Long-Term Effect of Aromatase Inhibition in Aromatase Excess Syndrome

Abstract

Aromatase excess syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of aromatase and enhanced aromatization of androgens. Long-term treatment effects of aromatase inhibitors are unknown. Retrospectively we collected data from file records of 7 boys (three sibling pairs and one sporadic case) with AEXS. Genetic analysis revealed upstream of CYP19A1 a 165,901 bp deletion in 4 German cousins, a 198,662 bp deletion in 2 Japanese brothers and a 387,622 bp tandem duplication in a Japanese boy. All boys developed prepubertal gynecomastia, at 9.0 yr of age (median; range: 7.0 - 11.0). Height was +1.20 SDS (-0.24 - +1.98); predicted adult height was -1.29 (-3.29 - +1.09 SDS). Four boys were treated with anastrozole 1.0 mg daily, while three reached adult height untreated. Treatment with anastrozole was stopped after 5.6 yr (4.0 - 6.8). Three treated boys exceeded height prognosis by 2.4, 6.9 and 8.1 cm; while one untreated fell below prognosis by 8.6 cm. One treated with a low dose and two untreated reached their prognosis. Adult heights were -0.91 SDS with anastrozole (-2.86 - -0.29) and -0.15 SDS without (-2.31 - -0.03). Distance to target height was -0.22 SDS with anastrozole (-1.72 - +0.52) and +0.54 SDS without treatment (+0.23 - +1.30). Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by aromatase inhibitor anastrozole (1 mg daily) promotes adult height in boys with AEXS.