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, Ptrend = 0.01) compared with those with menopause onset at age 50+ years, particularly among ever-smokers (IRR for age at menopause ≤45 years: 1.53, 95% CI: 1.15-2.04; PIntx = 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.

中文翻译：

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激素和生殖因子对女性膀胱癌风险的影响：《护士健康研究》和《护士健康研究》 II的结果。

背景技术在男性发生的四分之三的新膀胱癌（BCa）病例中，存在明显的性别差异。我们旨在使用两个美国大型女性前瞻性队列研究激素和生殖因子在BCa风险中的作用。方法我们的研究人群包括分别在护士健康研究（NHS）和NHS II中招募的118 256名女性注册护士和115 383名女性注册护士。生殖和激素因素及其他相关数据记录在两年一次的自我管理调查表中。进行Cox回归分析以估计年龄和多变量调整后的发病风险比（IRR）和95％置信区间（CI）。使用方差加权加权荟萃分析来汇总各组的估计值。结果在长达36年的随访中，确认了629例BCa病例。在NHS中，基线时绝经后为22566名女性（占21.3％），而在NHS II中则为2723名女性（占2.4％）。在NHS中，与50岁以上更年期发病的女性相比，更年期更年轻（≤45岁）与BCa风险增加有关（IRR：1.41，95％CI：1.11-1.81，Ptrend = 0.01）。年，尤其是吸烟者（绝经年龄≤45岁的IRR：1.53，95％CI：1.15-2.04； PIntx = 0.16）。月经初潮和初生年龄，胎次，口服避孕药和绝经后激素的使用与BCa风险无关。结论总体而言，在这些前瞻性队列研究中，我们几乎没有发现女性生殖因子与BCa风险之间存在关联。绝经年龄越早，BCa的风险就越高，尤其是在吸烟者中，这表明存在残留混杂的可能性。