Levonorgestrel-releasing intrauterine system vs. systemic medication or blank control for women with dysmenorrhea: Systematic review and meta-analysis of randomized controlled trials

AIMS: To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with systemic medication or blank control in the treatment of dysmenorrhea. METHODS: PubMed, EMBASE, the China National Knowledge Infrastructure (CNKI) and Wanfang Data were searched to collect randomized controlled trials (RCTs) comparing LNG-IUS with systemic medication or blank control among women diagnosed with primary dysmenorrhea or secondary dysmenorrhea (adenomyosis or endometriosis) from inception to 2020.04. Der Simonian-Laird random-effect model was used to pool data. RESULTS: Seventy-one RCTs (6551 patients) were included. Overall bias risk was medium. Sixty-two articles enrolled patients with adenomyosis; LNG-IUS significantly reduced the visual analogue scale (VAS) score compared with the systemic medication group among adenomyosis women at 3 months (standardized mean difference (SMD) = −0.81, 95% confidence interval (CI) −1.22 to −0.40); 6 months (SMD = −1.25, 95%CI: −1.58 to −0.92); 9 months (SMD = −1.23, 95%CI: −1.63 to −0.83); 12 months (SMD = −1.66, 95%CI: −2.14 to −1.18). No difference was found in the incidence of irregular vaginal bleeding (16 RCTs; RR = 0.91, 95%CI: 0.62−1.33, P = 0.63, I(2 )= 4%) and other adverse outcomes. Sensitivity analysis regarding randomization methods was robust. Nine RCTs enrolled endometriosis women. Pooling results showed no significant difference between LNG-IUS and systemic medication treatment in terms of VAS at 6 months (SMD = −0.27, 95% CI: −0.97–0.43). Moreover, LNG-IUS was associated with higher risk of irregular vaginal bleeding (26.8% vs. 0). CONCLUSIONS: LNG-IUS was associated with a reduced severity of dysmenorrhea compared with systemic medication; it was also beneficial for better control of menstrual blood loss and fewer adverse outcomes. Owing to small sample sizes, further well-designed RCTs are warranted to confirm these findings and long-term effects of LNG-IUS in the treatment of dysmenorrhea. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021228343.