ESPE Abstracts (2014) 82 P-D-1-3-167

Aromatase Inhibitors in Girls: Anastrazole Combined to an LHRH Analogue is a Safe and Effective Strategy in Girls with Early or Precocious Puberty with Compromised Growth Potential

Dimitrios T Papadimitrioua,b, Eleni Dermitzakia, Vassiliki Papaevangeloua & Anastasios Papadimitrioua

aDivision of Pediatric Endocrinology, 3rd Department of Pediatrics, Attikon Univeristy Hospital, Athens, Greece; bDivision of Pediatric Endocrinology, Athens Medical Center, Athens, Greece

Background: Third generation aromatase inhibitors have been used to increase predicted adult height (PAH) in boys but in girls only in McCune–Albright 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.

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