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.