Neurobiology Research Unit (Larsen, Ozenne, Frokjaer) and Department of Gynecology, Fertility, and Obstetrics, Juliane Marie Center (Mikkelsen, Lidegaard), Copenhagen University Hospital, Rigshospitalet, Copenhagen; Department of Clinical Medicine (Larsen, Lidegaard, Frokjaer) and Department of Public Health, Section of Biostatistics (Ozenne), University of Copenhagen, Copenhagen; Department of Gynecology and Obstetrics, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark (Mikkelsen); Psychiatric Research Unit, Department of Clinical Research, University of Southern Denmark, Odense (Munk-Olsen); National Center for Register-Based Research, Aarhus University, Aarhus, Denmark (Munk-Olsen); Psychiatric Center Copenhagen, Mental Health Services in the Capital Region of Denmark, Copenhagen (Frokjaer).
Am J Psychiatry. 2024 Sep 1;181(9):834-841. doi: 10.1176/appi.ajp.20230909. Epub 2024 Jul 10.
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).
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.
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.
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.
作者比较了初次使用低、中、高剂量左炔诺孕酮宫内释放系统（LNG-IUS）的患者发生抑郁的相关风险。
本项全国性队列研究基于丹麦登记处 2000 年至 2022 年初次使用 LNG-IUS 的年龄在 15-44 岁的患者数据。采用 Cox 回归和 G 公式估计器报告了 1 年平均绝对风险、风险差异和事件性抑郁的风险比（定义为开始使用抗抑郁药或接受抑郁诊断），按日历年份、年龄、教育程度、父母精神疾病史、子宫内膜异位症、月经过多、多囊卵巢综合征、痛经、子宫肌瘤和产后起始进行了标准化。
共有 149200 名女性开始使用 LNG-IUS，其中 22029 名使用了低剂量（平均年龄 22.9 岁[SD=4.5]），47712 名使用了中剂量（平均年龄 25.2 岁[SD=6.2]），79459 名使用了高剂量（平均年龄 30.2 岁[SD=5.6]）。随后，与低剂量和中剂量 LNG-IUS 使用者相比，使用高剂量 LNG-IUS 的患者在接下来的 1 年中发生抑郁的风险分别为 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）。对于高剂量 LNG-IUS 的使用者，与低剂量和中剂量 LNG-IUS 的使用者相比，风险比分别为 1.52（95%CI=1.30-1.74）和 1.26（95%CI=1.10-1.41）。对于中剂量 LNG-IUS 的使用者，与低剂量 LNG-IUS 的使用者相比，风险比为 1.21（95%CI=1.03-1.39）。
初次使用 LNG-IUS 与 LNG 剂量呈依赖性相关，与低、中、高剂量 LNG-IUS 均与事件性抑郁相关。尽管研究的观察性设计不允许进行因果推断，但剂量-反应关系有助于证明左炔诺孕酮暴露与抑郁风险之间存在关联。
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