Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women

This study was conducted to investigate the effect of therapeutic estrogen on cytochrome P450 1A2-mediated metabolism in postmenopausal women using ca ffeine as a model substrate. Twelve healthy postmenopausal women underwent estrogen replacement therapy in the form of estradiol (Estrace). Estradiol was initiated at a dose of 0.5 mg a day and titrated to achieve a steady-st ate plasma concentration of 50 to 150 pg/ml. Caffeine metabolic ratios (CMR ; paraxanthine/caffeine) were assessed both before and after 8 weeks of est rogen replacement. For the 12 subjects, there was a mean reduction in CMR o f -29.2 +/- 25.0 (p = 0.0019). Consistent with previous results found in yo unger women, these results indicate that exogenous estrogen in older women may inhibit CYP1A2-mediated caffeine metabolism. Journal of Clinical Pharma cology, 1999;39:936-940 (C) 1999 the American College of Clinical Pharmacol ogy.