Anastrozole Improves Near Adult Height in Boys With Compromised Height Potential, as Monotherapy or in Combination With a GnRH Analogue

Abstract

Background: Bone maturation depends mainly on locally produced estrogens by aromatization. Third generation aromatase inhibitors (AIs) are being widely used off-label to improve predicted adult height (PAH) in boys as well as in girls, either as monotherapy or in combination with growth hormone and/or puberty inhibition. They induce reverse binding inhibiting the activity of aromatase (a cytochrome P450 enzyme), which catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively. While numerous studies have shown that AIs delay bone maturation and improve PAH, data on near-adult height (NAH) of children treated with AIs are lacking. Aims: To compare results on NAH of boys treated with anastrozole either as monotherapy or in combination with pubertal inhibition (for at least 1yr at onset). Methods: 159 boys with advanced bone age (BA) and PAH <170 cm that received anastrozole 1 mg/day p.o. either as monotherapy (n=76, group A) or as co-therapy with a GnRH analogue for at least 1yr and then as monotherapy (n=83, group B) until bone age of 15-16 yrs were included. Data on boys that reached NAH (BA at least 16 yrs with height velocity <2 cm/yr) were analyzed: group A, n=16 with PAH 167.3 and TH 170.9 and group B, n=10 with PAH 165.5 and TH 171.7 cm. Measurements were made on the same height meter by the same examiner. The choice of therapeutic intervention was made randomly. Groups A and B did not differ in terms of age at intervention onset, TH or PAH. During treatment, they underwent a 6-month follow-up that included clinical examination, BA, and laboratory tests at 8:00 hrs (general blood count, lipid chart, LH, FSH, testosterone, estradiol, estrone, and complete calcium metabolism), with lumbar spine DEXA (Dual Energy X-ray Absorptiometry) and X-ray performed annually. Results: The duration of anastrozole treatment was 3.9 yrs in group A, and 4.6 yrs in group B (where the GnRHa was administered for at least 1 yr) and the median age at intervention onset was 11.04 and 11.8 yrs, respectively. Both groups had a statistically significant gain in NAH with no difference between them: for group A 3.6 cm (+0.53 SD, p=0.002) and for group B 4.8 cm (+0.71 SD, p=0.0007). Thus, distance from TH was finally 0 cm for group A and -1.5 cm (0.19 SD) for group B. According to the definition of NAH, the adult height of the two groups is expected to be about 2% higher. Follow-up showed no side effects on their biochemical or lipid profile, bone density and vertebral architecture. Conclusions: Anastrozole therapy is safe and effective in improving adult height in boys with advanced puberty and poor height prediction, either as monotherapy or in combination with pubertal inhibition.