Based on a 2021 Cochrane meta-analysis of four randomised controlled trials involving 157 women, the evidence supporting post-operative levonorgestrel-releasing intrauterine system (LNG-IUD) use for endometriosis is of very low to low certainty, primarily due to risk of bias and imprecision. Compared to expectant management, two studies suggested LNG-IUD may improve dysmenorrhoea at 12 months (RCT 1: median VAS 81 vs. 50, p= 0.006; RCT 2: VAS fall by 50 vs. 30, p= 0.021), but a meta-analysis was not possible. One study reported a significant improvement in quality of life with LNG-IUD (mean change to 70.3 vs. 57.0, p= 0.014), and another found higher patient satisfaction (RR 1.5; 95% CI 0.90 to 2.49). However, LNG-IUD was also associated with significantly higher rates of adverse events, specifically melasma (p=0.015) and bloating (p=0.021). In a single comparison with GnRH-a, the analysis found no conclusive evidence that LNG-IUD was superior for chronic pelvic pain at 12 months (MD -2.0; 95% CI -20.2 to 16.2) or dysmenorrhoea at six months (MD 1.70; 95% CI -0.14 to 3.54), though adverse event profiles differed. No studies reported on the primary outcome of overall pain. The authors concluded that there is no high-quality evidence to support this common practice, highlighting an urgent need for larger, well-designed trials focused on core outcomes like overall pain, the most troublesome symptom, and quality of life. [1]
A 2018 meta-analysis evaluated the efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS) as a postoperative maintenance therapy for endometriosis across seven studies involving a total of 491 patients. The analysis included four randomized controlled trials, one prospective cohort study, and two retrospective studies, utilizing databases such as MEDLINE, EMBASE, and Cochrane Library for literature spanning from 1986 to 2018. Outcomes were quantified using mean difference (MD), risk ratios (RR), or odds ratios (OR) within a meta-analysis model. The primary findings indicated that LNG-IUS significantly reduced pain following surgery, with a mean difference of 12.97 (95% CI 5.55 to 20.39), and demonstrated a similar effectiveness in pain reduction when compared to gonadotropin-releasing hormone analogues (MD -0.16; 95% CI -2.02 to 1.70). Furthermore, the LNG-IUS was effective in decreasing the recurrence rate of endometriosis (RR 0.40; 95% CI 0.26 to 0.64) and showed comparable outcomes to oral contraceptives and danazol. Patients reported higher satisfaction with LNG-IUS compared to oral contraceptives, as indicated by an odds ratio of 8.60 (95% CI 1.03 to 71.86). Despite these positive outcomes, an increased incidence of vaginal bleeding was observed among the LNG-IUS group, noted to be significantly higher than that in the gonadotropin-releasing hormone analogue group (RR 27.0; 95% CI 1.71 to 425.36). This rigorous meta-analysis underscores the potential of LNG-IUS as an effective postoperative maintenance strategy for endometriosis, particularly in terms of pain relief and patient satisfaction, while highlighting the need to manage side effects such as vaginal bleeding. [2]
A 2013 meta-analysis evaluated the efficacy, safety, and clinical benefits of the LNG-IUS compared to gonadotropin-releasing hormone analogues (GnRH-a) in premenopausal women with endometriosis. The analysis incorporated data from 5 RCTs, comprising 255 women who had undergone conservative surgery for endometriosis between January 1966 and April 2012 and had no immediate pregnancy plans. The results demonstrated that both LNG-IUS and GnRH-a were effective in reducing pain scores as measured by a visual analogue scale, with no statistically significant difference identified between the two treatment modalities (weighted mean difference [WMD] 0.03; 95% CI -0.53 to 0.59]). Additionally, significant reductions in serum CA125 levels (WMD -12.29; 95% CI -29.90 to 3.32) and improvements in American Society of Reproductive Medicine (ASRM) staging scores (WMD 1.10; 95% CI -27.98 to 30.18) were observed in both groups. Notably, the LNG-IUS also exhibited beneficial effects on lipid profiles, with significant reductions in total cholesterol (WMD 56.40; 95% CI 13.35 to 99.45; p= 0.01) and low-density lipoprotein cholesterol levels (WMD 39.30; 95% CI 6.74 to 71.86; p= 0.02) compared to GnRH-a. Side effects associated with LNG-IUS included irregular bleeding and simple ovarian cysts, while vasomotor symptoms and amenorrhea were more prevalent in the GnRH-a group. This meta-analysis underscored the potential of LNG-IUS as a cost-effective, convenient alternative with a favorable safety profile for the long-term management of endometriosis-associated symptoms. [3]
A 2020 systematic review and network meta-analysis evaluated the relative efficacy of various pharmacological interventions for the treatment of endometriosis-related pain. The study included 36 RCTs (N= 7,942 patients) and focused on primary outcomes such as changes in the severity of pelvic pain, dysmenorrhea, non-menstrual pelvic pain, and dyspareunia scores. Employing a frequentist approach, the study results indicated that, at the three-month mark, Dienogest, combined hormonal contraceptives (CHCs), and Elagolix ranked highest in reducing pelvic pain severity, whereas at six months, GnRH analogues, LNG-IUS, and Dienogest were most effective. For dysmenorrhea, GnRH analogues were superior at three months, while CHCs took precedence at six months. Additionally, GnRH analogues and Elagolix consistently emerged as the leading treatments for mitigating dyspareunia. The analysis concluded that these pharmacological interventions, alongside progesterone, present the most effective strategies for alleviating endometriosis-related pain. However, it highlighted a lack of robust evidence for the use of NSAIDs despite their prevalent use in clinical practice. [4]