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November 14, 2019
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Autism, ADHD risks increased for adolescents with hypogonadism, delayed puberty

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Children with hypogonadotropic hypogonadism or delayed puberty are more likely to develop neurodevelopment disorders, such as autism spectrum disorder, ADHD and intellectual disabilities, compared with those who undergo normal puberty, according to findings published in the Journal of Neuroendocrinology.

Kristiina Tammimies

“Clinicians should be aware of the reported comorbidity between hypogonadotropic hypogonadism, delayed puberty and neurodevelopment disorders, and if there are reports of learning, social and attention difficulties in their patients with hypogonadotropic hypogonadism or delayed puberty [should] pursue needed clinical psychological investigations,” Kristiina Tammimies, PhD, an assistant professor in the division of neuropsychiatry of the department of women’s and children’s health at Karolinska Institutet in Stockholm, told Endocrine Today.

Tammimies and colleagues analyzed data from the National Patient Register, Multi-Generation Register, Habilitation Register, Swedish Prescribed Drug Register, Swedish Register of Education, Total Population Register, Clinical Database for Child and Adolescent Psychiatry, Small Area Market Statistics and the Swedish Medical Birth Register. These registries allowed the researchers to assess autism spectrum disorder, ADHD and intellectual disability diagnoses among adolescents with hypogonadotropic hypogonadism (n = 264; 32% girls) and adolescents with delayed puberty (n = 7,447; 23% girls) as well as 10 controls per case matched by age, sex and country of origin.

Among those with hypogonadotropic hypogonadism, 3.8% had autism spectrum disorder vs. 0.7% of controls. The odds of having autism spectrum disorder were more than 5 times higher for those with vs. without hypogonadotropic hypogonadism (OR = 5.68; 95% CI, 2.56-12.59).

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Children with hypogonadotropic hypogonadism or delayed puberty are more likely to develop neurodevelopment disorders, such as autism spectrum disorder, ADHD and intellectual disabilities, compared with those who undergo normal puberty.

For those with delayed puberty, 3% had autism spectrum disorder vs. 2.1% of controls. The odds of having autism spectrum disorder were higher for those with vs. without delayed puberty (OR = 1.47; 95% CI, 1.27-1.69).

Among those with hypogonadotropic hypogonadism, 8% had ADHD vs. 2.8% of controls. The odds of having ADHD were tripled for those with vs. without hypogonadotropic hypogonadism (OR = 3.04; 95% CI, 1.82-5.07).

For those with delayed puberty, 8.2% had ADHD vs. 5% of controls. The odds of having ADHD were higher for those with vs. without delayed puberty compared (OR = 1.72; 95% CI, 1.57-1.88).

Among those with hypogonadotropic hypogonadism, 8.3% had an intellectual disability vs. 0.5% of controls. The odds of having an intellectual disability were 18 times higher for those with vs. without hypogonadotropic hypogonadism (OR = 17.97; 95% CI, 8.88-36.34).

For those with delayed puberty, 3.5% had an intellectual disability vs. 1.25% of controls. The odds of having an intellectual disability were almost 3 times higher for those with vs. without delayed puberty (OR = 2.95; 95% CI, 2.56-3.39).

The researchers noted that incorporating adjustments, stratifications and exclusions to the data “did not markedly affect the results.”

“There is limited evidence how the dysregulation of sex hormones that leads to hypogonadotropic hypogonadism and delayed puberty affect the brain development and associated disorders,” Tammimies said. “If further studies can identify mechanisms or specific genes behind these associations between conditions, there is possibility to earlier provide guidance and interventions for the conditions.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.