Reproductive Factors in the Risk of Bladder Cancer and Upper Urinary Tract Cancer: The Japan Public Health Center-Based Prospective Study

Background: Reproductive factors are hypothesized to play a role in the incidence of bladder cancer and upper urinary tract cancer (UUTC, together, urothelial cancer). However, evidence regarding these associations is limited, particularly in Asian populations.Methods: We analyzed data from 55,882 females ages 40 to 69 years, and performed Cox proportional hazards regression analyses with three types of adjustment, namely age; reproductive factor of interest and covariates in addition to age (conventional model); and other reproductive factors in addition to the multivariable adjusted model (reproductive model).Results: During an average of 20.2 years of follow-up, 194 urothelial cancer cases (145 bladder cancer cases and 49 UUTC cases) were identified. Early age at natural menopause (<44 years, compared with 49-51 years) increased bladder cancer risk in the reproductive model (HR, 2.09; 95% CI, 1.04-4.20). An association between urothelial cancer/bladder cancer and age at menopause, including both natural and surgical/induced, was significant in the reproductive model (HR, 1.74; 95% CI, 1.09-2.77; and HR, 1.94; 95% CI, 1.15-3.28, respectively). Early age at natural menopause was suggested to increase urothelial cancer risk in the reproductive model (HR, 1.78; 95% CI, 0.93-3.42).Conclusions: Our findings suggest a significant association between age at menopause and incidence of urothelial cancer/bladder cancer among Asian populations. This study aids understanding the role of reproductive factors in urothelial cancer/bladder cancer incidence.Impact: In Japanese populations, age at menopause is suggested to be associated with urothelial cancer/bladder cancer incidence, especially regarding early natural menopause.