Endometriosis and menopausal hormone therapy impact the hysterectomy-ovarian cancer association

• Type of Material: Article
• Authors: Lilah Khoja, University of Michigan; Rachel Palmieri Weber, Duke University; Penelope M Webb, QIMR Berghofer Medical Research Institute; Susan J Jordan, University of Queensland; Aruna Muthukumar, University of Michigan; Jenny Chang-Claude, German Cancer Research Center (DKFZ); Renée T Fortner, German Cancer Research Center (DKFZ); Allan Jensen, Danish Cancer Society; Susanne K Kjaer, Danish Cancer Society; Harvey Risch, Yale School of Public Health; Jennifer A Doherty, University of Utah; Holly R Harris, Fred Hutchinson Cancer Research Center; Marc T Goodman, Cedars-Sinai Medical Center; Francesmary Modugno, Magee Womens Res Inst; Kirsten Moysich, Roswell Park Comprehens Canc Ctr; Andrew Berchuck, Duke University; Joellen Schildkraut, Emory University; Daniel Cramer, Harvard TH Chan School of Public Health; Kathryn L Terry, Harvard TH Chan School of Public Health; Hoda Anton-Culver, University of California Irvine; Argyrios Ziogas, University of California Irvine; Tung Phung Minh, University of Michigan; Gillian E Hanley, University of British Columbia; Anna H Wu, University of Southern California; Bhramar Mukherjee, University of Michigan; Karen McLean, University of Michigan; Kathleen Cho, University of Michigan; Malcolm C Pike, University of Southern California; Celeste Leigh Pearce, University of Michigan; Alice W Lee, California State University Fullerton
• Language: English
• Date: 2021-12-27
• Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ygyno.2021.10.088
• Title of Journal or Parent Work: GYNECOLOGIC ONCOLOGY
• Volume: 164
• Issue: 1
• Start Page: 195
• End Page: 201
• Grant/Funding Information: AUS: The Australian Ovarian Cancer Study (AOCS) was supported by the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health and Medical Research Council of Australia (199600, 400413 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania and Cancer Foundation of Western Australia (Multi-State Applications 191, 211 and 182). AOCS gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Foundation; CON: This work was supported by the National Institutes of Health (grant numbers R01-CA063678, R01-CA074850, R01-CA80742); DOV: National Institutes of Health R01-CA112523 and R01-CA87538; GER: This work was supported by the German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (grant number 01 GB 9401) and the German Cancer Research Center (DKFZ); HAW: U.S. National Institutes of Health (R01-CA58598, N01-CN-55424 and N01-PC-67001); HOP: University of Pittsburgh School of Medicine Dean’s Faculty Advancement Award (F. Modugno), Department of Defense (DAMD17-02-1-0669); MAL: This work was supported by the National Cancer Institute at the National Institutes for Health (grant number R01- CA61107), the Danish Cancer Society (grant number 94 222 52), and the Mermaid I and III projects; NCO: This work was supported by the National Institutes of Health (grant number 1-R01-CA76016) and Department of Defense (grant DAMD17-02-1-0666); NEC: This work was supported by the National Institutes of Health (R01-CA54419 and P50-CA105009) and Department of Defense (W81XWH-10-1-02802); UCI: This work was supported by the National Institutes of Health (grant number R01-CA058860) and the Lon V Smith Foundation (grant number LVS-39420); USC: This work was supported by the National Institutes of Health (P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148,R03CA115195, N01CN025403, P30CA046592), California Cancer Research Program (00-01389V-20170, 2II0200). AWL was supported in part through a Scientific Scholar Award from the Rivkin Center for Ovarian Cancer. MCP was supported in part through the NIH/NCI Support Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center.
• Keywords: Obstetrics & Gynecology; TUBAL-LIGATION; Oncology; Hysterectomy; HISTORY; WOMEN; RISK-FACTORS; Endometriosis; Science & Technology; BENIGN; Ovarian cancer; Life Sciences & Biomedicine; UNITED-STATES; EPIDEMIOLOGY; TIME; ORAL-CONTRACEPTIVE USE; OOPHORECTOMY; Hormone therapy

Abstract

Objective: To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. Methods: We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). Results: Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09–1.31 and OR = 1.20, 95% CI 1.09–1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94–1.16 and OR = 1.06, 95% CI 0.95–1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69–1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48–0.99). Conclusions: The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.