Absence of hepatotoxicity after long-term, low-dose flutamide in hyperandrogenic girls and young women


Por: Ibañez-Toda L, Jaramillo A, Ferrer A and de Zegher F

Publicada: 1 jul 2005
Resumen:
BACKGROUND: Flutamide is a pure non-steroidal anti-androgen that may be hepatotoxic, when given in highdose (750 mg/d). Low- to ultralow-doses (250-62.5 mg/day) have been recently explored in patients with Polycystic Ovary Syndrome (PCOS), and these lower doses were found to confer benefit on multiple PCOS markers. There is a need for evidence on the potential hepatotoxicity of low- and ultralow-dose flutamide therapy. METHODS: We assessed circulating levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as markers of hepatotoxicity in a total of 190 hyperandrogenic girls and young women receiving low- or ultralow-dose flutamide because of established (n = 150) or incipient (n = 40) PCOS without obesity. Assessments were performed before start of flutamide, after 3 months, and subsequently at least twice yearly. RESULTS: AST and ALT results were normal at baseline, and they remained so on flutamide treatment, including between 3 months and last assessment, which was after a mean time of 19 months on low- or ultralow-dose flutamide (range 3-54 months). None of the AST or ALT levels at any time during flutamide treatment was >= 45 U/L. CONCLUSION: We found no evidence for hepatotoxicity in 190 hyperandrogenic girls or young women receiving low- or ultralow-dose flutamide for up to 54 months. These results may represent a first step in a long process whereby the status of low- and ultralowdose flutamide may gradually evolve from 'absence of evidence on toxicity' towards 'evidence of absence of hepatic toxicity'. Ultralow-dose flutamide may become a key component within future therapies for hyperandrogenic states in girls and young women.

Filiaciones:
Ibañez-Toda L:
 Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.

Jaramillo A:
 Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.

Ferrer A:
 Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.

de Zegher F:
 Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.

Univ Barcelona, Hosp Sant Joan Deu, Endocrinol Unit, Barcelona, Spain
Katholieke Univ Leuven, Dept Pediat, Louvain, Belgium
ISSN: 02681161





HUMAN REPRODUCTION
Editorial
OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 20 Número: 7
Páginas: 1833-1836
WOS Id: 000230359600012
ID de PubMed: 15802316
imagen Bronze

MÉTRICAS