The impact of hormones and reproductive factors on the risk of bladder cancer in women: Results from the Nurses’ Health Study and Nurses’ Health Study II

Background: With three out of four new bladder cancer (BCa) cases occurring in men, an apparent gender disparity exists. We aimed to investigate the role of hormonal and reproductive factors in BCa risk using two large female US prospective cohorts. Methods: Our study population comprised 118 256 and 115 383 female registered nurses who were recruited in the Nurses’ Health Study (NHS) and NHS II, respectively. Reproductive and hormonal factors and other relevant data were recorded in biennial self-administered questionnaires. Cox-regression analyses were performed to estimate age- and multivariable-adjusted incidence risk ratios (IRRs) and 95% confidence intervals (CIs). Inverse-variance-weighted meta-analysis was used to pool estimates across cohorts. Results: During up to 36 years of follow-up, 629 incident BCa cases were confirmed. In the NHS, 22 566 women (21.3%) were postmenopausal at baseline, compared with 2723 women (2.4%) in the NHS II. Among women in the NHS, younger age at menopause (≤45 years) was associated with an increased risk of BCa (IRR: 1.41, 95% CI: 1.11–1.81, P_trend ¼ 0.01) compared with those with menopause onset at age 50þ years, particularly among ever-smokers (IRR for age at menopause ≤45 years: 1.53, 95% CI: 1.15–2.04; P_Intx ¼ 0.16). Age at menarche and first birth, parity, oral-contraceptive use and postmenopausal hormone use were not associated with BCa risk. Conclusions: Overall, we found little support for an association between female reproductive factors and BCa risk in these prospective cohort studies. Earlier age at menopause was associated with a higher risk of BCa, particularly among smokers, indicating the potential for residual confounding.