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Key content Hormone replacement therapy (HRT) is the most effective treatment for symptoms of estrogen deficiency. When HRT is individually tailored women gain maximum advantages and the risks are minimised. Several types and regimens of HRT and different routes of delivery exist. Results from studies using only one type and route may not therefore apply to all users. The use of HRT is an individual decision, which a woman can only make once she has been given correct information and advice from healthcare professionals. HRT should be recommended in women with premature ovarian insufficiency with advice to continue until the average age of the menopause at 51.4 years. Learning objectives To review the current research and the evidence on the use of HRT in women. Application of the evidence in relation to the management of the symptomatic menopausal woman. To promote confidence in prescribing HRT in most symptomatic women. To have a general overview of prescribing in women with relative contraindications. Ethical issues The use of HRT is a patient informed choice. Where evidence is limited and quality of life a priority, then a multidisciplinary approach may be necessary and informed written consent documented.

This randomized controlled trial (RCT) by Tasma et al. reports on pain at hysteroscopy. This is an important subject since hysteroscopy is the single most common procedure in gynaecology. There has been limited or conflicting evidence regarding misoprostol for cervical priming prior to hysteroscopy. Although there have been three meta-analyses and 25 RCTs published to date, the heterogeneity among regimens, doses, and route of administration plus clinical diversity, make analysis of the data difficult. This article is protected by copyright. All rights reserved.

Key content Patients with postmenopausal bleeding (PMB) have a 10–15% chance of having endometrial carcinoma; they should therefore be seen within 2 weeks of referral. Cervical and vulval cancers remain important components of the differential diagnosis and can only be assessed by clinical examination. There are well-developed and evidence-based strategies on how best to investigate women with PMB. These strategies are formulated in several guidelines. Learning objectives To understand that the completion of investigations of patients with PMB should include test performance and patient characteristics. To be able to evaluate the various investigations for women with PMB. To be able to describe the appropriate management of women with PMB on tamoxifen, and unscheduled PMB in women undergoing hormone replacement therapy. Ethical issues Incidental finding of thickened endometrium on transvaginal sonography (TVS) in asymptomatic individuals carries a management dilemma. Approach to benign pathology: should subsequent evaluation for benign abnormalities be performed after malignancy has been ruled out? Ongoing work and technology development will evolve our strategy in managing PMB.

OBJECTIVE: To estimate the accuracy of endometrial thickness measurement in the detection of endometrial cancer among women with postmenopausal bleeding with individual patient data using different meta-analytic strategies. DATA SOURCES: Original data sets of studies detected after reviewing the included studies of three previous reviews on this subject. An additional literature search of published articles using MEDLINE databases was preformed from January 2000 to December 2006 to identify articles reporting on endometrial carcinoma and sonographic endometrial thickness measurement in women with postmenopausal bleeding. METHODS OF STUDY SELECTION: We identified 90 studies reporting on endometrial thickness measurements and endometrial carcinoma in women with postmenopausal bleeding. TABULATION, INTEGRATION, AND RESULTS: We contacted 79 primary investigators to obtain the individual patient data of their reported studies, of which 13 could provide data. Data on 2,896 patients, of which 259 had carcinoma, were included. Several approaches were used in the analyses of the acquired data. First, we performed receiver operator characteristics (ROC) analysis per study, resulting in a summary area under the ROC curve (AUC) calculated as a weighted mean of AUCs from original studies. Second, individual patient data were pooled and analyzed with ROC analyses irrespective of study with standardization of distributional differences across studies using multiples of the median and by random effects logistic regression. Finally, we also used a two-stage procedure, calculating sensitivities and specificities for each study and using the bivariate random effects model to estimate summary estimates for diagnostic accuracy. This resulted in rather comparable ROC curves with AUCs varying between 0.82 and 0.84 and summary estimates for sensitivity and specificity located along these curves. These curves indicated a lower AUC than previously reported meta-analyses using conventional techniques. CONCLUSION: Previous meta-analyses on endometrial thickness measurement probably have overestimated its diagnostic accuracy in the detection of endometrial carcinoma. We advise the use of cutoff level of 3 mm for exclusion of endometrial carcinoma in women with postmenopausal bleeding. (Obstet Gynecol 2010;116:160-7)

In this article we present the protocol of the Birmingham Registry for Twin Heritability Studies (BiRTHS), which aims to establish a long-term prospective twin registry with twins identified from the antenatal period and subjected to detailed follow-up. We plan to investigate the concordance in anthropo-metrics and early childhood phenotypes between 66 monozygotic and 154 dizygotic twin pairs in the first 2 years of recruitment. In this project we plan to determine the relative contributions of heritability and environment to fetal growth, birth size, growth in infancy and development up to 2 years of age in an ethnically mixed population. Twins will be assessed with the Griffitth's Mental Development Scales, which will enable us to obtain detailed information on development. As maternal depression may have an effect on the twins' neurodevelopment, the Edinburgh Postnatal Depression Scale will be used at various stages during pregnancy and after delivery to assess maternal depressive symptoms. The increasing prevalence of obesity in both adults and children has raised concerns about the effect of maternal obesity in pregnancy on fetal growth. The prospective study design gives us the opportunity to obtain data on maternal nutrition (reflected by body mass index) and ante- and postnatal growth and development of twins.

OBJECTIVE: To develop a multivariable approach to determine the added value of tests in routine practice where some diagnostic information is already available from clinical history. METHODS: Multivariable logistic regression models were built in a stepwise fashion, considering the clinical sequence used in the rapid access ambulatory diagnosis clinic (clinical history followed by transvaginal ultrasonography and hysteroscopy). The reference standard for confirmation of diagnosis was endometrial biopsy. The diagnostic accuracy of the models was determined by the area under the receiver operating characteristic curve. RESULTS: The area under the receiver operating characteristic curve for the model including historical features alone was 0.78. When hysteroscopy and ultrasonography were each added to the model, it increased to 0.81 (P = .008 for improvement) and 0.82 (P = .02 for improvement), respectively. CONCLUSION: The type of stepwise analysis we have developed is crucial in facilitating meaningful clinical interpretation about the value of diagnostic technology. Our finding that hysteroscopy or ultrasonography marginally but significantly increased the prediction of serious endometrial pathology above that predicted from patient history alone needs validation in an independent data set. The use of this approach is recommended when evaluating strategies for diagnosis.

Objectives: To evaluate the significance of various risk factors associated with endometrial polyps in women with abnormal uterine bleeding. Methods: A prospective cohort study of 248 consecutive patients evaluated for abnormal uterine bleeding in a Rapid Access Ambulatory Diagnostic (RAAD) clinic was carried out from 1996 to 1997. Endometrial polyps were diagnosed using outpatient hysteroscopy and their histological nature was confirmed in all patients by performing inpatient polypectomy. Multivariate logistic regression modeling was used to evaluate the effects of age, parity, menopausal status, hormone replacement therapy and tamoxifen treatment on the occurrence of polyps. Results: In an analysis adjusted for the effects of age, parity and menopausal status, tamoxifen treatment was associated with endometrial polyps (adjusted odds ratio 11.21, 95% confidence interval 2.70–46.46, P=0.0009) but hormone replacement therapy was not (adjusted odds ratio 1.48, 95% confidence interval 0.68–3.20, P=0.32). Conclusion: Our study confirmed that tamoxifen is associated with endometrial polyps. However, it rejects the hypothesis that hormone replacement therapy is a risk factor for endometrial polyps.

Objective To evaluate the underlying endometrial pathology in breast cancer patients receiving long-term tamoxifen and presenting with abnormal bleeding. Design Prospective cohort study (1996–97). Setting Minimal access surgical training centre in a large teaching hospital. Methods Outpatient ultrasound scan, hysteroscopy and endometrial sampling were carried out in 24 breast cancer patients with abnormal uterine bleeding who were receiving tamoxifen. If these outpatient procedures failed, inpatient hysteroscopy and endometrial sampling was undertaken. On diagnosis of an endometrial polyp, inpatient hysteroscopy, polypectomy and curettage were carried out. Results Hysteroscopy revealed polyps in 17 of 24 patients (71%). Histologically, 13 polyps were benign, three polyps had hyperplasia (one simple and two complex), and one polyp was malignant. Endometrial thickness (ET) on ultrasound scan was associated with hyperplasia or cancer only at ET ≥ 10 mm. Conclusion In breast cancer patients receiving tamoxifen and presenting with abnormal bleeding, a high rate of pathological endometrial lesions was observed. All the polyps were diagnosed hysteroscopically but prediction of premalignant/malignant lesions, which were confirmed by histological assessment, could not be done hysteroscopically. There is a need to assess the accuracy, acceptability and cost-effectiveness of the various tests for evaluating endometrial pathology.

Objective. To evaluate the risk of premalignant and malignant pathology among endometrial polyps. Design. Prospective cohort study. Setting. Minimal Access Surgical Training (MAST) center in a large teaching hospital. Methods. Among 248 patients seen in outpatient hysteroscopy clinic (1996-97), 62 had endometrial polyps. All patients had endometrial sampling for histological assessment. To determine the magnitude of malignant potential among polyps, we compared the pathological findings in polyps (cases) with non-polypoidal specimens (controls). Results. Out of 62 polyps, histologically 53 (85.5%) were benign, seven (11.3%) had hyperplasia, and two (3.2%) were associated with malignancy. Hyperplasia was more frequent in endometrial specimens with polyps than in those without (11.3% vs 4.3%, p =0.04), but the incidence of carcinoma in the two groups was the same (3.2% vs 3.2%, p =1.0). Conclusion. In abnormal uterine bleeding, hyperplasia was, but cancer was not, more common in women with endometrial polyp...

Objective To determine the accuracy of outpatient miniature hysteroscopy in the diagnosis of premalignant and malignant endometrial lesions. Design A prospective cohort study (1996–1997). Setting Minimal access surgical training centre in a large teaching hospital. Methods Outpatient hysteroscopy and endometrial sampling was carried out on 248 patients with abnormal uterine bleeding. Any patients unable to undergo these outpatient procedures were admitted for a formal inpatient hysteroscopy and curettage. Test performance characteristics were computed for hysteroscopy, comparing its findings with the histological diagnosis which served as a ‘gold standard’. Main outcome measures The estimate of the accuracy of the hysteroscopic findings was based, for binary results, on sensitivity, specificity and predictive values. For multilevel results, the diagnostic accuracy was computed using likelihood ratios (LRs). With a normal hysteroscopy result, an LR of 1 indicated an increased probability that such a lesion was present. Results Hysteroscopy revealed features of normal endometrium in 228 women, of whom 12 were found histologically to have premalignant hyperplasia/cancer. Hysteroscopic features of premalignant/malignant endometrial lesions were suspected in 20 patients but the diagnosis was confirmed histologically in six cases only. This amounted to a sensitivity of 33.3% (95% confidence intervals (CI) 14.4–58.8), a specificity of 93.9% (95% CI 89.8–96.5), a positive predictive value of 30.3%. (95% CI 12.8–54.3), and a negative predictive value of 94.7%. (95%CI 90.8–97.1). Analysis using likelihood ratios revealed that for a normal hysteroscopy the LR was 0.7 (95% CI 0.5–0.9). The LR was 1.9 (95% CI 0.5–6.6) when there was intermediate abnormality (increased endometrial thickness, abnormal vascularization, polypoid formations, mamillations and cerebroid irregularities). The LR was 51.1 (95% CI 7.9–326.9) when there was definite hysteroscopic abnormality (intermediate abnormality features associated with irregular polylobular friable excrescences with necrosis or bleeding). Conclusion The probability of the presence of a premalignant/malignant lesion is not particularly altered by the finding of normal hysteroscopic appearances or of intermediately abnormal features. However, if the hysteroscopic findings are definitely abnormal, the probability of there being a premalignant/malignant lesion is substantially increased. Normal findings at hysteroscopy are not conclusive and do not eliminate the need for endometrial sampling as they are not a substitute for benign findings on histological investigation.

We examined the relative significance of hysteroscopic and ultrasonographic evidence of endometrial atrophy in relation to insufficient sample on outpatient endometrial biopsy in women with abnormal uterine bleeding. Multivariate logistic regression modelling was used to evaluate the independent effects of age, menopausal status, hysteroscopic findings and sonographic endometrial thickness on outpatient endometrial sampling (sufficient or insufficient) used as the binary dependent variable. Insufficient sample on endometrial biopsy was associated with hysteroscopic finding of endometrial atrophy (OR 4.79, 95% CI 1.05-21.91, P = 0.04) and sonographic endometrial thickness below 5 mm (OR 0- 19. 95% CI 0.07-0.53, P = 0.001). There was no association with patient's age and menopausal status. In conclusion, when reassuring women with insufficient sample on outpatient endometrial biopsy, one can be confident about absence of pathology provided the hysteroscopic and sonographic endometrial assessment is consistent with endometrial atrophy.

Healthcare providers are facing increasing demands for improvement in quality of life for patients. Improvements in service provision for women are being ensured by the introduction of minimally invasive technologies into all spheres of gynaecologic practice. Ambulatory hysteroscopy (direct endoscopic visualization of the endometrial cavity) is an extremely exciting and rapidly advancing field of gynaecologic practice. It advanced dramatically during the 1990s, shifting the focus in healthcare away from inpatient diagnosis and treatment. Hysteroscopy is used extensively in the evaluation of common gynaecological problems that were previously evaluated with blind and inaccurate techniques (e.g. premenopausal menstrual disorders, infertility and postmenopausal bleeding). It allows direct visualization of the uterine cavity and the opportunity for targeted biopsy, safe removal of endometrial polyps, and treatment of submucous fibroids, septa and adhesions. Ambulatory hysteroscopy is safe, with a low incidence of serious complications; it has a small failure rate. There is a general consensus that hysteroscopy is the current gold standard for evaluating intrauterine pathology, including submucous myomas, polyps, hyperplasia and cancer. Hysteroscopy in the ambulatory setting appears to have an accuracy and patient acceptability equivalent to inpatient hysteroscopy under general anaesthetic. The primary goal of this chapter is to provide a high-quality, evidence-based text on ambulatory diagnostic and operative hysteroscopy. The chapter includes in-depth analysis of the indications for outpatient hysteroscopy, its contraindications, the accuracy of diagnostic hysteroscopy, relevant risk management issues and, training and teaching.

Background. Carcinomaof the vulva has predominantly been a disease of the elderly. Although occasionally it occurs in women under the age of 40 years, carcinoma of the vulva has been rarely diagnosed in pregnancy. Bone marrow hypoplasia can occur as a transient, pregnancy-related event; however, the recurrence of this pathology in future pregnancies is quite rare in the literature. Case. A 29-year-old woman in her second pregnancy that was complicated by bone marrow hypoplasia had developed a squamous vulvar carcinoma. Each of these two conditions are quite rare in pregnancy, they may have occurred by chance, but there is a hypothetical possibility that bone marrow hypoplasia is an autoimmune disorder, with vulvar carcinoma occurring as a further complication in this immunoimpaired individual. Conclusion. This case also emphasizes the need to consider malignancy as a differential diagnosis in vulvar ulcers occurring in young women.