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. 2024 Aug 27;8(10):bvae141.
doi: 10.1210/jendso/bvae141.

Anastrozole vs Letrozole to Augment Height in Pubertal Males With Idiopathic Short Stature: A 3-Year Randomized Trial

Walter Zegarra  1 , Sayali Ranadive  2 , Diane Toulan  2 , E Kirk Neely  1
Affiliations

Anastrozole vs Letrozole to Augment Height in Pubertal Males With Idiopathic Short Stature: A 3-Year Randomized Trial

Walter Zegarra et al. J Endocr Soc. .

Abstract

Context: Insufficient efficacy and safety data for off-label use of aromatase inhibitors to augment height in boys with short stature.

Objective: To compare anastrozole and letrozole in treatment of idiopathic short stature in pubertal boys.

Design: Open-label trial with 2 treatment arms.

Setting: Pediatric Endocrine Clinic at Stanford.

Participants: A total of 79 pubertal males ≥10 years with bone age (BA) ≤ 14 years, predicted adult height (PAH) < 5th percentile or >10 cm below mid-parental height.

Intervention: Anastrozole 1.0 mg or letrozole 2.5 mg daily for up to 3 years.

Main outcome measures: Annual hormone levels and growth parameters during treatment and a year posttherapy; annual BA and PAH (primary outcome measure); spine x-rays and dual energy X-ray absorptiometry at baseline and 2 years.

Results: Compared with anastrozole (n = 35), letrozole (n = 30) resulted in higher testosterone levels, lower estradiol and IGF-1 levels, and slower growth velocity and BA advance. The PAH increase observed at year 1 in both groups did not persist at years 2 and 3. Change in PAH from baseline was not different between treatment groups. In groups combined, PAH gain over 3 years vs baseline was +1.3 cm (P = .043) in linear mixed models.

Conclusion: Letrozole caused greater deviations than anastrozole in hormone levels, growth velocity, and BA advancement, but no group differences in PAH or side effects were found. Change in PAH after 2 to 3 years of treatment was minimal. The efficacy of AI as monotherapy for height augmentation in pubertal boys with idiopathic short stature may be limited, and safety remains an issue.

Keywords: anastrozole; aromatase inhibitor; height; letrozole; puberty.

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Figures

Figure 1.
Figure 1.
Boxplots of height (A) and growth velocity (B) over time by treatment arm.
Figure 2.
Figure 2.
Boxplots of annual bone age (A) and predicted adult height (B) by treatment arm through year 3.
Figure 3.
Figure 3.
Boxplots of serum testosterone (A), estradiol (B), and IGF-1 (C) at baseline, 1, 2, and 3 years of treatment, and at posttreatment follow-up by treatment arm.
Figure 4.
Figure 4.
Boxplots of DXA whole-body (A) and lumbar spine (B) Z-scores at baseline and 2 years by treatment arm. Only subjects with a study at both time points are included.
See this image and copyright information in PMC

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