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Randomized Controlled Trial
. 2016 Dec;101(12):4984-4993.
doi: 10.1210/jc.2016-2891. Epub 2016 Oct 6.

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

Nelly Mauras  1 , Judith L Ross  1 , Priscila Gagliardi  1 , Y Miles Yu  1 , Jobayer Hossain  1 , Joseph Permuy  1 , Ligeia Damaso  1 , Debbie Merinbaum  1 , Ravinder J Singh  1 , Ximena Gaete  1 , Veronica Mericq  1
Affiliations
Randomized Controlled Trial

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

Nelly Mauras et al. J Clin Endocrinol Metab. 2016 Dec.

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.

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Figures

Figure 1.
Figure 1.
Changes in mean (SE) height SDS (top panel) and bone age (bottom panel) over 24 months in the groups treated with AIs, GH, and AI/GH. *, P < .0012 (top panel); and **, P = .002 (bottom panel) represent the probability of difference in mean changes between groups for all parameters (ANCOVA). n = 76 (baseline), 72 (12 months), and 65 (24 months).
Figure 2.
Figure 2.
Top panel shows mean (SE) differences in near-final height (cm) (n = 71) in the AI, GH, and AI/GH groups regardless of length of treatment (n = 21, 25, and 25, respectively) (P < .001 within groups; *, P = .19 among groups). Bottom panel shows net gain in height (cm) in the same three groups (*, P = .01 among groups; **, P = .002 between AI and AI/GH groups). Average height and net gain in height of young men of similar ages with height SDS −2.0 are shown for comparison on the far right bars (CDC data).
Figure 3.
Figure 3.
Changes in FFM (top panel) and percentage fat mass (%FM) (bottom panel) over 24 months in the AI, GH, and AI/GH groups by DXA [mean (SE)]. FFM, P < .001 within each group; *, P = .015 among groups; %FM, P = .50. AI, 0.0012; GH, < .0001; AI/GH, **, P = .003 among groups. n = 76 (baseline), 72 (12 months), 63 (24 months).
Figure 4.
Figure 4.
Changes in mean (SE) concentrations of T (top panel), estradiol (middle panel), and IGF-1 (bottom panel) in the AI, GH, and AI/GH groups (*, P < .0001 among groups for T and IGF-1; **, P < .001 for estradiol). n = 76 (baseline), 72 (12 months), 65 (24 months).
See this image and copyright information in PMC

References

    1. Mauras N, Attie KM, Reiter EO, Saenger P, Baptista J. High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. Genentech, Inc., Cooperative Study Group. J Clin Endocrinol Metab. 2000;85(10):3653–3660. - PubMed
    1. Mericq MV, Eggers M, Avila A, Cutler GB, Jr, Cassorla F. Near final height in pubertal growth hormone (GH)-deficient patients treated with GH alone or in combination with luteinizing hormone-releasing hormone analog: results of a prospective, randomized trial. J Clin Endocrinol Metab. 2000;85(2):569–573. - PubMed
    1. Pucarelli I, Segni M, Ortore M, Arcadi E, Pasquino AM. Effects of combined gonadotropin-releasing hormone agonist and growth hormone therapy on adult height in precocious puberty: a further contribution. J Pediatr Endocrinol Metab. 2003;16(7):1005–1010. - PubMed
    1. Reiter EO. A brief review of the addition of gonadotropin-releasing hormone agonists (GnRH-Ag) to growth hormone (GH) treatment of children with idiopathic growth hormone deficiency: previously published studies from America. Mol Cell Endocrinol. 2006;254–255:221–225. - PubMed
    1. Scalco RC, Melo SS, Pugliese-Pires PN, et al. Effectiveness of the combined recombinant human growth hormone and gonadotropin-releasing hormone analog therapy in pubertal patients with short stature due to SHOX deficiency. J Clin Endocrinol Metab. 2010;95(1):328–332. - PMC - PubMed

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