title: Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women.
abstract: This study was conducted to investigate the effect of therapeutic estrogen on cytochrome P450 1A2-mediated metabolism in postmenopausal women using caffeine 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-state plasma concentration of 50 to 150 pg/ml. Caffeine metabolic ratios (CMR; paraxanthine/caffeine) were assessed both before and after 8 weeks of estrogen replacement. For the 12 subjects, there was a mean reduction in CMR of -29.2 +/- 25.0 (p = 0.0019). Consistent with previous results found in younger women, these results indicate that exogenous estrogen in older women may inhibit CYP1A2-mediated caffeine metabolism.
authors.affiliation: Geriatric Psychopharmacology Program, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Pollock
authors.forename: M
authors.initials: M
authors.lastname: Wylie
authors.forename: J A
authors.initials: JA
authors.lastname: Stack
authors.forename: D A
authors.initials: DA
authors.lastname: Sorisio
authors.forename: D S
authors.initials: DS
authors.lastname: Thompson
authors.forename: M A
authors.initials: MA
authors.lastname: Kirshner
authors.forename: M M
authors.initials: MM
authors.lastname: Folan
authors.forename: K A
authors.initials: KA
authors.lastname: Condifer
mesh_terms: D000368:Aged; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000502:physiology*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008593:Menopause / Q000378:metabolism*; D008875:Middle Aged; D013806:Theophylline / Q000097:blood*
chemical_list: D000697:Central Nervous System Stimulants; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D002110:Caffeine; D004958:Estradiol; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2; C021183:1,7-dimethylxanthine