INHIBITION OF 17-BETA-ESTRADIOL METABOLISM BY GRAPEFRUIT JUICE IN OVARIECTOMIZED WOMEN

In an open, randomized, cross-over study the concentrations of 17 beta -estradiol and estrone in serum were measured over 192 hours in 8 ovar iectomized women after a single oral dose intake of 2 mg micronized 17 beta-estradiol. The subjects were studied with and without grapefruit juice intake containing the three natural flavonoids, naringenin, que rcetin and kaempherol, which are found as glycosides in citrus fruit. These flavonoids interact with the metabolism of drugs such as 17 beta -estradiol and other steroids that are extensively metabolised through the P-450NF (P-450 IIIA4) enzyme or closely related P-450 systems. Af ter administration of grapefruit juice, peak estrone (between 2-6 hour s after tablet intake) concentrations increased significantly. The AUC (0-48) and AUC(0-192) for estrone but not 17 beta-estradiol, resulting from a single administration of micronized 17 beta-estradiol, were si gnificantly altered. Combined measured estrogens (i.e. 17 beta-estradi ol and estrone) also increased significantly. The relationship between the AUCs for 17 beta-estradiol and estrone was not altered by juice i ntake indicating that a metabolic step after estrone, i.e, further A a nd/or D ring conversion was inhibited. This study demonstrates that gr apefruit juice may alter the metabolic degradation of estrogens, and i ncrease the bioavailable amounts of 17 beta-estradiol and its metaboli te estrone, presumably by affecting the oxidative degradation of estro gens. This food interaction may be one factor behind the interindividu al variability in 17 beta-estradiol, estrone and estriol serum concent rations after exogenous administration of 17 beta-estradiol. to patien ts.