Gonadal function following chemotherapy for childhood Hodgkin's disease

Gonadal function was assessed in 101 postpubertal subjects after chemotherapy for childhood Hodgkin's disease. All had received ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisolone) chemotherapy alone, with no radiotherapy below the diaphragm. Gonadotropin levels were available in 46 (79.3%) male and 32 (74.4%) female subjects. The mean age at diagnosis in the male cohort was 12.2 years (range 8.2-15.3) and in the females 13.0 years (9.0-15.2). The males and the females were studied at a median of 6 years (range 2.5-11.1) and 4.3 years (range 1.9-11.5) from diagnosis, respectively. Forty-one (89.1%) male subjects had elevated follicle-stimulating hormone (FSH) levels, confirming severe germinal epithelial damage. Germinal epithelial damage was seen in subjects up to 10 years out of therapy. Subtle Leydig cell dysfunction was identified in 24.4% with raised luteinzing hormone (LH) levels. All subjects, however, progressed spontaneously through puberty. Seventeen (53%) women had raised gonadotropin levels, with variable estradiol levels. Of these, 10 subjects presented with symptomatic ovarian failure and 6 received hormone replacement therapy (HRT). Nine women had 11 successful pregnancies, two of whom had previously had symptoms of ovarian failure with one requiring HRT. A much higher prevalence of ovarian failure has been observed, than has previously been considered in the prepubertal and pubertal female following combination chemotherapy. These conclusions have important implications for future counseling, management, and research in this population.