Depression risk in users of different doses of levonorgestrel intrauterine systems:a nationwide prospective cohort study

Background 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. Methods 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. Findings 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. Interpretation 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 ...