Hepatotoxicity with low- and ultralow-dose flutamide: a surveillance study on 203 hyperandrogenic young females.
OBJECTIVE
To investigate the impact of low- and ultralow-dose regimens of flutamide on liver function of young hyperandrogenic females.


METHODS
A 10-year surveillance study.


METHODS
University teaching hospital.


METHODS
Two hundred three hyperandrogenic young females (mean age: 20.9 ± 4.9 years).


METHODS
Inclusion criterion was receiving low- or ultralow-dose of flutamide as antiandrogenic treatment. Patients were categorized into Groups A and B, according to the administered dose (Group A = 62.5 mg/daily, Group B = 125 mg/daily). The two groups were further subdivided into subgroups (A1, A2, B1, B2) depending on the coadministration of estroprogestagen oral contraceptives (OCs) (A2, B2).


METHODS
Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were periodically evaluated and used as markers of hepatotoxicity.


RESULTS
Mild-to-severe increase of circulating AST/ALT was detected in 19 (9.4%; 95% CI = 5.9%-14.4%) patients during the first year of treatment (mild = 16 [7.9%, 95% CI = 4.7%-12.7%], moderate = 2 [0.9%, 95% CI = 0.1%-3.9%], severe = 1 [0.5%, 95% CI = 0.0%-3.1%]). No statistical differences were observed in relation to flutamide dose regimens and coadministration of OC. The median time to hypertransaminasemia was 12 weeks (range: 2-48) with no difference between Group A and Group B. A significant correlation was observed between hepatotoxicity and pretreatment BMI, ALT basal level, and AST basal level.


CONCLUSIONS
Hepatotoxicity is a rare but possible event using low- and ultralow-dose regimens of flutamide. We need larger study populations in order to identify risk patterns for hepatotoxicity development.
Department of Science for Woman and Child Health, University of Florence, Florence, Italy.
Vincenzina
V
Bruni
Elena
E
Peruzzi
Metella
M
Dei
Sara
S
Nannini
Viola
V
Seravalli
Giovanni
G
Sisti
Massimiliano
M
Fambrini
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D003276:Contraceptives, Oral / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage; D005260:Female; D005485:Flutamide / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy* / Q000453:epidemiology*; D009652:Norpregnenes / Q000008:administration & dosage; D011159:Population Surveillance; D012307:Risk Factors; D055815:Young Adult
D000726:Androgen Antagonists; D015415:Biomarkers; D003276:Contraceptives, Oral; D004338:Drug Combinations; D009652:Norpregnenes; C494367:estroprogestin; D004997:Ethinyl Estradiol; D005485:Flutamide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase