The effect of hormone replacement therapy on CYP3A activity

Background: The effect of menopause and hormone replacement therapy on hepa tic and intestinal wall CYP3A activity is poorly defined. This study was th erefore designed to determine the effect of menopause and estrogen replacem ent therapy on hepatic and intestinal CYP3A activity with a specific CYP3A substrate, midazolam. Methods: Twelve young women (27 +/- 5 years), 10 elderly women receiving es trogen replacement therapy (71 +/- 6 years), and 14 elderly women not recei ving estrogen replacement therapy (71 +/- 5 years) received simultaneous in travenous (0.05 mg/kg over 30 minutes) and oral (3 to 4 mg of a stable isot ope, N-15(3)-midazolam) doses of midazolam, Serum and urine samples were as sayed for midazolam, N-15(3)-midazolam, and metabolites by use of gas chrom atography-mass spectrometry. Results: No significant (P > .05) differences were observed in systemic cle arance and oral clearance between the three groups. Likewise, no difference s were observed in oral, hepatic, or intestinal availability. A significant correlation was observed between oral and intestinal availability and not hepatic availability. Conclusion: Neither menopause nor menopause with estrogen replacement thera py altered intestinal or hepatic CYP3A activity relative to that in a contr ol group of young women.