Ⅰ型子宫腺肌病患者放置左炔诺孕酮宫内节育系统前应用不同剂量米非司酮预处理疗效比较

Comparison of curative effect of different doses of mifepristone in pretreatment of type Ⅰ adenomyosis patients before placement of levonorgestrel-releasing intrauterine system

目的探讨Ⅰ型子宫腺肌病(AM)患者放置左炔诺孕酮宫内节育系统前应用不同剂量米非司酮预处理的疗效及不良反应。方法选择2017年1月至2019年5月徐州医科大学附属连云港东方医院收治的子宫明显增大且不愿接受手术治疗的Ⅰ型AM患者150例为研究对象,按照数字表法将患者随机分为A组、B组和C组,每组50例。3组患者均于月经周期第1~3天开始口服米非司酮进行预处理,每晚睡前1次。A组、B组和C组患者服用米非司酮的剂量分别为6.25、12.50、25.00 mg。直至宫腔深度≤8 cm时放置左炔诺孕酮宫内节育系统。分别于预处理前及预处理3个月后检测3组患者的宫腔深度、子宫体积、子宫内膜厚度、月经量及痛经疼痛程度,采用酶联免疫吸附法检测3组患者血清中雌二醇、孕酮、促卵泡生成素、糖类抗原125(CA125)水平;使用血细胞分析仪检测3组患者血红蛋白水平。记录药物预处理时间及药物不良反应;记录患者置入左炔诺孕酮宫内节育系统后6个月内左炔诺孕酮宫内节育系统相关不良反应发生情况。结果预处理前3组患者的宫腔深度、子宫体积、子宫内膜厚度、月经失血图(PBAC)评分及痛经视觉模拟评分法(VAS)评分比较差异均无统计学意义(P>0.05)。预处理3个月后3组患者的宫腔深度、子宫体积、子宫内膜厚度、PBAC评分及痛经VAS评分低于预处理前(P<0.05)。预处理3个月后,B组和C组患者的宫腔深度、子宫体积、子宫内膜厚度、PBAC评分及痛经VAS评分均低于A组(P<0.05);B组与C组各指标比较差异均无统计学意义(P>0.05)。3组患者预处理前血清中雌二醇、孕酮、促卵泡生成素、CA125及血红蛋白水平比较差异均无统计学意义(P>0.05)。3组患者预处理3个月后雌二醇、孕酮、促卵泡生成素、CA125水平低于预处理前,血红蛋白水平高于预处理前(P<0.05)。预处理3个月后,B组和C组患者的雌二醇、孕酮、促卵泡生成素及CA125水平低于A组,血红蛋白高于A组(P<0.05);C组患者的雌二醇、孕酮、促卵泡生成素及CA125水平低于B组,血红蛋白高于B组(P<0.05)。A组患者米非司酮预处理时间长于B组和C组(P<0.05);B组与C组患者米非司酮预处理时间比较差异无统计学意义(P>0.05)。A组、B组、C组患者药物不良反应发生率分别为4.0%(2/50)、18.0%(9/50)、42.0%(21/50),A组患者药物不良反应发生率低于B组(χ^(2)=5.005,P<0.05);B组患者药物不良反应发生率低于C组(χ^(2)=6.857,P<0.05)。A组、B组、C组患者左炔诺孕酮宫内节育系统相关不良反应发生率分别为34.0%(17/50)、12.0%(6/50)、8.0%(4/50),B组和C组患者左炔诺孕酮宫内节育系统相关不良反应发生率低于A组(χ^(2)=6.832、10.187,P<0.05);B组与C组患者左炔诺孕酮宫内节育系统相关不良反应发生率比较差异无统计学意义(χ^(2)=0.444,P>0.05)。结论米非司酮每日12.5 mg的剂量用于Ⅰ型AM患者放置左炔诺孕酮宫内缓释系统前预处理临床疗效较好,不良反应少,值得临床推荐。

Objective To investigate the efficacy and side effects of different doses of mifepristone in pretreatment of type Ⅰ adenomyosis(AM) patients before placement of levonorgestrel-releasing intrauterine system.Methods A total of 150 type I AM patients with significantly enlarged uterus and unwilling to receive surgical treatment in Lianyungang Municipal Oriental Hospital Affiliated to Xuzhou Medical University from January 2017 to May 2019 were selected as the research objects.The patients were randomly divided into group A,group B and group C according to the digital table method, with 50 cases in each group.All patients began to take orally mifepristone on the first day to the third day of the menstrual cycle, once every night before going to bed.The doses of mifepristone in group A,group B,group C were 6.25,12.50 and 25.00 mg respectively.Levonorgestrel-releasing intrauterine system was placed until the depth of uterine cavity ≤ 8 cm.Before and 3 months after pretreatment, the depth of uterine cavity, uterine volume, endometrial thickness, menstrual volume and degree of dysmenorrhea of patients in the three groups were detected;the serum levels of estradiol, progesterone, follicle stimulating hormone and carbohydrate antigen 125(CA125) of patients in the three groups were detected by enzyme-linked immunosorbent assay;the hemoglobin level of patients in the three groups was detected by blood cell analyzer.The time of drug pretreatment and adverse drug reactions were recorded;the incidence of adverse reactions related to levonorgestrel-releasing intrauterine system in 6 months after levonorgestrel-releasing intrauterine system was implanted.Results There was no significant difference in depth of uterine cavity, uterine volume, endometrial thickness, pictorial blood loss assessment chart(PBAC) score and dysmenorrhea visual analogue scale(VAS) score of patients among the three groups before pretreatment(P>0.05).The depth of uterine cavity, uterine volume, endometrial thickness, PBAC score and VAS score of dysmenorrhea of patients after 3 months of pretreatment were lower than those before pretreatment in the three groups(P<0.05).After 3 months of pretreatment, the depth of uterine cavity, uterine volume, endometrial thickness, PBAC score and dysmenorrhea VAS score of patients in group B and group C were lower than those in group A(P<0.05);there was no significant difference in above indexes of patients between group B and group C(P>0.05).There was no significant difference in the levels of estradiol, progesterone, follicle stimulating hormone, CA125 and hemoglobin of patients among the three groups before pretreatment(P>0.05).After 3 months of pretreatment, the levels of estradiol, progesterone, follicle stimulating hormone and CA125 of patients were lower than those before pretreatment, and the level of hemoglobin was higher than that before pretreatment(P<0.05).After 3 months of pretreatment, the levels of estradiol, progesterone, follicle stimulating hormone and CA125 of patients in group B and group C were lower than those in group A,and the level of hemoglobin of patients was higher than that in group A(P<0.05);the levels of estradiol, progesterone, follicle stimulating hormone and CA125 of patients in group C were lower than those in group B,and the level of hemoglobin was higher than that in group B(P<0.05).The pretreatment time of mifepristone in group A was longer than that in group B and group C(P<0.05);there was no significant difference in pretreatment time of mifepristone between group B and group C(P>0.05).The incidence of adverse drug reactions in group A,group B and group C were 4.0%(2/50),18.0%(9/50) and 42.0%(21/50),respectively.The incidence of adverse drug reactions in group A was lower than that in group B(χ^(2)=5.005,P<0.05);the incidence of adverse drug reactions in group B was lower than that in group C(χ^(2)=6.857,P<0.05).The incidence of adverse reactions related to levonorgestrel-releasing intrauterine system in group A,group B and group C were 34.0%(17/50),12.0%(6/50) and 8.0%(4/50),respectively.The incidence of adverse reactions related to levonorgestrel-releasing intrauterine system in group B and group C was lower than that in group A(χ^(2)=6.832,10.187;P<0.05);there was no significant difference in the incidence of adverse reactions related to levonorge-strel-releasing intrauterine system between group B and group C(χ^(2)=0.444,P>0.05).Conclusion The daily dose of 12.5 mg of mifepristone for pretreatment before placement of levonorgestrel intrauterine sustained release system in type I AM patients has good clinical efficacy and less adverse reactions, which is worthy of clinical recommendation.