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

Lilah Khoja; Rachel Palmieri Weber; Australian Ovarian Cancer Study Group; Penelope M Webb; Susan J Jordan; Aruna Muthukumar; Jenny Chang-Claude; Renée T Fortner; Allan Jensen; Susanne K Kjaer; Harvey Risch; Jennifer Anne Doherty; Holly R Harris; Marc T Goodman; Francesmary Modugno; Kirsten Moysich; Andrew Berchuck; Joellen M Schildkraut; Daniel Cramer; Kathryn L Terry; Hoda Anton-Culver; Argyrios Ziogas; Minh Tung Phung; Gillian E Hanley; Anna H Wu; Bhramar Mukherjee; Karen McLean; Kathleen Cho; Malcolm C Pike; Celeste Leigh Pearce; Alice W Lee

doi:10.1016/j.ygyno.2021.10.088

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

Gynecol Oncol. 2022 Jan;164(1):195-201. doi: 10.1016/j.ygyno.2021.10.088. Epub 2021 Nov 12.

Authors

Lilah Khoja¹, Rachel Palmieri Weber²; Australian Ovarian Cancer Study Group; Penelope M Webb³, Susan J Jordan⁴, Aruna Muthukumar⁵, Jenny Chang-Claude⁶, Renée T Fortner⁷, Allan Jensen⁸, Susanne K Kjaer⁹, Harvey Risch¹⁰, Jennifer Anne Doherty¹¹, Holly R Harris¹², Marc T Goodman¹³, Francesmary Modugno¹⁴, Kirsten Moysich¹⁵, Andrew Berchuck¹⁶, Joellen M Schildkraut¹⁷, Daniel Cramer¹⁸, Kathryn L Terry¹⁹, Hoda Anton-Culver²⁰, Argyrios Ziogas²¹, Minh Tung Phung²², Gillian E Hanley²³, Anna H Wu²⁴, Bhramar Mukherjee²⁵, Karen McLean²⁶, Kathleen Cho²⁷, Malcolm C Pike²⁸, Celeste Leigh Pearce²⁹, Alice W Lee³⁰

Affiliations

¹ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. Electronic address: lkhoja@umich.edu.
² Department of Community and Family Medicine, Duke University Medical Center, Durham, NC 27705, USA. Electronic address: rachel.weber@epividian.com.
³ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia. Electronic address: penny.webb@qimrberghofer.edu.au.
⁴ School of Public Health, The University of Queensland, Brisbane, Queensland 4006, Australia. Electronic address: s.jordan@uq.edu.au.
⁵ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. Electronic address: arumuthu@umich.edu.
⁶ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: j.chang-claude@dkfz.de.
⁷ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: r.fortner@dkfz-heidelberg.de.
⁸ Department of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, DK-2100, Denmark. Electronic address: allan@cancer.dk.
⁹ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, DK-2100, Denmark; Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, DK-2100, Denmark. Electronic address: susanne@cancer.dk.
¹⁰ Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT 06510, USA. Electronic address: harvey.risch@yale.ed.
¹¹ Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: Jen.Doherty@hci.utah.edu.
¹² Department of Epidemiology, University of Washington, Seattle, WA 98195, USA; Program in Epidemiology, Department of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: hharris@fredhutch.org.
¹³ Cancer Prevention and Genetics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: Marc.Goodman@cshs.org.
¹⁴ Women's Cancer Research Center, Magee-Women's Research Institute and Hillman Cancer Center, Pittsburgh, PA 15213, USA; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address: fm@cs.cmu.edu.
¹⁵ Division of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA. Electronic address: Moysich@roswellpark.org.
¹⁶ Department of Gynecologic Oncology, Duke University Medical Center, Durham, NC 277170, USA. Electronic address: berch001@mc.duke.edu.
¹⁷ Emory University Rollins School of Public Health, Atlanta, GA 30322, USA. Electronic address: joellen.m.schildkraut@emory.edu.
¹⁸ Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA 02115, USA; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: dcramer@bwh.harvard.edu.
¹⁹ Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA 02115, USA; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: kterry@bwh.harvard.edu.
²⁰ Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA 92617, USA. Electronic address: hantoncu@hs.uci.edu.
²¹ Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA 92617, USA. Electronic address: aziogas@uci.edu.
²² Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. Electronic address: phungmt@umich.edu.
²³ Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: gillian.hanley@vch.ca.
²⁴ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA. Electronic address: anna.wu@med.usc.edu.
²⁵ Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: bhramar@umich.edu.
²⁶ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Electronic address: karenmcl@umich.edu.
²⁷ Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Electronic address: kathcho@med.umich.edu.
²⁸ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: pikem@mskcc.org.
²⁹ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. Electronic address: lpearce@umich.edu.
³⁰ Department of Public Health, California State University, Fullerton, CA 92831, USA. Electronic address: alicelee@fullerton.edu.

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.

Keywords: Endometriosis; Hormone therapy; Hysterectomy; Ovarian cancer.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Endometriosis*
Estrogen Replacement Therapy*
Female
Humans
Hysterectomy*
Menopause*
Ovarian Neoplasms*

Abstract

Publication types

MeSH terms

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