ESPE Abstracts (2016) 86 P-P1-141

Off-Label Use of the Aromatase Inhibitor Letrozole in Pubertal Boys to Improve Final Height: Laboratory, Auxological and Bone Age Data

Heinrich Schmidt, Claudia Weissenbacher, Susanne Bechtold-Dalla Pozza, Julia Roeb & Carmen Sydlik

Dr. v. Haunersches Children’s Hospital, Ludwigs-Maximilians-Universität München, Munich, Germany

Background and aims: The aromatase inhibitor letrozole is used to improve final height in boys with predicted short stature by delaying bone age (BA) maturation due to suppression of estradiol levels. There are few data regarding its effects, especially when used as single medication.

Methods: Ten pubertal boys with predicted low final height treated with letrozole 2.5 mg/d p.o. (no other medication) for up to 24 months were analysed for auxological, laboratory and BA data.

Results: Height-SDS showed only small changes during the time of treatment (means between −0.06 and +0.10 SDS) with wide interindividual variability (−0.65 to +0.89 SDS). BMI raised between 0 and 6 months of treatment (mean: +0.42 SDS) remaining quite constant afterwards. While BA was average in most patients at start (mean difference between BA and chronological age (CA): −0.63 years) and even advanced during the first 6 months (mean difference BA - CA: +0.34 years compared to values at start), an increasing delay compared to the initial values was first seen at 12 month (−0.19 years). This trend continued until 24 months (mean: −0.29 years), but in the whole, the additional delay was relatively small. IGF-I SDS decreased in all with the largest difference between 0 and 6 months, but continued to descent until 24 months, falling below −2 SDS in four patients. Testosterone clearly increased between 0 and 6 months (mean: +440 ng/dl), then remaining unchanged. Suppression of estradiol, the main effect of letrozole, was achieved only in in 5 of the 10 patients after 6 months but in 5 of 6 after 12 months. Changes of predicted final height varied widely interindividually (−5.0 to +6.95 cm at 18 months compared to start, mean: +1.92 cm, median: +2.91 cm) and also intraindividually during the course of treatment. There were no significant correlations of the changes in delay of BA or predicted final height with any of the initial data.

Conclusion: Letrozole as a monotherapy increases final height in the majority, but not in all treated boys. Decrease of IGF-I SDS by letrozole could eventually reduce the value of the gain of growth potential. Delay of maturation of BA as well as estradiol suppression were achieved only after 12 months, so it is to discuss if a higher dose of letrozole, at least during the first 6–12 months could further improve the effect.

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