Lifetime ovulations and epithelial ovarian cancer risk and survival: A systematic review and meta-analysis

Zhuxuan Fu; Sarah Taylor; Francesmary Modugno

doi:10.1016/j.ygyno.2022.04.001

Lifetime ovulations and epithelial ovarian cancer risk and survival: A systematic review and meta-analysis

Gynecol Oncol. 2022 Jun;165(3):650-663. doi: 10.1016/j.ygyno.2022.04.001. Epub 2022 Apr 23.

Authors

Zhuxuan Fu¹, Sarah Taylor², Francesmary Modugno³

Affiliations

¹ University of Pittsburgh Graduate School of Public Health, Department of Epidemiology, Pittsburgh, PA, USA.
² Magee-Womens Research Institute and Hillman Cancer Center, Womens Cancer Research Center, Pittsburgh, PA, USA; University of Pittsburgh School of Medicine, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, USA.
³ University of Pittsburgh Graduate School of Public Health, Department of Epidemiology, Pittsburgh, PA, USA; Magee-Womens Research Institute and Hillman Cancer Center, Womens Cancer Research Center, Pittsburgh, PA, USA; University of Pittsburgh School of Medicine, Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, PA, USA. Electronic address: modugnof@upmc.edu.

PMID: 35473671
DOI: 10.1016/j.ygyno.2022.04.001

Abstract

Objective: To assess the relationship between lifetime ovulatory years (LOY) and Epithelial ovarian cancer (EOC) risk and survival.

Methods: A systematic review was performed in accordance with PRISMA guidelines. Relevant studies were identified from PubMed, MEDLINE, and Embase through December 31, 2021 combining the following search: [("ovulation" or "ovulation cycles" or "ovulatory age" or "ovulatory cycles") and ("ovarian cancer" or "ovarian neoplasms") and ("humans" and "female")]. Reference lists of identified articles were searched for additional studies. Studies were excluded from consideration if they were not a published, peer-review article; not in English; lacked data on effect sizes; had data included in another publication; or were a review article, cross-sectional study, or case report. Two independent investigators screened abstracts and full texts for eligibility, extracted study-level data, and assigned study quality. Disagreements between abstractors were discussed and resolved by consensus.

Results: Thirty-one reports were included in the qualitative review of LOY and EOC risk, inclusive of 24 studies with sufficient data to be included in the meta-analysis. Women with the highest level of LOY had 2.26 times higher odds of EOC than women with the lowest level of LOY (95% CI 1.94-2.83). LOY was associated with risk of serous (pooled OR 2.31, 95% CI 1.60-3.33) and endometrioid tumors (pooled OR 3.05, 95% CI 2.08-4.45) but not mucinous disease (pooled OR 1.52, 95% CI 0.87-2.64). There were only four studies examining the LOY-survival association, which precluded a quantitative assessment; however, three of the published studies reported worse outcome with greater LOY.

Conclusion: LOY is a risk factor for specific EOC histotypes and may also influences EOC survival. Standard definitions of LOY, participant-level data, and larger sample size will enable more precise quantitation of the LOY-EOC association, which can inform EOC risk assessment models.

Keywords: Epithelial ovarian cancer; Incessant ovulation; Lifetime ovulatory cycles; Lifetime ovulatory years; Menarche; Menopause; Ovulation.

Publication types

Case Reports
Meta-Analysis
Review
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Ovarian Epithelial / complications
Cross-Sectional Studies
Female
Humans
Neoplasms, Glandular and Epithelial* / complications
Neoplasms, Glandular and Epithelial* / epidemiology
Ovarian Neoplasms* / pathology
Ovulation