Cancer Causes & Control

, Volume 30, Issue 11, pp 1201–1211 | Cite as

Circulating estrogens and postmenopausal ovarian and endometrial cancer risk among current hormone users in the Women’s Health Initiative Observational Study

  • Britton TrabertEmail author
  • Sally B. Coburn
  • Roni T. Falk
  • JoAnn E. Manson
  • Louise A. Brinton
  • Margery L. Gass
  • Lewis H. Kuller
  • Thomas E. Rohan
  • Ruth M. Pfeiffer
  • Lihong Qi
  • Marcia L. Stefanick
  • Nicolas Wentzensen
  • Garnet L. Anderson
  • Xia Xu
Original Paper



Menopausal hormone therapy (MHT) use induces alterations in circulating estrogens/estrogen metabolites, which may contribute to the altered risk of reproductive tract cancers among current users. Thus, the current study assessed associations between circulating estrogens/estrogen metabolites and ovarian and endometrial cancer risk among MHT users.


We conducted a nested case–control study among postmenopausal women using MHT at baseline in the Women’s Health Initiative Observational Study (179 ovarian cancers, 396 controls; 230 endometrial cancers, 253 controls). Multivariable logistic regression was utilized to estimate odds ratios and 95% confidence intervals overall and by subtype.


Estrogen/estrogen metabolite levels were not associated with overall or serous ovarian cancer risk, examined separately. However, unconjugated estradiol was positively associated with non-serous ovarian cancer risk [quintile 5 vs. quintile 1: 3.01 (1.17–7.73); p-trend = 0.03; p-het < 0.01]. Endometrial cancer risk was unrelated to estrogen/estrogen metabolite levels among women who took combined estrogen/progestin therapy (EPT).


These findings provide novel evidence that may support a heterogeneous hormonal etiology across ovarian cancer subtypes. Circulating estrogens did not influence endometrial cancer risk among women with EPT-induced high-estrogen levels. Larger studies are needed to delineate the relationship between ovarian/endometrial cancer subtypes and estrogen levels in the context of MHT use.


Endogenous estrogens Estrogen metabolites Ovarian cancer Endometrial cancer Nested case–control study Current hormone therapy users 



The authors would like to also acknowledge the following short list of WHI investigators: Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg. Investigators and Academic Centers: (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker. Women’s Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker. For a list of all the investigators who have contributed to WHI science, please visit:


This work was supported in part by the Intramural Research Program of the National Cancer Institute (Grant No. ZIA CP010126-24). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through Contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.

Compliance with ethical standards

Conflicts of interest

All authors declare they have no conflicts of interest.


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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply  2019

Authors and Affiliations

  • Britton Trabert
    • 1
    Email author
  • Sally B. Coburn
    • 1
  • Roni T. Falk
    • 1
  • JoAnn E. Manson
    • 2
  • Louise A. Brinton
    • 1
  • Margery L. Gass
    • 3
  • Lewis H. Kuller
    • 4
  • Thomas E. Rohan
    • 4
    • 5
  • Ruth M. Pfeiffer
    • 1
  • Lihong Qi
    • 6
  • Marcia L. Stefanick
    • 7
  • Nicolas Wentzensen
    • 1
  • Garnet L. Anderson
    • 8
  • Xia Xu
    • 9
  1. 1.Division of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaUSA
  2. 2.Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  3. 3.Women’s Health Institute, Cleveland ClinicClevelandUSA
  4. 4.Department of EpidemiologyUniversity of PittsburghPittsburghUSA
  5. 5.Department of Epidemiology and Population HealthAlbert Einstein College of MedicineBronxUSA
  6. 6.Public Health Sciences, School of MedicineUC DavisSacramentoUSA
  7. 7.Department of MedicineStanford University School of MedicineStanfordUSA
  8. 8.Division of Public Health Sciences, Cancer Prevention ProgramFred Hutchinson Cancer Research CenterSeattleUSA
  9. 9.Frederick National Laboratory for Cancer Research, Cancer Research Technology ProgramLeidos Biomedical Research, Inc.FrederickUSA

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