{"paper_id":"5d55f2bf-5bfb-4de2-97c0-7b98d78ba3f9","body_text":"INTRODUCTION \nReview question / Objective: The aim of \nthis systematic review is to compare \nleuprolide acetate combined with Mirena \nand leuprolide acetate or Mirena or \nPlacebo alone in terms of e fficacy and \nacceptability in the adenomyosis to better \ninform clinical practice. To this end, the \nproposed systematic review will address \nthe following question: Which is the best \nchoice to reduce VRS dysmenorrhea score \nor PBAC menstrual volume score or Serum \nmatrix metalloproteinase (MMP) 2 and 9 or \nvascular endothelial growth factor (VEGF) \nin adenomyosis, leuprolide acetate \ncombined with Mirena or leuprolide acetate \nor Mirena or Placebo alone. \nINPLASY 1\nInternational Platform of Registered Systematic Review and Meta-analysis Protocols\nINPLASY\nPROTOCOL\nThe efficacy and safety of leuprolide \nacetate combined with Mirena in the \ntreatment of adenomyosis: a systematic \nreview and meta-analysis\nChen, JM1; Wu, M2; Li, WJ3; Jian, ZP4.\nTo cite: Chen et al. The \nefficacy and safety of \nleuprolide acetate combined \nwith Mirena in the treatment of \nadenomyosis: a systematic \nreview and meta-analysis. \nInplasy protocol 2021100059. \ndoi: \n10.37766/inplasy2021.10.0059\nReceived: 17 October 2021\nPublished: 17 October 2021\nReview question / Objective: The aim of this systematic \nreview is to compare leuprolide acetate combined with Mirena \nand leuprolide acetate or Mirena or Placebo alone in terms of \nefficacy and acceptability in the adenomyosis to better inform \nclinical practice. To this end, the proposed systematic review \nwill address the following question: Which is the best choice \nto reduce VRS dysmenorrhea score or PBAC menstrual \nvolume score or Serum matrix metalloproteinase (MMP) 2 and \n9 or vascular endothelial growth factor (VEGF) in \nadenomyosis, leuprolide acetate combined with Mirena or \nleuprolide acetate or Mirena or Placebo alone. \nInformation sources: A systematic search conducts in the \nCochrane library, Embase, Pubmed and Web of Science. \nCNKI, CBM, et al. \nINPLASY registration number: This protocol was registered with \nthe International Platform of Registered Systematic Review and \nMeta-Analysis Protocols (INPLASY) on 17 October 2021 and was \nlast updated on 17 October 2021 (registration number \nINPLASY2021100059). \nCorresponding author: \nChen Jinman \n021323@gzucm.edu.cn \nAuthor Affiliation:                  \nGuangzhou University of \nChinese medicine. \nSupport: No Support. \nReview Stage at time of this \nsubmission: Preliminary \nsearches. \nConflicts of interest:          \nNone declared.\nChen et al. Inplasy protocol 2021100059. doi:10.37766/inplasy2021.10.0059\nChen et al. Inplasy protocol 2021100059. doi:10.37766/inplasy2021.10.0059 Downloaded from https://inplasy.com/inplasy-2021-10-0059/\n\nCondition being studied: Adenomyosis is a \nb e n i g n u t e r i n e d i s o rd e r i n w h i c h \nendometrial glands and stroma are \npathologically demonstrated in the \nm y o m e t r i u m . Wo m e n affe c t e d b y \nadenomyosis may present with abnormal \nuterine bleeding (AUB), dysmenorrhea, \ndyspareunia, or infertility but one third of \nthem are asymptomatic. The treatment of \nadenomyosis includes drug treatment and \nsurgical treatment. Patients who are young \nor have fertility requirements could choose \ndrug treatment; those who do not have \nfertility requirements, have severe \nsymptoms, and have failed conservative \ntreatment can choose surgical treatment; \nthose with prominent dysmenorrhea \nsymptoms can be treated with conservative \nsurgery. Surgical treatment includes total \nhysterectomy; conservative surgery \ni n c l u d e s e n d o m e t r i a l a b l a t i o n , \nh y s t e r o s c o p i c e n d o m e t r i a l a n d \nadenomyoma resection, but conservative \nsurgery is controversial, and exists risks for \npatients with fertility requirements. \nTherefore, more and more patients choose \nmedication. Based on the pathogenic \nmechanism, several drug hormonal and \nnon-hormonal treatments are used to treat \npain and bleeding and improve fertility \nr e s u l t s . F o r e x a m p l e , G n R H a , \nprogesterone, levonorgestrel intrauterine \nsustained release system (LNG-IUS ，\nMirena) and so on. In recent years, related \nstudies have found that the combined \ntreatment of leuprolide acetate and Mirena \nis effective in the treatment of muscular \nadenomyosis. The article conducts a \nsystematic review and meta-analysis of the \ncombined treatment of leuprolide acetate \nand Mirena in the treatment of muscular \nadenomyosis，in order to provide more \nclinical evidence for the treatment of \nmuscular adenomyosis. \nMETHODS \nParticipant or population: Patients with \nadenomyosis. \nIntervention: Leuprolide acetate combined \nwith Mirena. \nComparator: Leuprolide acetate or Mirena \nor other interventions. \nStudy designs to be included: Randomized \ncontrolled trials (RCTs). \nEligibility criteria: Inclued：(1) randomized \ncontrolled studies; (2) Patients in the \nexperimental group were treated with \nleuprolide acetate combined with Mirena \nwhile patients in the control group received \nother medications, such as leuprolide \nacetate or Mirena or Placebo alone; (3) The \nprimary outcome is the improvement in \npain associated with endometriosis, other \noutcomes include side effects and changes \nin the clinical laboratory parameters. Meta-\na n a l y s e s , r e v i e w s , c a s e r e p o r t s , \nconference abstracts, cohort studies ，\nretrospective studies and trails without \navailable data are excluded. \nInformation sources: A systematic search \nconducts in the Cochrane library, Embase, \nPubmed and Web of Science. CNKI, CBM, \net al. \nMain outcome(s): The primary efficacy \noutcome is changes in VRS dysmenorrhea \nscore, PBAC menstrual volume score; \nSerum matrix metalloproteinase (MMP) 2 \nand 9/vascular endothelial growth factor \n(VEGF) and so on. \nQuality assessment / Risk of bias analysis: \nTo assess study quality, the Cochrane risk \nof bias assessment tool will be used. Seven \ndomains related to risk of bias are \nassessed in each study: (1) random \nsequence generation; (2) allocation \nconcealment; (3) blinding of participants \nand personnel; (4) blinding of outcome \nassessment; (5) incomplete outcome data; \n(6) selective reporting; (7) other bias. \nStrategy of data synthesis: The Review \nManager 5.3 software are used to conduct \nt h e m e t a - a n a l y s i s . I f t h e re i s n o \nheterogeneity, choose fixed effects to \nmerge data; if there is heterogeneity, first \nexamine the source of the heterogeneity, \nand then choose an appropriate method to \nmerge. For example, if the source of \nINPLASY 2\nChen et al. Inplasy protocol 2021100059. doi:10.37766/inplasy2021.10.0059 Downloaded from https://inplasy.com/inplasy-2021-10-0059/\nChen et al. Inplasy protocol 2021100059. doi:10.37766/inplasy2021.10.0059\n\nheterogeneity is statistical heterogeneity, \nwe would choose to merge data with \nrandom effects. \nSubgroup analysis: Divide into subgroups \nbased on control measures，Subgroup 1: \nLeuprolide acetate alone; Subgroup 2: \nMirena; Subgroup 3: Placebo. \nSensitivity analysis: If a sufficient number \nof studies are identified for inclusion, we \nwill conduct sensibility analysis by \neliminating studies one by one to find the \nsource of heterogeneity. \nCountry(ies) involved: China. \nKeywords: Adenomyosis; leuprolide \nacetate; Mirena.  \nContributions of each author: \nAuthor 1 - Chen Jinman. \nAuthor 2 - Wu Man. \nAuthor 3 - Li Weijie. \nAuthor 4 - Jian Zhengpu. \nINPLASY 3\nChen et al. Inplasy protocol 2021100059. doi:10.37766/inplasy2021.10.0059 Downloaded from https://inplasy.com/inplasy-2021-10-0059/\nChen et al. Inplasy protocol 2021100059. doi:10.37766/inplasy2021.10.0059","source_license":"CC0","license_restricted":false}