Levels of tibolone and estradiol and their nonsulfated and sulfated metabolites in serum, myometrium, and vagina of postmenopausal women following treatment for 21 days with tibolone, estradiol, or estradiol plus medroxyprogestrone acetate

Tibolone has estrogenic effects on the vagina but not on the uterus. To explain this, levels of tibolone and estradiol and their metabolites were determined in serum, myometrium, and vagina. Thirty-four postmenopausal women with uterine prolapse received either no treatment, tibolone, E2or E2+ medroxyprogesterone acetate (MPA) for 21 days, or a single dose of tibolone. Twenty ± 6 hours after administration, >98% of the 3-hydroxytibolone metabolites in serum and tissues were disulfated. Of the unconjugated metabolites, the estrogenic 3α-hydroxytibolone predominated in serum, whereas the progestagenic/ androgenic Δ4-tibolone predominated in myometrium and vagina. Levels of disulfated metabolites in serum and tissues were higher (3- to 5-fold) after multiple dosing than after a single dose. Tissue:serum ratios were <1, except for Δ4- tibolone. In all groups, E2tissue levels were higher than serum levels; the percentage of serum E1S was >90%. Tibolone did not affect endogenous E1, E2, or E1S levels in serum, but in myometrium and vagina, E1levels were significantly higher and E1S levels tended to be lower than in controls. Serum and tissue levels of endogenous and exogenous E1, E2, and E1S were markedly increased 20 hours after E2or E2+ MPA; the percentage of E1S and tissue:serum ratios were not affected. MPA had no effect on the degree of sulfation of E1. Compared with serum, tissue levels of E2were high in all groups; absolute E2levels in control and tibolone groups were much lower than in the E2groups. Tibolone metabolite patterns are different in serum, myometrium, and vagina.

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