History of Infertility and Risk of Endometrial Cancer in the Women’s Health Initiative

Background: Several studies have suggested an association between infertility and risk of endometrial cancer. However, most studies have evaluated this relationship in premenopausal people, yet the mean age of endometrial cancer is 60 years, after the average age of menopause. Methods: Our study included Women’s Health Initiative participants who self-reported whether they had a history of infertility. Cox proportional hazards models were used to examine the association between infertility and incident endometrial cancer. Given that all infertility diagnoses occurred prior to study enrollment, we conducted secondary analyses using logistic regression examining prevalent endometrial cancer cases diagnosed before study baseline. Results: Approximately 18% of participants reported a history of infertility. No statistically significant association was observed between infertility and risk of incident endometrial cancer overall [incident cases = 1,622; HR = 1.12; 95% confidence interval (CI) = 0.99–1.26]. Although point estimates suggested an increase in risk of endometrial cancer among women with body mass index (BMI) ≥25 (HR = 1.15; 95% CI = 0.99–1.33), none of the associations were statistically significant. There was an association between history of infertility and prevalent endometrial cancer cases (OR = 1.19; 95% CI = 1.06–1.34), with the strongest association for infertility diagnosis due to endometriosis (OR 2.42; 95% CI = 1.83–3.19). Conclusions: In a population of postmenopausal participants, we observed a modest, but not statistically significant, association between overall infertility and incident endometrial cancer, with the suggestion of a higher risk among those with a BMI ≥ 25. Impact: Our findings highlight, as observed in previous studies, that risk factors for endometrial cancer may vary by BMI.