雌、孕激素受体表达及性激素治疗与宫腔粘连预后的相关性研究
发布时间：2018-10-17 16:02
【摘要】：一、研究背景:宫腔粘连(IUAs)是指因子宫内膜损伤引起宫腔内粘连形成,进而发生月经减少、闭经、周期性腹痛和生育力低下等并发症。宫腔镜下宫腔粘连分离术(TCRA)已成为治疗IUAs的标准术式。然而,术后的粘连复发已成为临床医生的挑战之一。补充雌激素被认为是IUAs综合治疗的重要组成部分,但很多学者关于雌激素对IUAs的疗效以及应用剂量仍存在争议,目前尚未形成共识。研究表明,当雌激素受体(ER)与孕激素受体(PR)含量不足或功能异常时,可影响子宫内膜的生长,其表达异常与IUAs的发病及预后存在相关性。因此,本研究拟比较不同程度的IUAs患者子宫内膜ER、PR与正常育龄妇女的表达差异,探讨其与IUAs发病及预后的相关性;观察患者术后应用不同剂量雌激素的临床疗效及ER、PR表达变化,为临床IUAs患者TCRA术后雌激素的应用提供理论依据。二、方法:1.研究对象及分组:本研究收集2012年7月至2016年6月南方医科大学珠江医院及深圳市第八人民医院IUAs患者及正常对照组的临床资料。共分4组,年龄18～40岁。其中正常对照组43例,为宫颈上皮内瘤变、输卵管性不孕症患者;其余3组均为IUAs患者,根据美国生育协会评分(AFS)标准,分为轻度组37例、中度组35例、重度组50例。2.治疗方案:IUAs组在首次宫腔镜手术中取内膜检测,中重度组术后宫腔内放置防粘连膜(因特隙)包裹的圆形环。术后第5d开始服用戊酸雌二醇(补佳乐),连续口服21d,第12d加服地屈孕酮10mg,共3个周期。轻度组给予小剂量雌激素治疗;中度组及重度组分别给予中剂量或大剂量雌激素治疗。小剂量为每日2～3mg补佳乐,每日1次口服;中剂量为每日6mg、大剂量为每日1Omg,均分2次口服。正常对照组在术中轻刮少许内膜送检。3.疗效评估:治疗期间,门诊随访记录患者月经量。于第3周期行宫腔镜二次检查,记录AFS评分,术中仍取子宫内膜检测。4.子宫内膜组织检测子宫内膜标本行HE染色及ERα、PRA免疫组化染色。采集图片用Image Proplus软件进行分析,以累积光密度值反映ER、PR的表达情况。三、结果:1.ER及PR表达情况ER与PR在各组子宫内膜腺体及间质的表达相近,二者的表达在正常组和轻度组中相近,差异无统计学意义(P0.05),中度组低于正常组(P0.05),重度组低于其它三组、表达最低(P0.05)。各组二次手术与初次手术时相比,ER、PR平均表达均提高,差异有统计学意义(P0.05)。在中度组中进行组内比较,不同剂量雌激素治疗后其ER、PR表达无差异(P0.05);重度组内,大剂量雌激素治疗后ER及PR表达上升较中剂量组更为显著,差异有统计学意义(P0.05)。2.不同剂量雌激素疗效三组IUAs患者二次手术与初次手术相比,AFS评分均有所降低,差异有统计学意义(P0.05)。中度组的中剂量和大剂量治疗组相比,AFS评分差异无统计学意义(P0.05);重度组大剂量雌激素治疗AFS评分较中剂量组降低,差异有统计学意义(P0.05)。四、结论:1.IUAs患者的子宫内膜ER、PR较正常对照组低,且随着AFS评分升高,ER及PR的表达呈下降趋势,提示子宫内膜损伤导致ER、PR表达下降,影响内膜修复。2.TCRA联合雌激素治疗为主的多种辅助措施可以明显改善IUA,而且对于重度IUA患者,TCRA联合大剂量雌激素也有助于疾病好转。3.雌、孕激素序贯治疗后,IUAs患者子宫内膜ER及PR的表达较前提升,且ER及PR表达与AFS评分呈负相关,提示雌、孕激素治疗可能通过诱导ER及PR表达而促进子宫内膜增生以改善IUAs预后。
[Abstract]:1. Background: Intrauterine adhesion (IUAs) refers to complications such as menstrual decreased, amenorrhea, recurrent abdominal pain, and low fertility due to endometrial damage. Hysteroscopic intrauterine adhesions separation (T10A) has become a standard technique for IUAs. However, postoperative adhesion recurrence has become one of the challenges of clinicians. Supplementary estrogen is considered to be an important part of IUAs comprehensive treatment, but many scholars still have no consensus on the efficacy and dosage of estrogen on IUAs. The study showed that when the content of estrogen receptor (ER) and progesterone receptor (PR) was insufficient or the function was abnormal, the growth of endometrium could be affected, and its abnormal expression was correlated with the incidence and prognosis of IUAs. Therefore, the difference between ER, PR and the expression of ER, PR and normal women of childbearing age in IUAs patients was studied. To provide a theoretical basis for the application of estrogen in patients with IUAs. II. Method: 1. Study Object and Group: This study collected clinical data from July 2012 to June 2016 at Zhujiang Hospital of Southern Medical University and IUAs patients and normal control group in Shenzhen No. 8 People's Hospital. There were 4 groups, aged 18 ~ 40 years old. Among them, 43 cases of normal control group were cervical intraepithelial neoplasia and tubal infertility. The other three groups were IUAs patients. According to the American Fertility Association score (AFS) standard, there were 37 mild groups, 35 moderate group and 50 cases with severe group. Treatment plan: The IUAs group took the endometrial test during the first hysteroscope operation, and placed the circular ring wrapped in the anti-adhesion film (due to the clearance) in the uterine cavity of the moderate and severe group. At the 5th day of the operation, estradiol valerate was administered (supplement of Jia Le), continuous oral administration of 21days, and droggestrel 10mg on day 12d for 3 cycles. Mild groups were given low-dose estrogen therapy; moderate and severe groups were given a median dose or a large dose of estrogen therapy, respectively. The dosage is 2-3 mg daily, twice daily; the daily dosage is 6mg daily, and the bolus dose is 1Omg daily, and is administered orally for 2 times. In the normal control group, a few endometrial samples were scraped lightly during the operation. Efficacy: During the treatment, the outpatient follow-up records the amount of menstruation in the patient. In Cycle 3, hysteroscopy was performed twice, and AFS scores were recorded, and endometrial abnormality was still detected during the procedure. 4. Endometrial tissue samples were stained by HE staining and ER staining and PRA immunohistochemical staining. The acquired images were analyzed with Image Proplus software to reflect the expression of ER and PR in cumulative optical density values. Results: The expression of ER and PR was similar between ER and PR in each group of endometrial glands and stroma. The expression of ER and PR was similar in normal group and mild group (P0.05). The expression was lowest (P0.05). The mean expression of ER and PR increased and the difference was statistically significant (P0.05). There was no difference in ER and PR expression of ER and PR after estrogen therapy in moderate group (P0.05). Compared with the primary operation, the AFS scores decreased and the difference was statistically significant (P <0.05). There was no significant difference in AFS scores (P0.05). Conclusion: 1. The endometrial ER and PR in IUAs patients were lower than that in the normal control group, and the expression of ER and PR decreased with the increase of AFS score, suggesting that the expression of ER and PR decreased in the endometrium. The combination of estrogen therapy with TATB can obviously improve the IUA, and in severe IUA patients, the combination of T10A and large-dose oestrogen also contributes to the improvement of the disease. The expression of ER and PR was negatively correlated with the expression of ER and PR and the expression of ER and PR was negatively correlated with AFS, suggesting that the treatment of ER and PR could promote endometrial hyperplasia by inducing ER and PR expression to improve the prognosis of IUAs.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.74
[Abstract]:1. Background: Intrauterine adhesion (IUAs) refers to complications such as menstrual decreased, amenorrhea, recurrent abdominal pain, and low fertility due to endometrial damage. Hysteroscopic intrauterine adhesions separation (T10A) has become a standard technique for IUAs. However, postoperative adhesion recurrence has become one of the challenges of clinicians. Supplementary estrogen is considered to be an important part of IUAs comprehensive treatment, but many scholars still have no consensus on the efficacy and dosage of estrogen on IUAs. The study showed that when the content of estrogen receptor (ER) and progesterone receptor (PR) was insufficient or the function was abnormal, the growth of endometrium could be affected, and its abnormal expression was correlated with the incidence and prognosis of IUAs. Therefore, the difference between ER, PR and the expression of ER, PR and normal women of childbearing age in IUAs patients was studied. To provide a theoretical basis for the application of estrogen in patients with IUAs. II. Method: 1. Study Object and Group: This study collected clinical data from July 2012 to June 2016 at Zhujiang Hospital of Southern Medical University and IUAs patients and normal control group in Shenzhen No. 8 People's Hospital. There were 4 groups, aged 18 ~ 40 years old. Among them, 43 cases of normal control group were cervical intraepithelial neoplasia and tubal infertility. The other three groups were IUAs patients. According to the American Fertility Association score (AFS) standard, there were 37 mild groups, 35 moderate group and 50 cases with severe group. Treatment plan: The IUAs group took the endometrial test during the first hysteroscope operation, and placed the circular ring wrapped in the anti-adhesion film (due to the clearance) in the uterine cavity of the moderate and severe group. At the 5th day of the operation, estradiol valerate was administered (supplement of Jia Le), continuous oral administration of 21days, and droggestrel 10mg on day 12d for 3 cycles. Mild groups were given low-dose estrogen therapy; moderate and severe groups were given a median dose or a large dose of estrogen therapy, respectively. The dosage is 2-3 mg daily, twice daily; the daily dosage is 6mg daily, and the bolus dose is 1Omg daily, and is administered orally for 2 times. In the normal control group, a few endometrial samples were scraped lightly during the operation. Efficacy: During the treatment, the outpatient follow-up records the amount of menstruation in the patient. In Cycle 3, hysteroscopy was performed twice, and AFS scores were recorded, and endometrial abnormality was still detected during the procedure. 4. Endometrial tissue samples were stained by HE staining and ER staining and PRA immunohistochemical staining. The acquired images were analyzed with Image Proplus software to reflect the expression of ER and PR in cumulative optical density values. Results: The expression of ER and PR was similar between ER and PR in each group of endometrial glands and stroma. The expression of ER and PR was similar in normal group and mild group (P0.05). The expression was lowest (P0.05). The mean expression of ER and PR increased and the difference was statistically significant (P0.05). There was no difference in ER and PR expression of ER and PR after estrogen therapy in moderate group (P0.05). Compared with the primary operation, the AFS scores decreased and the difference was statistically significant (P <0.05). There was no significant difference in AFS scores (P0.05). Conclusion: 1. The endometrial ER and PR in IUAs patients were lower than that in the normal control group, and the expression of ER and PR decreased with the increase of AFS score, suggesting that the expression of ER and PR decreased in the endometrium. The combination of estrogen therapy with TATB can obviously improve the IUA, and in severe IUA patients, the combination of T10A and large-dose oestrogen also contributes to the improvement of the disease. The expression of ER and PR was negatively correlated with the expression of ER and PR and the expression of ER and PR was negatively correlated with AFS, suggesting that the treatment of ER and PR could promote endometrial hyperplasia by inducing ER and PR expression to improve the prognosis of IUAs.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.74
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