异常子宫出血与雌孕激素水平及其受体关系的研究

目的　探讨异常子宫出血时雌、孕激素水平和子宫内膜组织中相应受体的量化关系。方法　使用宫腔镜技术对 13 0例异常子宫出血的子宫内膜定位取材 ,运用葡聚糖活性炭饱和分析法 (DCC法 )对雌激素受体(ER)与孕激素受体 (PR)定量检测。用放免法同步测定雌激素 (E2 )孕激素 (P)水平 ,结合病理检查结果进行分析 ,并与 3 0例月经正常、输卵管阻塞妇女对照。结果　①无排卵型功能血 :E2 水平及ER、PR含量与子宫内膜增生程度呈正相关。②黄体功能不全 :E2 水平和ER、PR含量均低于对照组 (B) (P <0 0 5 )。③黄体功能萎缩不全 :P水平明显低于对照组 (B) (P <0 0 5 )。ER、PR含量均高于对照组 (B) (P <0 0 5 )。④子宫内膜息肉 :E2 水平和ER、PR含量均高于对照组 (A) (P <0 0 1,P <0 0 5 )。⑤子宫肌瘤引起的异常子宫出血 :E2 和P水平和ER、PR含量均高于对照组 (A) ( P <0 0 1,P <0 0 5 )。⑥药流术后出血 (除外妊娠物残留 ) :E2 水平和ER含量均高于对照组 (A) (P <0 0 1)。P水平和PR含量低于对照组 (A) (P <0 0 5 )。结论　从激素受体角度探讨激素水平与异常子宫出血的关系 ,为诊治异常子宫出血开辟了新途径     

孕三烯酮对大鼠血清雌孕激素及在位和异位子宫内膜雌孕激素受体的影响

目的:探讨孕三烯酮(gestrinone)治疗子宫内膜异位症的作用机理。方法:用自体移植术建立大鼠子宫内膜异位症动物模型,随机分组给药,3周后剖腹,取血测定雌二醇(E2)、孕酮(P)浓度,取出子宫及移植物,固定、切片,免疫组化SP法测定各组动物子宫及移植物的雌激素受体(ER)和孕激素受体(PR)的表达。结果:孕三烯酮高剂量使大鼠血清E2、P水平降低,而中低剂量对E2、P水平影响不大。免疫组化结果则显示移植物的ER、PR含量较子宫内膜低,孕三烯酮高、中剂量可下调在位和异位子宫内膜ER、PR表达,而低剂量孕三烯酮则不能明显改变ER、PR的表达量。结论:孕三烯酮可通过降低体内雌孕激素水平以及下调在位及异位子宫内膜ER、PR的表达,发挥对子宫内膜异位症的治疗作用。     

雌、孕激素受体表达与宫腔粘连分离术后雌孕激素治疗疗效的相关性研究

目的:研究宫腔粘连(IUA)患者子宫内膜组织中雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)的表达,探讨其与术后雌孕激素治疗疗效的关系。方法:采用免疫组化法检测55例中重度IUA患者子宫内膜组织的ER、PR表达;患者均行宫腔镜下IUA分离术,术后给予雌孕激素周期治疗。随访患者的月经改善情况,结合宫腔镜复查结果,分析PR、ER受体与预后的相关性。结果:ER、PR在腺体及间质中的表达均无显著差异(P=0.727,P=0.453);PR低表达组、高表达组患者术后雌孕激素治疗的有效率分别为63.64%和54.55%,两组比较无显著差异(P=0.503);ER低表达组、高表达组患者术后雌孕激素治疗的有效率分别为33.33%和70.27%,两组比较差异显著(P=0.018)。结论:患者子宫内膜PR的表达不能预测预后;ER表达水平与疗效呈正相关,其可能成为IUA术后雌孕激素治疗疗效的预测指标。     

子宫内膜癌组织中雌激素及孕激素受体亚型的表达研究

目的探讨子宫内膜癌组织中雌激素受体(ER)亚型mRNA及孕激素受体(PR)亚型mRNA和蛋白表达水平的变化及其意义。方法采用RT-PCR法检测66例子宫内膜癌和30例正常子宫内膜组织ER、PR亚型mRNA的表达,采用蛋白印迹法检测PR亚型蛋白的表达。结果(1)ERαmRNA在子宫内膜癌和正常子宫内膜组织中的表达水平分别是8.00±7.77、3.84±2.57,而ERβmRNA的表达水平分别是4.15±3.55、0.41±0.29,子宫内膜癌组织中ERα、ERβmRNA表达水平均高于正常子宫内膜,两种组织间分别比较,差异均有统计学意义(P<0.05)。(2)PR、PRA和PRB蛋白表达及PR mRNA表达的降低与子宫内膜癌的发生有关(P<0.05),而PRA与PRB蛋白表达的比值和PRB mRNA的表达与子宫内膜癌的发生无明显相关性(P值分别为0.550、0.901)。(3)子宫内膜癌组织中PRB mRNA与ERβmRNA的表达水平呈正相关关系(r=0.43,P<0.01)。结论子宫内膜癌组织中ER亚型mRNA表达上调、PR蛋白和mRNA表达的下调可能参与了子宫内膜癌的发生;PRB mRNA与ERβmRNA表达呈正相关关系。     

子宫肌瘤中雌、孕激素受体在月经周期中的变化

子宫肌瘤的发病机理尚未完全清楚。近年对雌、孕激素受体 (ER、PR)的基础研究取得了很大突破 ,并且通过大量的临床对照研究 ,指出EP、PR各亚型在子宫肌瘤、正常子宫肌层和内膜中的表达不同 ,并随月经周期中雌、孕激素 (E、P)水平的改变而发生波动 ,为子宫肌瘤的病因学研究提出了新的途径。现对ER、PR各个亚型的分子结构、功能区、组织学分布以及与子宫肌瘤的关系等作一简要综述     

米非司酮治疗绝经过渡期功血的子宫内膜改变

目的探讨米非司酮治疗绝经过渡期功血对子宫内膜的影响。方法选择绝经过渡期功血患者50例,诊断性刮宫后每日口服米非司酮10mg,6个月一疗程。观察治疗前后子宫内膜厚度、子宫内膜病理变化、子宫内膜组织中雌激素受体(ER)、孕激素受体(PR)及ki-67的表达情况。结果米非司酮治疗期间所有患者均出现闭经,根据B超检查结果,米非司酮治疗前子宫内膜厚度为(8.58±1.77)mm,治疗后为(3.82±0.71)mm,两者相比,差异有显著性意义(P<0.01)。子宫内膜转化良好。米非司酮治疗后子宫内膜组织中ER、PR及ki-67的表达均较治疗前降低,差异有显著性。结论米非司酮能明显抑制子宫内膜增殖,降低子宫内膜组织中雌、孕激素受体表达,对细胞周期有明显抑制作用,从而发挥其对绝经过渡期功血的治疗作用。     

复方米非司酮对人早孕蜕膜组织雌孕激素受体的影响

观察服用复方米非司酮片 (米非司酮 + AF-5 3)后早孕妇女蜕膜组织雌孕激素受体的变化。 6 0名孕 6～ 7周的妇女被随机分为 6组 ,A组 :对照组 ;B组 :米非司酮 40 mg/次 ;C组 :米非司酮 75 mg/次 ;D组 :复方米非司酮 1片 (米非司酮 2 0 mg+ AF-5 35 mg) ;E组 :复方米非司酮 1片 (米非司酮 30 mg+ AF-5 35 mg) ;F组 :复方米非司酮 1片 (米非司酮40 mg+ AF-5 35 mg)。以上各服药组 ,均为上述剂量每日 1次 ,连服 2日。服药 48h后手术终止妊娠 ,取蜕膜组织 ,放射性配体结合试验测定其胞浆、胞核雌、孕激素受体浓度。结果显示 :复方米非司酮各配伍组均显著降低孕激素受体 (PR) ,升高雌激素受体 (ER) ,改变 ER/PR,促进流产发生。 E组使胞浆雌激素受体 (Ec R)显著高于其它各用药组 ,可能有利于流产后雌激素尽快作用于 ER,促进内膜恢复。结论提示复方米非司酮中米非司酮与AF-5 3配伍具有协同作用 ,改变了雌孕激素受体比例 ,促进流产的发生 ,E组有利于子宫内膜的恢复     

不孕症子宫内膜息肉雌激素受体和孕激素受体表达的研究

目的:探讨不孕妇女子宫内膜息肉中雌激素受体(ER)和孕激素受体(PR)的表达及意义。方法:选择2009年9月至2010年4月在广东省计划生育专科医院就诊伴发子宫内膜息肉的50例不孕妇女(EP组)作为研究组,同期就诊宫腔镜检查正常的29例不孕妇女作为对照组。采用免疫组化方法测定ER和PR在子宫内膜息肉和正常增殖期子宫内膜中的表达,同时采用化学发光法测定所有患者血清的基础性激素(血清卵泡刺激素、黄体生成素、催乳素、雌二醇和睾酮)水平,并对两组的基本情况(年龄、不孕类型、不孕原因、不孕年限及取材时间)进行比较。结果:两组基础性激素水平和基本情况的比较中,仅EP组血清雌二醇水平显著高于对照组(223.39±125.47pmol/Lvs169.96±87.46pmol/L,P=0.046),其他各项指标的比较,差异均无统计学意义(P>0.05)。ER和PR在子宫内膜息肉和增殖期子宫内膜中的表达比较,差异均无统计学意义(P=0.085,P=0.527)。结论:对于无月经改变的不孕症子宫内膜息肉,长期较高水平的雌二醇刺激可能与息肉形成有关,但子宫内膜息肉上ER、PR表达未见异常。     

子宫内膜息肉患者增殖期及种植窗期性激素及激素受体的改变及意义

目的:探讨子宫内膜息肉不孕患者增殖期及种植窗期性激素及雌激素受体(ER)和孕激素受体(PR)的改变及意义。方法:选择100例宫腔镜检查见赘生物并经病理证实为子宫内膜息肉(EP)的患者作为EP组,其中,增殖期检查者50例,种植窗期检查者50例。选择60例已生育宫腔镜检查示宫腔正常并经病理证实者作为对照组,其中,增殖期检查者30例,种植窗期检查者30例。采用化学发光法测定患者血清的性激素水平,免疫组织化学方法检测子宫内膜组织中雌激素受体(ER)、孕激素受体(PR)的表达,并进行比较。结果:EP组血清基础雌二醇(E2)水平显著高于对照组(235.59±109.47 pmol/L vs 159.89±87.48 pmol/L,P0.05),EP组种植窗期孕酮(P)/E2比值显著低于对照组(0.077 vs 0.090,P0.05),其他各项性激素指标及ER各组及各期间比较,差异均无统计学意义(P0.05)。PR在EP组EP组织种植窗期子宫内膜间质中的表达显著低于EP周围正常内膜与对照组(P0.05)。结论:对于无月经改变的子宫内膜息肉患者,长期较高水平的E2刺激,PR在分泌期EP间质中处于低水平、相对不足状态可能与息肉形成有关。     

类固醇受体辅助活化因子-1和核受体辅阻遏子在子宫腺肌病中的表达

目的:通过检测子宫腺肌病组织芯片中雌激素受体(ER)、孕激素受体(PR)、类固醇受体辅助活化因子-1(SRC-1)和核受体辅阻遏子(NCoR)的表达,观察SRC-1、NCoR与ER、PR之间的关系,探讨其在子宫腺肌病发生、发展中的作用。方法:用组织芯片技术和免疫组化方法检测42例子宫腺肌病患者异位子宫内膜组织(异位内膜组)和15例因子宫肌瘤行子宫切除术患者非瘤区对照子宫内膜组织(对照内膜组)中ER、PR、SRC-1和NCoR的阳性细胞的平均光密度值(IOD),及两组子宫内膜组织的增殖期和分泌期的IOD值,并进行比较。结果:ER、PR在异位内膜组中的IOD值显著低于对照内膜组(P<0.05);SRC-1在异位内膜组中IOD值明显高于对照内膜组(P<0.05);NCoR在异位内膜组中IOD值明显低于对照内膜组(P<0.05);异位内膜组中SRC-1、NCoR、ER和PR的IOD值增殖期和分泌期的比较,差异无统计学意义(P>0.05);对照内膜组中SRC-1、NCoR、ER和PR的IOD值增殖期高于分泌期(P<0.05)。结论:低表达的ER存在时,SRC-1在异位内膜组织中表达增高,低表达的PR可能降低NCoR的表达,SRC和NCoR可能导致子宫腺肌病异位内膜组织增生活性增高,可能与子宫腺肌病的种植和侵袭有关。     

Endometrial hormone receptors in women with dysfunctional uterine bleeding

Objective The objective was to study the estrogen receptor (ER) and progesterone receptor (PR) expression in endometrium of women with dysfunctional uterine bleeding (DUB) as compared to women with normal menstrual cycles.Methods In this study, 30 patients and 20 controls were selected. Transvaginal ultrasound and endometrial sampling for histology and ER and PR estimation immunohistochemically was carried out for all the subjects. Students t-test and linear correlation was used for statistical analysis. Their response to treatment was assessed by clinical follow-up.Results Endometrial thickness and ER and PR levels in DUB patients were significantly higher. In cases showing hyperplastic endometria, ER and PR levels were higher than patients with normal histology. In contrast to hyperplastic tissue, steroid receptor levels decrease in hyperplastic tissue containing atypia.Conclusion Altered endometrial morphology and increased receptor levels in DUB patients suggest that unopposed estrogen effect could have an important role in the pathogenesis of DUB. Cases of DUB, which showed atypical hyperplasia, may have a down-regulation of these receptors and could be a precursor lesion to carcinoma and thus do not respond to medical therapy by hormones.     

Norplant皮下埋植后子宫内膜形态和雌、孕激素受体含量的变化

目的探讨Ｎｏｒｐｌａｎｔ皮下埋植后子宫内膜形态和雌、孕激素受体（ＥＲ、ＰＲ）含量的变化与子宫异常出血的关系。方法应用免疫组化、ＷｅｓｔｅｒｎＢｌｏｔ和原位杂交技术结合计算机图像分析,观察１６例Ｎｏｒｐｌａｎｔ皮下埋植后和２３例正常周期的内膜的形态学改变、细胞增殖状态及ＥＲ、ＰＲ蛋白及其ｍＲＮＡ的表达。结果埋植Ｎｏｒｐｌａｎｔ后,内膜ＤＮＡ含量降低;螺旋动脉数量减少,腺体的构成比例降低;腺体构成比例与雌二醇（Ｅ２）水平呈正相关,与子宫异常出血呈负相关,与年龄和体重无相关性,随使用期延长,腺体构成比增加。埋植后,内膜ＥＲ含量低于月经周期各期水平,但ＰＲ含量相当于或高于月经周期最高水平。ＥＲ、ＰＲｍＲＮＡ表达减弱,以ＥＲｍＲＮＡ表达降低更明显。结论内膜腺体和螺旋动脉再生修复不良和ＥＲ、ＰＲ表达异常,可能是Ｎｏｒｐｌａｎｔ致子宫异常出血的病理学基础     

射频热凝固子宫内膜去除治疗功能失调性子宫出血两种术式和止血机理探讨

目的探讨应用射频热凝固（radiofrequency thermocoagulation,RFT）使子宫内膜去除治疗功能失调性子宫出血（功血）两种手术方法和止血机制。方法应用两种RFT子宫内膜去除术式,分别使全部宫腔子宫内膜热凝固去除（A-RFT）和选择性保留部分子宫内膜（B-RFT）。研究组为1196例功血患者,根据年龄为分两组：≥45岁者427例为A-RFT组,采用A-RFT,以闭经为治疗目的;〈45岁者769例为B-RFT组,采用B-RFT,以月经减量为目的。平均随访72个月。以前两组中检测子宫内膜生存素（survivin）、雌激素受体（ER）和孕激素受体（PR）表达者76例为混合组,并选择同期采用激素治疗的38例功血患者作为对照组。结果①术后即时宫腔镜和内子宫膜诊刮病理显示,A-RFT组子宫内膜全部全层凝固性坏死,B-RFT组大部子宫内膜全层凝固性坏死,少部分子宫内膜遗存;②术后6个月时宫腔镜和诊刮病理显示,A-RFT组子宫内膜全部为纤维组织替代,B-RFT组为纤维组织夹杂少数腺体。③RFT治疗功血3个月内总有效率为94.8%（1134/1196）,其中A-RFT组为96.5%（412/427）,B-RFT组为93.9%（722/769）。治疗痛经的有效率为83.5%（106/127）,其中A-RFT组为86.4%（38/44）;B-RFT组为80.7%（67/83）。术后1年、2年和3年以上的有效率分别是92.6%（969/1047）、93.9%（866/922）和93.7%（609/650）。④混合组RFT6个月后子宫内膜组织Survivin、ER和PR的表达水平明显低于治疗前（P〈0.05）。⑤主要并发症是术后1～2个月不规则阴道少量出血,占8.0%（96/1196）;3个月后月经量多,占5.2%（62/1196）。前者为机化组织脱落不全所致,行清宫处理;后者因子宫内膜残留过多所致,经再次RFT后达到疗效。无子宫切除患者。结论两种RFT术式治疗功血安全、有效和微创,对子宫内膜的直接热凝固具有迅速和短期止血作用。治疗后子宫内膜纤维化和Survivin、ER和PR的表达下降,可能是RFT治疗功血远期有效和复发的重要机制。     

Activin A and follistatin in menstrual blood: low concentrations in women with dysfunctional uterine bleeding

Activin A and follistatin are growth factors produced by several organs, comprising the endometrium, where they modulate cell and tissue differentiation. In this study, the authors tested whether activin A and follistatin are measurable in menstrual blood and whether their concentrations change in women with dysfunctional uterine bleeding (DUB). The authors evaluated healthy women with regular menstrual cycles (n = 15) and women with DUB (n = 12). Activin A and follistatin were measured in both menstrual and peripheral blood samples using highly sensitive enzyme immunoassays, whereas their respective mRNAs were quantified by real-time polymerase chain reaction in endometrial samples collected during the perimenstrual period. Activin A concentrations were 4-fold higher in menstrual than in peripheral serum of healthy women (mean +/- SE, 4.24 +/- 0.18 vs 1.00 +/- 0.15 ng/mL, P < .001) and were significantly lower in women with DUB compared to healthy subjects (P < .001). Follistatin concentration was 8-fold higher in menstrual than in peripheral serum of healthy women (3.94 +/- 0.49 vs 0.49 +/- 0.04 ng/mL, P < .001) and was significantly lower in the menstrual serum of women with DUB compared to controls (P < .001). There was no correlation between menstrual and peripheral serum concentrations of both proteins. The endometrial expression of activin A and follistatin mRNA was lower in women with DUB compared to controls (P < .05). Both activin A and follistatin are measurable in high concentrations in human menstrual blood and are relatively lower in women with DUB. The quantitative assessment of activin A and follistatin in menstrual serum might be a putative clinical marker of endometrial function.     

米非司酮对离体异位与在位子宫内膜雌、孕激素受体含量的影响

目的　探讨子宫内膜异位症(内异症)的异位与在位内膜雌、孕激素受体(ER、PR)含量,及米非司酮对其影响。方法　采用免疫细胞化学法,分析22例内异症患者的在位内膜细胞和其中12例患者的异位内膜细胞体外培养后的ER、PR含量,观察不同浓度米非司酮(1×10-6mol/L和1×10-4mol/L)作用后的变化,并以13例正常子宫内膜作对照。结果　内异症的在位内膜ER、PR含量呈明显周期性变化,分泌早期腺体PR含量显著高于正常子宫内膜［组织化学评分(下同)为2.77±0.32与2.20±0.26,P<0.05］。内异症的异位内膜,增殖期ER(腺体0.65～2.17,间质0.45～1.03)、PR含量(腺体0.55～1.77,间质0.40～1.27)显著低于在位内膜(ER腺体1.50～3.23,间质0.80～1.96;PR腺体1.55～3.34,间质0.98～2.50,P<0.05～0.01);分泌早期无差异;分泌晚期腺体ER含量(3.27±0.31)、PR含量(3.33±0.23)与间质ER含量(1.87±0.31)显著高于在位内膜(分别为0.28±0.11、0.36±0.23和0.26±0.15,P<0.01),而间质PR含量无差异。米非司酮可明显降低内异症的异位和在位内膜ER、PR含量(P<0.01),且米非司酮浓度越高,ER、PR含量降低越明显。结论　内异症的异位和在位内膜ER、PR含量明显不同,米非司酮可下调异位和在位内膜ER、PR的含量。     

Mast cells in the normal uterus and in dysfunctional uterine bleeding

Mast cells in the human uterus were examined following fixation in 10% formalin and staining with Azure B. Mast cells were present in all parts of the corpus uteri. Cyclical changes were observed by light microscopy for mast cell numbers/mm2 in the functional endometrium, basal endometrium and the endometrial/myometrial border throughout the menstrual cycle. No significant differences were found for mast cell numbers in the menstrual, proliferative or secretory phases of the menstrual cycle in dysfunctional uterine bleeding (DUB). No correlation was found between mast cell numbers in the uterine wall in the secretory phase of the menstrual cycle and average menstrual blood loss for patients with DUB.     

Decreased ratio of total progesterone to total estradiol receptor levels in endometria of women with adult dysfunctional uterine bleeding

Total estradiol and progesterone receptor levels (TRE2, TRP) were measured in endometria of women with adult dysfunctional uterine bleeding (n = 2) and compared to those of controls. The women in both groups were comparable with respect to age, history, light and electron microscopic endometrial morphology and dating; plasma levels of LH, FSH, estradiol and progesterone were similar in both groups. A wide range of TRE2 and TRP levels was measured in both groups; however, the levels of the ratio of TRP/TRE2 for each case were significantly lower in 18 of the 22 women with adult dysfunctional uterine bleeding and were in the range of the controls in the remaining 4. Possible explanations for these findings are presented.     

左炔诺孕酮宫内缓释系统治疗功能失调性子宫出血的临床观察

目的:观察左炔诺孕酮宫内缓释系统(LNG-IUS)治疗功能失调性子宫出血的临床效果。方法:48例确诊为功能失调性子宫出血的患者,放置LNG-IUS。置宫内节育器前后均行宫腔镜检查、月经量评分、测量子宫内膜厚度;检测卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)和孕酮(P)浓度及子宫内膜雌、孕激素受体(ER/PR)。结果:置宫内节育器3个月后,月经量明显减少,PBAC法月经量评分由置宫内节育器前(128.9±41.5)降至(52.2±13.8),具有统计学意义(P<0.01);子宫内膜由(12.9±4.2)mm降至(8.4±2.0)mm,差异具有统计学意义(P<0.05)。置宫内节育器6个月后,宫腔镜下观察,子宫内膜菲薄,病理显示内膜呈轻度分泌现象及间质蜕膜样变;ER、PR的表达均显著下调(P<0.01)。结论:LNG-IUS能有效地减少月经量,对增生的子宫内膜具有逆转作用,治疗功能失调性子宫出血效果好。     

ER, PR and Ki-67 expression status in granulomatous and chronic non-specific endometritis

AIM: To study the changes in the histological pattern, distribution and intensity of sex steroid receptors (estrogen and progesterone) and cell proliferation by Ki-67 expression by semi-quantitative scores in granulomatous and chronic non-specific endometritis in the premenstrual phase. METHODS: A retrospective study was conducted on 20 cases of granulomatous endometritis, 10 of chronic non-specific endometritis and 30 age matched (2 years) controls with no endometrial lesions. Morphological changes were noted on histological examination and semi-quantitative scoring of Estrogen Receptor (ER), Progesterone Receptor (PR) and Ki-67 expression was done by immunohistochemistry. RESULTS: There was significantly higher ER, PR and Ki-67 expression in endometrial glandular and stromal cells in inflamed endometria as compared with the controls (all P-values < 0.02) regardless of the character of the inflammation. The cases with morphology not conforming to the secretory phase at which biopsy was taken had significantly higher ER, PR and Ki-67 expression in both endometrial and stromal cells indicating a lag in the endometrial maturation (all P-values < 0.02). Interestingly, all parameters except PR expression in glandular cells had a significantly higher expression even in cases with secretory morphology indicating disturbances in local milieu. CONCLUSION: Endometrial inflammation interferes with local expression of ER, PR and Ki-67. This may contribute to infertility regardless of other factors and other endometrial dysfunctional states.