Are reproductive factors and endometrial cancer risk associated?

By Vijay Kumar MalesuSep 8 2023Reviewed by Lily Ramsey, LLM

In a recent study published in JAMA Network Open, researchers assessed the association between specific reproductive factors and the risk of endometrial cancer among women based on data from 13 cohort studies.

Study: Reproductive Factors and Endometrial Cancer Risk Among Women. Image Credit: megaflopp/Shutterstock.com

Background 

In 2020, endometrial cancer, ranking sixth in global cancer occurrences among women, represented 2% of new cases and caused 1% of cancer deaths.

The incidence rate of endometrial cancer varies by 21.1 per 100,000 people in North America and 8.2 in Eastern Asia. The United States (U.S.) stands at 28.0 for non-Hispanic Whites and 22.6 for Asians and Pacific Islanders. 

While reproductive factors linked to this cancer have been studied in the U.S. and Europe, research from Asian countries remains sparse.

Due to estrogen and progesterone levels, the endometrium's structure changes with the menstrual cycle, and increased estrogen exposure can lead to endometrial hyperplasia, elevating cancer risks; factors like parity and age at menarche further influence this exposure and associated risk.

Some studies correlate early menopause and higher parity with reduced risk, but other factors' impact remains debated. 

About the study

The ACC (Asia Cohort Consortium) consists of various prospective studies in Asia, with thirteen cohort studies targeting endometrial cancer: eight in Japan, three in Korea, one in China, and one in Singapore.

Each study provided data on reproductive factors, endometrial cancer incidence, and other potential influencing factors. After setting several exclusion criteria related to age, sex data, endometrial cancer history, and specific Body Mass Index (BMI) figures, a total of 332,625 participants were included in the study.

The National Cancer Center Japan granted ethical approval, and each study adhered to institutional ethics guidelines; to ensure consistency, the ACC working group harmonized data across all cohorts.

Questions revolved around reproductive factors like the number of deliveries, age of first delivery, age at menarche, menopause status, and others.

Local cancer registries verified the incidence of endometrial cancer in each study, and confounding variables like age, BMI, and smoking status were factored in.

Analysis occurred between September 2019 and April 2023, assessing the relationship between reproductive factors and endometrial cancer occurrence.

Using specific statistical methods and software, hazard ratios (HRs) were calculated with adjustments for age, smoking, drinking, and other variables, ensuring precision and thoroughness through meticulous techniques and considering a wide range of factors.

Study results 

In the present study, encompassing 332,625 women with an average age of 54.3 years during the baseline from 13 cohort studies, 1,005 cases of endometrial cancer were identified.

Upon analysis, the mean age of participants at baseline ranged from 49.5 to 61.2 years, while over 90% had experienced pregnancy, excluding those in the Life Span Study (LSS). Most reported menarche between the ages of 13 to 16 and menopause between 45 to 54 years.

Participants who had experienced pregnancy had a considerably lower risk of endometrial cancer than those who had not (HR, 0.54).

Further, women with 1-2, 3-4, and 5 or more deliveries consistently exhibited reduced risks compared to those without childbirth, indicating that multiple deliveries were associated with a decreased risk.

The age of participants during their menarche and menopause influenced endometrial cancer risk, with a younger age at menarche and an older age at menopause being linked to lower risks.

Age at first delivery, hormone therapy use, and breastfeeding were not conclusively linked to endometrial cancer risk, even though some data hinted towards potential connections. The research's robustness was tested by excluding each study one by one, with results remaining broadly consistent.

When segmenting the results based on factors like BMI, menopausal status, and parity, the findings largely echoed the primary analyses. However, specific segmentations did lead to some statistical insignificance, likely due to reduced sample sizes post-segmentation.

Additionally, when results were reviewed, excluding the LSS, which did not collect data on the number of deliveries, there were changes in the statistical significance, specifically regarding age at menarche.

This comprehensive analysis found that certain reproductive factors, such as the experience of pregnancy and the number of deliveries, were significantly associated with reduced endometrial cancer risks.

Moreover, ages at menarche and menopause also played significant roles. The extensive sample size and rigorous stratification and analysis methodologies ensured the credibility of these findings.

Conclusions 

In the present study of 332,625 Asian women from 13 cohorts, factors like parity, multiple deliveries, later onset of menstruation, and early menopause were linked to a reduced risk of endometrial cancer.

While previous studies have indicated a similar trend, few were focused on Asia. The study also found no significant connection between breastfeeding and endometrial cancer, contrasting with some Western research.

The average age of menarche in Asian women is typically higher than in Western counterparts, but its association with endometrial cancer risk remains consistent.

Notably, the study lacked data on factors like oral contraceptive (OC) use and specific hormone therapies.