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

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.