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.