Increased Risk for Early Gonadarche Associated With Oxandrolone Treatment

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Klinefelter syndrome is associated with testosterone deficiency, neurodevelopmental delays, and cardiometabolic disorders.
Klinefelter syndrome is associated with testosterone deficiency, neurodevelopmental delays, and cardiometabolic disorders.

Oxandrolone treatment is associated with increased risk for early gonadarche in pre-pubertal boys with Klinefelter syndrome, according to a study in The Journal of Clinical Endocrinology and Metabolism.

The study was a double-blind randomized controlled trial of oxandrolone treatments vs placebo in a single tertiary care referral center. Participants were boys with Klinefelter syndrome aged between 4.0 and 12.9 years and a karyotype 47,XXY, 48,XXYY or 48,XXXY with <50% mosaicism for a 46,XY cell line. Each of the 80 participants were randomly assigned to receive oxandrolone (n=43) or an identical-appearing placebo (n=37). Those in the oxandrolone group were given 0.06 mg/kg/day rounded to the nearest 1.25 mg with minimums set at 1.25 mg/day and 3.75 mg/day, respectively. Study visits were required every 6 months for a period of 2 years. At each visit, Tanner staging was used to assess participant pubic hair and breast tissue, and the Prader orchidometer was used to estimate testicular volume.

The onset of gonadarche (testicular volume ≥4 mL) was more likely during the 2 years of follow-up in the oxandrolone group, with 20.5 times higher odds (95% CI, 6.5-77.8). The oxandrolone group also had 28.1 times higher odds of reaching pubarche (Tanner 2 pubic hair) (95% CI, 8.8-110.4) during the 2 years of follow-up. Both conditions presented at an earlier age in the oxandrolone group (gonadarche 9.8±1.5 vs 12.1±1.0 years, P =.001; pubarche 10.2±1.1 vs 11.6±1.3 years, P =.02). Serum concentrations of testicular hormones were not affected by oxandrolone treatment.

Although this study shows an increased risk for earlier onset of gonadarche in pre-pubertal boys with Klinefelter syndrome treated with oxandrolone, further research should be done to determine the underlying mechanism of these findings. Future studies using oxandrolone in pre-pubertal children should also evaluate hormone concentrations, potential sequelae of precocious puberty, and signs of puberty. Parents should be informed of the risk for early gonadarche if pre-pubertal androgen treatment is under consideration.

Reference

Davis SM, Lahlou N, Cox-Martin M, Kowal K, Zeitler PS, Ross JL. Oxandrolone treatment results in an increased risk of gonadarche in prepubertal boys with Klinefelter syndrome [published online June 20, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-00682

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