Meta-analysis Of The Safety And Efficacy Of GnRH-a Combined With Add-back Therapy In The Treatment Of Endometriosis

Objectives: The aim of this meta-analysis was to evaluate the efficacy and safety of GnRH-a combined with add-back therapy for long-term integrated management of endometriosis.Method: Such databases as CNKI,Wanfang,China Biomedical Literature Database(CBM),Pubmed,OVID,Embase,Medline,Cochrane Library were searched from inception of each database until March 2019.No language restrictions were applied.All randomized controlled trials(RCTs)of GnRH-a combined with add-back therapy for endometriosis were included.Two reviewers independently extracted the data and analyzed them in the RevMan Manager 5.3 software.Outcome: Nineteen RCTs were analyzed.(1)The serum estradiol level in the add-back group was higher than that in the blank or placebo group after treatment,and the difference was statistically significant [WMD = 51.29,95% CL(45.6-57.0),P< 0.001].The serum FSH level in the add-back group was lower than that in the blank or placebo group after treatment,and the difference was statistically significant[WMD=-1.93,95% CL(-2.40-1.46),P < 0.001].(2)The improved Kuperman score of GnRH-a combined with add-back group was lower than that of blank or placebo group after treatment.Add-back therapy could effectively improve the perimenopausal symptoms caused by GnRH-a.The difference was statistically significant [WMD=-8.13,95% CL(-13.05-3.20),P =0.001].The incidence of hot flashes in the add-back group was lower than that in the blank control group or placebo group,and the difference was statistically significant [OR= 0.06,95% CL(0.02-0.15),P < 0.001].(3)The bone mineral density of lumbar spine in the add-back group was higher than that in the blank or placebo group after treatment,and the difference was statistically significant [WMD = 0.03,95% CL(0.00-0.05),P = 0.02].(4)Bone mineral density decline rate of GnRH-a combined with add-back in Europe and America was less than that of blank or placebo group,the difference was statistically significant [WMD=-4.46,95% Cl(-4.89,-4.03),P < 0.001].GnRH-acombined with estrogen and progesterone in the treatment of bone loss in Asia was less than that in the blank or placebo group,the difference was statistically significant[WMD=-1.58,95% Cl(-2.75,-0.42),P < 0.001].(5)There was no statistical difference between GnRH-a combined with add-back and placebo pelvic pain score[WMD = 0.09,95% Cl(-0.07,0.24),P = 0.29].(6)There was no significant difference in serum LDL level between the add-back group and the blank control or placebo group [WMD = 0.00,95% Cl(-0.24,0.23),P = 0.98].There was no significant difference in serum triglyceride levels between the add-back group and the blank control group or the placebo group [WMD=-0.06,95% Cl(-0.19,0.06),P=0.34].The serum total cholesterol in the add-back group was higher than that in the blank control group or the placebo group,and the difference was statistically significant [WMD = 0.39,95% Cl(0.05,0.73),P = 0.03].Conclusion: Patients with endometriosis using GnRH-a combined with add-back therapy can effectively improve peri-menopausal symptoms,prevent bone loss,improve quality of life,and not affect the effect of GnRH-a on pelvic pain treatment.No significant impact at present,with good effectiveness and safety.