Early Menarche and Late Menopause Key Determinants of Ovarian Cancer Risk: JAMA
Korea: Researchers have found in a new study that across both premenopausal and postmenopausal women, early menarche, later age at menopause, and a longer reproductive span were associated with a higher risk of ovarian cancer, whereas higher parity was consistently associated with a lower risk of ovarian cancer.
The findings are from a large nationwide cohort study published in JAMA Network Open by Jin-Hwi Kim, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Uijeongbu St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, and colleagues. The investigators explored how reproductive factors influence ovarian cancer risk, examining whether these associations vary according to menopausal status and birth cohort.
For this purpose, the researchers analyzed data from the Korean National Health Insurance Service (NHIS), which covers nearly the entire population of South Korea. The study included 2,285,774 women aged 40 years or older who underwent national health screening in 2009 and had detailed reproductive and clinical information available. Participants were followed until a diagnosis of ovarian cancer, death, or December 31, 2022. The average follow-up period was 10.7 years, during which 10,729 cases of ovarian cancer were identified.
The analysis revealed the following findings:
- Early menarche (≤12 years) was associated with a significantly higher risk of ovarian cancer compared with menarche after 16 years in both premenopausal and postmenopausal women.
- Having two or more children was linked to a substantially lower risk of ovarian cancer across both menopausal groups.
- Among premenopausal women, breastfeeding for 12 months or longer was associated with a reduced risk of ovarian cancer.
- Oral contraceptive use for at least one year was associated with lower ovarian cancer risk in premenopausal women.
- In postmenopausal women, menopause at age 55 years or older was associated with increased ovarian cancer risk.
- A reproductive span of 40 years or more was linked to a higher risk in postmenopausal women.
- Hormone replacement therapy use for two to five years was associated with increased ovarian cancer risk in postmenopausal women.
- The protective effect of higher parity appeared weaker among women born in the 1960s compared with earlier birth cohorts, though this interaction was not statistically significant.
Overall, the findings suggest that cumulative lifetime exposure to endogenous and exogenous hormones may play a key role in ovarian cancer development, with variations depending on menopausal status and generational reproductive trends. In aging societies with declining fertility rates, such as South Korea, these shifting reproductive patterns may have meaningful implications for cancer prevention strategies.
The authors noted several limitations, including self-reported reproductive data, potential recall bias, a lack of tumor subtype details, and the absence of key confounders such as family history, BRCA status, and tubal ligation. As an observational study, it cannot prove causation. However, the findings align with previous biological and epidemiological research, underscoring the need for individualized risk assessment and tailored prevention strategies.
Reference:
Kim J, Hwang I, Lee S, Kim C, Lee S, Han K. Reproductive Shifts and Ovarian Cancer Risk in Women Aged 40 Years or Older. JAMA Netw Open. 2026;9(2):e2556840. doi:10.1001/jamanetworkopen.2025.56840
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