section name header

Evidence summaries

Levonorgestrel-Releasing Intrauterine System for Endometrial Hyperplasia

Levonorgestrel-releasing intrauterine system is effective for endometrial hyperplasia and appears to be more effective than non-intrauterine progestogens. Level of evidence: "A"

The level of evidence is downgraded by study quality and upgraded by large magnitude of effect.

Summary

A Cochrane review [Abstract] 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 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 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.

Clinical comments

Note

Date of latest search: 2024-03-11

    References

    • Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev 2020;(9):CD012658. [PubMed]
    • 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. Int J Gynaecol Obstet 2023;161(2):661-666 [PubMed]
    • 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 cancer. Results from the NOWAC Study. Gynecol Oncol 2018;149(1):127-132 [PubMed]

Primary/Secondary Keywords