Estrogen and Tibolone Metabolite Levels in Blood and Breast Tissue of Postmenopausal Women Recently Diagnosed With Early-Stage Breast Cancer and Treated With Tibolone or Placebo for 14 Days

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Vol. 14; no. 2; pp. 151 - 159
• Main Authors: Kloosterboer, Helenius J., Löfgren, Lars, von Schoulz, Eva, von Schoultz, Bo, Verheul, Herman A. M.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA Sage Publications 01.02.2007; Sage
• Subjects: Aged; Androstenols - blood; Biological and medical sciences; Breast - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - surgery; Chromatography, Liquid; Double-Blind Method; Estradiol - blood; Estradiol - metabolism; Estrenes - blood; Estrenes - metabolism; Estrone - analogs & derivatives; Estrone - blood; Estrone - metabolism; Female; Gas Chromatography-Mass Spectrometry; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Neoplasm Staging; Norpregnenes - analysis; Norpregnenes - blood; Norpregnenes - metabolism; Norpregnenes - therapeutic use; Postmenopause - blood; Postmenopause - metabolism; Selective Estrogen Receptor Modulators - metabolism; Selective Estrogen Receptor Modulators - therapeutic use; Tandem Mass Spectrometry; Tissue Distribution; Tumors; tissue level; estrogenmetabolites; breast; Tibolonemetabolites; postmenopausal; Metabolite; Tibolone; Estrogen; Early stage; estrogen metabolites; Blood; Tibolone metabolites; Postmenopause; Adult; Female; Diagnosis; Mammary gland; Woman; Human; Corticosteroid; Gynecology; Breast cancer; Malignant tumor; Obstetrics; Ovarian hormone; Mammary gland diseases; Treatment; Placebo; Breast; Sex steroid hormone
• ISSN: 1933-7191; 1933-7205; 1933-7205
• DOI: 10.1177/1933719106298679

Unlike estrogens plus progestagens, tibolone, a selective tissue estrogenic activity regulator, does not increase breast tenderness and mammographic density. To elucidate this, serum and breast levels of tibolone and estrogenic metabolites are measured. Postmenopausal women (n = 102) with early-stage, ER + ve, primary breast cancer received tibolone or placebo for 14 days in an exploratory, double-blind, randomized trial (STEM carcinoma tissue). Baseline and presurgery sera were collected; tumor tissues were obtained at surgery. E1 (estrone), E2 (estradiol), E1S (estrone-sulfate), tibolone—its nonsulfated, monosulfated, and disulfated 3-hydroxymetabolites—and Δ 4-tibolone were measured by validated gas chromatography and mass spectrometry and liquid chromatography with tandem mass spectrometry assays. More than 12 hours after the final dose, serum E1, E 2, and E1S levels were unchanged with placebo, whereas tibolone significantly increased E1S and the E1S/(E1 + E2) ratio. In tumors, E1 and E2 levels were higher than in serum, and E1S levels were lower, with placebo and tibolone administration. The percentage of E1S was about 90% in serum and 16% in tissue. Tibolone did not affect tissue levels of endogenous estrogens. Serum levels of estrogenic 3α- and 3β-hydroxytibolone, progestagenic/androgenic Δ 4-tibolone, and monosulfate metabolites were low. Serum 3αS,17βS-tibolone and 3 βS,17βS-tibolone levels were 250 and 52 ng/mL, respectively. Tumor levels of 3α- and 3β-hydroxytibolone and Δ 4-tibolone were higher than in serum, but disulfate levels were lower. The percentage of sulfated tibolone metabolites was 99% in serum and 96% in tumor. Serum metabolite patterns of estradiol and tibolone are different from those in tissues and are compatible with neutral effects of tibolone on breast Ki67 expression.