Efficacy and safety of hormone therapies for treating adenomyosis-associated pelvic pain: a systematic review and network meta-analysis of randomized controlled trials

Background: To date, there are no clear guidelines available on the treatment of adenomyosis-associated pelvic pain (AAPP); however, numerous hormonal treatments (HTs) are currently being used off-label. We conducted a systematic review and network metanalysis with the aim of assessing the efficacy and safety of HTs to reduce AAPP and ranking the available options. Methods: MEDLINE, LILACS, EMBASE, Scielo.br, PROSPERO, Cochrane Library, conference proceedings, and international registries were searched with no time, region, or language restrictions. Randomized controlled trials that analyzed AAPP in women undergoing HTs were deemed suitable. Results: Six studies (563 women affected by adenomyosis) were included. At 3 months, women who received a placebo or a levonorgestrel-based intrauterine system (LNG-IUS) experienced more AAPP than those who received dienogest [mean difference of visual analog scale (VAS) pain scores (MD) 4.10 (95% CI 0.49 to 7.71); high evidence; MD 3.05 (95% CI 0.45 to 5.65); high evidence]. At 6 months, women who received dienogest experienced significantly less AAPP compared to those who received combined oral contraceptives [MD -2.85 (95% CI -5.30 to -0.39); moderate evidence], while the prevalence of AAPP was higher among those who received a LNG-IUS than those who received dienogest [MD 1.79 (95% CI 0.06 to 3.53); low evidence]. Conclusion: Dienogest seems to be the most effective HT for AAPP. However, although rare, it is also related to more adverse effects compared to other HTs. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024535472.