Nelly Mauras1, Judith L Ross1, Priscila Gagliardi1, Y Miles Yu1, Jobayer Hossain1, Joseph Permuy1, Ligeia Damaso1, Debbie Merinbaum1, Ravinder J Singh1, Ximena Gaete1, Veronica Mericq1. 1. Nemours Children's Health System, Division of Endocrinology (N.M., P.G., J.P., L.D.), Jacksonville, Florida 32207; (J.L.R.), Philadelphia, Pennsylvania 19107; and (Y.M.Y.), Orlando, Florida 32827; Nemours Children's Health System, Division of Biostatistics (J.H.), Wilmington, Delaware 19803; and Nemours Children's Health System, Department of Radiology (D.M.), Jacksonville, Florida 32207; Mayo Clinic (R.J.S.), Department of Biochemistry, Rochester, Minnesota 55905; and University of Chile (X.G., V.M.), Division of Endocrinology, 1058 Santiago, Chile.
Abstract
CONTEXT: Growth of short children in puberty is limited by the effect of estrogen on epiphyseal fusion. OBJECTIVES: 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. DESIGN: Randomized three-arm open-label comparator. SETTING: Outpatient clinical research. PATIENTS: Seventy-six pubertal boys [mean (SE) age, 14.1 (0.1) years] with ISS [height SD score (SDS), -2.3 (0.0)]. INTERVENTION: Daily AIs (anastrozole or letrozole), GH, or AI/GH for 24-36 months. OUTCOMES: Anthropometry, bone ages, dual x-ray absorptiometry, spine x-rays, hormones, safety labs. RESULTS: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. CONCLUSIONS: 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.
RCT Entities:
CONTEXT: Growth of short children in puberty is limited by the effect of estrogen on epiphyseal fusion. OBJECTIVES: 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. DESIGN: Randomized three-arm open-label comparator. SETTING:Outpatient clinical research. PATIENTS: Seventy-six pubertal boys [mean (SE) age, 14.1 (0.1) years] with ISS [height SD score (SDS), -2.3 (0.0)]. INTERVENTION: Daily AIs (anastrozole or letrozole), GH, or AI/GH for 24-36 months. OUTCOMES: Anthropometry, bone ages, dual x-ray absorptiometry, spine x-rays, hormones, safety labs. RESULTS: 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. CONCLUSIONS: 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.
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