Transvaginal endometrial sonography in postmenopausal women taking tamoxifen

OBJECTIVE: To evaluate sonographic measurements of endometrial thickness in postmenopausal women taking adjuvant tamoxifen therapy for breast cancer, and to correlate sonographic and pathologic findings to symptoms and duration of tamoxifen therapy. METHODS: Medical records and sonograms of 80 postmenopausal women treated for breast cancer with adjuvant tamoxifen therapy were reviewed retrospectively. Endometrial thickness was recorded as a single-layer thickness and considered abnormal when greater than 2.5 mm for postmenopausal women. Sonographic endometrial thickness was correlated to histologic findings, symptoms, and duration of tamoxifen therapy. RESULTS: Fifty-seven of 80 postmenopausal women (69%) had single-layer endometrial thicknesses of 2.5 mm or greater, measured by transvaginal sonography, and 55 of 57 had endometrial biopsies or dilatations and curettage. Biopsies detected 24 cases of abnormal endometria, including endometrial carcinoma (two), breast carcinoma metastatic to the endometrium (one), endometrial polyps (13), tubal metaplasia (three), and benign endometrial hyperplasia (five). Using a single-layer endometrial thickness greater than 2.5 mm by transvaginal ultrasound, 21 of 24 (87.5%) women with abnormal endometria were detected. Women with abnormal pathologic findings had a significantly thicker mean single-layer endometrial thickness than those with normal findings, 7 mm versus 4 mm (P < .01). Twelve women had postmenopausal bleeding, all of whom had a single-layer endometrial thickness greater than 2.5 mm on transvaginal sonography. CONCLUSION: With a sensitivity of detecting endometrial abnormalities of 84%, transvaginal sonography was useful for studying postmenopausal tamoxifen-treated women.     

他莫昔芬对乳腺癌患者子宫内膜影响的前瞻性临床病理研究

目的:前瞻性研究他莫昔芬对乳腺癌患者子宫内膜的影响。方法:对2005年1月~2008年10月于温州医学院附属第二医院乳腺外科手术的155例乳腺癌患者进行随访,以阴道B超、宫腔镜及子宫内膜活检评价服用他莫昔芬前后子宫内膜情况。结果:可评价患者共135例,其中绝经前46例,绝经后89例。服用他莫昔芬后,未绝经组36例(78.26%)出现异常阴道流血,9例(19.56%)出现子宫内膜病变,绝经组22例(24.72%)发生异常阴道流血,出现子宫内膜病变29例(32.60%),其中术前绝经组18例(18/59,30.51%),化疗后绝经组11例(11/30,36.67%)。阴道B超对绝经后子宫内膜病变诊断的灵敏度为52.3%,特异度为90.2%,宫腔镜诊断相应的灵敏度为81.8%,特异度为100%。结论:他莫昔芬导致绝经后妇女子宫内膜病变发生增加,对绝经前妇女的影响还不确定。阴道B超可作为初步检测手段,宫腔镜检查可提高诊断的准确率。     

Hysteroscopic myomectomy in postmenopausal women

STUDY OBJECTIVE: To review the findings in postmenopausal patients undergoing hysteroscopic myomectomy. DESIGN: Retrospective case-controlled study (Canadian Task Force classification II-2). SETTING: Private practice. PATIENTS: Eighteen women with postmenopausal bleeding and two asymptomatic women with abnormal ultrasounds. INTERVENTIONS: Hysteroscopic myomectomy in 19 patients, with concomitant destruction of the endometrium in 4 patients, and resectoscopic biopsy in 1 patient. MEASUREMENTS AND MAIN RESULTS: Three patients underwent subsequent gynecologic surgery. One had hysteroscopy to evaluate and remove an asymptomatic residual myoma found on ultrasound. A sarcoma was found in two of the symptomatic patients. Two patients underwent hysterectomy-one for a sarcoma and the other for a carcinoma of the cervix. One patient has had further postmenopausal bleeding. CONCLUSION: Women who have a submucosal myoma that becomes symptomatic in the menopausal period may be at increased risk for a sarcoma.     

Sonographic, hysteroscopic, and histologic evaluation of the endometrium in postmenopausal women with breast cancer receiving tamoxifen

STUDY OBJECTIVE: To evaluate the estrogenic effects of tamoxifen on the endometrium in postmenopausal women with breast cancer. DESIGN: Consecutive study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Thirty-three women. Interventions. All patients underwent transvaginal sonography (TVS) and color flow Doppler of endometrial vessels, hysteroscopy, and, if necessary, endometrial biopsy or other operative hysteroscopic procedures. MEASUREMENTS AND MAIN RESULTS: In four women the endometrium was thin on TVS and atrophic at hysteroscopic assessment. In 29 women with thick endometrium on TVS, hysteroscopy and endometrial biopsy showed atrophy (11 patients), hyperplasia (5), polyps (11), and well-differentiated adenocarcinoma (2). The two endometrial cancers were present in women with uterine bleeding. In women with positive histologic findings, the endometrium was significantly thicker (p = 0.04) and duration of tamoxifen therapy longer than in those with negative findings, although this was not statistically significant (p = 0.067). CONCLUSION: We believe regular assessment of the endometrium by TVS should be performed in postmenopausal patients at the start of the tamoxifen therapy, and hysteroscopy in women with a thick endometrium or postmenopausal bleeding. We believe that patients with thin endometrium on TVS at the beginning of tamoxifen therapy, who have no abnormal uterine bleeding should be screened with these examinations for 2 years.     

Cytologic evaluation of the endometrium in women with postmenopausal bleeding

The records of 143 patients who had postmenopausal bleeding and underwent diagnostic curettage were reviewed. Of these patients 69% had benign endometrial tissue and in 8% there was insufficient tissue for histologic interpretation; 23% of the patients had endometrial carcinoma. In order to ascertain if endometrial cytology could predict which patients which patients may be harboring endometrial carcinoma, a prospective study was carried out on 69 patients complaining of postmenopausal bleeding. Prior to curettage, an endometrial cell sample was obtained with a disposable endometrial cell sampler. The preliminary data indicate good correlation between endometrial cytology and histology. There was one false-negative cytology report and one false positive report. Such a technique could eliminate an endometrial curettage in those patients in whom there is no clinical suspicion of endometrial carcinoma and the cytology is negative.     

Hysteroscopic evaluation of the uterine cavity in postmenopausal women with uterine bleeding

Postmenopausal uterine bleeding is the most characteristic and frequent endometrial adenocarcinoma symptom. Patient with uterine bleeding appeared at least 12 months after the last menstruation needs diagnostic management before initiation of any treatment. OBJECTIVES: Evaluation of hysteroscopy for the recognition of pathologies causing postmenopausal uterine bleeding. MATERIALS AND METHODS: Seventy-nine women aged 48-80 without hormonal replacement therapy hospitalized in the 1st Department of Gynecology and Gynecological Oncology of the Medical University of ?ód? between 1998-2002 because of postmenopausal uterine bleeding were included in the study. In each case diagnostic hysteroscopy with visualisation of the uterine cavity was performed and then histopathologic biopsy by a curretage was taken. Hysteroscopic images were analyzed and compared with the histopathological results. RESULTS: 2 women had the oncologically suspected hysteroscopic images. In both cases endometrial adenocarcinoma was histopathologically confirmed. Among 5 patients with hysteroscopic images suggesting non-malignant endometrial proliferation 4 cases of endometrial hyperplasia were found. 11 times hysteroscopic visualisation of endometrial polyps enabled their complete deletion. In 8 cases intrauterine adhesions were found and dissected: 11 patients presented submucous myomas during hysteroscopy. In 3 cases visualisation of the uterine cavity was not possible because of technical failure. Any patient with absence of hysteroscopically found uterine abnormalities had a poor histopathological result. CONCLUSIONS: Hysteroscopic investigation in postmenopausal women with uterine bleeding reduce the risk of false negative histopathological result. Hysteroscopy is useful method of the uterine cavity visualisation. Thanks to localization and elimination of the pathologies like endometrial polyps and intrauterine adhesions the repeated bleeding and the second time admission of the patient for the same reason can be avoided.     

Pretreatment and prospective assessment of endometrium in menopausal women taking tamoxifen for breast cancer

OBJECTIVES: To estimate the pretreatment incidence of endometrial pathology and to prospectively assess the endometrial morbidity emerging during tamoxifen intake for breast cancer. STUDY DESIGN: One-hundred and forty-six menopausal breast cancer patients, candidate to receive tamoxifen underwent endometrial assessment by Transvaginal Ultrasonography (TU) before the start of therapy. A double-layered endometrial stripe measuring more than 4mm indicated hysteroscopy and endometrial biopsy. Endometrial abnormalities detected before the start of tamoxifen were treated by operative hysteroscopy or by hysterectomy; no therapy and yearly hysteroscopic follow-up was scheduled for patients showing non-atypical hyperplasias. All women were asked to undergo TU on a yearly basis; during the follow-up period, indication for hysteroscopy and endometrial biopsy were the following: (i) an endometrial lining measured above 4mm at the first time, (ii) at least a 50% increase of endometrial thickness since the last finding in patients previously assessed by hysteroscopy, (iii) a recorded vaginal bleeding, and (iv) previous findings of endometrial hyperplasia. Histopathologic result from biopsy or hysterectomy was the reference test to establish the baseline prevalence of endometrial pathology and the emerging prevalences of morbidity after 12, 24, 36, 48 and 60 months of tamoxifen therapy. RESULTS: One-hundred and five patients were followed for 60 months, whereas 113, 126, 137 and 141 patients were evaluated up to 48, 36, 24 and 12 months, respectively. In 44 out of 146 patients, pretreatment TU showed an endometrium thicker than 4mm and in 31 (21.2%) of these patients abnormalities consisting of 16 endometrial polyps, seven polyps harboring simple hyperplasia, four simple hyperplasias, three atypical hyperplasias and one adenocarcinoma were found. During tamoxifen intake benign endometrial abnormalities were detected in 36 out of 114 assessable patients showing normal endometrium before the start of tamoxifen therapy (31.5%) and in seven out of 27 patients with baseline endometrial abnormalities (25.9%). Overall, an endometrial pathology emerged in 30.4% of patients during tamoxifen administration and in no patients we found an atypical lesion. CONCLUSIONS: In menopausal breast cancer patients the incidence of endometrial abnormalities before the start of tamoxifen therapy is high and includes 2.7% of atypical pathology. After the diagnosis and treatment of baseline atypical lesions were accomplished, no atypical endometrial lesion emerged after the start of tamoxifen administration. Based on these findings, we believe that pretreatment assessment of endometrium is recommended in all menopausal women candidate to receive tamoxifen therapy.     

Surveillance of the endometrium in tamoxifen treated women

There is much debate about the risks and benefits of tamoxifen, most specifically about the incidence of associated endometrial cancer. Nearly all of the published trials on the subject have been criticized for methodological flaws and various forms of bias, making resolution of this controversy difficult. There is a consensus, however, that tamoxifen results in an increased incidence of both premalignant and malignant lesions of the endometrium. As the indications for tamoxifen continue to broaden, a larger number of women will be subjected to the potential adverse effects of tamoxifen. Many techniques for screening patients on tamoxifen for the development of endometrial abnormalities have been suggested. None of these methods appears to be consistently clinically or cost effective. We have reviewed the literature on endometrial surveillance in tamoxifen treated women with a focus on the larger publications reported within the past year. From this, we have provided what we hope to be safe and cost-effective recommendations for the management of these patients.     

Hysteroscopic polypectomy in 240 premenopausal and postmenopausal women

OBJECTIVE: To ascertain the therapeutic efficacy and safety of hysteroscopic polypectomy in 240 premenopausal and postmenopausal patients. DESIGN: Retrospective study. SETTING: Tertiary university hospital. PATIENT(S): Two hundred forty patients with intrauterine endometrial polyps, who mostly suffered from abnormal uterine bleeding and infertility. INTERVENTION(S): Hysteroscopic polypectomy using various instruments including microscissors, grasping forceps, or electrosurgery either with a monopolar probe or a resectoscope. MAIN OUTCOME MEASURE(S): Operating time, amount of glycine absorption, complications, resumption of normal menstruation, cumulative pregnancy rate, and recurrent rate of polyps after hysteroscopic surgery. RESULT(S): Resectoscopic polypectomy needed more operating time, had more glycine absorption and complications, but less recurrence than other hysteroscopic techniques. The resectoscope had a 0% recurrence rate and that grasping forceps had a 15% recurrence rate. A total of 21 (8.7%) complications occurred, but no major complications were noted. After long-term follow-up of 9 years and 2 months, those with abnormal uterine bleeding resumed normal menstruation in 93.1% and those with infertility had a cumulative pregnancy rate of 42.3%. There was no statistical difference in reproductive outcome between patients having polyps < or = 2.5 cm and >2.5 cm. CONCLUSION(S): We found hysteroscopic polypectomy to be effective, safe, minimally invasive procedure with low rate and mild complications. Restoration of reproductive ability did not depend on the size of the removed lesion. Resectoscopic surgery is more preferable to prevent recurrence of polyps.     

Transvaginal sonography of the endometrium in postmenopausal women

The purposes of this study were to compare transvaginal sonographic scanning of the uterus and endometrium with histology obtained by endometrial biopsy or curettage and to determine whether the sonographic technique might be useful in the evaluation of postmenopausal women. Eighty postmenopausal women were studied. Of these, 65 were asymptomatic (38 on no hormone therapy and 27 on hormone replacement). Fifteen women underwent evaluation because of postmenopausal bleeding. In both groups, endometrial thickness of 4 mm or less as depicted by sonography correlated well with endometrial characteristics of decreased estrogen stimulation. However, in women with measured endometrial thickness between 5-8 mm, proliferative endometrium could not be distinguished from hyperplastic endometrium or, in one case, low-grade carcinoma. Large polyps and invasive carcinoma with myometrial extension were easily recognized.     

Transvaginal ultrasonography of the endometrium in postmenopausal Japanese women

AIMS: To determine the cut-off level of endometrial thickness for detecting endometrial disease on a large scale of screening and to examine the usefulness of transvaginal ultrasonography (TVS) for endometrial disease screening in asymptomatic postmenopausal Japanese women. METHODS: The study involved 1,400 postmenopausal women in whom endometrial thickness was measured with TVS, and then compared with the histopathological diagnosis of endometrial specimens. RESULTS: The prevalence of endometrial disease in asymptomatic and symptomatic cases was 2.3 and 21%. In symptomatic cases, at a cut-off limit of 3 mm for endometrial thickness, the sensitivity for detecting endometrial disease was 94%, specificity 70% and positive predictive value 46%. With an endometrial thickness < or = 3 mm, the probability that endometrial disease would be overlooked was 0.025. In asymptomatic cases, the corresponding figures at a cut-off limit of 3 mm were 90, 84, 12% and 0.003. CONCLUSIONS: TVS does not appear to be an effective screening method in asymptomatic postmenopausal Japanese women because of the low prevalence of endometrial disease in this population. We recommend a normal cut-off level for endometrial thickness of 4 mm in symptomatic postmenopausal Japanese women.     

Apoptosis in the endometrium of postmenopausal women receiving tibolone

BACKGROUND/AIM: Tibolone, a synthetic derivative of the 19-nortestosterone family, induces atrophy of the endometrium, especially via its progestogenic Delta(4) isomer. The aim of the study was to determine whether tibolone induces apoptosis in the endometrium of postmenopausal women. METHODS: Twenty healthy postmenopausal women (mean age +/- SD 52.4 +/- 4.21 years) who had amenorrhea for at least 1 year and who had no history of any systemic illness and estrogen replacement therapy were enrolled in the study. All patients were offered office endometrial samplings, and then tibolone was prescribed (2.5 mg/day p.o., once daily) to all patients. Repeat endometrial samples were obtained after completion of the 6-month course of tibolone therapy. All samples were immunohistochemically analyzed for the presence of apoptotic cells. RESULTS: There was no significant difference in the median proportion of apoptotic nuclei between the pre- and posttreatment samples (2 vs. 3%; p > 0.05). CONCLUSIONS: The results showed that tibolone did not affect the rate of apoptosis in the postmenopausal endometrium. Further studies are needed to clarify the role of apoptosis in overall effects of hormonal compounds on the postmenopausal endometrium.     

Hysteroscopic evaluation of menopausal patients with sonographically atrophic endometrium

STUDY OBJECTIVE: To assess the diagnostic and operative potential of hysteroscopy in postmenopausal patients selected by ultrasound criteria. DESIGN: Prospective evaluation (Canadian Task Force classification II-2). SETTING: Outpatient ultrasound and hysteroscopy department of a university-affiliated hospital. PATIENTS: Two hundred twelve women with an endometrial thickness less than 4 mm on ultrasound and in menopause for at least 1 year. INTERVENTIONS: Transvaginal ultrasound and office hysteroscopy, with eye-directed biopsy specimens obtained with a 5-mm, continuous-flow operative hysteroscope, and performed without anesthesia. MEASUREMENTS AND MAIN RESULTS: Only 13 (6%) patients were symptomatic (irregular bleeding). Hysteroscopic diagnosis of endometrial polyps in three women (23%) was confirmed by histology. In the remaining 199 (94%) asymptomatic patients with atrophic endometrium on ultrasound, hysteroscopy showed an endometrial pathology in 10% (16 polyps, 4 submucous myomas); in one patient histologic evaluation disclosed focal adenocarcinoma in an endometrial polyp. CONCLUSION: Hysteroscopy allows a proper histologic diagnosis, even in asymptomatic postmenopausal women with atrophic endometrium on ultrasound.     

Hysteroscopic treatment of intrauterine lesions in premenopausal and postmenopausal women

STUDY OBJECTIVE: To compare the safety and efficacy of hysteroscopic surgery in the management of intrauterine lesions in premenopausal and postmenopausal women and, in particular, to investigate whether glycine absorption is different between these populations. DESIGN: Comparative study (Canadian Task Force classification II-2). SETTING: Tertiary care university hospital. PATIENTS: Thirty postmenopausal and 78 premenopausal women with intrauterine polyps or myomas. INTERVENTION: Hysteroscopic myomectomy or polypectomy. MEASUREMENTS AND MAIN RESULTS: One hundred eight procedures were completed successfully by hysteroscopy; in two cases myomectomy was completed in a second operation for a deeply embedded myoma. No major complications occurred in either group. Median operating time, mean glycine absorption, and median postoperative hospital stay were not significantly different between groups. During mean follow-up of 15 months (range 1-39 mo), four women underwent hysterectomy (1 for endometrial cancer, 1 for complex hyperplasia with atypia, 2 for pelvic pain and menorrhagia). CONCLUSION: Hysteroscopic surgery is an effective and safe therapeutic option for intrauterine lesions regardless of a woman's menopausal status.     

Adenocarcinoma of the endometrium in women taking sequential oral contraceptives.

Abnormal bleeding while taking oral steroidal contraceptives has been managed by changes in pill or addition of estrogen or progestin moieties. Diagnostic procedures, classically indicated, are universally not undertaken or postponed. Three cases of adenocarcinoma of the endometrium in relatively young patients using sequential oral contraceptives for cause are presented to reiterate the need for tissue diagnosis when abnormal bleeding occurs as a common side-effect of contraceptive therapy.     

The effects of phytoestrogen therapy on the endometrium in postmenopausal women

AIM: The purpose of the present study was to carry out a comparative histological analysis of the endometrium in postmenopausal women who made use of phytoestrogens in order to assess the efficacy and possible side effects of this therapy. METHODS: This study was carried out by forming 2 groups in order to compare the results. One group was given a dietary supplement of phytoestrogens for 24 months, whereas the other was given a placebo for the same period of time. At the beginning of this study endometrial bioptical samples were taken from those patients who had been previously selected at our University Centre. This study was started only with those postmenopausal patients whose bioptical sample was histologically suitable, and it was neither hyperplastic, nor cancerous and nor secretive. During these 24 months there have been frequent contacts aimed at verifying the standard therapeutic behaviour, symptoms and appearance of side effects. At the end of the study new and final bioptical samples of endometrium were taken from both groups. RESULTS: One-hundred and forty-one patients completed the study. Five patients (3.4%) who were submitted to phytoestrogens therapy showed a weak proliferative endometrium bioptical sample. All the other biopsies at the beginning and at the end of the study showed an atrophic and inactive sample. Hot flushes, night sweats, vaginal dryness and dyspareunia improved at the end of the study for the group treated with phytoestrogens as compared to the one treated with a placebo. Although there have not been very significant differences ias to symptoms and side effects, it was noted that insomnia was the most common symptom in the group treated with non-hormonal therapy based on phytoestrogens. CONCLUSIONS: Phytoestrogens did not cause any sensitive and worrisome stimulation of the endometrial mucosa. Insomnia was more frequent in the group treated pharmacologically in the 24 months of the study, whereas hot flushes, night sweats, vaginal dryness and dyspareunia persisted or increased as compared to the beginning of the study in the group treated with a placebo, but this did not occur for the group treated with phytoestrogens.