title: Primary Gonadal Insufficiency in Male and Female Childhood Cancer Survivors in a Long-Term Follow-Up Clinic.
abstract: Childhood cancer survivors (CCS) are at increased risk of primary gonadal insufficiency (PGI). This study evaluated the prevalence and clinical characteristics of PGI in CCS.
  
  
  
  In this single-center, retrospective, observational, longitudinal study, we characterized CCS with PGI attending the oncology Long-Term Follow-Up (LTFU) Clinic at an Australian university hospital (January 2012-August 2014). From a cohort of 276 CCS, 54 (32 males) met criteria for PGI: elevated gonadotropins plus low estradiol/amenorrhoea (females) or low testosterone/small testicles for age (males).
  
  
  
  Median age at primary diagnosis was 4.8 years (inter-quartile range [IQR] 3.0-9.7 years) and at LTFU, it was 22.3 years (IQR 18.2-25.7 years). Fifty-three participants (98.1%) were treated with known highly gonadotoxic therapies: alkylating chemotherapy (96.3%), radiotherapy (70.3%), total body irradiation (29.6%), bone marrow transplantation (51.9%), or multimodal protocols (68.5%). At primary diagnosis, 86.7% participants were Tanner stage I and at LTFU, 89.1% participants were Tanner stage V. More females (95.5%; n = 21) than males (40.6%; n = 13) were treated with hormone development therapy (HDT) (p < 0.01). Of these, more than half (n = 18; 7 males) required pubertal induction. There was no significant difference in serum luteinizing hormone/follicle stimulating hormone (LH/FSH), testosterone/estradiol between those untreated and those treated with HDT. Among those on HDT, 60.7% had persistently elevated FSH±LH and 33.3% had low testosterone or estradiol. Six males had semen analysis (five azoospermic, one oligospermic). Psychological assessment was documented in 61.1% of participants, and two-thirds reported fertility concerns.
  
  
  
  PGI is an evolving phenotype that is common in CCS. Suboptimal treatment and non-adherence occur frequently. Ongoing assessment is essential to ensure prompt diagnosis, adequate intervention and to promote HDT adherence.
authors.affiliation: 1 Academic Department of Adolescent Medicine, The Children's Hospital at Westmead , Sydney, New South Wales, Australia .|2 Discipline of Child and Adolescent Health, The University of Sydney , Sydney, New South Wales, Australia .
authors.forename: Harriet M
authors.initials: HM
authors.lastname: Gunn
authors.affiliation: 3 The Faculty of Medicine and Health Sciences, Linköping University , Linköping, Sweden .
authors.forename: Ida
authors.initials: I
authors.lastname: Rinne
authors.affiliation: 3 The Faculty of Medicine and Health Sciences, Linköping University , Linköping, Sweden .
authors.forename: Hanna
authors.initials: H
authors.lastname: Emilsson
authors.affiliation: 4 Long Term Follow Up Clinic, Department of Oncology, The Children's Hospital at Westmead , Sydney, New South Wales, Australia .
authors.forename: Melissa
authors.initials: M
authors.lastname: Gabriel
authors.affiliation: 2 Discipline of Child and Adolescent Health, The University of Sydney , Sydney, New South Wales, Australia .|5 Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead , Sydney, New South Wales, Australia .
authors.forename: Ann M
authors.initials: AM
authors.lastname: Maguire
authors.affiliation: 1 Academic Department of Adolescent Medicine, The Children's Hospital at Westmead , Sydney, New South Wales, Australia .|2 Discipline of Child and Adolescent Health, The University of Sydney , Sydney, New South Wales, Australia .
authors.forename: Katharine S
authors.initials: KS
authors.lastname: Steinbeck
mesh_terms: D000073116:Cancer Survivors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D015995:Prevalence; D012189:Retrospective Studies
keywords: fertility; gonadal failure; hormone therapy; late effects; primary gonadal insufficiency