18 to 64 years) up to 153 months after chemotherapy. Additionally, 51 of these patients were investigated in a longitudinal trial before and up to 5 years after chemotherapy. All patients received at least 2 courses of different cisplatin based chemotherapy regimens: cisplatin/vinblastine/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide, cisplatin/etoposide/bleomycin, cisplatin/vinblastine/bleomycin/ifosfamide/etoposide. Additionally, 11 patients with germ cell tumors (age 22 to 38 years, stage I) were investigated within the first year after orchiectomy and retroperitoneal lymphadenectomy but without chemotherapy.


RESULTS
In the transversal trial, 24 of 73 patients investigated during the first year after chemotherapy showed elevated luteinizing hormone concentrations, 5 had subnormal serum testosterone and 65 had elevated serum follicle-stimulating hormone, reflecting spermatogenesis deficits. In 28 patients studied longer than 8 years after chemotherapy (median followup 8.5 years, range 8.0 to 12.6), luteinizing hormone increased after chemotherapy and 60 months after treatment, and follicle-stimulating hormone was elevated in 1 patient, follicle-stimulating hormone was increased in 18 and testosterone was subnormal in 1. Patients without chemotherapy treatment showed gonadotropin and testosterone within normal range and 3 patients had elevated serum follicle-stimulating hormone. In the longitudinal study, mean serum luteinizing hormone plus or minus standard deviation (3.45 +/- 0.05 IU/l.), follicle-stimulating hormone (7.79 +/- 0.13 IU/l.) and testosterone (18.6 +/- 0.17 nmol./l.) were within the normal range before chemotherapy; serum follicle-stimulating hormone was still significantly elevated (16.9 +/- 0.71 IU/l., 19 cases, p < 0.001). Mean luteinizing hormone and testosterone levels were within the normal range, but 60 months after therapy the testosterone-to-luteinizing hormone ratio was still lower than before treatment (p < 0.05).


CONCLUSIONS
In patients with germ cell tumors, a compensated insufficiency of the function of the Leydig cells was still observed up to 60 months after chemotherapy. Of these patients 68% showed elevated follicle-stimulating hormone levels, which reflected a functional insufficiency of the Sertoli cells with impaired spermatogenesis. This study shows that impairment of germinative functions is more severe and protracted than the impairment of the endocrine functions.
Brennemann
W
W
Department of Clinical Biochemistry, University of Bonn, Hildesheim, Germany.
Stoffel-Wagner
B
B
Helmers
A
A
Mezger
J
J
Jäger
N
N
Klingmüller
D
D
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003430:Cross-Sectional Studies; D005047:Etoposide / Q000008:administration & dosage; D005640:Follicle Stimulating Hormone / Q000097:blood; D005854:Germ Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018237:Germinoma / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D013739:Testosterone / Q000097:blood; D014747:Vinblastine / Q000008:administration & dosage
D001761:Bleomycin; D013739:Testosterone; D014747:Vinblastine; D005047:Etoposide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002945:Cisplatin; D007069:Ifosfamide