Primary Gonadal Insufficiency in Male and Female Childhood Cancer Survivors in a Long-Term Follow-Up Clinic

Harriet M Gunn; Ida Rinne; Hanna Emilsson; Melissa Gabriel; Ann M Maguire; Katharine S Steinbeck

doi:10.1089/jayao.2016.0007

Primary Gonadal Insufficiency in Male and Female Childhood Cancer Survivors in a Long-Term Follow-Up Clinic

J Adolesc Young Adult Oncol. 2016 Dec;5(4):344-350. doi: 10.1089/jayao.2016.0007. Epub 2016 May 19.

Authors

Harriet M Gunn^{1

2}, Ida Rinne³, Hanna Emilsson³, Melissa Gabriel⁴, Ann M Maguire^{2

5}, Katharine S Steinbeck^{1

2}

Affiliations

¹ 1 Academic Department of Adolescent Medicine, The Children's Hospital at Westmead , Sydney, New South Wales, Australia .
² 2 Discipline of Child and Adolescent Health, The University of Sydney , Sydney, New South Wales, Australia .
³ 3 The Faculty of Medicine and Health Sciences, Linköping University , Linköping, Sweden .
⁴ 4 Long Term Follow Up Clinic, Department of Oncology, The Children's Hospital at Westmead , Sydney, New South Wales, Australia .
⁵ 5 Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead , Sydney, New South Wales, Australia .

PMID: 27195593
DOI: 10.1089/jayao.2016.0007

Abstract

Purpose: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: fertility; gonadal failure; hormone therapy; late effects; primary gonadal insufficiency.

MeSH terms

Cancer Survivors*
Child
Child, Preschool
Cohort Studies
Female
Follow-Up Studies
Humans
Hypogonadism / diagnosis
Hypogonadism / etiology*
Hypogonadism / physiopathology
Longitudinal Studies
Male
Prevalence
Retrospective Studies