Increased Risk for Early Gonadarche Associated With Oxandrolone Treatment

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