雌、孕激素受體表達(dá)及性激素治療與宮腔粘連預(yù)后的相關(guān)性研究
發(fā)布時(shí)間：2018-10-17 16:02
【摘要】：一、研究背景:宮腔粘連(IUAs)是指因子宮內(nèi)膜損傷引起宮腔內(nèi)粘連形成,進(jìn)而發(fā)生月經(jīng)減少、閉經(jīng)、周期性腹痛和生育力低下等并發(fā)癥。宮腔鏡下宮腔粘連分離術(shù)(TCRA)已成為治療IUAs的標(biāo)準(zhǔn)術(shù)式。然而,術(shù)后的粘連復(fù)發(fā)已成為臨床醫(yī)生的挑戰(zhàn)之一。補(bǔ)充雌激素被認(rèn)為是IUAs綜合治療的重要組成部分,但很多學(xué)者關(guān)于雌激素對(duì)IUAs的療效以及應(yīng)用劑量仍存在爭(zhēng)議,目前尚未形成共識(shí)。研究表明,當(dāng)雌激素受體(ER)與孕激素受體(PR)含量不足或功能異常時(shí),可影響子宮內(nèi)膜的生長(zhǎng),其表達(dá)異常與IUAs的發(fā)病及預(yù)后存在相關(guān)性。因此,本研究擬比較不同程度的IUAs患者子宮內(nèi)膜ER、PR與正常育齡婦女的表達(dá)差異,探討其與IUAs發(fā)病及預(yù)后的相關(guān)性;觀察患者術(shù)后應(yīng)用不同劑量雌激素的臨床療效及ER、PR表達(dá)變化,為臨床IUAs患者TCRA術(shù)后雌激素的應(yīng)用提供理論依據(jù)。二、方法:1.研究對(duì)象及分組:本研究收集2012年7月至2016年6月南方醫(yī)科大學(xué)珠江醫(yī)院及深圳市第八人民醫(yī)院IUAs患者及正常對(duì)照組的臨床資料。共分4組,年齡18～40歲。其中正常對(duì)照組43例,為宮頸上皮內(nèi)瘤變、輸卵管性不孕癥患者;其余3組均為IUAs患者,根據(jù)美國(guó)生育協(xié)會(huì)評(píng)分(AFS)標(biāo)準(zhǔn),分為輕度組37例、中度組35例、重度組50例。2.治療方案:IUAs組在首次宮腔鏡手術(shù)中取內(nèi)膜檢測(cè),中重度組術(shù)后宮腔內(nèi)放置防粘連膜(因特隙)包裹的圓形環(huán)。術(shù)后第5d開(kāi)始服用戊酸雌二醇(補(bǔ)佳樂(lè)),連續(xù)口服21d,第12d加服地屈孕酮10mg,共3個(gè)周期。輕度組給予小劑量雌激素治療;中度組及重度組分別給予中劑量或大劑量雌激素治療。小劑量為每日2～3mg補(bǔ)佳樂(lè),每日1次口服;中劑量為每日6mg、大劑量為每日1Omg,均分2次口服。正常對(duì)照組在術(shù)中輕刮少許內(nèi)膜送檢。3.療效評(píng)估:治療期間,門診隨訪記錄患者月經(jīng)量。于第3周期行宮腔鏡二次檢查,記錄AFS評(píng)分,術(shù)中仍取子宮內(nèi)膜檢測(cè)。4.子宮內(nèi)膜組織檢測(cè)子宮內(nèi)膜標(biāo)本行HE染色及ERα、PRA免疫組化染色。采集圖片用Image Proplus軟件進(jìn)行分析,以累積光密度值反映ER、PR的表達(dá)情況。三、結(jié)果:1.ER及PR表達(dá)情況ER與PR在各組子宮內(nèi)膜腺體及間質(zhì)的表達(dá)相近,二者的表達(dá)在正常組和輕度組中相近,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),中度組低于正常組(P0.05),重度組低于其它三組、表達(dá)最低(P0.05)。各組二次手術(shù)與初次手術(shù)時(shí)相比,ER、PR平均表達(dá)均提高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。在中度組中進(jìn)行組內(nèi)比較,不同劑量雌激素治療后其ER、PR表達(dá)無(wú)差異(P0.05);重度組內(nèi),大劑量雌激素治療后ER及PR表達(dá)上升較中劑量組更為顯著,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。2.不同劑量雌激素療效三組IUAs患者二次手術(shù)與初次手術(shù)相比,AFS評(píng)分均有所降低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。中度組的中劑量和大劑量治療組相比,AFS評(píng)分差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);重度組大劑量雌激素治療AFS評(píng)分較中劑量組降低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。四、結(jié)論:1.IUAs患者的子宮內(nèi)膜ER、PR較正常對(duì)照組低,且隨著AFS評(píng)分升高,ER及PR的表達(dá)呈下降趨勢(shì),提示子宮內(nèi)膜損傷導(dǎo)致ER、PR表達(dá)下降,影響內(nèi)膜修復(fù)。2.TCRA聯(lián)合雌激素治療為主的多種輔助措施可以明顯改善IUA,而且對(duì)于重度IUA患者,TCRA聯(lián)合大劑量雌激素也有助于疾病好轉(zhuǎn)。3.雌、孕激素序貫治療后,IUAs患者子宮內(nèi)膜ER及PR的表達(dá)較前提升,且ER及PR表達(dá)與AFS評(píng)分呈負(fù)相關(guān),提示雌、孕激素治療可能通過(guò)誘導(dǎo)ER及PR表達(dá)而促進(jìn)子宮內(nèi)膜增生以改善IUAs預(yù)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.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：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.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R711.74
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