Reproductive factors strongly influence ovarian cancer risk in postmenopausal women

Early menarche, late menopause and a long reproductive span are associated with a high risk of ovarian cancer, according to a nationwide Korean study published today in Obstetrics and Gynecology.

A team of researchers, including Sung-Jong Lee, M.D., Ph.D., from the division of gynecologic oncology at Seoul St. Mary’s Hospital at The Catholic University of Korea, gathered the data of 2,285,774 women using the National Health Insurance Service, which covers 97% of the South Korean population.

This total includes 932,637 premenopausal women and 1,353,137 postmenopausal women.

Lee and his colleagues followed up with participants for approximately 10 years and found that 3,354 premenopausal women and 7,375 postmenopausal women developed ovarian cancer.

Specifically, among postmenopausal women, ovarian cancer risk was higher in women who had undergone menopause later, at least at age 55 (36%); who had had a reproductive span of at least 40 years (21%) and who had used hormone replacement therapy for 2 to 5 years (20%).

Early menarche, defined as beginning earlier than age 12, was also associated with higher ovarian cancer risk in both premenopausal women (37%), potentially because they have had more ovulations, and postmenopausal women (24%).

“Meta-analyses have reported a 5% to 8% higher risk per year with earlier menarche and a 20% to 30% lower risk with each additional birth, although most evidence derives from Western populations with historically higher fertility and greater oral contraceptive use,” Lee and his team said in the study.

Breastfeeding for 12 months or longer and oral contraceptive use for at least 1 year were associated with lower risk in premenopausal women (0.86%) than in postmenopausal women (0.75%).

Parity of 2 or more births was associated with lower risk in both groups (0.68% and 0.71%, respectively).

The significantly smaller parity-related risk reduction can be explained by a rapid fertility decline in South Korea, where rates went from being higher than 4.0 in the early 1970s to 0.72 in 2022, Lee and his colleagues explain.

Fertility is measured using an Anti-Müllerian Hormone (AMH) blood test, which measures the quality of the remaining eggs in the ovaries. For women under the age of 35, a normal AMH test score is between 1.0 and 4.0.

Ovarian cancer is one of the leading causes of death for women. In the United States in 2026, the American Cancer Society estimates that 21,010 women will be diagnosed with ovarian cancer and 12,450 will die as a result. Ovarian cancer is also more common in older women, with half of all cases diagnosed in women over the age of 63.

“This cohort study found that reproductive factors were associated with ovarian cancer risk, with distinct patterns across menopausal status and birth cohorts,” Lee and his colleagues write. “These findings highlight the need for tailored prevention strategies in aging, low-fertility populations. Further research that incorporates histologic subtypes, genetic factors, and detailed exposure histories is needed.”