OBJECTIVE The authors compared the associated risk of incident depression between first-time users of low-, medium-, and high-dose levonorgestrel-releasing intrauterine systems (LNG-IUSs). METHODS This national cohort study was based on Danish register data on first-time users of LNG-IUSs, 15-44 years of age, between 2000 and 2022. Cox regression and a G-formula estimator were used to report 1-year average absolute risks, risk differences, and risk ratios of incident depression, defined as initiation of an antidepressant or receipt of a depression diagnosis, standardized for calendar year, age, education level, parental history of mental disorders, endometriosis, menorrhagia, polycystic ovary syndrome, dysmenorrhea, leiomyoma, and postpartum initiation. RESULTS In total, 149,200 women started using an LNG-IUS, among whom 22,029 started a low-dose one (mean age, 22.9 years [SD=4.5]), 47,712 a medium-dose one (mean age, 25.2 years [SD=6.2]), and 79,459 a high-dose one (mean age, 30.2 years [SD=5.6]). The associated subsequent 1-year adjusted absolute risks of incident depression were 1.21% (95% CI=1.06-1.36), 1.46% (95% CI=1.33-1.59), and 1.84% (95% CI=1.72-1.96), respectively. For the users of high-dose LNG-IUSs, the risk ratios were 1.52 (95% CI=1.30-1.74) and 1.26 (95% CI=1.10-1.41) compared with users of the low- and medium-dose LNG-IUSs, respectively. For users of medium-dose LNG-IUSs, the risk ratio was 1.21 (95% CI=1.03-1.39) compared with users of low-dose LNG-IUSs. CONCLUSIONS First-time use of an LNG-IUS was positively associated with incident depression in an LNG-dose-dependent manner across low-, medium-, and high-dose LNG-IUSs. Although the observational design of the study does not permit causal inference, the dose-response relationship contributes to the body of evidence suggesting a relationship between levonorgestrel exposure and risk of depression.

中文翻译：

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宫内系统激素剂量与抑郁风险之间的关联。


目的 作者比较了首次使用低剂量、中剂量和高剂量左炔诺孕酮宫内缓释系统 (LNG-IUS) 时发生抑郁症的相关风险。方法 这项全国队列研究基于丹麦 2000 年至 2022 年间 15-44 岁首次使用 LNG-IUS 使用者的登记数据。使用 Cox 回归和 G 公式估计器报告 1 年平均绝对值发生抑郁症的风险、风险差异和风险比，定义为开始服用抗抑郁药物或接受抑郁症诊断，按日历年、年龄、教育水平、父母精神障碍史、子宫内膜异位症、月经过多、多囊卵巢综合征、痛经进行标准化、平滑肌瘤和产后起始。结果 总共有 149,200 名女性开始使用 LNG-IUS，其中 22,029 名女性开始使用低剂量的 LNG-IUS（平均年龄，22.9 岁 [SD=4.5]），47,712 名女性开始使用中剂量的 LNG-IUS（平均年龄，25.2 岁 [SD=4.5]）。 6.2]），79,459 名高剂量患者（平均年龄，30.2 岁 [SD=5.6]）。随后 1 年调整后发生抑郁症的绝对风险分别为 1.21% (95% CI=1.06-1.36)、1.46% (95% CI=1.33-1.59) 和 1.84% (95% CI=1.72-1.96)。分别。对于高剂量 LNG-IUS 使用者，与中低剂量 LNG-IUS 使用者相比，风险比分别为 1.52（95% CI=1.30-1.74）和 1.26（95% CI=1.10-1.41）。 ， 分别。与低剂量 LNG-IUS 用户相比，中剂量 LNG-IUS 用户的风险比为 1.21（95% CI=1.03-1.39）。结论 首次使用 LNG-IUS 与低、中、高剂量 LNG-IUS 的抑郁事件呈正相关，且呈 LNG 剂量依赖性。 尽管该研究的观察性设计不允许因果推断，但剂量反应关系有助于提供大量证据，表明左炔诺孕酮暴露与抑郁症风险之间存在关系。