Hormone Therapy for Menopause Reviewed CME/CE
Laurie Barclay, MD, Penny Murata, MD

April 8, 2010 Women must be informed of the potential benefits and risks of all treatment options for menopausal symptoms and concerns and should receive individualized care, according to a review of the role of perimenopausal hormone therapy published in the April issue of Obstetrics & Gynecology.

"With the first publication of the results of the Women's Health Initiative (WHI) trial in 2002, the use of HT [hormone therapy] declined dramatically," write Jan L. Shifren, MD, and Isaac Schiff, MD, from Harvard Medical School and Massachusetts General Hospital in Boston. "Major health concerns of menopausal women include vasomotor symptoms, urogenital atrophy, osteoporosis, cardiovascular disease, cancer, cognition, and mood.... Given recent findings, specifically regarding the effect of the timing of HT initiation on coronary heart disease [CHD] risk, it seems appropriate to reassess the clinician's approach to menopause in the wake of the recent reanalysis of the WHI."

Many therapeutic options are currently available for management of quality of life and health concerns in menopausal women. Treatment of vasomotor hot flushes and associated symptoms is the main indication for hormone therapy, which is still the most effective treatment of these symptoms and is currently the only US Food and Drug Administrationapproved option. For healthy women with troublesome vasomotor symptoms who begin hormone therapy at the time of menopause, the benefits of hormone therapy generally outweigh the risks.

However, hormone therapy is associated with a heightened risk for coronary heart disease. Based on recent analyses, this higher risk is attributable primarily to older women and to those who reached menopause several years previously. Hormone therapy should not be used to prevent heart disease, based on these analyses. However, this evidence does offer reassurance that hormone therapy can be used safely in otherwise healthy women at the menopausal transition to manage hot flushes and night sweats.

Although hormone therapy may help prevent and treat osteoporosis, it is seldom used solely for this indication alone, particularly if other effective options are well tolerated. Short-term treatment with hormone therapy is preferred to long-term treatment, in part because of the increased risk for breast cancer associated with extended use. The lowest effective estrogen dose should be given for the shortest duration required because risks for hormone therapy increase with advancing age, time since menopause, and duration of use.

Low-dose, local estrogen therapy is recommended vs systemic hormone therapy when only vaginal symptoms are present. Alternatives to hormone therapy should be recommended for women with or at increased risk for disorders that are contraindications to hormone therapy use. These include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active hepatic or gallbladder disease.

In addition to estrogen therapy, progestin alone, and combination estrogen-progestin therapy, there are several nonhormonal options for the treatment of vasomotor symptoms. Lifestyle interventions include reducing body temperature, maintaining a healthy weight, stopping smoking, practicing relaxation response techniques, and receiving acupuncture. Although efficacy greater than placebo is unproven, nonprescription medications that are sometimes used for treatment of vasomotor symptoms include isoflavone supplements, soy products, black cohosh, and vitamin E.

There are several nonhormonal prescription medications sometimes used off-label for treatment of vasomotor symptoms, but they are not approved by the Food and Drug Administration for this purpose. These drugs, and their accompanying potential adverse effects, include the following :

• Clonidine, 0.1-mg weekly transdermal patch, with potential adverse effects including dry mouth, insomnia, and drowsiness.

• Paroxetine (10 - 20 mg/day, controlled release 12.5 - 25 mg/day), which may cause headache, nausea, insomnia, drowsiness, or sexual dysfunction.

• Venlafaxine (extended release 37.5 - 75 mg/day), which is associated with dry mouth, nausea, constipation, and sleeplessness.

• Gabapentin (300 mg/day to 300 mg 3 times daily), with possible adverse effects of somnolence, fatigue, dizziness, rash, palpitations, and peripheral edema.

"Women must be informed of the potential benefits and risks of all therapeutic options, and care should be individualized, based on a woman's medical history, needs, and preferences," the review authors write. "For women experiencing an early menopause, especially before the age of 45 years, the benefits of using HT until the average age of natural menopause likely will significantly outweigh risks. The large body of evidence on the overall safety of oral contraceptives in younger women should be reassuring for those experiencing an early menopause, especially given the much lower estrogen and progestin doses provided by HT formulations."

Dr. Shifren serves as a scientific advisory board member for the New England Research Institutes. She has been a research study consultant for Eli Lilly & Co and Boehringer Ingelheim and has received research support from Proctor & Gamble Pharmaceuticals.

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Physical activity in pregnancy: a qualitative study of the beliefs of overweight and obese pregnant women
Zoe Weir, Judith Bush, Stephen C Robson, Catherine McParlin, Judith Rankin, Ruth Bell

ABTRACT
Background Whilst there has been increasing research interest in interventions which promote physical activity during pregnancy few studies have yielded detailed insights into the views and experiences of overweight and obese pregnant women themselves. The qualitative study described in this paper aimed to: (i) explore the views and experiences of overweight and obese pregnant women; and (ii) inform interventions which could promote the adoption of physical activity during pregnancy.

Methods
The study was framed by a combined Subtle Realism and Theory of Planned Behaviour (TPB) approach. This enabled us to examine the hypothetical pathway between beliefs and physical activity intentions within the context of day to day life. The study sample for the qualitative study was chosen by stratified, purposive sampling from a previous study of physical activity measurements in pregnancy.

Research participants for the current study were recruited on the basis of Body Mass Index (BMI) at booking and parity. Semi-structured, in-depth interviews were conducted with 14 overweight and obese pregnant women. Data analysis was undertaken using a Framework Approach and was informed by TPB.

Results Healthy eating was often viewed as being of greater importance for the health of mother and baby than participation in physical activity. A commonly cited motivator for maintaining physical activity during pregnancy is an aid to reducing pregnancy-related weight gain. However, participants often described how they would wait until the postnatal period to try and lose weight. A wide range of barriers to physical activity during pregnancy were highlighted including both internal (physical and psychological) and external (work, family, time and environmental). The study participants also lacked access to consistent information, advice and support on the benefits of physical activity during pregnancy.

Conclusions Interventions to encourage recommended levels of physical activity in pregnancy should be accompanied by accessible and consistent information about the positive effects for mother and baby. More research is required to examine how to overcome barriers to physical activity and to understand which interventions could be most effective for overweight/obese pregnant women. Midwives should be encouraged to do more to promote activity in pregnancy.

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Vitamin D and Mood Disorders Among Women: An Integrative Review
Pamela K. Murphy, CNM, MS, IBCLC; Carol L. Wagner, MD

Abstract
This integrative review evaluates research studies that investigated the association between vitamin D and mood disorders affecting women to determine whether further research comparing these variables is warranted. A literature search using CINAHL, PsycINFO, MEDLINE, and PubMed databases was conducted to locate peer-reviewed mood disorder research studies that measured serum 25-hydroxyvitamin D (25[OH]D) levels. Four of six studies reviewed imparted significant results, with all four showing an association between low 25(OH)D levels and higher incidences of four mood disorders: premenstrual syndrome, seasonal affective disorder, non-specified mood disorder, and major depressive disorder. This review indicates a possible biochemical mechanism occurring between vitamin D and mood disorders affecting women, warranting further studies of these variables using rigorous methodologies.

Introduction
Vitamin D not only is integral to maintaining bone health, but it also plays a role in several other biochemical mechanisms within the human body. Vitamin D receptors are located in bone, skeletal muscle, immune cells, and several body tissues, including the brain, prostate, breast, and colon. The associated cell signaling by vitamin D may account for the mounting evidence that links vitamin D deficiency with an increased risk for a variety of diseases, including cancer, autoimmune disorders, bone disease, cardiovascular disease, and mood disorders. This article reviews the sources and physiology of vitamin D, followed by an overview of the association between vitamin D deficiency and several disease processes, with an emphasis on the relationship between vitamin D deficiency and mood disorders affecting women.

Sources of Vitamin D
Vitamin D is metabolized from dietary sources and from ultraviolet B (UVB) sunlight. However, the majority of women in their childbearing years who reside in the United States have vitamin D insufficiency and/or deficiency that results from lower amounts of UVB exposure because of lifestyle preferences, work schedules, and fear of skin damage and cancer. Protective clothing and sunscreen are often used as barriers to UVB exposure, which prevent the skin's ability to manufacture adequate levels of vitamin D. Darker skin pigmentation also limits the skin's ability to manufacture vitamin D from UVB exposure. Therefore, dietary sources of vitamin D are essential in attaining adequate levels of vitamin D to meet daily requirements.

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Measurement of Blood Loss: Review of the Literature
Mavis N. Schorn, CNM, PhD

Abstract
It is important to recognize excessive blood loss during childbirth, which is a significant cause of morbidity and mortality. This article reviews methods to measure blood loss that could be used during childbirth. PubMed, CINAHL, and MEDLINE databases were searched using the phrases "blood loss" and "measurement." The bibliographies of publications were scanned for applicable references. A total of 46 publications are included in this review. The methods used to measure blood loss are categorized into visual estimation, direct measurement, gravimetric, photometry, and miscellaneous. Methods are described and compared. A combination of direct measurement and gravimetric methods are the most practical. Photometry is the most precise, but also the most expensive and complex to use. A variety of miscellaneous methods are presented, but none is a practical or reliable method. Visual estimation of blood loss is so inaccurate that its continued use in practice is questionable and it should not be used in research to evaluate treatment.

Introduction
Excessive blood loss during childbirth and the resultant morbidity and mortality is a problem that has occurred throughout history. Williams[1] made reference to researchers who attempted to quantify blood loss during childbirth in the late 1800s. Today, hemorrhage continues to be one of the leading causes of maternal mortality in the United States[2] and around the world. Obstetric care has changed in an attempt to decrease blood loss, yet postpartum hemorrhage (PPH) still confounds and alarms birth attendants because of the rapidity of its onset and danger it represents if uncontrolled.

Most blood loss related to childbirth occurs within the first hour after birth, and the most frequent cause of hemorrhage is early postpartum uterine atony. For a vaginal birth, hemorrhage is considered a blood loss of > 500 mL. In clinical practice, the amount of blood lost during childbirth is typically visually estimated by the birth attendant. Even with repetitive studies identifying the limitations and inaccuracies of estimation, it is the easiest and most common method of quickly gauging blood loss. Research has been focused on determining the amount of blood loss that is normal, identifying the frequency of PPH, identifying those women who require intervention for excessive blood loss, evaluating intervention strategies to ameliorate blood loss thereby preventing PPH, and evaluating treatment methods for PPH. The accurate measurement of blood loss iscritical for these research purposes.

The purpose of this article is to present a review of methods to measure blood loss that can be used during a vaginal birth. PubMed, CINAHL, and MEDLINE databases were searched without date limits. The phrases "blood loss" and "measurement" were used in combination to find articles specific to measuring blood loss. The bibliographies of publications were scanned for applicable references. Articles in languages other than English were omitted. Articles that applied the measurement to intervention effectiveness were not included. Reviews were not restricted to measurement of blood loss at childbirth or only to human blood loss because the focus was on blood measurement methods. Simulation, human, and animal research was included. Forty-six publications were included in this review (Table 1). Methods of measuring blood loss were divided into five categories: visual estimation, direct measurement, gravimetric, photometry, and miscellaneous methods. Each of these methods is described along with its strengths and weaknesses.

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Evidence-Based Approaches to Managing Nausea and Vomiting in Early Pregnancy
Tekoa L. King, CNM, MPH; Patricia Aikins Murphy, CNM, DrPH

Abstract
Nausea and vomiting in pregnancy is a continuum that ranges from mild discomfort to significant morbidity. Systematic assessment with the use of the Pregnancy-Unique Quantification of Emesis/Nausea (PUQE) index and timely treatment using evidence-based protocols can decrease the time that many women spend using treatment recommendations that are inadequate. This article reviews the epidemiology of nausea and vomiting in pregnancy, use of the PUQE index, and the evidence for specific nonpharmacologic and pharmacologic treatment regimens. A protocol for clinical management is presented.

Introduction
Nausea and vomiting are among the cardinal signs of early pregnancy, recognized as such since at least the time of Hippocrates. In contemporary Western societies, an estimated 50% to 80% of pregnant women experience nausea and/or vomiting during the first trimester of pregnancy.

The problem is generally time-limited, with onset about the fifth week after the last menstrual period (LMP), a peak at 8 to 12 weeks, and resolution by 16 to 18 weeks for most women; approximately 5% of women will have symptoms throughout pregnancy. Although commonly termed "morning sickness," only 17% of women report being affected only in the morning. In a prospective study in which 160 women provided daily diaries in early pregnancy, 74% reported nausea with a mean duration of 34.6 days, "morning sickness" occurred in only 1.8%, and 80% reported nausea lasting all day. Only half of women reported relief by 14 weeks, but 90% had relief by 22 weeks.

The most severe manifestations of nausea and vomiting of pregnancy (NVP) result in hyperemesis gravidarum (HG). Although there is no standard definition of HG, most diagnostic criteria include: persistent vomiting before 9 weeks after the LMP, weight loss >5% of initial body weight, electrolyte imbalance (hypokalemia), and dehydration and/or ketonuria. Severe HG symptoms are the second most common reason for prenatal hospitalizations in the United States (11.4% of all nondelivery antenatal admissions).

Risk factors for HG include: clinical hyperthyroid disorders, prepregnancy psychiatric diagnosis, previous pregnancy complicated by HG, molar pregnancy, multiple gestation with a male and female fetus, diabetes, and gastrointestinal disorders. Women 30 years of age and older and women who smoke have a lower risk of HG.

Quality of life (QOL) and work efficiency are adversely affected by NVP for women who have these symptoms. Fifty percent of women say NVP affects their ability to work, as many as 35% require time off from jobs (mean, 62 hours), 50% say it affects their relationships with family and partners, and 55% report being depressed.[9,10] When QOL measures are used in research studies, the scores for women with NVP are worse than the scores of women who report chronic depression. More than 80% of women with HG who responded to a recent survey stated that NVP caused adverse psychosocial effects, including concerns about economics and employment, depression, anxiety, and fear about future pregnancies. Among women with severe NVP or HG, 76% changed plans for future children, 15% terminated pregnancy secondary to HG, and 7% reported long-term psychological sequelae. A 2002 study estimated reduced productivity, visits to health care professionals, and the cost of medications and other remedies at $2947 per woman with moderate to severe NVP.

Conversely, nausea in pregnancy is sometimes a positive sign. The absence of nausea is one of the factors associated with spontaneous miscarriage. Because there is a close temporal relationship between NVP and beta-human chorionic gonadotropin (â-hCG) levels, some have theorized that nausea-associated nutrient restriction during early pregnancy may be beneficial to fetal and placental development. Nonetheless, given the widespread prevalence of NVP, potential severity, and adverse effects on QOL, pregnant women and their providers need treatments that are effective yet safe to use during the period of embryonic and early fetal development. This article provides an evidence-based review of effective and safe treatments for NVP.

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Antidepressant Medication Use in Pregnancy
Barbara Hackley, CNM, MSN

Abstract
Depression has been estimated to occur in approximately 12% of women, making it one of the most commonly encounteredmedical conditions affecting pregnancy. Yet many health care providers feel unprepared to manage this condition in pregnancy. This article provides women's health providers the background needed to effectively manage depression and in particular focuses on the use of antidepressant medication in pregnancy.

Introduction
Depression is one of the most commonly encountered conditions in primary care and is particularly common among women. Lifetime prevalence rates have been reported to be 6.3% in men and 12.6% in women. Given the high prevalence rates in the general population, it is not surprising that depression may be the most common medical condition affecting pregnant women.

Depression has been reported to occur in 12% to 15% of women in the perinatal period ; these prevalence rates are even higher than those reported for gestational diabetes (4%8%) or preeclampsia (3%). Yet depression is a condition for which many women's health care providers feel unprepared to detect or manage. Recent reports of neonatal complications associated with the use of some commonly used antidepressants makes the management of depression even more complex. An earlier article in this journal covered the specifics of screening, diagnosis, counseling, and medication management in the general population. This article will focus on the safety of antidepressants and the medication management of depression during pregnancy.

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Pregnancy Outcome in Women Infected With HIV-1 Receiving Combination Antiretroviral Therapy Before Versus After Conception
E.S. Machado; C.B. Hofer; T.T. Costa; S.A. Nogueira; R.H. Oliveira; T.F. Abreu; L.A. Evangelista; I.F.A. Farias; R.T.C. Mercadante; M.F.L. Garcia; R.C. Neves; V.M. Costa; J.S. Lambert

Abstract
Objective: The potential adverse effects of antiretroviral drugs during pregnancy are discrepant and few studies, mostly from Europe, have provided information about pregnancy outcomes of those already on treatment at conception. The aim of this study was to investigate the impact of antiretrovirals (ARVs) on pregnancy outcome according to the timing of treatment initiation in a cohort of pregnant women from Brazil infected with HIV.

Methods: A prospective cohort of 696 pregnant women followed up in one single centre between 1996 and 2006 was studied. Patients who had ARV treatment before pregnancy were compared with those treated after the first trimester. The outcomes evaluated were preterm delivery (under 37 weeks), severe preterm delivery (under 34 weeks), low birth weight(under 2500 g) and very low birth weight (under 1500 g).

Results: Patients who were using ARVs pre-conception had higher rates of LBW (33.3% vs 16.5%) and a similar trend for PTD (26.3% vs 17.7%). Stratification by type of therapy (dual vs highly active antiretroviral therapy (HAART)) according to timing of initiation of ARVs showed that patients who use HAART pre-conception have a higher rate of PTD (20.2% vs 10.2%) and LBW (24.2% vs 10.2%). After adjusting for several factors, HAART used pre-conception was associated with an increased risk for PTD and LBW.

Conclusions: We identified an increased risk for LBW and PTD in patients who had HAART prior to pregnancy.

Introduction
Over the last decade, treatment for the prevention of mother to child transmission (MTCT) of HIV has moved from zidovudine (AZT) monotherapy to the use of highly active antiretroviral therapy (HAART) resulting in transmission rates of 1-2%. In Brazil, vertical transmission of HIV-1 has been responsible for almost 11 000 cases of AIDS in children younger than 13 years between 1996 and 2005; however, less than 350 cases were notified during the year of 2006.

Discrepant results on the risk of adverse pregnancy outcomes in women infected with HIV treated with HAART have been reported. European studies have shown that exposure to any combination therapy increases the risk of premature delivery (PTD), with the use of protease inhibitors being the highest risk, and also an increased risk for low birth weight (LBW) and stillbirths. In contrast with these findings, several studies in the USA and Latin America failed to show a higher risk of adverse outcomes, although a report from one single site in the USA showed a correlation between PTD and protease inhibitor use.

The impact of antiretroviral (ARV) drugs administered prior to conception has not been fully explored. The European Collaborative Study found a twofold increased risk of premature delivery and a fourfold increased risk for severe premature delivery in women who started combination therapy pre-conception. More recently, a 3.4-fold in the risk of PTD in patients treated with HAART was seen in a German/Austrian cohort where 52% of the patients were already being treated with HAART at conception.

There has been an increase in pregnant women who are HIV positive receiving antenatal therapy. This might be an effect of the increasing age in the population of pregnant women with HIV, repeated pregnancies or changes in CD4 threshold for starting treatment in patients infected with HIV. The aim of this study was to investigate the impact of ARVs on preterm delivery and LBW according to the timing of the initiation of the therapy in pregnancy.

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The role of surgery in the management of endometrial cancer
ROBERTO TOZZI, MD, DAVID BENAYOUN, MD, STEFANO CIRILLO, MD, RICCARDO GARRUTO CAMPANILE, MD, RAFFAELLA GIANNICE, MD.
Division of Gynaecologic Oncology and Minimal Invasive Surgery, IRCCS Humanitas Clinical Institute, Milan; Nuffield Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, Churchill Cancer Centre, Headington Oxford

ABSTRACT The role of surgery in the treatment of patients with endometrial cancer is of paramount importance. It provides accurate diagnostic information on the extension of disease and, at the same time, it is the single best treatment modality. The adequacy of the surgical staging is based on the compliance with the FIGO guidelines. Such guidelines are equally met by traditional laparotomy and by laparoscopy, as emerged in the last ten years. While there is no evident difference in the survival outcome, the laparoscopic approach is able to reduce the overall morbidity. The use of pelvic and para-aortic lymphadenectomy is still debated, despite several studies, including clinical trials, have been conducted. Currently, the FIGO guidelines delegate to the surgeon the choice of which patients should undergo lymphadenectomy and to which extension. The final issue to resolve is to investigate in a clinical trial if the performance of lymphadenectomy can spare the radiotherapy and provide survival benefit.

Key words endometrial cancer, surgery, lymphadenectomy, hysterectomy


WHY SURGERY? Since 1970s, patients with endometrial cancer (EC) have undergone staging according to the FIGO (International Federation of Gynaecology and Obstetrics) guidelines. Due to co-existing severe medical conditions, initially most patients were not candidate for surgery. Therefore, clinical staging was used based on pre-operative findings. Meanwhile, the refinement of anaesthetic technique together with improvement of pre- and post-operative care has increased the number of patients eligible for surgery. Later on, in the 1980s, the publication of the GOG-33 trial has identified several surgical prognostic factors and has showed a wide discrepancy between clinical and surgical findings (1-2). Finally, the non-surgical treatment (radiotherapy and chemotherapy alone) of patients with EC has not been as successful
as for patients with other gynaecological tumours. Therefore, at the annual meeting in Rio de Janeiro (1988), the FIGO decided to move endometrial cancer patients to a full surgical staging system (3).

The advantages of surgical staging on patients with EC are both diagnostic and therapeutic. In fact, surgery has been demonstrated to be the best single modality of treatment in terms of survival outcomes when compared to radiotherapy or chemotherapy alone. It also has the advantage to address patients for adjuvant treatment (in the form of radiotherapy or chemo-radiotherapy) on the basis of precise surgical findings and prognostic factors.

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The role of lymphadenectomy from the point of the clinical oncologist
NAWAZ WALJI, MB, MRCP, FRCR, INDRAJIT N FERNANDO, MB, MRCP, FRCR

The Cancer Centre, Queen Elizabeth Hospital, Birmingham

ABSTRACT Endometrial cancer is the fourth commonest female cancer in the United Kingdom and its incidence continues to rise. Whilst removal of regional lymph nodes remains a cardinal principle of surgical oncology for the management of the majority of invasive cancers, the role of lymphadenectomy in endometrial cancer remains controversial. We examine the current evidence for lymphadenectomy in endometrial cancer from the point of view of a practicing clinical oncologist.

Key words endometrial cancer; lymphadenectomy; radiotherapy; brachytherapy; chemotherapy


INTRODUCTION The incidence of endometrial cancer is ten times higher in North America and Western Europe compared to less developed countries (1). In the United Kingdom it is the fourth commonest female cancer and the incidence is rising (2). The majority of women present with early disease and a good prognosis overall. Table 1 summarizes the current International Federation of Gynaecologists and Obstetricians (FIGO) staging for endometrial cancer (3). Independent prognostic factors include the surgical FIGO stage; lymph node metastasis; myometrial invasion; histological type; and differentiation grade (4). Age greater than sixty years, presence of lymphovascular invasion and tumour distance from serosa are also considered important prognostic factors. Table 2 summarizes the 5-year overall survival (OS) of women with endometrial cancer (5).

In 1988 the criteria for staging endometrial cancer were altered from clinical to pathological staging including pelvic and para-aortic lymphadenectomy (6). The removal of regional lymph nodes remains a cardinal principle in the surgical management of the vast majority of invasive cancers yet its role for the comprehensive staging of all patients with endometrial cancer remains controversial. A wide variation in practices exist, from complete lymphadenectomy in all patients, to selective lymph node sampling in high-risk patients, to no lymphadenectomy being performed in any patients. This chapter reviews the current evidence and presents the point of view of a practicing clinical oncologist for the role of lymphadenectomy in endometrial cancer.

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The role of radiation in endometrial cancer
MELANIE EB POWELL, MD.
Department of Radiotherapy, St Bartholomews Hospital, West Smithfield, London

ABSTRACT The value of radiotherapy in endometrial cancer has become the subject of international debate. In particular, with the recent publication of the ASTEC study, doubts
regarding the benefits of irradiation in stage I disease have been raised. This review will discuss published trials looking at adjuvant radiotherapy in endometrial cancer and suggest
evidence based treatment guidelines.

Key words endometrial cancer, external beam radiotherapy, vaginal vault brachytherapy, FIGO stage


INTRODUCTION The role of adjuvant radiotherapy in endometrial cancer has become a controversial topic, particularly in early-stage disease. Traditionally, either brachytherapy and/or
external beam radiotherapy has been offered postoperatively. However, studies from The Netherlands (PORTEC) and the UK and Canada (ASTEC and EN.5) have called into question
the benefits of irradiation for women with stage I disease. This overview will discuss the evidence for adjuvant radiotherapy for the different stages of epithelial endometrial cancer.

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Management of postmenopausal bleeding
NATALIE AM COOPER, MB., T. JUSTIN CLARK MD.

Birmingham Womens Hospital, Birmingham

ABSTRACT
This review article will discuss the evidence supporting the use of outpatient radiological, histological and endoscopic tests for evaluating the endometrium in women presenting with postmenopausal bleeding (PMB). In addition to examining the accuracy and cost-effectiveness of available tests, the review will consider the clinical context in which testing takes place, the impact of patient preferences, the problem of recurrent postmenopausal bleeding and contemporary delivery of rapid access diagnostic services.

Key words endometrium, bleeding, postmenopausal, diagnosis


INTRODUCTION
Postmenopausal bleeding (PMB) is a common clinical problem in both general practice and secondary care, hospital settings. Women are most likely to present with PMB in the sixth decade of life, where consultation rates in primary care are 14.3/1000 population. Similarly, in the hospital setting, abnormal patterns of uterine bleeding account for up to 50% of all gynaecological consultations in the peri- and post-menopausal years (1). The probability of
serious premalignant or malignant endometrial disease (i.e. endometrial cancer and endometrial hyperplasia with cytological atypia) in women presenting with PMB is between 5-15% (2-4) and therefore prompt referral of such women for further investigation is mandatory in order to detect endometrial cancer at an early stage and effect a cure. However, whilst detecting malignant disease is important, we should be mindful that the majority of women have benign causes
for their PMB (Table 1) and so it is imperative that diagnostic testing strategies do not lead to over investigation as this will induce unnecessary inconvenience and morbidity to women
and waste scarce health care resources.

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Management of uterine papillary serous carcinoma
KAVITA SINGH, MD., JÁNOS BÁLEGA, MD.

Pan-Birmingham Gynaecological Cancer Centre, Birmingham

ABSTRACT Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer accounting for 10% of all uterine cancers, but it is responsible for 40% of diseaserelated
deaths. It has got an aggressive biological and clinical behaviour with the propensity to spread even in early stage. Since its relative rarity, there are only limited prospective randomised data available helping clinicians in planning the management of patients with UPSC. The aim of this paper is to summarise the evidence on the management of UPSC.

Key words serous papillary carcinoma, endometrium, prognosis, management



INTRODUCTION
Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer (EC), is nonoestrogen dependent and occurs more commonly in elderly,
non-obese, parous women. It accounts for 10% of all uterine cancers but is responsible for 40% of disease-related deaths (1-2).

It was first identified as a distinct histological entity in 1981 by Lauchlan (3). Hendrickson and colleagues (4) in 1982 correlated this histological subtype with their aggressive biological behaviour and identified their association with increased myometrial infiltration, increased metastatic spread to lymphatics, and higher incidence of upper abdominal relapse compared to cancers with endometrioid histology. Bokhman (5) in 1983 sub-classified endometrial cancer into two types. The most common subtype is endometrioid adenocarcinoma (Type I), which accounts for 80% of uterine cancers and are oestrogen-dependent, and have a relatively indolent course on the background of endometrial hyperplasia. They occur more frequently in obese, nulliparous women with diabetes and polycystic ovaries. They are usually oestrogen (ER) and progesterone receptor (PR) positive unlike the Type II uterine cancer (UPSC) which arises in atrophic endometrium and is ER- and PR- negative but always stain positive for p53 mutation (6). Histologically, UPSC resembles ovarian papillary serous carcinoma (OPSC), and psammoma bodies might be present (7). Its biological behaviour and clinical presentation is similar to ovarian, tubal, and peritoneal serous carcinomas, though the outcome is even poorer as it has a lower response rate to chemotherapy, which is 25-30% compared to 60-70% for ovarian cancer. In African-Americans, there is a higher preponderance of Type II uterine cancers as compared
to Caucasians (8).

UPSC metastasises early by haematogenous, lymphatic, contiguous surface spread or by exfoliation of tumour emboli directly into the peritoneal cavity. Extra-pelvic spread may be present even without any myometrial invasion, and therefore appropriate staging is vital for assessment of prognosis and selection of cases for adjuvant treatment (9).

Till date, the management of UPSC has not been standardised. Most studies have been retrospectively generated from single institutions and represent small case series of cases collected over a long period of time and with no uniform surgical or adjuvant treatment protocols. Majority of the studies reported also consist of heterogeneous group of patients treated with various forms of adjuvant treatment. The aim of this paper is to summarise the available evidence on the management of UPSC.

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The role of imaging in the management of endometrial cancer
ANWEN E JELBERT FRCR., NISHAT BHARWANI FRCR.,
ANDREA G ROCKALL FRCR.
Radiology Department, St Bartholomews Hospital, West Smithfield, London

ABSTRACT Imaging in endometrial cancer helps guiding delivery of the most appropriate surgical intervention and adjuvant therapy for the patient. In this article, we review the imaging literature and describe how imaging findings are integrated into the management of patients with endometrial cancer at our tertiary referral centre. We will discuss all imaging modalities, with a particular focus on magnetic resonance imaging (MRI) and how to maximise the staging information available prior to intervention. Our discussion will also highlight circumstances which may limit the accuracy of imaging staging and touch on the role of imaging in the detection of recurrent disease.

Key words: Imaging, management, MRI, endometrial cancer, FIGO stage


INTRODUCTION In the UK, there were 6,891 new cases of endometrial cancer in 2005, and 1,651 deaths in 2006 (1). The incidence has increased from 5,624 new cases in 2000, and is now more than that for ovarian cancer. The majority of patients present with inter-menstrual or post-menopausal bleeding, with 80% having early (stage I) disease at presentation (2-5). The UK mortality fell by 27% between 1971 and 2005 (1). As a result, endometrial carcinoma is not a common cause of cancer death (6), with a 10 year survival of 75% (1).

Ninety per cent of endometrial carcinomas are adenocarcinomas (2, 5). Less common histological subtypes include adenocarcinoma with squamous differentiation, adenosquamous carcinoma, clear cell carcinoma and papillary serous carcinoma (2). The latter two histological subtypes carry a worse prognosis (2, 5). Other poor prognostic factors include deep myometrial invasion, cervical invasion, extra-uterine spread, lymph node involvement and a high histological grade (4, 7).

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