In vivo and in vitro estrogenic activity of the antidepressant fluoxetine.

Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), insensitive populations, such as pregnant and lactating women. Although some evidence suggests a pos-sible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis.In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLXusing Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6–129 M) assays. Inthe Hershberger assay, no differences were observed in androgen-dependent organ weights. However,the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weightincreased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Addi-tionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic of estradiol in MCF-7 breast cancer cells transfected with luciferase.© 2012 Elsevier Inc. All rights reserved.