ESPE Abstracts (2018) 89 RFC13.4

Gain in Predicted Adult Height Using the Combination of an LHRH Analogue and an Aromatase Inhibitor in Early Maturing Girls with Compromised Growth for 2 yrs or Until the Age of 11 is Maintained and Further Improved by Aromatase Inhibitor Monotherapy: Results on Final Height of the 'GAIL' Study ISRCTN11469487

Dimitrios T Papadimitrioua, Eleni Dermitzakia, Maria Papagiannib, Kleanthis Kleanthousa,c, Achilleas Attilakosd, George Mastorakose & Anastasios Papadimitriouc

aDepartment of Pediatric - Adolescent Endocrinology & Diabetes, Athens Medical Center, Athens, Greece; bThird Department of Pediatrics, Aristotle University of Thessaloniki, Hippokrateion General Hospital, Thessaloniki, Greece; cDivision of Pediatric Endocrinology, Third Department of Pediatrics, ‘Attikon’ University Hospital, Haidari, Greece; dThird Department of Pediatrics, ‘Attikon’ University Hospital, Haidari, Greece; eEndocrine Unit, Aretaieion University Hospital, Athens, Greece

Background: Third generation aromatase inhibitors (AI) have never been used as monotherapy to increase predicted adult height (PAH) in girls. Our previously published GAIL study (J Endocrinol Invest. 2016 Apr;39(4):439–46) has shown that the combination of anastrozole to an LHRH analogue for 24 months is safe and effective in ameliorating PAH in girls with early puberty +1.21 SDS (+7.51 cm) compared to inhibition of puberty alone +0.31 SDS (+1.92 cm), P=0.001.

Objective and Hypotheses: We assessed the adult (i.e. age 16.5 years) or near adult height (i.e. at bone age 14 years) (NAH) of the girls who participated in the GAIL study compared to the PAH after 24 months of combined treatment and additionally the efficacy of anastrozole monotherapy after completion of the combined treatment in further improving NAH.

Methods: We measured the 40 girls who participated in the GAIL study and were divided in two groups Group A (20 girls on anastrozole+ leuprorelin) and Group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups. Group A1 (10 girls), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until bone age of 14 years with a 6-month follow-up. Group A2 (10 girls) had stopped the combined therapy at 24 months or 11 years of age and were recalled for NAH evaluation.

Results: NAH exceeded the PAH at the completion of the initial phase of the GAIL study in all three groups but the result was statistically significant only in Group A1: NAH-PAH = Group A1:+3.85 cm (+0.62 SDS) P=0.001, Group A2:+1.6 cm (+0.26 SDS) P=0.26, Group B: +1.7 cm (+0.3 SDS) P=0.09. Gain in Group A1 was significantly greater to that of Group A2 (P=0.046) and Group B (P=0.035).

Conclusion: Early maturing girls with compromised growth treated with the combination of anastrozole and LHRH analogue for up to 2 years or until the age of 11 years maintain the gain in the PAH after completion of combination therapy. Anastrozole monotherapy thereafter and until bone age 14 years further improves NAH by +2.25 cm (+0.36 SDS). In total, it seems that the addition of an AI to the treatment by an LHRH analogue followed by monotherapy with the AI may add 8.06 cm (+1.28 SDS) to the NAH.