The Effect of Hormonal Therapy on the Behavioral Outcomes in 47,XXY (Klinefelter Syndrome) Between 7 and 12 Years of Age

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2023 Jul 29

PMID 37510306

Authors

Mary P Hamzik

Andrea L Gropman

Michaela R Brooks

Sherida Powell

Teresa Sadeghin

Carole A Samango-Sprouse

Affiliations

Soon will be listed here.

Abstract

47,XXY, also known as Klinefelter syndrome, is the most commonly occurring sex chromosomal aneuploidy (SCA). Hormonal replacement therapy (HRT) has been associated with improved neurodevelopmental capabilities in boys with 47,XXY, although studies investigating HRT's possible positive effect on behavioral outcomes are scarce. This study explores the association between behavioral outcomes and HRT in boys ages 7-12. Patients were divided into 4 groups based on HRT status: untreated, early hormonal treatment (EHT), hormonal booster therapy (HBT), and both EHT and HBT. Analysis of Variance (ANOVA) and Kruskal-Wallis tests were conducted to determine group differences on the Child Behavior Checklist (CBCL) and the Behavior Rating Inventory of Executive Function (BRIEF). The treated groups were found to have better scores in emotional control, initiative, organization of materials, behavioral rating index, metacognition index, and global executive composite than the untreated group on the BRIEF. On the CBCL, the treated groups presented better scores for somatic complaints, social problems, thought problems, attention problems, aggressive behavior, internalizing problems, total problems, affective problems, somatic problems, ADHD problems, oppositional defiant problems, and sluggish problems in comparison to the untreated group. These results offer evidence that HRT, specifically the combination of both EHT and HBT, may be successful in mitigating some undesirable behavioral outcomes. Further research is necessary to determine the efficacy of the combination of EHT and HBT regarding dosage, specific ages, and long-term benefits.

Citing Articles

Testosterone Effects on Short-Term Physical, Hormonal, and Neurodevelopmental Outcomes in Infants with 47,XXY/Klinefelter Syndrome: The TESTO Randomized Controlled Trial.

Davis S, Howell S, Janusz J, Lahlou N, Reynolds R, Thompson T medRxiv. 2024; .

PMID: 39711709 PMC: 11661422. DOI: 10.1101/2024.12.09.24318726.

References

Samango-Sprouse C, Brooks M, Counts D, Hamzik M, Song S, Powell S . A longitudinal perspective of hormone replacement therapies (HRTs) on neuromotor capabilities in males with 47,XXY (Klinefelter syndrome). Genet Med. 2022; 24(6):1274-1282. DOI: 10.1016/j.gim.2022.03.004. View

Samango-Sprouse C, Stapleton E, Lawson P, Mitchell F, Sadeghin T, Powell S . Positive effects of early androgen therapy on the behavioral phenotype of boys with 47,XXY. Am J Med Genet C Semin Med Genet. 2015; 169(2):150-7. DOI: 10.1002/ajmg.c.31437. View

Raznahan A, Lee N, Greenstein D, Wallace G, Blumenthal J, Clasen L . Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development. Cereb Cortex. 2014; 26(1):70-9. PMC: 4701121. DOI: 10.1093/cercor/bhu174. View

Gil M, Accurti V, Santacruz B, Plana M, Nicolaides K . Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2017; 50(3):302-314. DOI: 10.1002/uog.17484. View

van Rijn S, Swaab H, Aleman A, Kahn R . Social behavior and autism traits in a sex chromosomal disorder: Klinefelter (47XXY) syndrome. J Autism Dev Disord. 2008; 38(9):1634-41. DOI: 10.1007/s10803-008-0542-1. View

Tartaglia N, Cordeiro L, Howell S, Wilson R, Janusz J . The spectrum of the behavioral phenotype in boys and adolescents 47,XXY (Klinefelter syndrome). Pediatr Endocrinol Rev. 2011; 8 Suppl 1:151-9. PMC: 3740580. View

Bojesen A, Juul S, Gravholt C . Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab. 2003; 88(2):622-6. DOI: 10.1210/jc.2002-021491. View

Salbenblatt J, Meyers D, Bender B, Linden M, Robinson A . Gross and fine motor development in 45,X and 47,XXX girls. Pediatrics. 1989; 84(4):678-82. View

van Rijn S . Salivary testosterone in relation to social cognition and social anxiety in children and adolescents with 47,XXY (Klinefelter syndrome). PLoS One. 2018; 13(7):e0200882. PMC: 6056033. DOI: 10.1371/journal.pone.0200882. View

10.

Ross J, Samango-Sprouse C, Lahlou N, Kowal K, Elder F, Zinn A . Early androgen deficiency in infants and young boys with 47,XXY Klinefelter syndrome. Horm Res. 2005; 64(1):39-45. DOI: 10.1159/000087313. View

11.

Samango-Sprouse C, Stapleton E, Sadeghin T, Gropman A . Is it all the X: familial learning dysfunction and the impact of behavioral aspects of the phenotypic presentation of XXY?. Am J Med Genet C Semin Med Genet. 2013; 163C(1):27-34. DOI: 10.1002/ajmg.c.31353. View

12.

Samango-Sprouse C, Grati F, Brooks M, Hamzik M, Khaksari K, Gropman A . Incidence of sex chromosome aneuploidy in a prenatal population: 27-year longitudinal study in Northern Italy. Ultrasound Obstet Gynecol. 2023; 62(2):266-272. DOI: 10.1002/uog.26201. View

13.

van Rijn S, Swaab H . Executive dysfunction and the relation with behavioral problems in children with 47,XXY and 47,XXX. Genes Brain Behav. 2015; 14(2):200-8. DOI: 10.1111/gbb.12203. View

14.

Morris J, Alberman E, Scott C, Jacobs P . Is the prevalence of Klinefelter syndrome increasing?. Eur J Hum Genet. 2007; 16(2):163-70. DOI: 10.1038/sj.ejhg.5201956. View

15.

Tran S, Samango-Sprouse C, Sadeghin T, Powell S, Gropman A . Hormonal replacement therapy and its potential influence on working memory and competency/adaptive functioning in 47,XXY (Klinefelter syndrome). Am J Med Genet A. 2019; 179(12):2374-2381. DOI: 10.1002/ajmg.a.61360. View

16.

Davis S, Reynolds R, Dabelea D, Zeitler P, Tartaglia N . Testosterone Treatment in Infants With 47,XXY: Effects on Body Composition. J Endocr Soc. 2019; 3(12):2276-2285. PMC: 6846330. DOI: 10.1210/js.2019-00274. View

17.

Zeger M, Zinn A, Lahlou N, Ramos P, Kowal K, Samango-Sprouse C . Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome. J Pediatr. 2008; 152(5):716-22. PMC: 6728163. DOI: 10.1016/j.jpeds.2007.10.019. View

18.

Samango-Sprouse C, Lasutschinkow P, Powell S, Sadeghin T, Gropman A . The incidence of anxiety symptoms in boys with 47,XXY (Klinefelter syndrome) and the possible impact of timing of diagnosis and hormonal replacement therapy. Am J Med Genet A. 2019; 179(3):423-428. DOI: 10.1002/ajmg.a.61038. View

19.

Samango-Sprouse C, Lasutschinkow P, McLeod M, Porter G, Powell S, St Laurent J . Speech and language development in children with 49,XXXXY syndrome. Am J Med Genet A. 2020; 185(12):3567-3575. DOI: 10.1002/ajmg.a.61767. View

20.

Stochholm K, Bojesen A, Jensen A, Juul S, Gravholt C . Criminality in men with Klinefelter's syndrome and XYY syndrome: a cohort study. BMJ Open. 2012; 2(1):e000650. PMC: 3289987. DOI: 10.1136/bmjopen-2011-000650. View