亮丙瑞林联合左炔诺孕酮宫内缓释系统治疗围绝经期异常子宫出血患者的临床研究

Clinical trial of leuprolide combined with levonorgestrel intrauterine sustained-release system in the treatment of perimenopausal abnormal uterine bleeding patients

目的 观察亮丙瑞林联合左炔诺孕酮宫内缓释系统治疗围绝经期异常子宫出血患者的疗效。方法 采用随机数字表法将围绝经期难治性异常子宫出血患者分为A组和B组。A组在进行诊刮术后月经来潮第4~5天给予左炔诺孕酮宫内缓释系统治疗,待其激素水平处于绝经状态后取出左炔诺孕酮宫内缓释系统。B组给予亮丙瑞林联合左炔诺孕酮宫内缓释系统治疗,在完成诊刮术后15 d,给予注射用醋酸亮丙瑞林微球皮下注射,每28天3.75 mg,并于注射2~3次注射用醋酸亮丙瑞林微球后,按照A组的方式放置左炔诺孕酮宫内缓释系统。2组均连续观察及治疗6个月。比较2组治疗6个月后的临床疗效,观察治疗前和治疗6个月后的出血量、子宫内膜厚度、血红蛋白(Hb)、性激素水平、血清一氧化氮(NO)、前列腺素E2(PGE2)、白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)水平,观察治疗期间出血停止的时间和药物不良反应发生情况。结果 A组和B组均纳入49例患者。治疗6个月后,A组和B组总有效率分别为77.55%和93.88%,差异有统计学意义(P<0.05)。治疗期间,B组和A组出血停止的时间分别为(12.34±1.65)和(16.82±4.35)d,差异有统计学意义(P<0.05)。治疗6个月后,B组和A组出血量分别为(58.35±5.43)和(76.32±5.43)mL;子宫内膜厚度分别为(4.08±0.23)和(5.43±0.76)mm;全血Hb水平分别为(100.65±8.21)和(92.54±8.63)g·L^(-1);血清雌二醇(E_(2))水平分别为(276.76±40.87)和(302.35±41.34)pmol·L^(-1);促卵泡激素(FSH)水平分别为(21.64±2.31)和(32.65±4.36)U·L^(-1);血清黄体生成素(LH)水平分别为(20.35±2.13)和(30.65±3.52)U·L^(-1);血清NO水平分别为(60.64±5.43)和(64.65±6.56)ng·mL^(-1);血清IL-2水平分别为(14.54±0.87)和(20.43±2.34)ng·L^(-1);血清TNF-α水平分别(12.53±0.97)和(18.76±2.41)ng·L^(-1),差异均有统计学意义(均P<0.05)。治疗期间,A组和B组药物不良反应发生率分别为12.24%和8.16%,差异无统计学意义(P<0.05)。结论 亮丙瑞林联合左炔诺孕酮宫内缓释系统可有效改善围绝经期异常子宫出血患者性激素水平,减轻机体炎症反应,并维持患者子宫内膜血管舒缩平衡,缩小患者子宫内膜厚度,减少患者出血量,并促进出血停止,有利于贫血症状的改善,具有较高临床疗效,且安全性良好。

Objective To investigate the efficacy of leuprolide combined with levonorgestrel intrauterine sustained-release system in the treatment of perimenopausal abnormal uterine bleeding patients.Methods Patients with perimenopausal refractory abnormal uterine bleeding were divided into the group A and the group B by random number table method.Group A was given levonorgestrel intrauterine sustained-release system treatment on the 4-5th day of menstrual cramps after curettage,and the levonorgestrel intrauterine sustained-release system was removed after the hormone level was in the menopausal state.Group B was given leuprolide combined with levonorgestrel intrauterine sustained-release system therapy,and 15 d after the completion of curettage,subcutaneous injection of leuprolide acetate microspheres,3.75 mg 28 d a course,and after 2 to 3 times injections of leuprolide acetate microspheres for injection,the levonorgestrel intrauterine sustained-release system was administered in the same way as the group A.Both groups were continuously observed and treated for 6 months.The clinical efficacy of the two groups after 6 months of treatment,the time to stop bleeding and adverse reactions during treatment,the amount of bleeding,endometrial thickness,the levels of hemoglobin (Hb),sex hormone,serum nitric oxide (NO),prostaglandin E2 (PGE2),interleukin (IL-2),tumor necrosis factor-α (TNF-α)before and after 6 months of treatment were compared between the two groups.Results The group A and the group Bwere both 49 cases.After 6 months of treatment,the total effective rates of group A and group B were 77.55%and93.88%and the difference was statistically significant (P<0.05).During the treatment period,the time to stop bleeding in group B and group A were (12.34±1.65) and (16.82±4.35) d and the difference was statistically significant(P<0.05).After 6 months of treatment,the bleeding volume of group B and group A were (58.35±5.43) and(76.32±5.43) m L;the endometrial thickness were (4.08±0.23) and (5.43±0.76) mm;the levels of whole blood Hb were (100.65±8.21) and (92.54±8.63) g·L^(-1);the levels of serum estradiol (E_(2)) were(276.76±40.87) and (302.35±41.34) pmol·L^(-1);the levels of serum follicle stimulating hormone (FSH) were(21.64±2.31) and (32.65±4.36) U·L^(-1);the levels of serum luteinizing hormone (LH) were (20.35±2.13)and (30.65±3.52) U·L^(-1);the levels of serum NO were (60.64±5.43) and (64.65±6.56) ng·m L^(-1);the levels serum of IL-2 were (14.54±0.87) and (20.43±2.34) ng·L^(-1);the levels of serum TNF-α were(12.53±0.97) and (18.76±2.41) ng·L^(-1);the differences were all statistically significant (all P<0.05).During the treatment period,the incidences of adverse drug reactions in group A and group B were 12.24%and8.16%and the difference was not statistically significant (P<0.05).Conclusion Leuprorelin combined with levonorgestrel intrauterine sustained-release system could effectively improve the levels of sex hormones in patients with perimenopausal abnormal uterine bleeding,reduced the body’s inflammatory reaction,maintained the balance of endometrial vascular relaxation and contraction,reduced the thickness of endometrium,reduced the amount of bleeding,promoted the cessation of bleeding,further improved the symptoms of anemia,and then improved the clinical efficacy,with good safety.