ESPE Abstracts (2018) 89 P-P1-201

ESPE2018 Poster Presentations Pituitary, Neuroendocrinology and Puberty P1 (19 abstracts)

Anastrozole is Safe as Monotherapy in Early Maturing Girls with Compromised Growth, Further Improving Gain in Predicted Adult Height by the Initial Combination Therapy of an LHRH Analogue and an Aromatase Inhibitor: Results from the ‘Gail’ Study ISRCTN11469487

Eleni Dermitzaki a , Kleanthis Kleanthous a, , Maria Papagianni c , Achilleas Attilakos d , George Mastorakos e , Anastasios Papadimitriou b & Dimitrios T Papadimitriou a

aDepartment of Pediatric – Adolescent Endocrinology and Diabetes, Athens Medical Center, Athens, Greece; bDivision of Pediatric Endocrinology, Third Department of Pediatrics, ‘Attikon’ University Hospital, Haidari, Greece; cThird Department of Pediatrics, Aristotle University of Thessaloniki, Hippokrateion General Hospital, Thessaloniki, 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, except for Mc Cune-Albright syndrome and autonomous ovarian cysts, to increase predicted adult height (PAH) in girls, mainly due to the theoretical concern of hyperandrogenism. 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 efficacy and safety of anastrozole monotherapy after completion of the combined treatment (Leuprorelin + Anastrozole) in further improving PAH in early maturing girls with compromised growth who participated in the GAIL study ISRCTN11469487.

Methods: Group A1 (10 girls), after completion of the combined therapy with anastrozole and leuprorelin for 24 months or until age 11, were randomized to receive anastrozole 1 mg/day as monotherapy until bone age of 14 yrs with a 6-month follow-up. Each visit comprised of physical examination, laboratory tests, bone age X-ray and pelvic ultrasound. DEXA scans were performed yearly.

Results: There was significant gain in PAH by 30 months (P=0.04). This was mainly achieved due to the reduction in the advancement rate of the bone age, extending the growth period in combination with the increase in girls’ height velocity S.D. (statistically significant at 12, 18, 24 and 30 months). Testosterone levels rose slightly in three girls, but none developed clinical hyperandrogenism. One girl presented ovarian stromal hyperplasia and one hyperlipidemia. Overall, hematocrit, lipid and biochemical profiles did not change significantly during treatment. DEXA scans showed normal BMD z scores for bone age without significant interpatient changes. Anastrozole monotherapy until bone age 14 yrs further improved adult height or near adult height by +3.85 cm (+0.62 SDS) P=0.001, related to the gain in the PAH at the end of the initial phase of the GAIL study.

Conclusion: Aromatase inhibitors in conjuction to an LHRH analogue as well as in monotherapy seem to be safe and effective in ameliorating PAH and adult or near-adult height in girls with accelerated bone age and compromised growth potential. Our results imply the possible role of aromatase inhibitors in the treatment of short stature in girls, even as monotherapy.

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