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Estrogen metabolism in menopausal hormone users in the Women's Health Initiative Observational Study: Does it differ between estrogen plus progestin and estrogen alone?

  1. Author:
    Falk, Roni T [ORCID]
    Manson, JoAnn E
    Barnabei, Vanessa M
    Anderson, Garnet L
    Brinton, Louise A
    Rohan, Thomas E
    Cauley, Jane A
    Chen, Chu
    Coburn, Sally B
    Pfeiffer, Ruth M
    Reding, Kerryn W
    Sarto, Gloria E
    Wentzensen, Nicolas
    Chlebowski, Rowan T
    Xu, Xia
    Trabert, Britton
  2. Author Address

    National Cancer Institute, Bethesda, MD., Brigham and Women 39;s Hospital, Harvard Medical School, Boston, MA., Jacobs School of Medicine and Biomedical Sciences University at Buffalo, Buffalo, NY., Fred Hutchinson Cancer Research Center, Seattle, WA., Albert Einstein College of Medicine, Bronx, NY., University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA., University of Washington School of Nursing, Seattle, WA., University of Wisconsin School of Medicine and Public Health, Madison, WI., City of Hope National Medical Center Duarte, CA., Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD.,
    1. Year: 2019
    2. Date: Feb 15
    3. Epub Date: 2018 09 05
  1. Journal: International journal of cancer
    1. 144
    2. 4
    3. Pages: 730-740
  2. Type of Article: Article
  3. ISSN: 0020-7136
  1. Abstract:

    The WHI found an unexpected reduced breast cancer risk in women using CEE alone. We hypothesized CEE alone induces estrogen hydroxylation along the 2-pathway rather than the competing 16-pathway, a pattern linked to reduced postmenopausal breast cancer risk. 1864 women in a WHIOS case-control study of estrogen metabolism and ovarian and endometrial cancer were studied of whom 609 were current E+P users (351 used CEE+MPA), while 272 used E alone (162 used CEE). Fifteen EM were measured, and analyses conducted for each metabolite, hydroxylation pathway (2-, 4-, or 16-pathway), and ratios of pathway concentrations using inverse probability weighted linear regression. Compared to E+P users, all EM were higher in E alone users (significant for unconjugated estrone, total/conjugated estradiol, total/unconjugated 2-methoxyestrone, 4-methoxyestrone and unconjugated estriol). The relative concentrations of 2- and 4-pathway EM did not differ between the MHT users (2-pathway EM comprised 15% and 4-pathway EM < 2% of the total), but 16-pathway EM were lower in E alone users (p=0.036). Ratios of 2- and 4-pathway EM compared to 16-pathway EM were significantly higher in E alone compared to E+P users. Similar but not significant patterns were observed in CEE-alone and CEE+MPA users. Our data suggest that compared to E+P users, women using E alone have more extensive metabolism via the 2- versus the competing 16-pathway. This is consistent with epidemiologic evidence of reduced postmenopausal breast cancer risk associated with this metabolic profile and may provide a clue to the breast cancer risk reduction in CEE alone users during the WHI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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External Sources

  1. DOI: 10.1002/ijc.31851
  2. PMID: 30183089
  3. WOS: 000454099100006

Library Notes

  1. Fiscal Year: FY2017-2018
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