Flutamide-induced hepatotoxicity: ethical and scientific issues

Flutamide (FLU) is a non-steroidal antiandrogen drug approved for the treatment of advanced prostate cancer. While this indication limits the use to male patients, FLU is widely prescribed to women, off-label, for the treatment of polycystic ovary syndrome (POCS) related hirsutism and acne. According to the literature, its assumption is associated with a higher incidence of adverse events in women than in male patients.

A literature search was conducted in main databases targeting unwilling FLU effects in hepatic and reproductive function. References in the selected paper were also considered as an additional source of data. Human- and animal-based studies were separately considered.

Twenty-three human-based studies were evaluated: ten were case reports, six were retrospective studies, four were prospective, two were surveillance studies, while the last was an observational study. Nine animal-based studies were also evaluated.

Scientific contributions highlight that FLU is responsible for specific hepatotoxic profiles in the female gender. From the ethical point of view, off-label prescribing of FLU in women is not only substantially unlawful, but also, without major safeguards being granted, a potential source of liability for prescribers.