Gonadal function of young adults after therapy of malignancies during childhood or adolescence.
As the survival rate of children with malignancies has increased over past decades, the follow up of adult long-term survivors (LTS) of childhood cancer should focus on late effects of disease and treatment. Gonadal function was therefore studied in 54 LTS (aged 17-29 years; 33 male, 21 female) 2-18 years after treatment for malignancies during childhood or adolescence. To analyse the sensitivity of different diagnostic methods, tests of endocrine function (n = 52), spermiograms (n = 14), gynaecological status (n = 20) and ultrasonography of the gonads (n = 53) were compared with the results of equivalent tests in 23 age-matched normal controls (12 male, 11 female). There were no differences between male and female LTS concerning age at diagnosis, gonadal dose of irradiation (XRT) and doses of applied chemotherapeutic agents. Whereas male LTS had elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) before (P < 0.05; P < 0.001) and after (P < 0.01; P < 0.001) stimulation with gonadotropin releasing hormone, female LTS exhibited normal endocrine function. Accordingly, male patients exhibited lower testicular volumes than normal controls, as measured with a Prader orchidometer (P < 0.01) or by ultrasonography (P < 0.001). Gynaecological status and ultrasonography of the gonads were normal in female LTS and controls. Whereas all spermiograms of normal controls (n = 8) showed a normal sperm cell density (SCD), only 2 of 14 male LTS exhibited a normal SCD (P < 0.001). Azoospermic LTS (n = 9) had been treated more often with alkylating agents and had received higher (P < 0.05) gonadal doses of XRT. All male LTS with testicular volumes below the normal range (< 13 ml) and basal FSH levels above the normal range (> 10 IU/l) exhibited azoospermia, whereas LTS with normal values for testicular volume and basal FSH had a normal SCD.


CONCLUSIONS
A sex-specific susceptibility for gonadal damage after treatment for malignancies might be responsible, in part, for the impaired gonadal function of male LTS. Therapy with alkylating agents and/or high gonadal doses of XRT were important risk factors for azoospermia. A simple method to estimate potential fertility in individual LTS is to measure testicular volume, using a Prader orchidometer, and basal FSH serum levels.
Müller
H L
HL
Kinderklinik, Julius-Maximilians-Universität, Würzburg, Germany.
Klinkhammer-Schalke
M
M
Seelbach-Göbel
B
B
Hartmann
A A
AA
Kühl
J
J
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006066:Gonads / Q000187:drug effects* / Q000503:physiopathology / Q000528:radiation effects*; D006801:Humans; D007246:Infertility / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012737:Sex Factors; D018709:Statistics, Nonparametric
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating