FP20-1 Randomization to Anastrozole vs. Letrozole in Short Pubertal Males: First Year Hormonal Data

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP20-Growth: Clinical Trials & Observational Studies
Clinical
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:45 AM
Room 122 (Moscone Center)

Poster Board SUN-626
Rajiv B. Kumar*1, Sydney L. Payne1, Diane I. Suchet2 and E. Kirk Neely1
1Stanford University Medical Center, Stanford, CA, 2Palo Alto Medical Foundation, Palo Alto, CA
Background: Aromatase inhibitors are used off-label in an effort to increase final height in boys. Several randomized controlled trials have shown an increase in predicted adult height (PAH), and one study using letrozole in boys with constitutional delay demonstrated an increase in near final height. We report preliminary data from an ongoing trial comparing anastrozole (A) and letrozole (L) in short pubertal boys.

Design: Inclusion criteria were male >10 years, bone age ≤ 14 years, height < 5th%ile and/or PAH >10 cm below mid-parental height, Tanner ≥ G2 (testicular volume ≥ 4cc), LH >0.3 IU/L, and testosterone >15 ng/dL. Subjects were randomized to standard oral daily doses of A (1 mg) or L (2.5 mg), with no untreated group. Baseline and follow-up visits included physical exam and hormone assessment every 6 months, annual bone age, and DXA and lateral spine film every 2 years.

Results: 45 patients have been randomized to date; 33 boys have completed 6 months of therapy, and 25 have completed 12 months. No boys were concurrently on growth hormone. At enrollment, average age was 14.2 ±1.3 y (range 10.2-16.0) with combined baseline lab values as follows (mean ±SD, performed at Esoterix): LH 2.1 ±1.2 IU/L, testosterone 202 ±152 ng/dL, estradiol 6.2 ±5.4 pg/mL, IGF-I 315 ±123 ng/mL, and IGFBP-3 3.2 ±0.7 mg/L, with no between-group differences in any parameters. At 6 months, significant differences were seen between the A and L groups, respectively: LH 2.8 ±1.2 vs. 6.8 ±3.9, testosterone 496 ±228 vs. 1067 ±397, estradiol 3.5 ±2.2 vs. 1.8 ±0.7, IGF-I 356 ±93 vs. 252 ±71, and IGFBP-3 3.4 ±0.7 vs. 2.8 ±0.7 (all p <0.02). Mean levels were unchanged between the 6 and 12 month visits, and the between-group differences persisted at 12 months. There were no adverse events in the first year.

Conclusion: Compared with anastrozole, letrozole results in higher serum levels of LH and testosterone, and lower levels of estradiol, IGF-I, and IGF-BP3, in the first year of therapy. Despite pubertal advance and a robust increase in testosterone in both treatment groups, especially with letrozole, IGFs failed to rise, possibly related to the intended suppression of estrogen levels. Aromatase inhibitors result in dramatic short-term hormonal alterations and should be utilized with caution until additional studies have reached final height.

Nothing to Disclose: RBK, SLP, DIS, EKN

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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