Positive effects of early androgen therapy on the behavioral phenotype of boys with 47,XXY

Abstract

47, XXY occurs in up to 1 in 650 male births and is associated with androgen deficiency, neurodevelopmental delays, and atypical social-behaviors. Previously, we showed that young boys with 47, XXY who received early hormonal therapy (EHT) had significantly improved neurodevelopment. The objective of this follow-up study was to examine the effects of EHT on social behavior in boys with 47, XXY. The study consisted of boys prenatally diagnosed with 47, XXY who were referred for evaluations. Twenty-nine boys received three injections of 25 mg testosterone enanthate and 57 controls did not receive EHT. Behavioral functioning was assessed using the Behavior Rating Inventory of Executive Function, Social Responsiveness Scale, 2nd Ed., and the Child Behavior Checklist for Ages 6-18. The hypothesis that EHT may affect behavior was formulated prior to data collection. Questionnaire data was prospectively obtained and analyzed to test for significance between two groups. Significant differences were identified between group's scores over time in Social Communication (P=0.007), Social Cognition (P=0.006), and Total T-score (P=0.001) on the SRS-2; Initiation (P=0.05) on the BRIEF; and Externalizing Problems (P=0.024), Affective Problems (P=0.05), and Aggressive Behaviors (P=0.031) on the CBCL. This is the third study revealing positive effects of EHT on boys with XXY. There was a significant improvements associated with the 47, XXY genotype in boys who received EHT. Research is underway on the neurobiological mechanisms, and later developmental effects of EHT.

Hypogonadotrophic hypogonadism, delayed puberty and risk for neurodevelopmental disorders

“…Furthermore, because genome‐wide clinical genetic testing is becoming standard in NDDs, the children at genetic risk for HH in this population could be detected years before the delay in sexual maturation, enabling the earlier diagnosis and treatment of HH. Indeed, early androgen therapy in boys with Klinefelter syndrome has been shown to improve neurodevelopmental outcomes, such as language development, cognitive functioning and social skills, compared to boys who did not receive the early treatment …”

The Klinefelter syndrome: current management and research challenges

“…She believes that EHT is not a cure but does help significantly to minimize the boys' developmental challenges and behavioral issues based on her and other publications (Rogol et al, 2014;Samango-Sprouse et al, 2015).…”

Screening for Sex Chromosome Aneuploidy by Cell-Free DNA Testing: Patient Choice and Performance

“…However, a qualitative interview survey of experts' opinions on the incidental prenatal diagnosis of SCAs shows that their early detection has benefits greatly exceeding counseling issues and possible parental decisions to terminate the pregnancy [19]. Recent findings also show positive effects of postnatal hormone therapy on the behavioral phenotype if applied earlier to these patients [20,21].…”