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. 2023 Sep 5;6(9):e2332296.
doi: 10.1001/jamanetworkopen.2023.32296.

Reproductive Factors and Endometrial Cancer Risk Among Women

Ryoko Katagiri  1   2 , Motoki Iwasaki  1   3 , Sarah Krull Abe  4 , Md Rashedul Islam  4   5 , Md Shafiur Rahman  4   6 , Eiko Saito  7 , Melissa A Merritt  8 , Ji-Yeob Choi  9 , Aesun Shin  10   11 , Norie Sawada  1 , Akiko Tamakoshi  12 , Woon-Puay Koh  13   14 , Ritsu Sakata  15 , Ichiro Tsuji  16 , Jeongseon Kim  17 , Chisato Nagata  18 , Sue K Park  11 , Sun-Seog Kweon  19 , Xiao-Ou Shu  20 , Yu-Tang Gao  21 , Shoichiro Tsugane  1 , Takashi Kimura  12 , Jian-Min Yuan  22   23 , Seiki Kanemura  16 , Yukai Lu  16 , Yumi Sugawara  16 , Keiko Wada  18 , Min-Ho Shin  19 , Habibul Ahsan  24 , Paolo Boffetta  25   26 , Kee Seng Chia  27 , Keitaro Matsuo  28   29 , You-Lin Qiao  30 , Nathaniel Rothman  31 , Wei Zheng  20 , Manami Inoue  4 , Daehee Kang  32
Affiliations

Reproductive Factors and Endometrial Cancer Risk Among Women

Ryoko Katagiri et al. JAMA Netw Open. .

Abstract

Importance: Despite evidence of an association between reproductive factors and endometrial cancer risk, prospective studies have been conducted mainly in non-Asian countries.

Objective: To assess the association between reproductive factors, such as number of deliveries, age at menarche, or menopause, and endometrial cancer risk.

Design, setting, and participants: This cohort study used pooled individual data from 13 prospective cohort studies conducted between 1963 and 2014 in the Asia Cohort Consortium. Participants were Asian women. Data analysis was conducted from September 2019 to April 2023.

Exposures: Reproductive factors were assessed using a questionnaire in each cohort.

Main outcomes and measures: The main outcome was time to incidence of endometrial cancer. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% CIs.

Results: A total of 1005 endometrial cancer cases were detected among 332 625 women (mean [SD] age, 54.3 [10.4] years) during a mean (SD) of 16.5 (6.4) years of follow-up. Increasing number of deliveries was associated with a decreased endometrial cancer risk in a dose-response manner (≥5 deliveries vs nulliparous [reference]: HR, 0.37; 95% CI, 0.26-0.53; P for trend < .001). Compared with menarche at younger than 13 years, menarche at 17 years or older had an HR of 0.64 (95% CI, 0.48-0.86; P for trend < .001). Late menopause (age ≥55 years) showed an HR of 2.84 (95% CI, 1.78-4.55; P for trend < .001) compared with the youngest age category for menopause (<45 years). Age at first delivery, hormone therapy, and breastfeeding were not associated with endometrial cancer risk.

Conclusions and relevance: This large pooled study of individual participant data found that late menarche, early menopause, and a higher number of deliveries were significantly associated with a lower risk of endometrial cancer. These convincing results from Asian prospective studies add to the growing body of evidence for the association between reproductive factors and endometrial cancer.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure.
Figure.. Stratified Analyses Between Reproductive Factors and Endometrial Cancer Risk by Body Mass Index (BMI), Menopausal Status, and Parous Status
The model for hormone therapy (HT) use included 8 cohorts and that for breastfeeding included 7 cohorts. Detailed results are in eTable 3 in Supplement 1. Models were adjusted for age at baseline, BMI, age at menarche, age at menopause (including premenopause), current smoking, current drinking, parity, HT use, and breastfeeding, except for the stratification variable. Japan Collaborative Cohort Study and Life Span Study included a question about the age at first pregnancy (not delivery). aSignificant (P < .05) trend of categories of each reproductive factor.
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