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Association of Endogenous Pregnenolone, Progesterone, and Related Metabolites with Risk of Endometrial and Ovarian Cancers in Postmenopausal Women: The B similar to FIT Cohort

  1. Author:
    Trabert, Britton
    Geczik, Ashley M.
    Bauer, Doug C.
    Buist, Diana S. M.
    Cauley, Jane A.
    Falk, Roni T.
    Gierach, Gretchen L.
    Hue, Trisha F.
    Lacey, James V.
    LaCroix, Andrea Z.
    Michels, Kara A.
    Tice, Jeffrey A.
    Xu,Xia
    Brinton, Louise A.
    Dallal, Cher M.

  2. Author Address

    NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.Huntsman Canc Inst, Canc Control & Populat Sci Res Program, Salt Lake City, UT USA.Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA.Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.City Hope Natl Med Ctr, Div Hlth Analyt, Dept Computat & Quantitat Med, Duarte, CA USA.Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, San Diego, CA 92103 USA.Leidos Biomed Res Inc, Frederick, MD USA.Univ Maryland, Sch Publ Hlth, College Pk, MD 20742 USA.
    1. Year: 2021
    2. Date: Nov
    3. Epub Date: 2021 08 31
  2. Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
  3. AMER ASSOC CANCER RESEARCH,
    1. 30
    2. 11
    3. Pages: 2030-2037
  5. Type of Article: Article
  6. ISSN: 1055-9965
  1. Abstract:

    Postmenopausal pregnenolone and/or progesterone levels in relation to endometrial and ovarian cancer risks have been infrequently evaluated. To address this, we utilized a sensitive and reliable assay to quantify pre-diagnostic levels of seven markers related to endogenous hormone metabolism. Hormones were quantified in baseline serum collected from postmenopausal women in a case-cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (B~FIT). Women using exogenous hormones at baseline (1992-1993) were excluded. Incident endometrial (n=65) and ovarian (n=67) cancers were diagnosed during 12 follow-up years and compared with a subcohort of 345 women (no hysterectomy) and 413 women (no oophorectomy), respectively. Cox models with robust variance were used to estimate risk. Circulating progesterone levels were not associated with endometrial [tertile(T)3 vs. T1 Hazard Ratio [HR] (95% confidence interval [CI]): 1.87 (0.85-4.11), p-trend 0.17] or ovarian cancer risk [1.16 (0.58-2.33), 0.73]. Increasing levels of the progesterone-to-estradiol ratio were inversely associated with endometrial cancer risk [T3 vs T1: 0.29 (0.09-0.95), 0.03]. Increasing levels of 17-hydroxypregnenolone were inversely associated with endometrial cancer risk [0.40 (0.18-0.91), 0.03] and positively associated with ovarian cancer risk [3.11 (1.39-6.93), 0.01]. Using sensitive and reliable assays, this study provides novel data that endogenous progesterone levels are not strongly associated with incident endometrial or ovarian cancer risks. 17-hydroxypregnenolone was positively associated with ovarian cancer and inversely associated with endometrial cancer. While our results require replication in large studies, they provide further support of the hormonal etiology of endometrial and ovarian cancers. Copyright ©2021, American Association for Cancer Research.

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External Sources

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  2. DOI: 10.1158/1055-9965.EPI-21-0669
  3. PMID: 34465588
  4. PMCID: PMC8568650
  5. View record in Web of Science®
  6. WOS: 000713822200006

Library Notes

  1. Fiscal Year: FY2021-2022
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