Hepatotoxicity, said to be an infrequent complication of treatment with the oral antiandrogen flutamide (Eulexin, Schering, Kenilworth, New Jersey) [1], was reported by Wysowski and colleagues in 19 patients treated with the drug for benign and malignant prostatic diseases [2]. We report the first association of flutamide with serious hepatotoxicity in a woman using the drug for the treatment of hirsutism [3].

In January 1993, a 20-year-old East Indian woman presented with a history of menstrual irregularity and increasing hirsutism since her menarche at age 12. She had been receiving oral contraceptive pills since age 15 and had also used both spironolactone and cyproterone without improvement. She considered her facial hair disfiguring. Her serum androgen levels were normal. She continued taking her oral contraceptive pill (Demulen-30, Searle Laboratories, Chicago, Illinois) and began taking flutamide, 250 mg orally twice daily, in late January. Early in March, she developed gastrointestinal symptoms and on 13 March presented with a 3-day history of severe pruritus, dark urine, and pale stools. She was deeply jaundiced. Laboratory results were as follows: bilirubin, 263 µmol/L (normal, 3 to 20 µmol/L); prothrombin time international normalized ratio, 1.9; alkaline phosphatase 180 IU/L (normal, 40 to 130 IU/L); and alanine aminotransferase, 1481 IU/L (normal, 5 to 55 IU/L). Her history and viral serologic results excluded other causes of liver disease. An ultrasound of the liver was normal, and her biliary tree was not dilated. Flutamide therapy was discontinued. The serum bilirubin level peaked at 480 µmol/L within several days. Thereafter her clinical condition began to improve. Liver enzyme levels returned to normal within 6 weeks. Her pruritus failed to respond to hydroxyzine HCl but was controlled by subcutaneous naloxone injections. Eventually, all symptoms resolved, and her bilirubin level returned to normal by early June. A liver biopsy specimen near the height of the illness showed changes typical of drug toxicity, including zonal hepatic necrosis with cholestasis and ballooning degeneration of surviving zone 1 hepatocytes.

The features of this case are quite conclusive, and the potential for a life-threatening adverse effect should dissuade physicians from using a drug for a benign condition such as hirsutism or, as Wysowski and colleagues [2] suggest, for benign prostatic hypertrophy.