Androstenedione was marketed as a dietary supplement to increase muscle mass during training. Due to concern over long-term use, the NTP evaluated the subchronic and chronic toxicity and carcinogenicity of
androstenedione in male and female F344/N rats and B6C3F1 mice. In subchronic studies, dose limiting effects were not observed. A chronic (2-year) exposure by gavage
at 10, 20, or 50 mg/kg in rats and male mice, and 2, 10, or 50 mg/kg in female mice (50 mg/kg, maximum feasible dose) was conducted. Increased incidences of lung alveolar/bronchiolar
adenoma and
carcinoma occurred in the 20 mg/kg male rats and increases in mononuclear cell
leukemia occurred in the 20 and 50 mg/kg female rats, which may have been related to
androstenedione administration. In male and female mice,
androstenedione was carcinogenic based upon a significant increase in hepatocellular
tumors. A marginal increase in pancreatic islet cell
adenomas in male (50 mg/kg) and female (2, 10, 50 mg/kg) mice was considered to be related to
androstenedione administration. Interestingly, incidences of male rat Leydig cell
adenomas and female rat mammary gland
fibroadenomas decreased. In conclusion,
androstenedione was determined to be carcinogenic in male and female mice, and may have been carcinogenic in rats.