Circulating antiandrogenic activity in children with congenital adrenal hyperplasia during peroral flutamide treatment.
BACKGROUND
The degree of androgen receptor blockade achieved with peroral flutamide is unknown.


OBJECTIVE
The aim of this study was to examine the contribution of flutamide to circulating antiandrogenic activity in children with congenital adrenal hyperplasia using a recombinant cell bioassay.


METHODS
We describe an open-label, prospective clinical study.


METHODS
The study was conducted at the Hospital for Children and Adolescents, University of Helsinki, or the Turku University Hospital, Finland.


METHODS
Seven children, age 7.2-10.5 yr, were included.


METHODS
As an experimental approach to improve control of height velocity and the rate of bone maturation, the patients received letrozole (2.5 mg/d) and flutamide (10 mg/kg.d) and were followed up at 3-month intervals for 3-12 months. Before employing the bioassay, two 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 supplemented with a constant amount of exogenous testosterone.


METHODS
The main outcome measure was 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 less than 10 mg/kg.d 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.
Hero
Matti
M
Hospital for Children and Adolescents, University of Helsinki, P.O. Box 281, FIN-00029 HUS, Finland.
Jänne
Olli A
OA
Näntö-Salonen
Kirsti
K
Dunkel
Leo
L
Raivio
Taneli
T
D000284:Administration, Oral; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood* / Q000188:drug therapy*; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D000728:Androgens / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D001681:Biological Assay; D002648:Child; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005485:Flutamide / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D011446:Prospective Studies; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use
D000726:Androgen Antagonists; D000728:Androgens; D013739:Testosterone; D005485:Flutamide