Context The degree of androgen receptor (AR) blockade achieved with peroral flutamide is unknown.

Objective To examine the contribution of flutamide to circulating antiandrogenic activity in children with congenital adrenal hyperplasia (CAH) using a recombinant cell bioassay.

Design Open-label, prospective clinical study.

Setting University central hospital.

Patients 7 children, aged 7.2-10.5 yr.

Intervention As an experimental approach to improve control of height velocity and the rate of bone maturation, the patients received letrozole (2.5 mg/day), and flutamide (10 mg/kg/day), and were followed up at 3-month intervals for 3-12 months. Before employing the bioassay, 2 pools of sera (obtained before and during flutamide treatment) were supplemented with increasing amounts of testosterone, and all sera (n = 27) of individual patients were spiked with a constant amount of exogenous testosterone.

Main outcome measure Circulating antiandrogenic activity.

Results Flutamide and/or its metabolites shifted the dose-response curve of testosterone, in that only the highest testosterone concentration, corresponding to 1803 ng/dl (62.5 nM) in human serum, was measurable by the bioassay. In individual sera supplemented with testosterone, flutamide treatment suppressed androgen bioactivity from 378 ± 20 ng/dl (13.1 ± 0.7 nM) (mean±SEM) (pretreatment) to 110 ± 20 ng/dl (3.8 ± 0.7 nM) (3 months), 83.7 ± 12 ng/dl (2.9 ± 0.4 nM) (6 months), 46.2 ± 6 ng/dl (1.6 ± 0.2 nM) (9 months), and 57.7 ± 9 ng/dl (2.0 ± 0.3 nM) (12 months) testosterone equivalents (P < 0.01).

Conclusions A dose of flutamide smaller than 10 mg/kg per day appears sufficient to inhibit AR in children. The recombinant cell bioassay employed herein offers a novel means to monitor the treatment of patients receiving antiandrogens.