Khalili Hamed, Granath Fredrik, Smedby Karin E, Ekbom Anders, Neovius Martin, Chan Andrew T, Olen Ola
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden.
Gastroenterology. 2016 Jun;150(7):1561-1567.e1. doi: 10.1053/j.gastro.2016.02.041. Epub 2016 Feb 23.
BACKGROUND & AIMS: Use of exogenous hormones, in the form of oral contraceptives (OCs), has been linked consistently to risk of Crohn's disease (CD). Nonetheless, it is not clear how OCs might contribute to the progression of CD.
We conducted a prospective study of female patients with CD (age, 16-51 y), identified from the inpatient and outpatient care components of the Swedish National Patient Register from January 2002 through December 2013. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005 and updated until December of 2013. Primary outcomes were defined as first CD-related surgery and first steroid prescription. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratios (MV-adjusted HRs).
We identified 482 incident cases of surgery among 4036 patients with CD, with a median follow-up period of 58 months. Compared with nonusers, the MV-adjusted HRs for surgery were 1.14 (95% confidence interval [CI], 0.80-1.63) for past users and 1.30 (95% CI, 0.89-1.92) for current users. The risk of surgery increased with longer duration of use (Ptrend = .036) and higher prescribed daily dose (Ptrend = .016). Specifically, for women with more than 3 years of OC use, the MV-adjusted HR for surgery was 1.68 (95% CI, 1.06-2.67). The association was confined to the combination type of OC. We estimated that for every 83 patients with CD receiving the combination type of oral contraceptives for at least 1 year, 1 extra surgery is required. The rate of steroid prescriptions did not appear to increase with past or current use of OCs, compared with patients who have not taken OCs (all Pcomparisons > .20).
In a nationwide analysis of patients in Sweden, long-term use of OCs, particularly the combination type, was associated with an increased risk of surgery among women with established CD. Clinicians carefully should evaluate and monitor contraceptive options among women with established CD.
口服避孕药（OCs）形式的外源性激素使用一直与克罗恩病（CD）风险相关。然而，尚不清楚OCs如何促使CD进展。
我们对2002年1月至2013年12月期间从瑞典国家患者登记处的住院和门诊护理部分识别出的女性CD患者（年龄16 - 51岁）进行了一项前瞻性研究。自2005年7月起从处方药登记处获取当前OC使用信息，并更新至2013年12月。主要结局定义为首次与CD相关的手术和首次使用类固醇药物。我们使用具有时变协变量的Cox比例风险模型来估计多变量调整风险比（MV调整HRs）。
我们在4036例CD患者中识别出482例手术事件，中位随访期为58个月。与未使用者相比，既往使用者手术的MV调整HR为1.14（95%置信区间[CI]，0.80 - 1.63），当前使用者为1.30（95%CI，0.89 - 1.92）。手术风险随使用时间延长（P趋势 = 0.036）和每日处方剂量增加（P趋势 = 0.016）而增加。具体而言，对于使用OCs超过3年的女性，手术的MV调整HR为1.68（95%CI，1.06 - 2.67）。该关联仅限于复方型OCs。我们估计，每83例接受复方型口服避孕药至少1年的CD患者中，就需要额外进行1次手术。与未服用OCs的患者相比，既往或当前使用OCs时类固醇药物处方率似乎并未增加（所有P比较 > 0.20）。
在瑞典对患者的全国性分析中，长期使用OCs，尤其是复方型，与已患CD的女性手术风险增加相关。临床医生应仔细评估和监测已患CD女性的避孕选择。
