Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.
Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.
Eur J Clin Pharmacol. 2021 Oct;77(10):1523-1529. doi: 10.1007/s00228-021-03137-6. Epub 2021 May 10.
Previous studies have indicated an increased risk of gallbladder disease with hormonal contraceptives although with discordant results. The potential increased risk of gallbladder disease with hormonal contraceptives is concerning given that women are at increased risk of this disease. Thus, the aim of this study was to examine risk of surgery-confirmed gallbladder disease (cholecystectomy) with oral contraceptives, intrauterine devices, and injectable hormonal contraceptives.
We conducted a retrospective cohort study. Females aged 15-45 who initiated hormonal contraceptive use were identified in the United States IQVIA Ambulatory electronic medical record database between 2008 and 2018. Cox proportional hazards models were used to estimate adjusted hazards ratios and 95% confidence intervals for cholecystectomy with eight formulations of contraceptives compared with levonorgestrel and ethinyl estradiol combined oral contraceptive. Sensitivity analysis was conducted by lagging exposure by 90 days and by excluding patients with history of gallbladder disease. Secondary analyses were conducted by cumulative duration of use.
We identified 1,425,821 females who initiated the use of hormonal contraceptives and generated 4417 cholecystectomy events. Overall, the use of medroxyprogesterone acetate (HR: 1.22, 95% CI: 1.07-1.40) and at least 1 year of levonorgestrel intrauterine device use (HR: 1.74: 95% CI: 1.19-2.54) were associated with increased risk of cholecystectomy when compared with levonorgestrel and ethinyl estradiol combined oral contraceptive. However, we did not observe an increased risk with other hormonal contraceptives. Consistent results were observed across sensitivity analyses.
In this large population-based study, there was an increased risk of cholecystectomy with medroxyprogesterone acetate and intrauterine device but not other hormonal contraceptives. Additional large observational studies are required to corroborate these findings.
尽管先前的研究结果存在差异，但已有研究表明激素避孕药会增加胆囊疾病的风险。鉴于女性患此病的风险增加，激素避孕药可能会增加胆囊疾病的风险，这令人担忧。因此，本研究旨在检查口服避孕药、宫内节育器和注射用激素避孕药与手术确诊的胆囊疾病（胆囊切除术）的风险。
我们进行了一项回顾性队列研究。在美国 IQVIA 门诊电子病历数据库中，2008 年至 2018 年间，确定了使用激素避孕药的年龄在 15-45 岁的女性。使用 Cox 比例风险模型估计了与左炔诺孕酮和炔雌醇联合口服避孕药相比，使用 8 种避孕药时胆囊切除术的调整后风险比和 95%置信区间。通过滞后暴露 90 天和排除有胆囊疾病史的患者进行敏感性分析。还进行了按累积使用时间的二次分析。
我们确定了 1425821 名开始使用激素避孕药的女性，并生成了 4417 例胆囊切除术事件。总体而言，与左炔诺孕酮和炔雌醇联合口服避孕药相比，使用醋酸甲羟孕酮（HR：1.22，95%CI：1.07-1.40）和至少使用 1 年的左炔诺孕酮宫内节育器（HR：1.74：95%CI：1.19-2.54）与胆囊切除术风险增加相关。然而，我们没有观察到其他激素避孕药有增加风险。敏感性分析结果一致。
在这项大型基于人群的研究中，醋酸甲羟孕酮和宫内节育器会增加胆囊切除术的风险，但其他激素避孕药则不会。需要开展更多的大型观察性研究来证实这些发现。
