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Testosterone Treatment in Infants With 47,XXY: Effects on Body Composition
Shanlee M Davis1,2, Regina M Reynolds3, Dana M Dabelea4
1University of Colorado School of Medicine, Department of Pediatrics, Section of Endocrinology, Aurora, Colorado.
Insights
Testosterone treatment in infants with XXY significantly reduced adiposity and improved body composition. Untreated XXY infants showed a 15% increase in adiposity compared to male controls by five months of age.
Area of Science:
- Pediatric Endocrinology
- Genetics
- Metabolic Disorders
Background:
- Infants with 47,XXY (Klinefelter syndrome) exhibit lower testosterone levels and increased adiposity risk.
- Previous research indicates higher adiposity and cardiovascular disease risk in older boys with XXY.
- No studies have investigated adiposity in XXY infants or the effects of testosterone replacement therapy.
Purpose of the Study:
- To assess the impact of testosterone administration on body composition in infants diagnosed with 47,XXY.
- To evaluate changes in adiposity, other body composition metrics, and growth parameters.
Main Methods:
- A prospective, randomized trial was conducted at a tertiary care pediatric center.
- Twenty infants aged 6 to 15 weeks with 47,XXY were enrolled.
- Participants received either intramuscular testosterone cypionate (25 mg monthly for three doses) or no treatment, with comparisons made to typical male infants.
Main Results:
- Testosterone-treated XXY infants showed a significant decrease in percent fat mass (z-scores), while untreated infants experienced an increase.
- The testosterone group exhibited greater improvements in total mass, fat-free mass, length (z-score), penile length, and growth velocity.
- By 5 months, untreated XXY infants had 26.7% adiposity versus 23.2% in controls; treated infants showed no significant difference compared to controls.
Conclusions:
- Infants with 47,XXY demonstrate significantly higher adiposity by 5 months of age compared to typical male infants.
- Testosterone replacement therapy in XXY infants leads to favorable changes in body composition and growth parameters.
- The treatment was well-tolerated with minimal, self-limiting side effects.
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.
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