Reproductive history, hormonal exposure, and ovarian cancer risk in post-menopausal women: evidence from a nationwide Korean cohort

초록

OBJECTIVE: This study aimed to evaluate the associations of parity, breastfeeding duration, oral contraceptive use, menopausal hormone replacement therapy, age at menarche, age at menopause, and reproductive lifespan with ovarian cancer risk in post-menopausal women using large-scale real-world data from the Korean National Health Insurance Service. METHODS: This nationwide, population-based retrospective cohort study used National Health Insurance Service health screening and claims data. The study included 3,754,906 post-menopausal women aged 40 to 79 years who underwent national health examinations between 2009 and 2012. Reproductive factors were assessed at baseline using standardized self-administered questionnaires, whereas menopausal hormone replacement therapy exposure was identified from prescription records. Incident ovarian cancer was defined as ≥3 claims with an International Classification of Diseases, 10th Revision (ICD-10) C56 diagnosis. Univariable and multi-variable Cox proportional hazards regression analyses were performed to estimate the hazard ratios and 95% confidence intervals. RESULTS: During follow-up, 7702 women (0.2%) developed ovarian cancer. Compared with nulliparity, having ≥2 births was associated with lower risk. Breastfeeding for ≥12 months and oral contraceptive use for ≥1 year were also associated with reduced risk. By contrast, menopause at ≥55 years and a reproductive lifespan of ≥40 years were associated with increased risk. Menopausal hormone replacement therapy use for ≥5 years was also associated with higher risk, whereas age at menarche showed no association with ovarian cancer. CONCLUSIONS: In this cohort, reproductive factors that reduce lifetime ovulatory exposure were associated with lower ovarian cancer risk, whereas factors that prolong ovulatory lifespan and long-term menopausal hormone replacement therapy were associated with higher risk. These observational findings may help refine ovarian cancer risk assessment and counseling in post-menopausal women, but do not establish causality. Copyright © 2026 European Society of Gynaecological Oncology and the International Gynecologic Cancer Society. Published by Elsevier Inc. All rights reserved.

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