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Aromatase Inhibitors in Precocious Puberty

Rationale and Experience to Date

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Treatments in Endocrinology

Abstract

Aromatase inhibitors have been used in the treatment of selective forms of precocious puberty since the mid-1980s. The primary aim of therapy is attenuation of the effects of estrogen on growth, skeletal maturation, and secondary sexual development. The first-generation agent, testolactone, has been demonstrated to be tolerable and effective in the treatment of familial male precocious puberty, while mixed results with testolactone have been achieved in girls with McCune-Albright syndrome. A favorable outcome with the use of testolactone in conjunction with conventional therapy in children with congenital adrenal hyperplasia has also been suggested. Although a few anecdotal reports of the use of newer generation aromatase inhibitors in precocious puberty exist, the extreme rarity of the relevant disorders remains a limiting factor in clinical investigation.

In this review, the pathophysiology, presentation, and treatment of precocious puberty are described. Particular attention is devoted to the specific disorders in which aromatase inhibitors have been utilized, which are forms of peripheral (gonadotropin-independent) precocious puberty. The impact of untreated precocious puberty on growth and adult stature is discussed, and the actions of estrogen in the human skeleton are summarized. Finally, a detailed description of the existing literature pertaining to aromatase inhibitors in the pediatric population is provided. Emerging potential new indications are discussed.

In conclusion, aromatase inhibitors, particularly testolactone, have a proven track record in the treatment of a few forms of precocious puberty. Continued exploration with new generation aromatase inhibitors in these disorders is ongoing. The wider application of aromatase inhibitors for the purposes of delaying skeletal maturation and increasing adult height in several conditions leading to short stature is currently a subject of intense investigation.

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Acknowledgments

Dr Eugster participates in clinical trials sponsored by Genentech, Eli Lilly and Company, AstraZeneca, Novo Nordisk, and Pfizer Inc. No sources of funding were used to assist in the preparation of this review.

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Eugster, E.A. Aromatase Inhibitors in Precocious Puberty. Mol Diag Ther 3, 141–151 (2004). https://doi.org/10.2165/00024677-200403030-00002

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