Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts.
Gastroenterology. 2012 Nov;143(5):1199-1206. doi: 10.1053/j.gastro.2012.07.096. Epub 2012 Jul 27.
BACKGROUND & AIMS: Estrogen has been proposed to modulate gut inflammation through an effect on estrogen receptors found on gastrointestinal epithelial and immune cells. The role of postmenopausal hormone therapy on risk of Crohn's disease (CD) and ulcerative colitis (UC) is unclear.
We conducted a prospective cohort study of 108,844 postmenopausal US women (median age, 54 years) enrolled in 1976 in the Nurses' Health Study without a prior history of CD or UC. Every 2 years, we have updated information on menopause status, postmenopausal hormone use, and other risk factors. Self-reported diagnoses of CD and UC were confirmed through medical record review by 2 gastroenterologists who were blinded to exposure information. We used Cox proportional hazards models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
Through 2008, with more than 1.8 million person-years of follow-up, we documented 138 incident cases of CD and 138 cases of UC. Compared with women who never used hormones, the multivariate-adjusted HR for UC was 1.71 (95% CI, 1.07-2.74) among women who currently used hormones and 1.65 (95% CI, 1.03-2.66) among past users. The risk of UC appeared to increase with longer duration of hormone use (P(trend) = .04) and decreased with time since discontinuation. There was no difference in risk according to the type of hormone therapy used (estrogen vs estrogen plus progestin). In contrast, we did not observe an association between current use of hormones and risk of CD (multivariate-adjusted HR, 1.19; 95% CI, 0.78-1.82). The effect of hormones on risk of UC and CD was not modified by age, body mass index, or smoking.
In a large prospective cohort of women, postmenopausal hormone therapy was associated with an increased risk of UC but not CD. These findings indicate that pathways related to estrogens might mediate the pathogenesis of UC.
雌激素被认为可以通过其在胃肠道上皮细胞和免疫细胞上的雌激素受体发挥作用，从而调节肠道炎症。绝经后激素治疗对克罗恩病（CD）和溃疡性结肠炎（UC）风险的影响尚不清楚。
我们对 1976 年参加护士健康研究的 108844 名无 CD 或 UC 既往病史的绝经后美国女性（中位年龄 54 岁）进行了一项前瞻性队列研究。每 2 年，我们都会更新关于绝经状态、绝经后激素使用和其他危险因素的信息。通过由 2 位对暴露信息不知情的胃肠病学家对病历进行审查，对 CD 和 UC 的自报告诊断进行确认。我们使用 Cox 比例风险模型计算调整后的风险比（HR）和 95%置信区间（CI）。
截至 2008 年，通过超过 180 万个人随访年，我们记录了 138 例新发 CD 和 138 例 UC。与从未使用过激素的女性相比，当前使用激素的女性 UC 的多变量调整 HR 为 1.71（95%CI，1.07-2.74），过去使用者的 HR 为 1.65（95%CI，1.03-2.66）。UC 的风险似乎随激素使用时间的延长而增加（P(trend) =.04），并随停药时间的延长而降低。激素类型的使用对风险无差异（雌激素与雌激素加孕激素）。相比之下，我们没有观察到当前使用激素与 CD 风险之间的关联（多变量调整 HR，1.19；95%CI，0.78-1.82）。激素对 UC 和 CD 风险的影响不受年龄、体重指数或吸烟的影响。
在一项大型前瞻性队列研究中，绝经后激素治疗与 UC 风险增加相关，但与 CD 无关。这些发现表明，与雌激素相关的途径可能介导 UC 的发病机制。
