Levonorgestrel-releasing Intrauterine System (LNG-IUS), 52 mg  Use in the treatment of endometriosis  

Clinical Data

• da Costa Porto et al (2024)¹ conducted a prospective, randomized open-label clinical trial to investigate the effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) compared to dienogest (DNG) in enhancing the quality of life (QoL) for women with deep infiltrating endometriosis (DIE) and no previous surgical treatment. Forty-two women were randomized but only 40 women were analyzed as 2 discontinued their treatment. Participants underwent a 3-month washout of hormonal treatments before receiving either LNG-IUS 52 mg (Mirena®) or DNG 2 mg (Kalist®) for six months. Since the route of drug administration was different, the participants and researchers were not blinded after the treatments were assigned. Participants received monthly follow-ups. QoL was measured using the Short Form 36 Health Survey (SF36) and the Endometriosis Health Profile Questionnaire (EHP30) at baseline and after 6 months of treatment.
  The two treatment groups showed no statistical difference with respect to age, body mass index and parity. At baseline, the SF36 questionnaire found no statistically significant difference in the perception of QoL between the 2 groups. After 6 months of treatment, both groups demonstrated significant improvements in QoL across all domains of the SF36 and EHP30, with no statistically significant differences between the two groups. Two adverse events were reported, one in each treatment group both resulting in discontinuation: LNG-IUS (expulsion, n=1) and DNG (intolerance, n=1).¹
• Zheng et al (2023)² conducted a meta-analysis of 44 randomized controlled trials (RCTs) (4576 patients, average age 32.5 years) to evaluate the efficacy and safety of LNG-IUS, DNG, leuprolide, danazol, gestrinone and mifepristone in relieving symptoms and delaying the recurrence of endometriosis cysts after fertility preservationg surgery. Comparing the surface under the cumulative ranking (SUCRA) of each outcome for each product showed that LNG-IUS and DNG were superior to the other 5 interventions at improving endometriosis symptoms and reducing the recurrence rate of endometriosis in patients undergoing fertile-preserving surgery, both with a tolerable safety profile.
• Chiu et al (2022)³ conducted a systematic review and network meta-analysis of 11 studies (2394 patients), which included 2 RCTs and 9 cohort studies, to compare the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (ie, oral contraceptive pills [OCPs], DNG, LNG-IUS) on endometrioma recurrence. Except for GnRHa, all interventions including combined therapy of GnRHa plus LNG-IUS intervention (odds ratio [OR] = 0.13; 95% Confidence Interval [CI], 0.03−0.66), SUCRA = 59.4, significantly decreased postoperative endometriotic recurrence compared to expectant management.
• Gibbons et al (2021)⁴ conducted a systematic review of medical databases and identified 4 RCTs (n=157) to determine if the levonorgestrel-releasing intrauterine device (LNG-IUD) improves pain symptoms, QoL, patient satisfaction and adverse events when inserted postoperatively in women undergoing surgery for endometriosis, compared with expectant management, postoperative placebo (inert IUD), or alternative postoperative medical treatment (e.g. GnRHa). With regard to pain symptoms for LNG-IUD versus GnRHa, no studies reported on the primary outcome of overall pain. There was uncertainty whether LNG-IUD improves chronic pelvic pain at 12 months when compared to GnRHa (visual analogue scale [VAS] pain scale) (mean difference [MD] -2.0, 95% CI -20.2 to 16.2, 1 RCT, n = 40, very low-certainty evidence). There was uncertainty whether LNG-IUD improves dysmenorrhoea at six months when compared to GnRHa (measured as a reduction in VAS pain score) (MD 1.70, 95%.CI -0.14 to 3.54, 1 RCT, n = 22, very low-certainty evidence).
• Margatho et al (2020)⁵ conducted an open-label, parallel-group randomized trial to 1) compare pain outcomes in women with endometriosis-associated dysmenorrhea (stage I-IV) and chronic pelvic pain; and 2) evaluate the correlation of levels of serum LNG and etonogestrel (ENG) with dysmenorrhea and chronic pelvic pain and the biomarkers CA-125 and soluble CD23.The participants (n=103) were randomized to receive the ENG implant (n=52) or the LNGIUS 52 mg (n=51). Follow-up was conducted every 6 months for up to 24 months after device placement. Both progestin-only contraceptives significantly reduced VAS scores for dysmenorrhea and chronic pelvic pain and reduced serum levels of soluble CD23 (P < 0.001). No correlation was found between pain scores and ENG or LNG serum levels over time (P > 0.005). The original RCT was conducted by Carvalho et al (2018)6 and described endometriosisassociated chronic pelvic pain scores up to 6 months for all participants (n=103). Both treatment groups improved significantly the mean VAS endometriosis-associated pelvic pain and dysmenorrhea and health-related QoL in endometriosis.
• Song et al (2018)⁷ conducted a systematic review and selected 7 studies (including 4 RCTs) that compared the efficacy of LNG-IUS with other treatments as postoperative maintenance therapy for endometriosis in terms of pain reduction, recurrence prevention, side effects and patient satisfaction. LNG-IUS significantly decreased pain associated with endometriosis (MD 12.97, 95% CI: 5.55-20.39). This pain reduction did not significantly differ compared to GnRHa (MD = -0.16, 95% CI: -2.02 to 1.70). LNG-IUS significantly reduced the recurrence of endometrioma or dysmenorrhea (risk ratio [RR] = 0.40, 95% CI: 0.26-0.64). There were no significant differences in terms of endometriosis and dysmenorrhea recurrence between LNG-IUS and oral contraceptives (OC) [OR = 1.00, 95% CI: 0.25-4.02]. There was no significant difference in the recurrence of endometrioma between LNG-IUS and danazol (RR = 0.30, 95% CI: 0.03-2.81). Patients treated with LNG-IUS had a significantly more frequent rate of irregular vaginal bleeding compared to GnRHa (RR = 27.0, 95% CI: 1.71-425.36). Patients treated with LNG-IUS had significantly higher patient satisfaction than those treated with OC (OR = 8.60, 95% CI: 1.03-71.86).