Anastrozole plus leuprorelin in early maturing girls with compromised growth: the "GAIL" study.
OBJECTIVE
Aromatase inhibitors have been used to increase predicted adult height (PAH) in boys but in girls only in McCune-Albright syndrome. We investigated whether anastrozole combined with leuprorelin for up to 2 years is safe and effective in improving PAH in girls with early puberty and compromised growth, compared to leuprorelin alone.


METHODS
The "GAIL" study: girls treated with an aromatase inhibitor and an LHRH analogue, ISRCTN11469487, was a 7-year prospective phase IIa study with parallel design, performed at Athens Medical Center (C-A), and Attikon University Hospital, Athens, Greece (C-B). Forty girls, consecutively referred for early puberty (onset 7.5-9 years) with a PAH <-2 or >1.5 SD lower than their target height (TH), were included. Twenty started on leuprorelin sc/im 0.3 mg/kg/month plus anastrozole 1 mg/d p.o. (group-A, C-A) and 20 on leuprorelin (group-B, C-B) for 2 years or until the age of 10 years. Groups did not differ in age, height, BMI, bone age advancement (BAA), and distance of PAH from TH. Follow-up was at 6, 12, 18, and 24 m.


RESULTS
Reduction in BAA was significantly higher in group-A compared to group-B already by 6 m. Despite the transiently significant decrease in height velocity in group-A, gain in PAH SD was almost double by 12 and 18 m vs group-B and reached the maximum of +1.21 ± 0.45 (7.51 cm) vs +0.31 ± 0.37 (1.92 cm, p = 0.001) in group-B at 24 m. Group-A had no clinical or biochemical hyperandrogenism, unchanged normal bone density, and lumbar spine X-rays.


CONCLUSIONS
The co-administration of anastrozole with leuprorelin safely improves PAH in girls with compromised growth.
Department of Pediatric-Endocrinology and Diabetes, Athens Medical Center, 58, av. Kifissias, Maroussi, 15125, Athens, Greece. info@pedoendo.gr.|Third Department of Pediatrics, "Attikon" University Hospital, Haidari, 12462, Athens, Greece. info@pedoendo.gr.
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Papadimitriou
Third Department of Pediatrics, "Attikon" University Hospital, Haidari, 12462, Athens, Greece.
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Dermitzaki
Third Department of Pediatrics, Hippokrateion General Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54642, Thessaloniki, Greece.
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Papagianni
Department of Radiology, Mitera Maternity and Children's Hospital, Maroussi, 15123, Athens, Greece.
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Papaioannou
Third Department of Pediatrics, "Attikon" University Hospital, Haidari, 12462, Athens, Greece.
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Papaevangelou
Third Department of Pediatrics, "Attikon" University Hospital, Haidari, 12462, Athens, Greece.
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Papadimitriou
D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001827:Body Height / Q000187:drug effects; D015519:Bone Density; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006115:Greece / Q000453:epidemiology; D006130:Growth Disorders / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D009570:Nitriles / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D011629:Puberty, Precocious; D012741:Sexual Maturation / Q000187:drug effects; D014230:Triazoles / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide
Anastrozole; Aromatase inhibitors; Early puberty; Girls; LHRH analogues