title: Gonadal function following chemotherapy for childhood Hodgkin's disease.
abstract: 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.
authors.affiliation: Department of Paediatric Oncology, The Christie Hospital, NHS Trust, Manchester, United Kingdom.
authors.forename: E J
authors.initials: EJ
authors.lastname: Mackie
authors.forename: M
authors.initials: M
authors.lastname: Radford
authors.forename: S M
authors.initials: SM
authors.lastname: Shalet
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002699:Chlorambucil / Q000008:administration & dosage / Q000009:adverse effects; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D011374:Progesterone / Q000097:blood; D013737:Testis / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000097:blood; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D002699:Chlorambucil; D011344:Procarbazine; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D014747:Vinblastine; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D011239:Prednisolone