The role of different LNG-IUS therapies in the management of adenomyosis: a systematic review and meta-analysis

Abstract

Objective: To summarize evidence on the efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) in managing adenomyosis (AM), both as a monotherapy and in combination with other therapies.

Methods: We searched Medical Literature Analysis and Retrieval System On-Line: Medline, The Cochrane Library, Embase, SinoMed, China National Knowledge Infrastructure, and Wanfang from the inception to Aug 12, 2024 for articles using the LNG-IUS both alone and combined with other therapies in patients with AM. The primary outcome included dysmenorrhea, menstrual bleeding, uterine volume, endometrial thickness and quality of life. The secondary outcome was the assessment of adverse events. Data synthesis was conducted using random-effects model with significant heterogeneity (I² > 50%), otherwise using fixed-effects model.

Results: The final analysis included 28 studies. Compared with etonogestrel, LNG-IUS was more effective in reducing uterine volume and associated with a lower risk of weight gain, but showed no significant difference in reducing dysmenorrhea and endometrial thickness. Comparing LNG-IUS with mifepristone, there was no significant difference in terms of quality of life. The combination of LNG-IUS with Gonadotropin-releasing hormone agonists (GnRH-a) was more effective than LNG-IUS alone, providing benefits in reducing dysmenorrhea (mean deviation, MD: -1.14), menstrual bleeding (MD: -11.94), uterine volume (MD: -30.39), endometrial thickness (MD: -0.89), and adverse events. The combination of LNG-IUS with surgical excision was more effective than surgical excision alone, providing benefits in reducing dysmenorrhea (MD: -1.49), menstrual bleeding (MD: -5.13) at 12 months, reducing uterine volume at 6 (MD: -9.23), 12 (MD: -16.53) and 24 (MD: -27.17) months. The combination of LNG-IUS with focused ultrasound ablation (FUA) was more effective than FUA alone, providing benefits in reducing dysmenorrhea (MD: -0.62), menstrual bleeding (MD: 0.17).

Conclusions: This study found no clear evidence to recommend single-drug therapy for improving pain and quality of life in AM management within 12 months. Combining LNG-IUS with GnRH-a is effective in alleviating pain, controlling heavy bleeding, reducing lesion volume, reducing the probability of expulsion and irregular bleeding. Postoperative LNG-IUS helps reduce long-term pain and bleeding. In combined FUA, LNG-IUS is effective for managing short-term pain and bleeding.

Trial registration: PROSPERO registration number: CRD42024578824.

Keywords: Adenomyosis; Efficiency; LNG-IUS; Safety; Treatment.

Fig. 1

PRISMA 2020 flowchart representing the study selection process

Fig. 2

Forest plot of the pain score after LNG-IUS insertion or etonogestrel subcutaneous implantation

Fig. 3

Forest plot of the uterus volume after LNG-IUS insertion or etonogestrel subcutaneous implantation

Fig. 4

Forest plot of the endometrial thickness after LNG-IUS insertion or etonogestrel subcutaneous implantation

Fig. 5

Forest plot of the adverse effects after LNG-IUS insertion or etonogestrel subcutaneous implantation

Fig. 6

Forest plot of the quality of life after LNG-IUS insertion or mifepristone treatment at 6-month follow-up

Fig. 7

Forest plot of the quality of life after LNG-IUS insertion or mifepristone treatment at 12-month follow-up

Fig. 8

Forest plot of the pain score after GnRH-a + LNG-IUS or LNG-IUS only

Fig. 9

Forest plot of the PBAC after GnRH-a + LNG-IUS or LNG-IUS only

Fig. 10

Forest plot of the uterine volume after GnRH-a + LNG-IUS or LNG-IUS only

Fig. 11

Forest plot of the endometrial thickness after GnRH-a + LNG-IUS or LNG-IUS only

Fig. 12

Forest plot of the adverse effects after GnRH-a + LNG-IUS or LNG-IUS only

Fig. 13

Forest plot of the pain score points after surgical excision + LNG-IUS insertion or surgical excision only

Fig. 14

Forest plot of the PBAC after surgical excision + LNG-IUS or surgical excision only

Fig. 15

Forest plot of the uterine volume after surgical excision + LNG-IUS or surgical excision only

Fig. 16

Forest plot of the change in the pain score after FUA + LNG-IUS or FUA only

Fig. 17

Forest plot of the effect of dysmenorrhea after FUA + LNG-IUS or FUA only

Fig. 18

Forest plot of the change in the PBAC after FUA + LNG-IUS or FUA only