The effects of tamoxifen and its metabolites on circulating estrogen metabolites among pre- and postmenopausal women
Abstract
Purpose: Circulating estrogen metabolites of the 2-, 4- or 16-hydroxyestrone (OH) pathways may be differentially associated with breast cancer risk due to varying estrogenic and genotoxic activity. However, little is known about the influence of tamoxifen, an effective endocrine therapy, or its metabolites on estrogen metabolism.
Methods: Among women referred to tamoxifen therapy, 15 circulating estrogens and estrogen metabolites (EMs) were measured at baseline (pre-tamoxifen) and 12 months post-tamoxifen initiation using liquid chromatography-tandem mass spectrometry. Changes in EMs were assessed among women postmenopausal at baseline (n = 23) using paired t-tests. Using linear regression, cross-sectional associations between circulating tamoxifen, its three metabolites, and EMs were assessed 12-months post-tamoxifen among pre- (n = 33) and postmenopausal women (n = 27; includes four women who transitioned to postmenopausal during follow-up).
Results: Twelve months post-tamoxifen initiation, mean total EM concentrations decreased by 13.8% among postmenopausal women, primarily driven by decreases in 2-OH (15.3%) and 16-OH (17.2%) metabolites (p < 0.05). Among women premenopausal at 12-month follow-up, circulating tamoxifen was positively associated with estrone (β = 1.24), estradiol (β =1.39), 2-OH metabolites (2-OHE1: β = 0.72, 2-ME1: β = 1.15), and all 16-OH metabolites (p < 0.05). The tamoxifen metabolite, endoxifen, was positively associated with estrone (β = 10.1) and…
How strong is the evidence?
Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 33 participants or records.
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