A nationwide study of more than 2 million South Korean women examined how reproductive factors influence the risk for ovarian cancer across different generations and menopausal stages.

The study findings, published in JAMA Network Open, suggested that reproductive factors are associated with the risk for ovarian cancer, with distinct patterns across menopausal status and birth cohorts.

What Did the Study Show?

The study tracked 2,285,774 women aged 40 years or older for more than a decade, identifying 10,729 ovarian cancer cases. Researchers found that, compared with nonparity, having two or more children reduced the risk for ovarian cancer by 32% in women born in the 1930s through 1950s, but showed no significant protective effect in women born in the 1960s.

The authors suggested that this dissipating protective effect of childbearing against ovarian cancer in younger generations relates to Korea’s rapid fertility decline. South Korea’s fertility rate declined from above 4.0 in the early 1970s to 0.72 in 2022, compressing reproductive shifts into a single generation.

“I think this hypothesis is very plausible,” said Barbara A. Goff, MD, professor and chair of the Department of Obstetrics and Gynecology at the School of Medicine, University of Washington, Seattle, who was not involved in the study. “Prior to the 1960s, average family size was larger, and women were having four babies or more. Whereas after the 1960s, the size of families started to dramatically decrease, so the length of exposure to pregnancy declined significantly.”

The authors explained that differences in the number of livebirths in the “two or more children” category across generations may have contributed to the attenuation of parity-related risk reduction in the 1960s birth cohort. In their discussion, they noted that in earlier, high-fertility generations, parity of two or more often meant four or more births, creating a much wider gap in ovulation exposure compared with women who had no children. But in the 1960s cohort, women in the “two or more” births category usually had only two or three children.

Why Would Fewer Children Mean Less Protection?

The authors explained that each pregnancy temporarily halts ovulation, reducing cumulative exposure to hormonal cycling that contributes to the risk for ovarian cancer through the incessant ovulation hypothesis. Goff noted that if oral contraceptive use, another ovulation suppressor, had been high in the Korean population, it might have compensated for the reduced protection from fewer pregnancies. However, the study showed that only 3.5%-6.3% of women reported using oral contraceptives for 1 year or longer.

How Do These Results Compare to Western Populations?

The findings of the Korean study confirm previous research in European and US populations, which has shown that late menopause is associated with a higher risk for ovarian cancer, whereas higher parity is associated with a lower risk. The Korean study also showed that early menarche increased the risk for ovarian cancer in both premenopausal and postmenopausal women, confirming previous findings. Goff explained that, even though the finding that reproductive factors are associated with the risk for ovarian cancer is not new, it is important to confirm how different reproductive variables correlate with the risk for ovarian cancer in different ethnic populations to enable population-specific prevention strategies.

However, the Korean study was the first study to have a large enough scale to allow the researchers to identify differences in reproductive factor associations by menopausal status and birth cohort within the same population, such as the weakened association between childbearing and risk for ovarian cancer in younger cohorts.

Breastfeeding for 12 months or longer and using oral contraceptives for at least 1 year reduced the risk for ovarian cancer, but only in premenopausal women. Among postmenopausal women, later menopause, longer reproductive span (the time between first period and menopause, reflecting total years of ovulation), and hormone replacement therapy use for 2-5 years all increased the risk for ovarian cancer.

What Does This Mean for Prevention Strategies?

The authors emphasized that prevention strategies are even more critical in countries where women have fewer children, since their study shows that traditional protective factors such as high parity may no longer apply in younger, low-fertility populations.

Goff outlined several approaches for the prevention of ovarian cancer. Understanding family history and pursuing genetic testing when appropriate can help identify women at higher risk who might benefit from risk-reducing surgery. Bilateral salpingectomy — removal of both fallopian tubes — can also offer protection.

“There is evidence that doing a bilateral salpingectomy, either at the time of a tubal ligation or at the time of another pelvic surgery, once childbearing has been complete, could decrease ovarian cancer by up to 50%,” Goff explained.

She added that roughly 70% of ovarian cancers originate in the fallopian tubes before spreading to the ovaries, and that recent population data from British Columbia have shown that compared with hysterectomy alone or tubal ligation, opportunistic bilateral salpingectomy reduces the risk for ovarian cancer by nearly 80%.

What Were the Study Limitations?

The study had limitations, including self-reported reproductive histories and the lack of histologic subtype data. The authors also acknowledged that information on tubal ligation, family history, and BRCA1/2 status was missing, leaving unanswered questions about the association of these factors with the risk for ovarian cancer in different generations.

Should Clinicians Change How They Counsel Patients?

The authors of the Korean study suggested the need for prevention strategies tailored to the specific risk profiles of aging, low-fertility populations, where traditional protective factors such as high parity may no longer apply.

Goff emphasized that in the absence of screening, early symptom recognition becomes essential.

“It’s really important to know the early warning signs of ovarian cancer,” she said. “Symptoms such as pelvic or abdominal pain, feeling full quickly, bloating, and urinary symptoms can indicate ovarian cancer. When these symptoms are new, and they persist for more than a couple of weeks, women should notify their physicians and should get checked out.”

Goff reported having no relevant financial relationships or conflicts of interest.

Christos Evangelou, PhD, is a freelance medical writer and science communications consultant.