Circulating antiandrogenic activity in children with congenital adrenal hyperplasia during peroral flutamide treatment.
CONTEXT: 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. DESIGN: We describe an open-label, prospective clinical study. SETTING: The study was conducted at the Hospital for Children and Adolescents, University of Helsinki, or the Turku University Hospital, Finland. PARTICIPANTS: Seven children, age 7.2-10.5 yr, were included. Intervention: 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. MAIN OUTCOME MEASURE: 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.[1]References
- Circulating antiandrogenic activity in children with congenital adrenal hyperplasia during peroral flutamide treatment. Hero, M., Jänne, O.A., Näntö-Salonen, K., Dunkel, L., Raivio, T. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
