The impact of childhood cancer and its treatment on puberty and subsequent hypothalamic pituitary and gonadal function, in both boys and girls

Wei, Christina; Crowne, Elizabeth

doi:10.1016/j.beem.2019.101291

Cited by 26 publications

(25 citation statements)

References 123 publications

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“…Despite the heterogeneity of the cohorts evaluated in different studies, the prevalence of spermatogenesis damage and LCF observed in our cohort was similar to those reported in literature data 24–26 …”

Section: Discussionsupporting

confidence: 89%

“…15,16 Despite the heterogeneity of the cohorts evaluated in different studies, the prevalence of spermatogenesis damage and LCF observed in our cohort was similar to those reported in literature data. [24][25][26] In females, we found a 26.2% cumulative incidence of POI, which is higher than that recently observed in a wide cohort of CCS. 27 gonadal failure after exposure to TBI, in both males and females.…”

Section: Discussioncontrasting

confidence: 75%

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Effects of treatments on gonadal function in long‐term survivors of pediatric hematologic malignancies: A cohort study

Felicetti

Castiglione

Biasin

et al. 2020

Pediatric Blood & Cancer

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Background: Potentially gonadotoxic protocols are currently used for the treatment of childhood hematologic malignancies. This study aims to evaluate the prevalence of gonadal dysfunction and the most important associated risk factors in a cohort of hematologic malignancy survivors. Procedure: We considered all patients referred to our long-term follow-up clinic for childhood cancer survivors, between November 2001 and December 2017. Inclusion criteria were: (a) previous diagnosis of hematologic malignancy; (b) age at hematologic malignancy diagnosis < 18 years; (c) at least five years after the end of anticancer treatments; (d) at least one evaluation of gonadal function after the 18th birthday. Patients diagnosed before January 1, 1990, were excluded. Results: Three hundred twenty-seven survivors (males = 196) were included. Isolated spermatogenesis damage was found in 58/196 (29.6%) of males, whereas 18/196 (9.2%) had Leydig cell failure. In females, 35/131 (26.7%) experienced premature ovarian insufficiency. In both sexes, abdominopelvic irradiation and hematopoietic stem cell transplantation were strongly associated with the risk of gonadal dysfunction. For every 1000 mg/m 2 increase in cyclophosphamide-equivalent dose exposure, the risk of spermatogenesis damage increased 1.52-fold and that of Leydig cell failure increased 1.34-fold, whereas the risk of premature ovarian insufficiency increased 1.80-fold. About 30% of those males who developed Leydig cell failure did so more than five years after the end of treatments. Conclusions: Gonadal dysfunction is still a significant late effect of therapies for pediatric hematologic malignancies. In males, the reevaluation of Leydig cell function may be useful even several years after the exposure to gonadotoxic treatments.

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Section: Discussionsupporting

confidence: 89%

Section: Discussioncontrasting

confidence: 75%

Effects of treatments on gonadal function in long‐term survivors of pediatric hematologic malignancies: A cohort study

Felicetti

Castiglione

Biasin

et al. 2020

Pediatric Blood & Cancer

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“…43,[261][262][263][264][265][266][267][268][269] These therapies can lead to several underlying conditions that can increase the risk for (components of) MetS, such as hypothalamic damage, growth hormone deficiency, pancreatic beta cell dysfunction, hypogonadism, hypothyroidism, and altered body composition with increased abdominal fat. 43,[261][262][263][264][265][266][267][268][269] Furthermore, it is well acknowledged that in CCS, the biological age progresses faster than their true age, as can be derived from their high level of frailty. [4][5][6][7][8][9] Previous studies have shown that the physiologic reserve of CCS with a median age of 33 is similar to that of adults in the general population who are aged 65 years.…”

Section: Other Non-enlisted Biomarkersmentioning

confidence: 99%

Can biomarkers be used to improve diagnosis and prediction of metabolic syndrome in childhood cancer survivors? A systematic review

et al. 2021

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Childhood cancer survivors (CCS) are at increased risk to develop metabolic syndrome (MetS), diabetes, and cardiovascular disease. Common criteria underestimate adiposity and possibly underdiagnose MetS, particularly after abdominal radiotherapy. A systematic literature review and meta-analysis on the diagnostic and predictive value of nine newer MetS related biomarkers (adiponectin, leptin, uric acid, hsCRP, TNF-alpha, IL-1, IL-6, apolipoprotein B (apoB), and lipoprotein(a) [lp(a)]) in survivors and adult non-cancer survivors was performed by searching PubMed and Embase. Evidence was summarized with GRADE after risk of bias evaluation (QUADAS-2/QUIPS). Eligible studies on promising biomarkers were pooled. We identified 175 general population and five CCS studies. In the general population, valuable predictive biomarkers are uric acid, adiponectin, hsCRP and apoB (high level of evidence), and leptin (moderate level of evidence). Valuable diagnostic biomarkers are hsCRP, adiponectin, uric acid, and leptin (low, low, moderate, and high level of evidence, respectively). Meta-analysis showed OR for hyperuricemia of 2.94 (age-/ sex-adjusted), OR per unit uric acid increase of 1.086 (unadjusted), and AUC for hsCRP of 0.71 (unadjusted). Uric acid, adiponectin, hsCRP, leptin, and apoB can be alternative biomarkers in the screening setting for MetS in survivors, to enhance early identification of those at high risk of subsequent complications.

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“…In girls with a diagnosis of HH secondary to parasellar lesion treatment, oestrogen replacement therapy should be started at the age of 12–13 years [78], beginning at a low dose (one-eighth to one-quarter of the adult dose) and increasing it gradually to full adult replacement levels. A possible dose regimen is a patch containing 25 μg of 17β-oestradiol/24 h cut into 4 equal-sized pieces, applying one to the skin before going to bed and removing it the following morning.…”

Section: Long-term Effects Of Parasellar Lesion Treatments On Female mentioning

confidence: 99%

Late Effects of Parasellar Lesion Treatment: Hypogonadism and Infertility

et al. 2020

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Central hypogonadism, also defined as hypogonadotropic hypogonadism, is a recognized complication of hypothalamic-pituitary-gonadal axis damage following treatment of sellar and parasellar masses. In addition to radiotherapy and surgery, CTLA4-blocking antibodies and alkylating agents such as temozolomide can also lead to hypogonadism, through different mechanisms. Central hypogonadism in boys and girls may lead to pubertal delay or arrest, impairing full development of the genitalia and secondary sexual characteristics. Alternatively, cranial irradiation or ectopic hormone production may instead cause early puberty, affecting hypothalamic control of the gonadostat. Given the reproductive risks, discussion of fertility preservation options and referral to reproductive specialists before treatment is essential. Steroid hormone replacement can interfere with other replacement therapies and may require specific dose adjustments. Adequate gonadotropin stimulation therapy may enable patients to restore gametogenesis and conceive spontaneously. When assisted reproductive technology is needed , protocols must be tailored to account for possible long-term gonadotropin insufficiency prior to stimulation. The aim of this review was to provide an overview of the risk factors for hypogonadism and infertility in patients treated for parasellar lesions and to give a summary of the current recommendations for management and follow-up of these dysfunctions in such patients. We have also briefly summarized evidence on the physiological role of pituitary hormones during pregnancy, focusing on the management of pituitary deficiencies.

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The impact of childhood cancer and its treatment on puberty and subsequent hypothalamic pituitary and gonadal function, in both boys and girls

Cited by 26 publications

References 123 publications

Effects of treatments on gonadal function in long‐term survivors of pediatric hematologic malignancies: A cohort study

Effects of treatments on gonadal function in long‐term survivors of pediatric hematologic malignancies: A cohort study

Can biomarkers be used to improve diagnosis and prediction of metabolic syndrome in childhood cancer survivors? A systematic review

Late Effects of Parasellar Lesion Treatment: Hypogonadism and Infertility

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