Meta-analysis and network pharmacology studies of the clinical efficacy of Guizhi Fuling capsules/pills combined with dienogest in treating endometriosis

Endometriosis (EMs) is a common chronic inflammatory gynecological disease that belongs to the classification of Traditional Chinese Medicine Syndromes "Zheng Jia," and the classic Chinese formula Guizhi Fuling (GZFL) demonstrates significant clinical efficacy in the treatment of this condition. This study aims to investigate GZFL's effect and potential mechanism in EMs. The search reviewed randomized controlled trials in 7 databases from inception to 2024, assessed quality with the Cochrane tool, and analyzed data with STATA 15 by 2 reviewers. In the network pharmacology study, we searched and screened the components and targets of GZFL, subsequently compared these targets to EMs targets, and used bioinformatics techniques to analyze and explore their potential interactions. Nine randomized controlled trials involving 897 participants were analyzed. Meta-analysis showed that GZFL combined with dienogest significantly enhanced the clinical effectiveness rate (odds ratio = 2.404, 95% confidence intervals [CI], 1.868 to 3.093; P < .001). Specifically, combination therapy with GZFL reduced serum carbohydrate antigen 125 (standardized mean differences [SMD] = -1.65, 95% CI = -2.13 to -1.17, P < .001), estradiol (SMD = -1.54, 95% CI = -1.89 to -1.19, P = .003), matrix metalloproteinases (SMD = -2.636, 95% CI = -2.993 to -2.279, P < .001), pain scores (SMD = -0.88, 95% CI = -1.11 to -0.67, P < .001) and the diameter of ectopic cysts (SMD = -1.7, 95% CI = -2.42 to -0.98, P < .001). Network pharmacology analysis identified 136 components and 145 common targets, focusing on interleukin-6, cellular tumor antigen p53, epidermal growth factor receptor, estrogen receptor alpha, Cyclooxygenase-2, and matrix metalloproteinases-9. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested GZFL modulates hormone receptors and inflammatory responses in EMs treatment. In conclusion, GZFL combination treatment could increase the clinical effectiveness rate of EMs patients, and reduce the serum level of carbohydrate antigen 125, estradiol, matrix metalloproteinases, pain scores, and the diameter of the ectopic cyst. The potential mechanism might be linked to the modulation of hormone receptors and inflammation.