A preliminary study of the effect of fluoxetine treatment on the 2:16-alpha-hydroxyestrone ratio in young women.

Cytochrome P450 isoenzymes are known to contribute to estrone metabolism. The authors hypothesized that fluoxetine, a known inhibitor of multiple P450 isoenzymes including 3A4, 2C9, and 2D6, would affect estrone metabolism, altering the 2-hydroxyestrone:16-alpha-hydroxyestrone (2OHE1:16OHE1) ratio. In this preliminary study, four of eight recruited women with regular menstrual cycles, aged 21-37 years, completed a 24-hour urine collection prior to initiation of fluoxetine therapy and after at least 5 weeks of antidepressant treatment. In three of the four women who were nonsmokers, the 2OHE1:16OHE1 ratio was significantly higher after 5 weeks of fluoxetine therapy (pretreatment, 2.08 +/- 0.11; posttreatment, 3.50 +/- 0.46; paired Student's t-test P = 4.72, P = 0.021).