Context: Boys with XXY have greater adiposity and a higher risk of cardiovascular disease. Infants with XXY have lower testosterone concentrations than typical boys, but no studies have evaluated adiposity in infants with XXY or the physiologic effects of giving testosterone replacement.
Objective: To determine the effect of testosterone on body composition in infants with XXY.
Design: Prospective, randomized trial.
Setting: Tertiary care pediatric referral center.
Participants: 20 infants 6 to 15 weeks of age with 47,XXY.
Intervention: Testosterone cypionate 25 mg intramuscularly monthly for three doses vs no treatment.
Main outcome measures: Difference in change in adiposity (percent fat mass z scores); other body composition measures, penile length, and safety outcomes between treated and untreated infants; and comparison with typical infants.
Results: The increase in percent fat mass (%FM) z scores was greater in the untreated group than in the treated group (+0.92 ± 0.62 vs -0.12 ± 0.65, P = 0.004). Increases in secondary outcomes were greater in the testosterone-treated group for total mass, fat-free mass, length z score, stretched penile length, and growth velocity (P < 0.002 for all). At 5 months of age, adiposity in untreated infants with XXY was 26.7% compared with 23.2% in healthy male infants of the same age (P = 0.0037); there was no difference in %FM between the treated XXY boys and controls. Reported side effects were minimal and self-limited; no serious adverse events occurred.
Conclusions: Adiposity of untreated infants was 15% greater than that of male controls by 5 months of age. Testosterone treatment for infants with XXY resulted in positive changes in body composition.
Keywords: Klinefelter syndrome; XXY; adiposity; mini-puberty; sex chromosome aneuploidy; testosterone.
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