Randomized Trial of Aromatase Inhibitors, Growth Hormone, or Combination in Pubertal Boys with Idiopathic, Short Stature.

Abstract

Growth of short children in puberty is limited by the effect of estrogen on epiphyseal fusion. To compare: 1) the efficacy and safety of aromatase inhibitors (AIs) vs GH vs AI/GH on increasing adult height potential in pubertal boys with severe idiopathic short stature (ISS); and 2) differences in body composition among groups. Randomized three-arm open-label comparator. Outpatient clinical research. Seventy-six pubertal boys [mean (SE) age, 14.1 (0.1) years] with ISS [height SD score (SDS), -2.3 (0.0)]. Daily AIs (anastrozole or letrozole), GH, or AI/GH for 24-36 months. Anthropometry, bone ages, dual x-ray absorptiometry, spine x-rays, hormones, safety labs. Height gain [mean (SE)] at 24 months was: AI, +14.0 (0.8) cm; GH, +17.1 (0.9) cm; AI/GH, +18.9 (0.8) cm (P < .0006, analysis of covariance). Height SDS was: AI, -1.73 (0.12); GH, -1.43 (0.14); AI/GH, -1.25 (0.12) (P < .0012). Those treated through 36 months grew more. Regardless of treatment duration, height SDS at near-final height [n = 71; age, 17.4 (0.2) years; bone age, 15.3 (0.1) years; height achieved, ∼97.6%] was: AI, -1.4 (0.1); GH, -1.4 (0.2); AI/GH, -1.0 (0.1) (P = .06). Absolute height change was: AI, +18.2 (1.6) cm; GH, +20.6 (1.5) cm; AI/GH, +22.5 (1.4) cm (P = .01) (expected height gain at -2.0 height SDS, +13.0 cm). AI/GH had higher fat free mass accrual. Measures of bone health, safety labs, and adverse events were similar in all groups. Letrozole caused higher T and lower estradiol than anastrozole. Combination therapy with AI/GH increases height potential in pubertal boys with ISS more than GH and AI alone treated for 24-36 months with a strong safety profile.