The level of evidence is downgraded by study quality and upgraded by large magnitude of effect.
A Cochrane review «Levonorgestrel‐releasing intrauterine system for endometrial hyperplasia»1 «Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev 2020;(9):CD012658. »1 included 13 studies with 1657 subjects. The levonorgestrel-intrauterine system (LNG-IUS) improved regression of endometrial hyperplasia (EH) compared with non-intrauterine progestogens at short-term follow-up (up to 6 months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, n=1108). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH was improved by LNG-IUS compared with non-intrauterine progestogens at 12 months (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, n=138). The LNG-IUS was associated with fewer hysterectomies, fewer withdrawals from treatment due to hormone-related adverse effects, and improved patient satisfaction compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting and less nausea compared to non-intrauterine progestogens.
A prospective trial «Gezer Ş, Köle E, Aksoy L. Vaginal micronized progesterone versus the levonorgestrel-releasing intrauterine system for treatment of non-atypical endometrial hyperplasia: A randomized controlled trial. »2 randomized 144 women with non-atypical endometrial hyperplasia to vaginal micronized progesterone (progesterone) or to LNG-IUS. The regression rate after 3 months was not different between the groups (95.8% with LNG-IUS vs. 90.8% with progesterone).
A cohort study «Jareid M, Thalabard JC, Aarflot M, et al. Levonorgestrel-releasing intrauterine system use is associated with a decreased risk of ovarian and endometrial cancer, without increased risk of breast cance»3 consisted of 104 318 women from the Norwegian Women and Cancer Study, 9144 of whom were ever users and 95 174 of whom were never users of LNG-IUS. Exposure information was taken from self-administered questionnaires, and cancer cases were identified through linkage to the Cancer Registry of Norway. Median age at inclusion was 52 years and mean follow-up time was 12.5 years, for a total of 1 305 435 person-years. Among ever users of LNG-IUS there were 18 cases of epithelial ovarian cancer, 15 cases of endometrial cancer, and 297 cases of breast cancer. When ever users were compared to never users of LNG-IUS, the multivariable RR of ovarian, endometrial, and breast cancer was 0.53 (95% CI 0.32 to 0.88), 0.22 (0.13 to 0.40), and 1.03 (0.91 to 1.17), respectively.