Disturbances of endometrial bleeding with hormone replacement therapy

Breakthrough bleeding is a common problem in postmenopausal women taking hormone replacement therapy (HRT) and is often the single most important factor deterring women from continuing to use HRT, or from starting it in the first place. The mechanisms which underlie this unscheduled bleeding are poorly understood. The benefits of HRT in terms of longevity and quality of life are becoming increasingly apparent, and a greater understanding of why this bleeding occurs and how we can prevent or treat it, will undoubtedly enable more women to reap the potential considerable benefits of long-term oestrogen and progestogen replacement. What sets postmenopausal women apart from their counterparts in the mid-reproductive years is the increased likelihood of endometrial adenocarcinoma in which unscheduled bleeding is the presenting symptom. Therefore, spontaneous postmenopausal bleeding must always be appropriately evaluated. Hence, the occurrence of unscheduled bleeding with HRT may provide a dilemma with diagnosis as well as a challenge to acceptability. Combined HRT regimens tend to be predominantly progestogenic, and there is increasing evidence to suggest that some of the vascular changes seen in women taking long-term, low-dose progestogen-only contraceptives may also occur in women taking HRT.     

宫腹腔镜联合诊治不孕症23例临床分析

<正>近年来,不孕症患者数量逐渐增加,妇科内镜技术不断发展,宫腹腔镜手术以其微创、出血少、恢复快、并发症少等优点成为越来越多不孕症患者愿意选择的手术治疗方法。我院对子宫、输卵管病变致不孕,采用宫腔镜联合腹腔镜治疗,取得了良好的临床效果,现总结如下。     

基于形态学重构的宫腔镜下子宫内膜腺体开口标记算法

目的在宫腔镜下为胚胎种植窗口期的子宫容受性提供一个量化的评价方法,提出一个宫腔镜下的子宫内膜腺体开口标记算法。方法采用数学形态学重构算法提取可能的腺体开口区域,利用多尺度的高斯滤波增强腺体区域去除噪声,最后使用数学形态学的区域最大值标记腺体开口。结果该标记算法的标记结果与专家标记结果进行比对,灵敏度为84.72%±8.00%,Dice相似度系数达83.80%±4.56%。结论经仿真和真实数据验证,提出的子宫内膜腺体开口标记算法是有效的。     

Factors associated with endometrial bleeding in continuous hormone replacement therapy

OBJECTIVE: To identify clinical and laboratory parameters associated with the occurrence of endometrial bleeding within the first 6 months of treatment in postmenopausal women taking continuous hormone replacement therapy. DESIGN: We performed a prospective study of 55 postmenopausal women who had amenorrhea for at least 12 months before baseline screening and were taking 0.625 mg conjugated estrogen and 5 mg medroxyprogesterone acetate daily on a continuous basis. Postmenopausal duration was defined as the interval, in months, between the last menstruation and the commencement of treatment. All subjects were instructed to monitor bleeding episodes in a diary and were followed up monthly for at least 12 months. RESULTS: Thirty-four women (62%) experienced bleeding within the first 6 months of treatment. Using a multivariate approach, a woman with a postmenopausal duration of 24 months or less had a relative risk of 8.2 (95% confidence limits: 1.3, 53.1) of bleeding, as compared with those with a postmenopausal duration of more than 24 months. Furthermore, pretreatment endometrial thickness greater than 5 mm (p < 0.05) and serum estradiol levels greater than 25 pg/mL (p < 0.01) were noted to be significantly correlated with the occurrence of bleeding in women with a postmenopausal duration of more than 24 months. CONCLUSIONS: Women with a postmenopausal duration of 24 months or less, a pretreatment endometrial thickness greater than 5 mm, and serum estradiol level greater than 25 pg/mL are at risk to have endometrial bleeding within the first 6 months of continuous hormone replacement therapy.     

Postmenopausal hormone replacement therapy: endometrial and breast effects

The history of hormone replacement therapy (HRT) dates back to the late 1800s, when animal extracts of ovaries were first used. With the development of synthetic hormones, widespread use in postmenopausal women extended throughout the industrialized world, so that by the late 1900s roughly one-third to one-half of all postmenopausal women in the United States and Europe were taking HRT. Two events changed the course of use of HRT: the association of an increased rate of endometrial carcinoma with estrogen-only HRT and the association of an increased breast cancer rate with combined estrogen and progestin HRT. This review explores the evidence of the effects of HRT on the endometrium and the breast, with emphasis on the pathologic changes.     

Combined laparoscopy and hysteroscopy in the treatment of tubal infertility

IntroductionInfertilityandsteffotyisoneofworldwideproblemsinmedicalscienceandsocialscience.IiialsoanhapobotgenecolwtaldiseaseandrelatetoObstetiics,Genecology,Sexology,Reproductiveendocrinology,Iryununology,FamilyPlanning,BinlogyandGeneticsetc.ThediagnoshcandtherapeuticlevelofinfechtytreatmentreflectthelevelofthehospitalareaandstatetosomeeXtant.tubalfactorsisabout209,6tO45%thecauseofinfeMity.Achievingpreunderthesecircumstancereqthedetherthemethodofmicros~orrecentlyassistedl.eproductivetecl…     

40岁以下妇女子宫内膜癌刮宫活检的病理诊断问题

目的 探讨40岁以下妇女子宫内膜癌刮宫活检的病理诊断。方法对20例40岁以下子宫内膜癌患者的临床病理资料进行回顾性分析。结果子宫内膜样腺癌18例,腺鳞癌(腺癌伴鳞状上皮分化)1例,浆液性乳头状癌并透明细胞癌1例。子宫内膜样腺癌的组织学特点是子宫内膜腺体失去极性,细胞核变大、变圆、核仁突出,染色质粗或呈空泡状,同时子宫内膜间质消失,代之为肉芽组织或纤维组织,常有炎性反应。子宫内膜样腺癌多数仅累及浅肌层,皆无转移。1例子宫内膜腺鳞癌呈双侧卵巢转移;1例浆液性乳头状癌有盆腔淋巴结转移。结论40岁以下妇女的子宫内膜癌多数为高分化子宫内膜样腺癌,应注意与子宫内膜不典型增生及不典型息肉状腺肌瘤鉴别。     

Conservative treatment of cervical pregnancy by curettage and local prostaglandin injection

Recently, various conservative regimens for the treatment of cervical pregnancy have been introduced to preserve fertility in young women, with methotrexate being one of the most widely used drugs. The success of conservative treatment depends on early preoperative diagnosis. We report three cases of first trimester cervical pregnancy, successfully treated by curettage to evacuate the conceptus, followed by local prostaglandin instillation to prevent severe haemorrhage. In one patient, intra-amniotic instillation of hyperosmolar glucose was necessary to terminate fetal cardiac activity. beta-Human chorionic gonadotrophin returned to normal within 3 weeks in one patient and within 7 weeks in another, both of whom became pregnant again within 1 year, resulting in term deliveries. The third patient was lost to follow-up after 1 week. The advantage of prostaglandin and curettage is the absence of major side-effects to the mother or the fetus of a subsequent pregnancy. The management strategies used in the treatment of cervical pregnancies and the results obtained since the introduction of methotrexate in 1989 are discussed in the context of previously published literature. The incidence of subsequent pregnancies among women treated medically versus women treated surgically is reported.      

The role of hormone replacement therapy in endometrial polyp formation

OBJECTIVE: To evaluate the iatrogenic effect of different protocols of hormone replacement therapy (HRT) on endometrial polyp formation adjusting for the confounding effects of other factors such as age, parity, weight and menopausal status at menopause. METHODS: Out of 2685 menopause patients 375 (13.9%) eligible patients were enrolled. Patients were randomized to three HRT types and three equal groups were formed. The first group received Premelle 2.5 mg (Group-I) (0.625 mg conjugated estrogen + 2.5 mg medroxyprogestorone), the second received Kliogest (Group-II) (2 mg estradiol + 1 mg norethisterone) and the last received Livial (Group-III) (2.5 mg tibolone) at least for 36 months without giving a break. After the first 18 months patients had their first office hysteroscopy and it was repeated in every 6 months until the end of third year to find out new and recurrent endometrial polyps. RESULTS: Multiple regression analysis revealed that the type of HRT, late menopause and obesity increased the occurrence of endometrial polyps. In Group-I five polyps, in Group-II ten polyps and in Group-III two polyps were detected. There were significant differences between G-II and G-I and G-II and G-III (P < 0.05), but there was no significant difference between G-I and G-III (P > 0.05). 82.3% of the polyps were detected in the third and fourth hysteroscopic examinations. Endometrial polyp recurrence was encountered in 4 (23.5%) patients, 1 in G-I and 3 in G-II without a significant difference (P > 0.05). No malignancy was detected in any of the specimen. CONCLUSION: We observed that endometrial polyp formation may be dependent on the type and dosage of the estrogen and progestogen. Especially a progestogen with high antiestrogenic activity may play an important preventive role in the development of endometrial polyps.     

Role of hysteroscopy with endometrial biopsy to rule out endometrial cancer in postmenopausal women with abnormal uterine bleeding

OBJECTIVE: To compare the diagnostic accuracy of ultrasonographic endometrial thickness and outpatient hysteroscopy, to establish the most appropriate exam for the diagnosis of endometrial cancer in postmenopausal women with abnormal uterine bleeding (AUB). The secondary aim was to develop a multivariable approach considering clinical history as an added value for these diagnostic procedures. METHODS: This prospective study was conducted on 220 consecutive postmenopausal patients with AUB, who underwent ultrasonographic evaluation of endometrial thickness, outpatient hysteroscopy and endometrial biopsy. Evaluation of sensitivity, specificity, positive and negative predictive value was performed. Receiver operator characteristic curve (ROC) was calculated to assess the global performance of ultrasonographic measurement of endometrial thickness and diagnostic hysteroscopy as tests for detecting endometrial cancer and atrophy. RESULTS: Histological findings for <4 mm level revealed that atrophy was present in 48 (65%) and in 2 cases (2.7%) endometrial cancer was found; for > or = 4 mm values polyps and myomas were present in 86 (59%) and there were 11 (7.5%) endometrial cancer. Sensibility and specificity for trans-vaginal ultrasound, with a cut-off value > or = 4 mm, was 55.6% and 49.7% while positive predictive value was 83.3% and negative predictive value 98.1% (ROC curve 0.597). Hysteroscopy revealed sensitivity 100%, specificity 49.6%, positive predictive value 81.3% and negative predictive value 100% (ROC curve 0.993). CONCLUSIONS: In conclusion, endometrial thickness <4 mm can miss malignancies but trans-vaginal ultrasound remains the first line diagnostic procedure in postmenopausal women without AUB, because it is not invasive and has high sensitivity for detecting endometrial cancer and other endometrial disease; according to our experience, outpatient hysteroscopy with biopsy is mandatory in all postmenopausal women with AUB.     

Tibolone and risk of endometrial polyps: a prospective, comparative study with hormone therapy

OBJECTIVE: To assess the incidence of endometrial polyps during postmenopausal replacement therapy with tibolone, using an appropriate control group. DESIGN: A total of 485 postmenopausal women were included in this open, prospective, comparative study for a duration of 36 months. Of this group, 249 women received 2.5 mg/day of tibolone and 244 women served as controls, receiving continuous-combined estrogen-progestogen therapy (HT). Transvaginal ultrasound, hysteroscopy, and directed biopsies were performed before treatment was initiated and at the end of the study. RESULTS: Two hundred twenty-one of the women receiving tibolone and 203 receiving continuous-combined HT completed the study. Endometrial polyps were detected in 74 women (33.4%) from the tibolone group and in 22 women (10.8%) from the HT group (P < 0.01). The vaginal bleeding rate did not differ between the groups. The frequency of atrophic polyps was significantly higher in the tibolone group (P < 0.01). No difference was found in the size of the polyps. CONCLUSIONS: Tibolone increases by threefold the risk for endometrial polyps.     

宫腔镜结合C—erbB-2、nm23及ER表达对子宫内膜癌早期诊断意义

目的 探讨宫腔镜结合C—erbB-2、nm23及ER表达在子宫内膜癌中的诊断意义。方法 宫腔镜检查2400例患者，对筛查出的35例子宫内膜癌、10例内膜不典型增生及10例正常内膜，用免疫组化SP法检测C—erbB-2、nm23和ER表达。结果C—erbB-2、nm23、ER阳性表达率依次为74．29％、51．43％、54．29％；50％、30％、60％；30％、10％、90％。三者nm23、ER阳性表达率明显升高，差异有显著性（P〈0．05）；C—erbB-2阳性表达率明显降低，差异有显著性（P〈0．05）。宫腔镜定位活检确诊子宫内膜癌35例（35／2400），占1．46％。结论 宫腔镜直观病灶，结合c—erbB-2、nm23及ER表达对内膜癌早期诊断有意义。     

Endocrinological features and endometrial morphology in climacteric women receiving hormone replacement therapy

Prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrone (E₁), and oestradiol (E₂) levels were determined in 204 women who were receiving hormone replacement therapy for their climacteric symptoms. The changes in these hormone levels and the endometrial morphology were studied in order to determine the effects of the replacement therapy. The women were divided into two groups: the first group of 120 women was treated with conjugated oestrogens administered cyclically, plus norethisterone acetate. The second group of 84 women received oral oestriol succinate, also administered cyclically but without additional progestogens. The oestrogen-progestogen therapy resulted in a disappearance of the climacteric symptoms and a significant decrease of FSH and LH levels. Oestriol therapy was less effective than the conjugated oestrogens as a replacement therapy. Oestriol therapy also resulted in a less remarkable decrease of gonadotrophin levels. There were no significant changes in prolactin levels in either group of women. The endometrial histology did not change significantly after either of the two hormone replacement therapies.     

Misoprostol versus curettage in women with early pregnancy failure after initial expectant management: a randomized trial

BACKGROUND: Little is known about the effectiveness of misoprostol treatment in women with early pregnancy failure who have been managed expectantly. We therefore performed a randomized trial on this subject. METHODS: Women with early pregnancy failure, who had been managed expectantly for at least 1 week, were assigned randomly (using a computer-generated list) to receive either vaginal misoprostol 800 microg or curettage. If, after 24 h, there had not been complete evacuation, a further 800 microg of misoprostol was administered. In the absence of complete evacuation after > days, curettage was performed. The primary end-point was the complete evacuation of the products of conception, with secondary end-points being the occurrence of side effects, pain intensity, need for analgesics, and intensity and duration of bleeding. RESULTS: In the misoprostol group, 47% (37/79) required curettage due to incomplete evacuation. After 1 week, evacuation was complete in 85% (67 out of 79) of the misoprostol group and 93% (70 out of 75) of the curettage group. Severity of pain, bleeding and emergency evacuation was higher in the misoprostol group. The complication rate was 0% for misoprostol and 4% for curettage. CONCLUSIONS: Curettage is superior to misoprostol in the evacuation of early pregnancy failure after failed expectant management. However, misoprostol could be clinically useful since it reduces the need for curettage by half and has a lower complication rate, at the expense of increased pain, vaginal bleeding and emergency evacuation.     

Lymphangiogenesis of normal endometrium and endometrial adenocarcinoma

BACKGROUND: Information about lymphatics and lymphangiogenesis in the human endometrium is limited. We investigated the distribution of endometrial lymphatic vessels during the normal menstrual cycle and in association with endometrial adenocarcinoma and investigated the expression of lymphangiogenic growth factors, vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor-3 (VEGF-R3). METHODS AND RESULTS: Full thickness uterine samples (n = 23 proliferative; n = 23 secretory) and endometrial adenocarcinoma samples (n = 7 grade I; n = 10 grade III) were collected for the study and analysed by immunohistochemistry and western blotting. Lymphatic vessels of the functionalis were significantly reduced compared with basalis (P = 0.001) across the menstrual cycle with lymphatics of the basalis sometimes intimately associated with spiral arterioles. Lymphatic vessels of endometrial adenocarcinomas were located intra-tumoural and peri-tumoural with significant increases in the peri-tumoural lymphatic vessels compared with normal basalis (P = 0.02). Interestingly, high-grade adenocarcinoma vessels containing tumour emboli demonstrated a mixed blood/lymphatic endothelial cell phenotype. VEGF-C and VEGF-D were immunolocalized in glandular epithelium and some stromal cells with the staining intensity of this localization increasing in endometrial adenocarcinoma. Protein analysis identified VEGF-C (58, 41, 31 and 21 kD) and VEGF-D (56, 41, 31 and 21 kD) and VEGF-R3 (148 and 65 kD) peptides in normal endometrium, with significant increases in several of these peptides for VEGF-C and VEGF-D and no changes in protein expression for VEGF-R3 in endometrial adenocarcinoma. CONCLUSION: Endometrial lymphatics are significantly reduced in the functionalis, and increases in endometrial adenocarcinoma peri-tumoural lymphatics are associated with increases in VEGF-C and VEGF-D peptides.     

Detection of endometrial adenocarcinoma with the ThinPrep Pap test

The ThinPrep Pap Test (Cytyc Corp., Boxborough, MA) was introduced in the Loyola University Medical Center (LUMC) Cytopathology Laboratory in March 1997. This study presents a 26-month retrospective review of the cervicovaginal specimens on all patients who had a cytologic diagnosis of adenocarcinoma either by conventional (CS) or ThinPrep (TP) methods. From March 1997 through May 1999, 16,139 conventional smears and 29,589 TP Pap tests were sent to the LUMC cytopathology laboratory. The three diagnostic glandular categories included: atypical glandular cells of undetermined significance (AGUS); suspicious for adenocarcinoma, endometrial adenocarcinoma, and adenocarcinoma; not otherwise specified (nos). Cytohistologic correlation was performed on all available cases. Since endometrial adenocarcinoma occurs most frequently in peri- and postmenopausal patients, the percentage of patients over the age of 50 was determined for each method; 4,669 (29%) of the women receiving a CS were age 50 or over and 6,839 (23%) of the women who received the TP Pap test were in this age group. Sixteen endometrial lesions were identified on cytology, one (adenocarcinoma) with the CS method and 15 (six AGUS; suspicious for adenocarcinoma, four endometrial adenocarcinomas, and five adenocarcinomas; nos) with the TP method. The one CS case had biopsy confirmation. Fourteen of the 15 TP cases (93%) were confirmed by biopsy; one (7%) case had no follow-up. The TP Pap test yielded a higher percentage of endometrial adenocarcinomas (0.05%) as compared to CS (0.01%). Traditionally, CS has not been a method for the early detection of endometrial glandular lesions. However, of the patients diagnosed as having an endometrial adenocarcinoma in this study, the TP Pap test contributed to an increase in the detection of these lesions as compared to CS. The age group for the two methods was comparable.     

Altered expression of alpha-methylacyl-coenzyme A racemase in prostatic adenocarcinoma following hormone therapy

alpha-Methylacyl-coenzyme A racemase (AMACR) is a sensitive and specific tissue marker for the diagnosis of prostatic carcinoma. However, limited data are available on AMACR expression in residual prostatic carcinoma following hormone therapy. We analyzed 64 residual or recurrent prostatic adenocarcinomas following hormonal therapy for the expression of AMACR using a monoclonal antibody (P504S) to AMACR. In 20 localized cases, AMACR staining was absent in 11 (55%), 1+ in 6 (30%), and 2+ or 3+ in 3 (15%). However, in 15 metastatic cases, AMACR was absent in 1 (7%), 1+ in 3 (20%), and 2+ or 3+ in 11 (73%). None of the 29 postradiotherapy cases showed complete absence of AMACR staining: 2 (7%) were 1+, and 27 (93%) were 2+ or 3+. AMACR expression was reduced significantly in the majority of posthormonal residual carcinomas, whereas in postradiotherapy and in hormone-refractory metastatic prostatic adenocarcinoma, AMACR expression was retained. Therefore, the diagnosis of residual prostatic carcinoma after hormonal therapy using AMACR immunostaining must be interpreted with caution. Furthermore, AMACR might have a role in the recurrence of prostatic adenocarcinoma after medical therapy.     

早期和较早期食管癌的光动力治疗

目的 分析光动力治疗10例食管癌的临床疗效及不良反应的预防.方法 观察、并随访2011年6月至2013年6月行光动力治疗的10例食管癌患者,静脉注射光敏剂(photosan)2 mg/kg,44～48 h后应用波长630 nm的半导体激光进行光动力照射治疗,连续两天为1个周期,1月后重复1个周期.术后1、3、6、12、18及24月复查胃镜并取病理,复查胸腹部CT,评价临床效果和不良反应发生情况,探讨光动力治疗的疗效以及不良反应的处理方法.结果 术后次日肿瘤组织开始水肿坏死.术后1个月左右,胃镜显示原病灶部分或完全消退.第2周期治疗后1个月复查胃镜显示病灶几乎完全消失,胃镜病理未见肿瘤细胞.随访2 ～ 24月,胃镜、胸腹部增强CT均未见肿瘤复发及转移.光动力治疗除光敏反应外,主要不良反应是一过性发热、胸痛、咳嗽咳痰、肺感染及吞咽困难,经对症处理均可缓解.2例食管癌患者治疗后2月出现食管瘢痕狭窄,经胃镜下扩张并放置食管支架后缓解.10例患者光动力治疗后均发生不同程度的高凝状态,l例发生急性冠脉综合征.结论 光动力治疗较早.期食管癌疗效确切,全身不良反应较轻,对于光动力治疗后的凝血功能异常的原因及发生机制尚有待一步研究.