Relationship between inhibin B, puberty, and secondary sex characteristics in childhood cancer survivors.

e22018 Background: Prognosis in childhood cancer improved with intensive tx regimens, improved survival,concerns&issues related to QOL become crucial point of interest. Methods: Gonadal functions were studied in 33M,22F survivors of childhood cancers treated w gonadotoxic chemotherapy,with HL,NHL, ALL,Osteosarcoma,Rhabdomyosarcoma. All event-free survivors for > 1year, postpubertal, > 15 years of age at the time of study, 8 pts received abdominal RT,9 pts had prophylactic cranial RT. Patients answered a questionnaire concerning sexual functions,underwent a comprehensive physical examination, clinical evaluation of pubertal development, secondary sex characteristics,menstrual history, measurement of FSH, LH,sex steroids, inhibinB, compared w age-matched controls. Results: All patients had normal pubertal development for age,Females showed no significant differences in secondary sex characteristics, than controls &the progression of puberty, adult-type hair growth in males were significantly late (P:0.002) than controls, low levels of testosterone were found in all.Pubertal development normal in female patients, w elevated FSH than control.(P:0.025)FSH levels in males didn't differ,inhibinB levels were significantly lower than control.(P:0.022).We couldn't demonstrate significant association with age at dx,time elapsed after tx,dx type,gonadotoxic agent.. Conclusions: Our study showed tx of childhood cancer could lead to gonadal toxicity.Our study investigating relationship between puberty,secondary sex characteristics,inhibinB in early postpubertal stage. Findings suggest that, even in the presence of gonadal toxicity, in females, secondary sex characteristics&puberty weren't affected.Inhibin B as a marker for gonadal toxicity is not superior to FSH. In fact that, we found a decrease in InhibinB as the only marker of gonadal dysfunction in males.With normal pubertal development &FSH levels in postpubertal males,low detection of inhibinB can be used as an early,sensitive marker for gonadal toxicity.Late adult-type hair growth with low testosterone demonstrating chemotherapy-induced testicular damage. Clinical trial information: BAP-2734.

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Dissociation of Pubertal Development Abnormality and Gonadal Dysfunction in Childhood Cancer Survivors

Journal of Adolescent and Young Adult Oncology ◽

10.1089/jayao.2019.0138 ◽

2020 ◽

Vol 9 (4) ◽

pp. 490-495

Author(s):

Bo Yu ◽

Rani Fritz ◽

Mario Vega ◽

Margret Merino

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Pubertal Development ◽

Childhood Cancer Survivors ◽

Gonadal Dysfunction

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Endocrine complications in long-term survivors of childhood cancers

Endocrine Related Cancer ◽

10.1677/erc-10-0002 ◽

2010 ◽

Vol 17 (3) ◽

pp. R141-R159 ◽

Cited By ~ 129

Author(s):

Wassim Chemaitilly ◽

Charles A Sklar

Keyword(s):

Childhood Cancer ◽

Pubertal Development ◽

Childhood Cancer Survivors ◽

Special Focus ◽

Mineral Density ◽

Cancer Treatments ◽

Gonadal Dysfunction ◽

Endocrine Disturbances ◽

Hypothalamic Pituitary Axis ◽

Endocrine Complications

Endocrine disturbances are among the most frequently reported complications in childhood cancer survivors, affecting between 20 and 50% of individuals who survive into adulthood. Most endocrine complications are the result of prior cancer treatments, especially radiotherapy. The objective of the present review is to discuss the main endocrine complications observed in this population, including disorders of the hypothalamic–pituitary axis, disorders of pubertal development, thyroid dysfunction, gonadal dysfunction, decreased bone mineral density, obesity, and alterations in glucose metabolism with a special focus on recent findings reported from the Childhood Cancer Survivor Study.

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High DHEAS Is Associated With Earlier Pubertal Events in Girls But Not in Boys

Journal of the Endocrine Society ◽

10.1210/js.2017-00120 ◽

2017 ◽

Vol 1 (7) ◽

pp. 800-808 ◽

Cited By ~ 3

Author(s):

Ana Pereira ◽

German Iñiguez ◽

Camila Corvalan ◽

Verónica Mericq

Keyword(s):

Ovarian Function ◽

Pubertal Development ◽

Sex Characteristics ◽

Premature Thelarche ◽

Logistic Regression Models ◽

Tanner Staging ◽

Secondary Sex Characteristics ◽

Premature Adrenarche ◽

The Relationship

Context: Premature adrenarche (PA) has been associated with increased metabolic risk. Objective: To describe the risk of precocious thelarche (PT; <8 years), pubarche (PP; girls <8 years, boys <9 years), and gonadarche (PG; <9 years) in children with high dehydroepiandrosterone sulphate (DHEAS [HD]) vs those with normal DHEAS (ND). Setting and Intervention: Longitudinal Chilean cohort (n = 1052, 49.9% girls). Annual clinical examination including secondary sex characteristics by Tanner staging. Logistic regression models were adjusted by age and BMI. Main Outcome: Assess the relationship between DHEAS and premature thelarche, gonadarche, and pubarche in both sexes. Results: At age of DHEAS determination, overweight/obesity was present in 44.3% of boys and 42.9% of girls. Incidences of any precocious event were observed in 17.2% of boys and in 25.4% of girls, presented as 8.7% of PG and 8.5% of PP in boys and as 21.3% of PT and 4.1% of PP in girls. In crude and adjusted models in boys, HD did not increase the risk of earlier pubertal events. Conversely, girls with HD had a 2.6 times greater risk of early thelarche and a three times greater risk of early pubarche compared with girls with ND concentrations. Conclusion: In Chilean adolescents, precocious events of pubertal development were in line with the worldwide secular trend of earlier sexual maturation. HD was only associated with PT and PP in girls. Continuous follow-up of this cohort is a unique opportunity to prospectively address and analyze the interrelationships among HD, early growth, and adiposity as determinants of gonadarche, pubertal rate/sequence progression, and ovarian function.

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Effect of Genetic Variation in CYP450 on Gonadal Impairment in a European Cohort of Female Childhood Cancer Survivors, Based on a Candidate Gene Approach: Results from the PanCareLIFE Study

Cancers ◽

10.3390/cancers13184598 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4598

Author(s):

M. Perk ◽

Linda Broer ◽

Yutaka Yasui ◽

Leslie Robison ◽

Melissa Hudson ◽

...

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Ovarian Function ◽

Meta Analysis ◽

Alkylating Agents ◽

Childhood Cancer Survivors ◽

P Value ◽

Candidate Gene Approach ◽

Gonadal Dysfunction ◽

The Impact

Background: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to evaluate associations between previously identified genetic polymorphisms in CYP450 enzymes and AA-related ovarian function among adult CCSs. Methods: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in a discovery cohort of adult female CCSs, from the pan-European PanCareLIFE cohort (n = 743; age (years): median 25.8, interquartile range (IQR) 22.1–30.6). Using two additive genetic models in linear and logistic regression, nine genetic variants in three CYP450 enzymes were analyzed in relation to cyclophosphamide equivalent dose (CED) score and their impact on AMH levels. The main model evaluated the effect of the variant on AMH and the interaction model evaluated the modifying effect of the variant on the impact of CED score on log-transformed AMH levels. Results were validated, and meta-analysis performed, using the USA-based St. Jude Lifetime Cohort (n = 391; age (years): median 31.3, IQR 26.6–37.4). Results: CYP3A4*3 was significantly associated with AMH levels in the discovery and replication cohort. Meta-analysis revealed a significant main deleterious effect (Beta (95% CI): −0.706 (−1.11–−0.298), p-value = 7 × 10−4) of CYP3A4*3 (rs4986910) on log-transformed AMH levels. CYP2B6*2 (rs8192709) showed a significant protective interaction effect (Beta (95% CI): 0.527 (0.126–0.928), p-value = 0.01) on log-transformed AMH levels in CCSs receiving more than 8000 mg/m2 CED. Conclusions: Female CCSs CYP3A4*3 carriers had significantly lower AMH levels, and CYP2B6*2 may have a protective effect on AMH levels. Identification of risk-contributing variants may improve individualized counselling regarding the treatment-related risk of infertility and fertility preservation options.

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The Interaction of Pubertal and Psychosocial Development During Adolescence

Pediatrics in Review ◽

10.1542/pir.12.8.249 ◽

1991 ◽

Vol 12 (8) ◽

pp. 249-255

Author(s):

Iris F. Litt

Keyword(s):

Psychosocial Development ◽

Developmental Process ◽

Pubertal Development ◽

Breast Development ◽

Growth Spurt ◽

Sex Characteristics ◽

Hormonal Changes ◽

Secondary Sex Characteristics ◽

Is Development ◽

Physical Changes

During the second decade of life, the physical changes of puberty interact with those of psychosocial and cognitive development to forge the young adult, who often bears little resemblance to the same individual as a child. This article reviews those elements of the developmental process that have an impact on the physician's ability to understand and care for the adolescent patient. PUBERTY Endocrine Changes Release of inhibition on the hypothalamus unleashes an outpouring of releasing hormones, which stimulate the secretion of gonadotropins and growth hormone by the pituitary. These are produced in a sleep-augmented, pulsatile fashion that characterizes the onset of pubertal development. As a result, within the few years between the onset and completion of puberty, levels of estradiol increase eightfold in females, and levels of testosterone increase 18-fold in males. These hormonal changes stimulate the growth spurt and development of secondary sex characteristics. Development of Secondary Sex Characteristics Breast Development. In females, one of the earliest signs of puberty is development of the breast bud. The subsequent progression of breast development is orderly and predictable, thus forming one of the bases for the categorization in females of the stages of puberty, often referred to as Tanner stages or SMRs (sex maturity ratings).

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