Background: Third generation aromatase inhibitors have been used to increase predicted adult height (PAH) in boys but in girls only in McCuneAlbright syndrome.
Objective and hypotheses: We overcame the theoretical concern of secondary hyperandrogenism by combining anastrazole to an LHRH analogue in a 6-year prospective study to test whether the combination therapy could significantly improve PAH compared to inhibition of puberty alone.
Method: Forty girls with idiopathic precocious or early puberty with PAH <−2 SDS or >1 SDS lower than their target height (TH) were enrolled for 2 years. Twenty (age 8.85, height −0.16, and PAH −2.61 SDS) started on anastrazole 1 mg/day p.o.+Leuprorelin/Triptorelin (group-A) and 20 (age 7.29, height +0.45, and PAH −1.91 SDS) on LHRH analogue only (group-B).
Results: Groups A and B did not differ in BMI, TH nor bone age advancement (BAA) +2.15 vs +1.91 years. Group-B showed a small gain in height (SDS) for bone age +0.29 only at 12 months (P=0.01) without further improvement: +0.22 at 24 months (P=0.24) from −1.33 at inclusion, whereas group A showed a significant gain +0.65 at 12 months (P<0.001) and furthermore +0.76 at 24 months (P<0.001) from −1.96 at inclusion. This led to a significant improvement in PAH: +4.5 cm in group-A at 12 months vs +2.23 cm in group-B (P=0.02) and even more +6.4 cm at 24 months vs +2.05 cm in group-B (P=0.03), due to the significantly less BAA of group-A despite an initial drop in height velocity. None of the girls in group-A developed clinical/biochemical hyperandrogenism nor ovarian stromal hyperplasia/cysts and all had normal BMD and lumbar spine X-rays checked annually.
Conclusion: The combination of anastrazole to an LHRH analogue is safe and effective in ameliorating PAH in girls with early or precocious or early puberty compared to inhibition of puberty alone.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology