促性腺激素释放激素激动剂联合戊酸雌二醇及地屈孕酮治疗子宫内膜异位症的临床疗效与安全性

目的 比较促性腺激素释放激素激动剂(GnRH-a)联合地屈孕酮和戊酸雌二醇(反向添加疗法)及单用GnRH-a对子宫内膜异位症(内异症)患者生殖激素水平、低雌激素症状、生活质量及骨密度等的影响.方法 选择经腹腔镜或开腹手术确诊并治疗两个月内的Ⅲ～Ⅳ期内异症患者70例,随机分为GnRH-a组和反加组各35例,GnRH-a组单用戈舍瑞林3.6 mg皮下注射,每28天注射1次,共3次,反加组在应用戈舍瑞林的同时,每天口服戊酸雌二醇0.5 mg及地屈孕酮5 mg.于治疗前后测定两组患者的疼痛症状视觉模拟评分(VAS)、简明健康量表(SF-36)得分、改良Kupperman评分、骨密度、外固血卵泡刺激素(FSH)、雌二醇及血清骨钙素(BGP)水平,并随访治疗结束后第1次月经复潮情况及VAS评分.结果 两组各有3例患者未完成随访.(1)生殖激素水平:治疗末反加组雌二醇水平为(94±71)pmol/L,明显高于GnRH-a组的(54±52)pmol/L,两组比较,差异有统计学意义(P<0.01);反加组FSH水平为(3.0±1.9)U/L,低于GnRH-a组的(5.7±2.9)U/L,两组比较,差异也有统计学意义(P<0.05);(2)VAS评分:两组治疗末VAS评分均较治疗前显著下降(P<0.05),并保持至治疗后第1次月经来潮;(3)Kupperman评分:治疗未反加组Kupperman评分为(10±8)分,明显低于GnRH-a组的(14±6)分,差异有统计学意义(P<0.05);(4)骨密度:GnRH-a组治疗末较治疗前骨密度显著下降,差异有统计学意义(P<0.05),反加组治疗前后骨密度比较,差异无统计学意义(P>0.05);治疗前两组外周血BGP水平比较,差异无统计学意义(P>0.05),治疗末GnRH-a组外周血BGP水平为(7932±5206)ng/L显著高于反加组的(5419±2917)ng/L,差异有统计学意义(P<0.05).结论 GnRH-a联合地屈孕酮及戊酸雌二醇能有效缓解内异症患者的疼痛症状,并可减轻GnRH-a引起的低雌激素症状,减少骨质丢失,是一种有效、安全的治疗方法.

Clinical efficacy and safety of gonadotropin releasing hormone agonist combined with estrogen-dydrogesteronea in treatment of endometriosis

Objective To compare clinical effect of gonadotropin releasing hormone agonist(GnRH-a) alone and GnRH-a combined with low-dose dydrogesteronea and estradiol valerate on sex hormone, hypoestrogenic symptoms, quality of life and bone mineral density (BMD)in treatment of endometriosis.Methods Seventy patients with moderate or severe endometriosis, who were diagnosed by laparotomy or laparoscopic surgery within two months, were randomly assigned into two groups.35 patients in GnRH-a group were treated by goserelin (3.6 mg)for three months, and 35 patients in add-back group were treated by goserelin (3.6 mg)combined with estradiol valerate 0.5 mg and dydrogesteronea 5 mg daily.Before and after the treatment, clinical parameters were recorded and analyzed, including visual analog scale (VAS), medical outcomes survey short form 36 (SF-36), Kupperman menopausal index(KMI), BMD, the serum level of follicle stimulating hormone (FSH), estradiol (E_2) and bone gla-protein (BGP) .The first menstruation and VAS were also followed up after treatment.Results Every 3 cases in two groups lost follow-up.(1)Reproductive hormone: the level of E_2 in add-back group (94 ± 71) pmol/L]was significantly higher than (54±52) pmol/L in GnRH-a group(P <0.01).The level of FSH in add-back group (3.0 ± 1.9) U/L]was significantly lower than (5.7 ± 2.9) U/L in GnRH-a group (P < 0.05).(2) VAS: after treatment, VAS in both group decreased significantly when compared with that before treatment(P < 0.05), and remained until menstruated.(3) KMI: KMI in add back-group (10 ± 8) was significantly lower than (14 ± 6) in GnRH-a group (P < 0.05).(4) BMD: compared with that before treatment, BMD decreased significantly after treatment in GnRH-a group (P < 0.05), no remarkable difference of BMD was observed before and after treatment in add-back group.Before treatment, serum BGP in both groups did not show statistical difference.After treatment, the level of BGP in GnRH-a group (7932±5206) ng/L]was significantly higher than (5419±2917) ng/L in add-back group (P <0.05).Conclusions GnRH-a combined with estrogen-progesterone regimen could relieve pain from endometriosis as effectively as GnRH-a alone and reduce hypoestrogenic symptoms and bone loss.Therefore,it is a safe and effective treatment.