Testosterone Effects on Short-term Physical, Hormonal, and Neurodevelopmental Outcomes (TESTO) in Infants With 47,XXY

Area of Science:

• Pediatric Endocrinology
• Genetics
• Neurodevelopmental Pediatrics

Background:

• 47,XXY (Klinefelter syndrome) is linked to impaired testicular function, growth, metabolism, and neurodevelopmental differences.
• Testosterone levels during infancy may influence clinical features of 47,XXY.

Purpose of the Study:

• To investigate the effects of exogenous testosterone on short-term physical, hormonal, and neurodevelopmental outcomes in infants with 47,XXY.
• To test the hypothesis that testosterone treatment positively impacts these outcomes.

Main Methods:

• Double-blind randomized controlled trial involving 71 infants (30-90 days old) with prenatally identified, non-mosaic 47,XXY.
• Intervention: Intramuscular testosterone cypionate injections (25mg every 4 weeks for 3 doses).
• Primary outcomes: Changes in % body fat mass z-scores and Alberta Infant Motor Scales (AIMS) percentile from baseline to 12 weeks.

Main Results:

• Testosterone treatment led to increased lean mass and improved % body fat mass z-scores (p=0.03).
• Testosterone significantly suppressed gonadotropins and inhibin B (p<0.001).
• No significant differences were observed in short-term motor, cognitive, or language outcomes between groups (p>0.15).

Conclusions:

• Testosterone injections in infants with 47,XXY induced physical changes related to androgen exposure but suppressed the hypothalamic-pituitary-gonadal axis.
• Neurodevelopmental outcomes were not impacted in the short term.
• Results do not support routine testosterone treatment in infants with 47,XXY; long-term follow-up is necessary.