OR15-05 Gain in Near Adult Height Using the Combination of an LHRH Analogue and an Aromatase Inhibitor in Early Maturing Girls with Compromised Growth. The “Gail” Study ISRCTN11469487

Background. Third generation aromatase inhibitors (AI), as monotherapy, have never been used to increase predicted adult height in girls. Our previously published GAIL study 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 (1). Objective and Hypotheses. We assessed the final height of the girls who participated in the GAIL study compared to the predicted after 24 months of combined treatment and additionally the efficacy of anastrozole monotherapy after completion of the combined treatment in further improving final height. Methods. We measured adult (i.e. age 16.5 yrs) or near adult height (i.e. at bone age 14 yrs) of 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 yrs with a 6-month follow-up. Group A2 (10 girls) had stopped the combined therapy at 24 months or 11 yrs of age and were recalled for adult (or near) height evaluation. Results. Adult or near adult height (NAH) exceeded the predicted 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. In early maturing girls with compromised growth, treatment for 2 yrs or until the age of 11 yrs with LHRH analogue plus anastrozole 1mg/day, the gain is +9.7cm in total when treated with anastrozole monotherapy until they reach NAH, whereas it is +7.4 cm if they do not continue with the monotherapy and only +3.6 cm when treated with an LHRHa only. As a result, the combination therapy continued with anastrozole monotherapy, ends in the shortest distance from target height. This implies that the addition of the anastrozole to an LHRHa apart from being safe, is effective in ameliorating substantially Near Adult Height making the intervention meaningful. Reference: (1) Papadimitriou DT, Dermitzaki E, Papagianni M, Papaioannou G, Papaevangelou V, Papadimitriou A. Anastrozole plus leuprorelin in early maturing girls with compromised growth: the “GAIL” study. Endocrinol Invest. 2016 Apr;39(4):439-46]