Lower risk in parous women suggests that hormonal factors are important in bladder cancer etiology.

Background: Urinary bladder cancer is two to four times more common among men than among women, a difference in risk not fully explained by established risk factors. Our objective was to determine whether hormonal and reproductive factors are involved in female bladder cancer.

Methods: We analyzed data from two population-based studies: the Los Angeles-Shanghai Bladder Cancer Study, with 349 female case-control pairs enrolled in Los Angeles and 131 female cases and 138 frequency-matched controls enrolled in Shanghai, and the California Teachers Study (CTS), a cohort of 120,857 women with 196 incident cases of bladder urothelial carcinoma diagnosed between 1995 and 2005. We also conducted a meta-analysis summarizing associations from our primary analyses together with published results.

Results: In primary data analyses, parous women experienced at least 30% reduced risk of developing bladder cancer compared with nulliparous women (Shanghai: OR = 0.38, 95% CI: 0.13-1.10; CTS: RR = 0.69, 95% CI: 0.50-0.95) consistent with results of a meta-analysis of nine studies (summary RR = 0.73, 95% CI: 0.63-0.85). The CTS, which queried formulation of menopausal hormone therapy (HT), revealed a protective effect for use of combined estrogen and progestin compared with no HT (RR = 0.60, 95% CI: 0.37-0.98). Meta-analysis of three studies provided a similar effect estimate (summary RR = 0.65, 95% CI: 0.48-0.88).

Conclusions: A consistent pattern of reduced bladder cancer risk was found among parous women and those who used estrogen and progestin for HT.

Impact: These results suggest that more research is warranted to investigate hormonal and reproductive factors as possible contributors to bladder cancer risk.