Skovlund Charlotte Wessel, Møller Amalie Lykkemark, Torp-Pedersen Christian, Mørch Lina Steinrud, Meaidi Amani
Cancer and Medicine, The Danish Cancer Institute, Copenhagen, Denmark.
Department of Public Health, University of Copenhagen, Denmark.
Lancet Reg Health Eur. 2024 Jan 5;38:100813. doi: 10.1016/j.lanepe.2023.100813. eCollection 2024 Mar.
Use of the high-dose levonorgestrel-releasing intrauterine system (LNG-IUS) has been associated with increased risk of incident depression. Evidence is lacking on the influence of use of two recently marketed low-dose LNG-IUS on risk of depression. This study aims to examine associations between use of different doses of LNG-IUS and risk of depression.
We conducted a nationwide prospective cohort study involving all first-time users of an LNG-IUS among all Danish nulliparous women aged 15-34 years with no medical history of depression, major psychiatric diseases, endometriosis, heavy menstrual bleeding, polyp, myoma, dysmenorrhoea, iron supplement use, abortion, and infertility treatment.
A total of 46,565 first-time users of LNG-IUS were followed for 80,516 person-years with 1,531 incident initiations of antidepressant use observed during follow-up. Use of the high-dose LNG-IUS containing 52 mg levonorgestrel was initiated by 9,902 (21%) women, while 20,665 (44%), and 15,998 (34%) initiated use of the low-dose LNG-IUS containing 19·5 mg and 13·5 mg levonorgestrel, respectively.The age-, calendar-time-, and education-standardised incidence rates of first-time depression per 1,000 person-years at full LNG-IUS duration were 30.8 (95% CI 23·6-39·5) for the 52 mg LNG-IUS, 19·8 (95% CI 16·1; 24·0) for the 19·5 mg LNG-IUS, and 17·7 (95% CI 14·4-21·5) for the 13·5 mg LNG-IUS-. Compared to the high-dose 52 mg LNG-IUS, the adjusted number of avoided depressions per 1,000 person-years were 11·0 (95% CI 7·1-14·9) for the 19·5 mg LNG-IUS and 13·1 (95% CI 9·6-16·6) for the 13·5 mg LNG-IUS. The corresponding adjusted rate ratios were 0·77 (95% CI 0·68; 0·88) and 0·85 (95% CI 0·75-0·96). The reduced risk of depression with low-dose LNG-IUS compared to high-dose LNG-IUS was observable throughout duration of use.
Use of low-dose LNG-IUS containing 19·5 mg and 13·5 mg levonorgestrel, respectively, were associated with a reduced risk of incident depression compared to use of the high-dose 52 mg LNG-IUS. The study suggests that low-dose LNG-IUS should be preferred over the high-dose LNG-IUS for contraceptive purpose.
Sygeforsikringen "Danmark" grant: 2021-0128.
使用高剂量左炔诺孕酮宫内节育系统（LNG-IUS）与新发抑郁症风险增加有关。目前缺乏关于两种近期上市的低剂量LNG-IUS的使用对抑郁症风险影响的证据。本研究旨在探讨不同剂量LNG-IUS的使用与抑郁症风险之间的关联。
我们在丹麦全国范围内开展了一项前瞻性队列研究，纳入了所有年龄在15至34岁、无抑郁症病史、无重大精神疾病、无子宫内膜异位症、无月经过多、无息肉、无肌瘤、无痛经、未使用铁补充剂、无流产史及未接受不孕症治疗的丹麦未生育女性中所有首次使用LNG-IUS的人群。
共有46565名首次使用LNG-IUS的女性被随访了80516人年，随访期间观察到1531例开始使用抗抑郁药的新发病例。9902名（21%）女性开始使用含52mg左炔诺孕酮的高剂量LNG-IUS，而分别有20665名（44%）和15998名（34%）女性开始使用含19.5mg和13.5mg左炔诺孕酮的低剂量LNG-IUS。在LNG-IUS全程使用中，每1000人年的年龄、日历时间和教育程度标准化的首次抑郁症发病率，52mg LNG-IUS为30.8（95%CI 23.6 - 39.5），19.5mg LNG-IUS为19.8（95%CI 16.1 - 24.0），13.5mg LNG-IUS为17.7（95%CI 14.4 - 21.5）。与高剂量52mg LNG-IUS相比，每1000人年19.5mg LNG-IUS避免抑郁症发生的调整人数为11.0（95%CI 7.1 - 14.9），13.5mg LNG-IUS为13.1（95%CI 9.6 - 16.6）。相应的调整率比分别为0.77（95%CI 0.68 - 0.88）和0.85（95%CI 0.75 - 0.96）。在整个使用期间，与高剂量LNG-IUS相比，低剂量LNG-IUS降低抑郁症风险的效果均明显可见。
与使用高剂量52mg LNG-IUS相比，分别使用含19.5mg和13.5mg左炔诺孕酮的低剂量LNG-IUS与新发抑郁症风险降低有关。该研究表明，出于避孕目的，低剂量LNG-IUS应比高剂量LNG-IUS更受青睐。
丹麦疾病保险基金资助：2021 - 0128。
