The risk of hepatotoxicity during long-term and low-dose flutamide treatment in hirsutism

Arch Gynecol Obstet. 2009 Mar;279(3):321-7. doi: 10.1007/s00404-008-0719-z. Epub 2008 Jul 8.

Abstract

Objective: Flutamide is an effective drug in treatment of hirsutism. Hepatotoxicity occasionally may occur with therapeutic doses (750-1500 mg/day), 3 months after initiation of treatment. Monitoring of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels is recommended to obviate serious hepatotoxicity.

Materials and methods: Two hundred and fourteen patients with mean age of 20.9+/-2.34 years suffering from hirsutism were included in the study. Of these 214 women, 117 had diagnosis of polycystic ovarian syndrome (PCOS), and 97 had diagnosis of idiopathic hirsutism. Thirty age-matched (mean age 20.3+/-2.0 years) normal women without signs of hirsutism and with normal menstrual cycle served as control group. Hirsutism was assessed using modified Ferriman-Gallwey method at the beginning and at the end of the treatment. Serum levels of luteinizing hormone (LH), follicle stimulant hormone (FSH), prolactin (PRL), estradiol (E2), androstenodion (A), testosterone (T), dehydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-P), sex hormone binding protein (SHBG), and ACTH were measured. Pelvic ultrasonography was performed for diagnosis of PCOS. Fifty-seven patients with PCOS (group 1) were given flutamide 125 mg/day + oral contraceptive. Sixty patients with PCOS (group 2) were given flutamide 250 mg/day + oral contraceptive. Forty-seven patients with IH (group 3) were given flutamide 125 mg/day alone, and 50 patients with IH (group 4) were given flutamide 250 mg alone. Thirty women in control group (group 5) were given placebo only. ALT and AST levels were measured in the beginning of the treatment, and repeated after 3, 6, 9 and 12 months.

Results: No incidence of increase in AST or ALT levels (>or= 45 U/L) was observed in any of the groups. No evidence of hepatotoxicity in any of the 214 hyperandrogenic women was observed on low-dose flutamide for 1 year.

Conclusion: We conclude that flutamide in a dosage of 125 or 250 mg daily is a safe drug in the long-term treatment of hirsutism. The follow-up of patients receiving flutamide can be done by monitoring AST or ALT levels for hepatotoxicity.

MeSH terms

  • Adolescent
  • Adult
  • Alanine Transaminase / blood
  • Androgen Antagonists / administration & dosage
  • Androgen Antagonists / adverse effects*
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury*
  • Dose-Response Relationship, Drug
  • Female
  • Flutamide / administration & dosage
  • Flutamide / adverse effects*
  • Hirsutism / blood
  • Hirsutism / drug therapy*
  • Humans
  • Liver Diseases / blood
  • Liver Diseases / enzymology
  • Young Adult

Substances

  • Androgen Antagonists
  • Flutamide
  • Aspartate Aminotransferases
  • Alanine Transaminase