Reproductive factors and menopausal hormone therapy and bladder cancer risk in the NIH‐AARP Diet and Health Study

Abstract

The incidence of bladder cancer among women is at least one third to one fourth that observed among men in many countries. Even after accounting for known risk factors, the reason for this gender disparity remains unexplained. We conducted a comprehensive evaluation of reproductive factors and exogenous hormone use with a primary focus on menopausal hormone therapy use and risk of bladder cancer in women in the NIH-AARP Diet and Health Study. Reproductive and hormonal factors were ascertained on the baseline questionnaire in 1995–1996 among 201,492 females who were followed until December 31, 2006. During follow-up, 651 cases of bladder cancer were diagnosed. A subset of women provided detailed information on use of MHT in a second questionnaire in 1996–1997. In this analysis, 127,361 females were followed through June 30, 2002 and 198 incident bladder cancer cases were identified. Cox proportional hazard models, adjusted for smoking status, cigarettes per day, and body mass index using age as the time metric, were used to obtain hazard ratios (HRs). A reduced risk was observed among parous women (HR=0.76; 95% CI 0.62–0.93) and women who reported late age at menarche (≥15 years) (HR=0.57; 95% CI 0.39–0.84). Women who reported ever using estrogen and progestin therapy had a decreased risk (HR=0.53; 95% CI: 0.34–0.83) compared to women who did not report MHT use. No association was observed for estrogen only users (HR=0.82; 95% CI: 0.58–1.15). Our results suggest a putative role for sex hormones in the etiology of bladder cancer among women.

Gender differences in incidence and outcomes of urothelial and kidney cancer

“…14 Finally, some data demonstrated a reduced risk of developing bladder cancer for women who used hormonal treatment (such as oral contraceptives and menopausal hormone therapy) but others found no significant differences between the two groups ( Figure 1). 15,16 Although these two studies had a similar design and included a large cohort, the disparity of the final results might be caused by misclassification of selfreported hormonal use and reproductive factors.…”

Anthropometric measures and bladder cancer risk: A prospective study in the EPIC cohort

“…Obesity entails increased endogenous estrogen levels in post‐menopausal women . However, studies on hormonal factors and bladder cancer show mixed results . The gender‐specific effects may also be related to sex‐specific anthropometric changes: With age, the lean mass of men approaches that of women, because men have a higher relative loss of lean body mass.…”

Sex differences in the MB49 syngeneic, murine model of bladder cancer

“…This striking difference between the sexes cannot be accounted for by lifestyle factors [ 2 ]. The most reliable contributor to bladder cancer risk is smoking and this has been specifically excluded from the possible explanations for an increased rate of bladder cancer among men [ 3 ] Therefore, significant effort has gone into exploring possible mechanisms of protection against bladder cancer which may originate in some uniquely female attribute or biological process [ 4 , 5 ]. Mouse models of bladder cancer that reproduce the decreased susceptibility of females would be useful for these efforts.…”