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Vol. 53. Núm. 4.
Páginas 318-323 (Octubre 2000)
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Vol. 53. Núm. 4.
Páginas 318-323 (Octubre 2000)
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Alteraciones en la función gonadal en varones pospuberales supervivientes de leucemia linfoblástica aguda y enfermedad de Hodgkin
Alterations in gonadal function in post-pubertal male survivors of acute lymphoblastic leukemia and hodgkin's disease
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L. Soriano Guillén, M.T. Muñoz Calvo*, J. Pozo Román, T. Contra Gómez, M. Buño Soto, J. Argente Oliver
Secciones de Endocrinología y Oncología Pediátricas. Hospital Universitario Niño Jesús. Universidad Autónoma. Madrid
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Objetivo

Estudiar la función gonadal en varones supervivientes de leucemia linfoblástica aguda (LLA) y enfermedad de Hodgkin (EH).

Pacientes y método

Se estudiaron 13 varones pospuberales (estadio V de Tanner), 9 con LLA y 4 con EH, que habían recibido poliquimioterapia durante el período prepuberal. El grupo control lo constituyeron 13 varones voluntarios de edad similar y de desarrollo puberal completo. Se determinó: tamaño testicular, espermiograma, valores séricos de hormonas foliculoestimulante (FSH) y luteinizante (LH), basales y tras estímulo con GnRH (hormona liberadora de gonadotropinas), y testosterona basal (T1). Se consideró que existía daño del epitelio germinal cuando se encontró, al menos, uno de los siguientes criterios: a) oligospermia/azoospermia; b) aumento de FSH basal o tras GnRH, o c) reducción del volumen testicular. Se consideró que existía lesión de las células de Leydig cuando los valores plasmásticos de testosterona basal se encontraron disminuidos, o los valores de LH, basales o tras estímulo, aumentados.

Resultados

Los pacientes diagnosticados de EH presentaron una clara alteración de la función germinal y, en menor medida, de la función de las células de Leydig, con diferencias significativas respecto al grupo control (p < 0,001) en: pico de FSH (19,7 ± 18 frente a 4,8 ± 1,8 mU/ml), pico de LH (49,2 ± 31 frente a 33,4 ± 10,0 mU/ml), testosterona (4,1 ± 0,6 ng/ml frente a 5,9 ± 0,3 ng/ml) y volumen testicular (16,6 ± 2,8 frente a 22,5 ± 2,4 ml). De los 4 pacientes con EH, tres presentaron azoospermia y uno oligoespermia. Los pacientes supervivientes de LLA no presentaron diferencias significativas en ninguno de los parámetros bioquímicos y clínicos con el grupo control, si bien, de los 9 pacientes estudiados, dos presentaron oligospermia.

Conclusiones

Los protocolos quimioterápicos empleados en el tratamiento de la EH y la LLA producen una elevada incidencia de daño germinal y de alteración subclínica de las células de Leydig en los varones con EH; mientras que en los pacientes diagnosticados de LLA se encuentra sólo una afectación leve de la línea germinal. El estado prepuberal no protege los testículos del efecto nocivo de la quimioterapia.

Keywords:
Gonadal function
Chemotherapy
Hodgkin's disease
Acute lymphoblastic leukemia
Palabras clave:
Función gonadal
Quimioterapia
Enfermedad de Hodgkin
Leucemia linfoblástica aguda
Objective

To study gonadal function in male patients surviving acute lymphoblastic leukemia (ALL) or Hodgkin's disease (HD).

Patients and method

Thirteen postpubertal males were studied (Tanner stage V), 9 with ALL and 4 with HD, who had received poly chemotherapy during the pre-puberal period. The control group was composed of 13 male volunteers of similar ages and with complete pubertal development. Testicular size, spermiogram, serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) before and after stimulus with gonadotropin-releasing hormone (GnRH), and serum testosterone levels were determined. The germinal epithelium was believed to be damaged when at least one of the following criteria was present: 1) oligospermia/azoospermia, 2) increase in serum FSH levels before or after GnRH, or 3) reduction in testicular volume. Lesions in Leydig's cells were thought to exist when serum testosterone levels were reduced or when serum LH levels, before or after stimulus, increased.

Results

Patients with HD presented clear alterations in germinal function and, to a lesser degree, in the function of Leydig's cells. Significant differences compared with the control group (p < 0.001) were found in peak FSH (19.7 ± 18 vs 4.8 ± 1.8 ???/mL), peak LH (49.2 ± 31 vs 33.4 ± 10.0 pUI/mL), serum testosterone (4.1 ± 0.6 vs 5.9 ± 0.3 ng/mL) and testicular volume (16.6 ± 2.8 vs 22.5 ± 2.4 mL). Of the four patients with HD, three presented azoospermia and one oligospermia. No significant differences in any of the clinical or biochemical parameters studied were found in patients surviving ALL compared with the control group, but two of the nine patients studied presented oligospermia.

Conclusions

The chemotherapy protocols used in the treatment of HD and ALL produced a high incidence of germinal cell damage and subclinical alterations in the Leydig's cell function in males with HD. In patients with ALL, the germinal line was only mildly affected. Prepubertal state does not protect the testes from the harmful effects of chemotherapy.

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