Inhibition of 17β-estradiol metabolism by grapefruit juice in ovariectomized women

Abstract

In an open, randomized, cross-over study the concentrations of 17β-estradiol and estrone in serum were measured over 192 hours in 8 ovariectomized women after a single oral dose intake of 2 mg micronized 17β-estradiol. The subjects were studied with and without grapefruit juice intake containing the three natural flavonoids, naringenin, quercetin and kaempherol, which are found as glycosides in citrus fruit. These flavonoids interact with the metabolism of drugs such as 17β-estradiol and other steroids that are extensively metabolised through the P-450NF (P-450 IIIA4) enzyme or closely related P-450 systems. After administration of grapefruit juice, peak estrone (between 2–6 hours after tablet intake) concentrations increased significantly. The AUC 0–48 and AUC 0–192 for estrone but not 17β-estradiol, resulting from a single administration of micronized 17β-estradiol, were significantly altered. Combined measured estrogens (i.e. 17β-estradiol and estrone) also increased significantly. The relationship between the ADCs for 17β-estradiol and estrone was not altered by juice intake indicating that a metabolic step after estrone, i.e. further A and/or D ring conversion was inhibited. This study demonstrates that grapefruit juice may alter the metabolic degradation of estrogens, and increase the bioavailable amounts of 17β-estradiol and its metabolite estrone, presumably by affecting the oxidative degradation of estrogens. This food interaction may be one factor behind the interindividual variability in 17β-estradiol, estrone and estriol serum concentrations after exogenous administration of 17β-estradiol to patients.