Pharmacokinetics and Pharmacodynamics of Anastrozole in Pubertal Boys with Recent-Onset Gynecomastia

Context: Use of aromatase inhibitors to suppress estrogen production is being actively investigated in a variety of experimental conditions in both females and males. Anastrozole (Arimidex) is a potent and selective reversible inhibitor of the aromatase enzyme in females. Objective: Our objective was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of anastrozole in adolescent males with gynecomastia of less than 1 yr duration. The effect of anastrozole on breast size was also assessed as an exploratory aim. Design: We conducted a PK/PD open-label study. Setting: This clinical research center study was undertaken at pediatric academic centers. Patients: Forty-two boys with gynecomastia (mean age 13 ± 1.8 yr; duration of gynecomastia 7.0 ± 2.5 months; body mass index 28.3 ± 5.9 kg/m2) were recruited. Interventions: Anastrozole, 1 mg, was given daily for 6 months. Main Outcomes: We assessed PK/PD of anastrozole after 14 d daily dosing and changes in breast size (exploratory aim) by manual tape measurements (area) and ultrasound (volume) after 6 months. Results: Anastrozole was rapidly absorbed orally (time to reach maximum concentration, 1 h) with a slow apparent clearance of 1.54 liters/h and a terminal half-life of 46.8 h. Testosterone/estradiol ratios increased significantly with concomitant increase in LH/FSH concentrations indicating aromatase blockade. There was a reduction in breast area (∼63%) and breast volume (∼57%) in the study group as compared with baseline (P = 0.004). The drug was well tolerated. Conclusions: Anastrozole is a potent aromatase inhibitor in adolescent males, with rapid absorption and slow elimination kinetics after oral dosing. Exploratory analysis of changes in breast size showed breast reduction in the cohort; this deserves further study. Pharmacokinetics of oral anastrozole in adolescent males with gynecomastia show rapid absorption and slow elimination kinetics; an observed reduction in breast size deserves further study.