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Introduction: The purpose of this study was to investigate the detailed nature of menstrual characteristics, bleeding and other symptoms in women with and without endometriosis. Pelvic pain symptoms in this cohort have been reported elsewhere. Method: This is a self-administered cross-sectional study and was conducted using a structural questionnaire. A total of 737 women completed the study: women with endometriosis (n = 529) and with no current gynaecological complaint, ‘control’ (n = 208). Results: Some of the key findings in this study included significant differences between the control and endometriosis subjects in terms of bleeding symptoms, increased length and heaviness of menses, rectal and bladder bleeding, infertility and obstetric complications which were all more common in the endometriosis group. Other symptoms found to have a highly significant positive association with endometriosis included abdominal bloating, low resistance to infection, fatigue, increased urinary frequency, diarrhoea and constipation (p Conclusion: The range of non-pain symptoms in women with endometriosis was generally much more diverse and extensive than recognised by most clinicians.

Objectives To evaluate if a simple method for characterizing vaginal bleeding patterns in etonogestrel contraceptive implant users can predict subsequent patterns and bleeding-related discontinuation over the first 2 years of use. Study Design We reanalyzed phase 3 study bleeding data for non-breastfeeding participants from the United States, Europe, Russia and Chile during the first 2 years of implant use to characterize and correlate bleeding patterns. We used 90-day reference periods with period 1.1 starting at Day 29 and ending at Day 118. We dichotomized bleeding patterns as “favorable” (amenorrhea, infrequent bleeding and normal frequency bleeding without prolonged bleeding) or “unfavorable’ (prolonged and/or frequent bleeding) and tracked user groups based on these bleeding patterns in reference period 1.1 through Year 1 and from Year 1 through Year 2, respectively. Results We evaluated data from 537 and 428 women with up to 1 and 2 years use, respectively. Of the 325 (60.5%) women with favorable bleeding in reference period 1.1, 275 (84.6%) reported favorable bleeding also in reference period 2, 197 (60.6%) reported favorable bleeding throughout Year 1, and favorable bleeding in 75–85% of reference periods in Year 2. Among 212 (39.5%) women with unfavorable bleeding in reference period 1.1, 118 (55.7%) continued with unfavorable bleeding in reference period 2, while about 40%–50% reported favorable patterns in RP 2, 3 and/or 4. Initial favorable bleeding resulted in lower discontinuation rates than initial unfavorable bleeding in years 1 (3.7% vs 12.7%, p≪.0001) and 2 (2.5% vs 16.5%, p≪.0001). Conclusion Implant users with favorable bleeding in the first reference period are likely to continue with favorable bleeding over the next 2 years. Initial bleeding patterns predict overall continuation rates in years 1 and 2. Implications Statement When evaluating vaginal bleeding in any 90-day reference period over 2 years of etonogestrel implant use, approximately 80% of women with favorable and 40% with unfavorable bleeding patterns will have favorable bleeding in the next reference periods. These findings can facilitate counseling regarding bleeding for women using the etonogestrel implant.

Objective:To investigate the detailed nature of pain symptoms reported by women with endometriosis and those without current gynecological complaint.Design:Self-administered cross-sectional study was conducted using a structured questionnaire.Setting:Teaching hospital clinic, specialist gynecologist, and family practice patients; endometriosis community support group members; and university staff and students.Subjects:A total of 737 women returned completed surveys: women with endometriosis ( n = 529) and with no current gynecological complaint ( n = 208).Intervention(s):None.Main outcome measure(s):Demographics, experience of pain symptoms: frequency, severity, and characteristics.Results:All pain symptoms were significantly more common among women with endometriosis compared with controls. Women with endometriosis all reported experiencing dysmenorrhea to some degree ( N = 527, two missing), although the severity was “slight” for 5%. Dyspareunia was reported by 92% of women with endometriosis, most commonly during intercourse, rather than at the start or post-coital. The other pain symptoms experienced by women with endometriosis, in order of frequency, were lower back pain (93%), pain at ovulation (87%), pelvic pain other than during menses, ovulation, urination or intercourse (79%), dysuria (71%), and rectal pain (67%). The great majority of women with endometriosis reported multiple sources and types of pain. Among women with endometriosis there were clear associations between the severity of dysmenorrhea and the frequency of experiencing dyspareunia and other pain symptoms.Conclusion:Pain symptoms in women with endometriosis were generally much more extensive and complex than recognized by most clinicians.

Baboon ( Papio anubis) models of endometriosis are thought to mimic the early stages of spontaneous human peritoneal endometriotic disease. The objective of this study was to investigate the presence and course of nerve fibre ingrowth during peritoneal lesion formation in specimens collected at 3 months (early stage of lesion development) and 15 months (late stage of lesion development) after disease initiation compared to pelvic peritoneum (control). Five-micron sections of paraffin-embedded peritoneal lesions were obtained from normally cycling baboons with 3-month (n = 12), 15-month (n = 12) induced endometriosis and pelvic peritoneum (n = 10) from baboons with no endometriosis. Immunohistochemical staining was performed with specific antibodies: protein gene product 9.5 – broad marker of nerve fibres and neurones, neuropeptide Y – sympathetic neurones, substance P – sensory neurones, vasoactive intestinal peptide – parasympathetic neurones, nerve growth factor – development of new neurones and high-affinity receptor for nerve growth factor (tropomyosin receptor kinase A) – neuronal differential. Significantly, more nerve fibres were identified in peritoneal endometriotic lesions collected 15 months after the initiation of experimental protocols compared with 3-month and control samples (p

Among young persons, ease of use, high efficacy, and high acceptability makes the etonogestrel contraceptive implant an important choice for this age group. Adolescent-friendly, patient-centered counseling considers the patient's cognitive development, the influence of friends and family, as well as their own preferences and values. Age-appropriate language, graphics, and models are useful to explain contraceptive options and relevant side effects. Effectiveness, reversibility, safety, noncontraceptive benefits, and side effects are important attributes and should be discussed when teens are choosing a contraceptive method. In this review we describe suggested best practices for counseling adolescents about the etonogestrel implant so they can make informed, prudent decisions about using this contraceptive method.

Symptoms related to menstruation are the commonest cause of gynaecological complaints during the reproductive years, and cause more work absences than any other disorders commonly seen in women. These disturbances of menstrual bleeding and menstruation-associated pain can have major impacts on quality of life, and can lead to the development of significant symptoms due to iron deficiency and anaemia. There is a range of common and rare underlying causes of abnormal uterine bleeding, which have been well classified using the PALM-COEIN system. Investigations should be targeted at defining the underlying causes and assessing the degree of iron deficiency. Treatment depends on the underlying cause, and a range of surgical and medical approaches can be considered—improved quality of life is the key aim. Effective treatment for heavy menstrual bleeding should be accompanied by effective treatment for iron deficiency. Amenorrhoea (absence of menstruation for a specified period of time) may be due to disturbances of almost any part of the hypothalamic–pituitary–ovarian–uterine system. Investigations should focus on the interplay of reproductive hormones and exclusion of structural pathology. Treatment is aimed at managing the underlying cause, taking into account the desires of the patient in relation to pregnancy. Menstrual pain may be caused by an imbalance of prostaglandin metabolism (primary dysmenorrhoea) or by structural pathologies, such as endometriosis (secondary dysmenorrhoea). Symptoms can vary greatly and a careful history can often distinguish realistically between primary and secondary dysmenorrhoea. Treatment is often medical, although structural pathologies may require surgical excision.

This paper investigates high-performance athletes’ development of their financial literacy and self-management skills and the related organisational support available to them during their athletic careers. The data were collected from 20 retired high-performance athletes (10 male and 10 female) representing six different countries (Japan, Mexico, Portugal, Singapore, South Korea, and the UK). Thematic analysis was applied to the processing of the data and five themes emerged: (1) Funding battles: financial challenges and misjudgements, (2) Coping Strategies, (3) Support from sponsors, parents, and sport organisations, (4) Development of Financial Literacy, and (5) Life After Sport. The data indicates that athletes experienced financial challenges due to a lack of organisational support, reduced or terminated funding, and limited opportunities to access sponsorship. Typically, athletes developed their financial literacy and self-management skills by ‘self-help’ or ‘trial and error’. The findings contribute to both literature and practice by providing empirical evidence on the coping strategies adopted by athletes in order to overcome financial challenges and on the methods used in order to develop their financial literacy and self-management skills. These findings inform sport organisations and governing bodies to develop support schemes for high-performance athletes as well as deepen our knowledge of athletes’ career development and transitions focusing on the financial aspect.

Many nonprofit organizations face revenue uncertainty due to funding cuts. It is crucial for them to supplement existing revenue streams by private donations, and apply thoughtful market segmentation in their pursuit of donors. We introduce the behavioral concept of “nudge” based on the possibility of loss aversion affecting willingness-to-donate, and investigate its implications for fund-raising strategies. Potential donors are nudged to donate by the hypothetical scenario of “losing” an existing exhibition, and also by that of “gaining” an additional exhibition. We observe significant loss aversion effects as frequent gallery-goers donate more to avoid losing an exhibition. While both prospective gain and loss scenarios are effective in nudging nonfrequent gallery-goers, the prospect of enjoying “one more” event is observed to be stronger. We argue that there may be scope to increase support for nonprofit organizations, particularly in the cultural sector, by exploiting the psychological characteristics of prospective donors.

The objective of this chapter is to present an overview of how menstruation, a normal bodily function, was and is perceived in various ethnic groups and cultures in the world, from ancient mythology, historical, or traditional practices to contemporary belief systems. Mythical tales about menstruation abound in the legends and prehistory of ancient cultures. These tales characterize menstrual blood variously as sacred, a gift from the gods, or a punishment for sin, but it is almost always magical and powerful. In contrast, most world religions view menstruation, with varying degrees of severity, as a major problem, a sign of impurity and uncleanliness, and therefore, menstruating women are isolated, prohibited from polluting the holy places, and shunned. Many of these myths and cultural misperceptions persist to the present day, reflected in a wide range of negative attitudes toward menstruation, which can have serious and direct implications for reproductive health. In view of the increasingly globalized nature of current clinical practice, it is crucial that health care providers are familiar with existing cultural and social views and attitudes toward the menstrual function. The ultimate goal is to be able to provide women culturally sensitive and medically appropriate therapies for their menstrual disorders. This biocultural approach to menstruation management is desirable in contemporary medical practice.

Hormonal treatment of abnormal uterine bleeding (AUB), especially bleeding related to endometrial causes (AUB-E), ovulatory dysfunction (AUB-O) and coagulopathy (AUB-C), and to some extent, uterine leiomyomas and adenomyosis, has become the first-line evidence-based management strategy during recent years. Hormonal treatment of heavy menstrual bleeding (HMB) is also endorsed as the first line of treatment in several international guidelines. In the present article, we review the efficacy of the commonly used and widely available hormonal treatments of AUB-O, AUB-E and AUB-C. The therapies include combined hormonal contraceptives, progestin-only preparations, and intrauterine release of levonorgestrel through the levonorgestrel-releasing intrauterine system. In addition, we make practical recommendations for patient management. We also review some of the current guidelines and their recommendations concerning the treatment of HMB. Finally, the effects of hormonal treatment on the overall management of AUB and its effects on the health care system and specialist training are discussed.(C) 2017 Published by Elsevier Ltd.

BACKGROUNDAdenomyosis is a benign uterine disorder where endometrial glands and stroma are pathologically demonstrated within the uterine myometrium. The pathogenesis involves sex steroid hormone abnormalities, inflammation, fibrosis and neuroangiogenesis, even though the proposed mechanisms are not fully understood. For many years, adenomyosis has been considered a histopathological diagnosis made after hysterectomy, classically performed in perimenopausal women with abnormal uterine bleeding (AUB) or pelvic pain. Until recently, adenomyosis was a clinically neglected condition. Nowadays, adenomyosis may also be diagnosed by non-invasive techniques, because of imaging advancements. Thus, a new epidemiological scenario has developed with an increasing number of women of reproductive age with ultrasound (US) or magnetic resonance imaging (MRI) diagnosis of adenomyosis. This condition is associated with a wide variety of symptoms (pelvic pain, AUB and/or infertility), but it is also recognised that some women are asymptomatic. Furthermore, adenomyosis often coexists with other gynecological comorbidities, such as endometriosis and uterine fibroids, and the diagnostic criteria are still not universally agreed. Therefore, the diagnostic process for adenomyosis is challenging.OBJECTIVE AND RATIONALEWe present a comprehensive review on the diagnostic criteria of adenomyosis, including clinical signs and symptoms, ultrasound and MRI features and histopathological aspects of adenomyotic lesions. We also briefly summarise the relevant theories on adenomyosis pathogenesis, in order to provide the pathophysiological background to understand the different phenotypes and clinical presentation. The review highlights the controversies of multiple existing criteria, summarising all of the available evidences on adenomyosis diagnosis. The review aims also to underline the future perspective for diagnosis, stressing the importance of an integrated clinical and imaging approach, in order to identify this gynecological disease, so often underdiagnosed.SEARCH METHODSPubMed and Google Scholar were searched for all original and review articles related to diagnosis of adenomyosis published in English until October 2018.OUTCOMESThe challenge in diagnosing adenomyosis starts with the controversies in the available pathogenic theories. The difficulties in understanding the way the disease arises and progresses have an impact also on the specific diagnostic criteria to use for a correct identification. Currently, the diagnosis of adenomyosis may be performed by non-invasive methods and the clinical signs and symptoms, despite their heterogeneity and poor specificity, may guide the clinician for a suspicion of the disease. Imaging techniques, including 2D and 3D US as well as MRI, allow the proper identification of the different phenotypes of adenomyosis (diffuse and/or focal). From a histological point of view, if the diagnosis of diffuse adenomyosis is straightforward, in more limited disease, the diagnosis has poor inter-observer reproducibility, leading to extreme variations in the prevalence of disease. Therefore, an integrated non-invasive diagnostic approach, considering risk factors profile, clinical symptoms, clinical examination and imaging, is proposed to adequately identify and characterise adenomyosis.WIDER IMPLICATIONSThe development of the diagnostic tools allows the physicians to make an accurate diagnosis of adenomyosis by means of non-invasive techniques, representing a major breakthrough, in the light of the clinical consequences of this disease. Furthermore, this technological improvement will open a new epidemiological scenario, identifying different groups of women, with a dissimilar clinical and/or imaging phenotypes of adenomyosis, and this should be object of future research.

Objectives To describe bleeding patterns among users of the segesterone acetate (SA) and ethinyl estradiol (EE) contraceptive vaginal system (CVS), and identify factors associated with unscheduled bleeding/spotting (B/S). Study design We pooled results from two multicenter, single-arm, open-label, pivotal, phase 3 studies of the SA/EE CVS conducted in 17 US and 7 international sites. Participants (age 18–40 years; BMI ≤29 kg/m2) followed a 21/7-day in/out schedule of CVS use for up to 13 cycles and recorded vaginal bleeding daily in paper diaries. Scheduled and unscheduled B/S were summarized by cycle. We used multiple logistic regression to identify factors associated with unscheduled bleeding/spotting, based on the first 4 cycles only. Results Analysis included data from 2070 participants (16,408 cycles). Ninety-eight percent documented scheduled B/S [mean (SD): 4.9 (1.1) days/cycle)]. Absence of scheduled B/S was 5–8% of women/cycle. Unscheduled B/S ranged from 13.2% to 21.7% of women per cycle. Few women (1.8%) discontinued prematurely due to unacceptable bleeding. Black women were more likely to report unscheduled B/S than White women [Adjusted odds ratio (AOR) = 1.49, 95% confidence interval (CI) = 1.14–1.94]. Women with fewer years of schooling [ Conclusions Participants using the SA/EE CVS up to 13 cycles reported good cycle control. Discontinuation due to unacceptable bleeding was very low. Further research into demographic/other differences with reported unscheduled bleeding is warranted. Implications Since good cycle control is a key factor influencing contraceptive selection, adherence and continuation of combined hormonal contraceptives, the favorable bleeding profiles experienced by women during the SA/EE CVS clinical trials provide reassuring information for prospective users.

The etiology of deep dyspareunia in endometriosis is unclear. Our objective was to determine whether nerve bundle density in the cul-de-sac/uterosacrals (zone II) is associated with deep dyspareunia in women with endometriosis. We conducted a blinded retrospective immunohistochemistry study (n = 58) at a tertiary referral center (2011-2013). Patients were stringently phenotyped into a study group and 2 control groups. The study group (tender endometriosis, n = 29) consisted of patients with deep dyspareunia, a tender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 1 (nontender endometriosis, n = 17) consisted of patients without deep dyspareunia, a nontender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 2 (tender nonendometriosis, n = 12) consisted of patients with deep dyspareunia, a tender zone II on examination, and a nonendometriosis lesion (eg, normal histology) in zone II excised at surgery. Protein gene product 9.5 (PGP9.5) immunohistochemistry was performed to identify nerve bundles (nerve fibers surrounded by perineurium) in the excised zone II lesion. PGP9.5 nerve bundle density (bundles/high powered field [HPF]) was then scored by a pathologist blinded to the group. We found a significant difference in PGP9.5 nerve bundle density between the 3 groups (analysis of variance, F2,55 = 6.39, P = .003). Mean PGP9.5 nerve bundle density was significantly higher in the study group (1.16 ± 0.56 bundles/HPF [±standard deviation]) compared to control group 1 (0.65 ± 0.36, Tukey test, P = .005) and control group 2 (0.72 ± 0.56, Tukey test, P = .044). This study provides evidence that neurogenesis in the cul-de-sac/uterosacrals may be an etiological factor for deep dyspareunia in endometriosis.

Iron deficiency and iron deficiency anemia are highly prevalent among women throughout their lives. Some females are particularly vulnerable to iron deficiency/iron deficiency anemia, including those with heavy menstrual bleeding (HMB) and pregnant/postpartum women. Despite the high prevalence of iron deficiency/iron deficiency anemia in women, the condition is still underdiagnosed and therefore undertreated, with serious clinical consequences. Areas covered: The following review examines the impact of iron deficiency and iron deficiency anemia on clinical outcomes and quality of life in women from adolescence to post-menopause, paying particular attention to guidelines and current recommendations for diagnostic tests and management. Expert commentary: There are numerous adverse health consequences of an iron-deficient state, affecting all aspects of the physical and emotional health and well-being of women. Guidelines must be developed to help clinicians better identify and treat women at risk of iron deficiency or iron deficiency anemia, particularly those with HMB, or who are pregnant or postpartum. Replacement therapy with oral or intravenous iron preparations is the mainstay of treatment for iron deficiency/iron deficiency anemia, with red blood cell transfusion reserved for emergency situations. Each iron therapy type is associated with benefits and limitations which impact their use.

The Faculty of Sexual & Reproductive Healthcare (FSRH) Clinical Effectiveness Unit is developing a guideline looking at contraceptive options for women with weight issues. We hope that this guideline will include information for those facing bariatric surgery as almost 80% of women requesting this procedure are in their reproductive years.1 These women are also advised to avoid pregnancy for up to 24 months following surgery, making effective, reversible contraception an ideal choice.2 With this in mind, we therefore asked women aged between 18 and 50 years on a bariatric surgery waiting list to complete a voluntary, anonymous online survey about their sexual and reproductive health. Ethical approval was granted by the National Health Service, University of Sunderland and City Hospitals Sunderland NHS Foundation Trust Research Ethics Committees. There were 42 responders with the majority (38%, n=16) aged between 35 and 44 years old, 92% (n=38) were heterosexual and 71% (n=30) had children. All participants …

Endometriosis is a benign gynecological condition that is estimated to affect 10% of women in the general population and appears to be increasing in incidence. It is an estrogen-dependent inflammatory disease, and is primarily characterized by dysmenorrhea, deep dyspareunia, chronic pelvic pain, and variable effects on fertility. The symptoms may greatly affect quality of life, and symptom control may be the primary aim of initial management, while contraceptive effect is often secondary. It is estimated that 30%-50% of women with endometriosis have an infertility problem, so a considerable number of endometriosis sufferers will require effective, planned contraception to maximize "protection of fertility" and prevent progression of the endometriotic condition. Ideally, this contraception should also provide symptom relief and improvement of physical, mental, and social well-being. At the present time, long-term progestogens appear to be the most effective choice for meeting all of these requirements, but other options need to be considered. It is becoming increasingly recognized that hormonal contraceptive systems are necessary for prevention of disease recurrence following surgical treatment of endometriosis. The personal preferences of the woman are an integral part of the final contraceptive choice. This article discusses the advantages and disadvantages of the contraceptive options available to women with endometriosis.

Menstrual symptoms are the commonest gynecologic complaints presenting to health professionals in most cultures, yet it is only very recently that the FIGO Menstrual Disorders Committee developed a pair of systems focusing on more logical and consistent terminologies, definitions and underlying causes relating to menstrual symptoms, signs, and pathologies. These initiatives have resulted in several ill-defined terminologies such as menorrhagia and dysfunctional uterine bleeding (DUB) becoming obsolete. In addition to intermenstrual spotting or bleeding, symptoms of abnormal uterine bleeding (AUB) are now primarily defined by regularity, frequency, duration and volume, and underlying causes are classified by the PALM-COEIN System. Heavy menstrual bleeding (HMB) is the commonest of these “bleeding symptoms” and has the greatest social and physical impacts on women and society, especially through iron deficiency and anemia.

Purpose – This paper aims to explore the application of the business risk audit (BRA) approach within non-Big-4 audit firms in the USA, the UK and Canada. This paper focuses on the motivation for adopting this approach for non-Big-4 audit firms in the three countries, and the advantages, disadvantages and aftermath of applying this method. Design/methodology/approach – A combination of qualitative and quantitative methods to obtain the data necessary to address the research questions was used. Findings – It is found that non-Big-4 audit firms in the three countries have adopted BRA; their motivation was primarily to follow the standards in each country, and the general trend in the industry. The advantages identified are consistent with previous research; a direct benefit was noted for audit effectiveness and risk management for both clients and auditors. One major disadvantage of applying BRA is the cost burden to both the audit firm and their clients. Some of the interviewees claimed that this method is better suited to large firms and large audits. Originality/value – This is an innovative study that addresses a contemporary auditing issue. The majority of the audit research studies concentrate on the big audit firm practices; this study is the first to examine the application of audit practices within smaller audit firms.

Several lines of recent evidence suggest that pelvic innervation is altered in endometriosis-affected women, and there is a strong presumption that nerve fibers demonstrated in eutopic endometrium (of women with endometriosis) and in endometriotic lesions play roles in the generation of chronic pelvic pain. The recent observation of sensory C, sensory A-delta, sympathetic and parasympathetic nerve fibers in the functional layer of endometrium of most women affected by endometriosis, but not demonstrated in most women who do not have endometriosis, was a surprise. Nerve fiber densities were also greatly increased in myometrium of women with endometriosis and in endometriotic lesions compared with normal peritoneum. Chronic pelvic pain is complex, and endometriosis is only one condition which contributes to this pain. The relationship between the presence of certain nerve fibers and the potential for local pain generation requires much future research. This paper reviews current knowledge concerning nerve fibers in endometrium, myometrium and endometriotic lesions, and discusses avenues of research that may improve our knowledge and lead to enriched understanding and management of endometriotic pain symptoms.

OBJECTIVE: To study the density of nerve fibers in cases of deep infiltrating endometriosis (DIE) of the rectovaginal septum in relation to various clinical factors. DESIGN: A research laboratory-based study. SETTING: A tertiary center together with a research laboratory. METHODS: Archived DIE tissue samples from 45 women operated upon for rectovaginal septum DIE were re-examined histologically and by immunohistochemistry. MAIN OUTCOME MEASURES: The effect of progestogens or combined oral contraceptives on the density of nerve fibers and the expression of nerve growth factor (NGF) and its high-affinity receptor (tyrosine kinase receptor A Trk-A). RESULTS: The use of hormonal therapy was associated with reduced densities of sympathetic parasympathetic and sensory nerve fibers in DIE lesions. Density of total nerve fibers (with pan-neuronal marker PGP9.5) was significantly lower (p < 0.05) in lesions collected from hormone-treated women (8.6/mm(2) 4.2-20.8/mm(2); median density from 25th to 75th quartiles) compared with that in lesions from untreated women (24.9/mm(2) 11.2-34.9/mm(2)). DIE lesions stained strongly for NGF and its receptor Trk-A. Expression of NGF but not of Trk-A was significantly reduced during use of hormonal therapy. CONCLUSIONS: Use of hormonal therapy was associated with significantly reduced nerve fiber density in DIE lesions. This may be an important mechanism of action of hormonal therapy for controlling DIE pain symptoms. The expression of estrogen-regulated NGF and its receptor was only partially suppressed during the use of hormonal therapy suggesting that local estrogen action is often maintained during conventional hormonal therapy in cases of DIE. (c) 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Background Heavy menstrual bleeding (HMB) exceeding 80 mL per cycle leads to considerable adverse impact on a woman’s iron metabolism, incidence of iron deficiency and anaemia, as well as her functioning in society. The objective of the study is to determine the potential efficacy of a Monophasic oestradiol-17β-nomegestrol acetate (E2/Nomac) combined oral contraceptive pill on measured menstrual blood loss as a pilot study in 12 women with objectively demonstrated HMB (>80 mL per cycle). The pilot study aimed to recruit 20 women. Method Consented women completed the HMB questionnaire. The blood was taken for haemoglobin, transferrin, iron saturation, TIBC, serum iron and ferritin. Women were given verbal and written detailed instructions for MBL collection for three control cycles and four treatment cycles. Results Forty-three women were enrolled, but 31 were ineligible and withdrawn (mainly for failure to meet eligibility criteria). Twelve women entered the treatment phase and commenced the E2/nomegestrol acetate (NOMAC) 24/4 combined pill treatment on the first day of their fourth cycle. All women with complete MBL measurements had >50% reduction in MBL on treatment (exact 95% confidence interval for proportion with MBL reduction >50%: 69 to 100%). The mean percent reduction in MBL between pretreatment and during treatment was 76.9%, and the median was 79% with a range of 53.7 to 100%. Conclusions This pilot study indicates that the E2/NOMAC COC will provide a useful potential option for treating HMB in women with FIGO classification AUB-E (primary endometrial causes) but requires a larger placebo-controlled study for confirmation.

Many women in the reproductive years have chronic medical conditions that are affected by pregnancy or in which the fetus is placed at increased risk. In most of these women, ongoing medical management of their conditions is greatly improved, even compared with a decade or two ago. However, their condition may still be seriously exacerbated by the physiological changes of pregnancy, and close monitoring of a carefully planned pregnancy is optimal. This requires effective and safe contraceptive use until pregnancy is desired and the medical condition is stabilised. Many contraceptives will also have adverse effects on some medical conditions, and there is now a considerable awareness of the complexities of some of these interactions. For this reason the World Health Organization has developed an excellent, simple and pragmatic programme of guidelines on a four point scale (the WHO "Medical Eligibility Criteria": WHO-MEC), summarising risk of specific contraceptive methods in women with specified chronic medical conditions. The general approach to contraceptive management of many of these conditions is addressed in this article.

Objective To assess the impact of anemia and iron deficiency on health-related quality of life (HRQoL) in women treated for heavy menstrual bleeding (HMB). Design Secondary analysis of a randomized controlled trial. Setting Five university hospitals in Finland. Sample A total of 236 women referred for HMB. Methods Women were randomized to treatment with hysterectomy or a levonorgestrel-releasing intrauterine system. We defined groups based on women's pretreatment hemoglobin [hemoglobin

Purpose Endometriosis is a gynecological disease often characterized by severe pelvic pain, including perimenstrual and intermenstrual pain and dyspareunia. Sensory nerve fibers within peritoneal lesions have previously been shown to contribute to generation of pain in endometriosis; however, their association with different types of pelvic pain is currently uncertain. Methods Peritoneal endometriotic lesions (n = 30) were sectioned and stained immunohistochemically with protein gene product 9.5 (PGP 9.5; pan-neuronal marker), neuropeptide Y (NPY; sympathetic), vasoactive intestinal polypeptide (VIP; parasympathetic), substance P (SP; sensory) and nerve growth factor (NGF) to identify nerve fibers and neurotrophin levels. Densities were assessed within stroma of the lesions and in the adjacent peritoneum. Pelvic pain scores were obtained using a visual analogue scale (VAS), and correlation analysis was performed. Results Increased density of nerve fibers was observed within the stroma of lesions. NGF expression was significantly increased in glandular epithelium, compared with stromal regions (p = 0.026) and correlated inversely with menstrual pain scores (p = 0.05). Sympathetic nerve fiber density (NPY) in stroma showed a significant positive correlation with intensity of menstrual pain (p = 0.04). Parasympathetic nerve fiber density (VIP) also showed a strong trend toward a positive correlation with menstrual pain intensity (p = 0.056). Conclusions There is increased neurogenesis in the stromal region. Innervation of lesions correlates to intensity of menstrual pain. NGF in glandular epithelium may promote growth of nerve fibers into the core of lesions; however, the inverse correlation between NGF expression in glandular epithelium and menstrual pain indicates that mechanisms of pain generation in endometriosis are complex.

Background Dysfunctional immune response may be implicated in endometriosis pathogenesis, and dendritic cells (DC) may play greater roles in this response than previously recognized. This study set out to evaluate peripheral blood and endometrial DC population changes in the presence and absence of endometriosis pathology. Methods Endometrial (n = 83) and peripheral blood samples (n = 30) were subjected to immunohistochemical techniques and flow cytometry, respectively, to assess DC populations in women with and without endometriosis. Three circulating DC subsets (MDC1, MDC2 and PDC, expressing CD1c, CD303 and CD141), and late-stage mature endometrial DCs (using DC-LAMP antibody) were investigated. Results A highly significant reduction in CD1c intensity on MDC1 populations in peripheral blood was observed between normal cycle proliferative and menstrual phases (p = 0.025), but not in women with endometriosis, in whom CD1c intensity was markedly increased at the time of menstruation (p = 0.05). A significant reduction in peripheral blood MDC2 (p = 0.016) and apparent reduction in endometrial DC-LAMP+ DC (trend, p = 0.062) were observed in women with endometriosis compared with controls, consistent with our preliminary DC data. Conclusions Cyclical variation in endometrial and circulating DC populations appears to be crucial during normal menstrual cycles and in the establishment of pregnancy. In endometriosis, circulating and endometrial DC populations are significantly dysregulated at a number of levels, and are likely to contribute to inefficient immunological targeting of endometrial fragments shed at menstruation, facilitating their survival and establishment of endometriosis.

This paper investigates the impact of corporate risk levels on aggregated, voluntary and mandatory risk disclosures in the annual report narratives of UK non-financial listed companies. We find that firms characterised by higher levels of systematic, financing risks and risk-adjusted returns and those with lower levels of stock return variability are likely to exhibit significantly higher levels of aggregated and voluntary risk disclosures. The results also show that firms of large size, high dividend-yield, high board independence, low (high) insider (outsider) ownership, and effective audit environments are likely to exhibit higher levels of aggregated and voluntary risk disclosures than other firms. Similarly, mandatory risk disclosures are influenced positively by firm size, dividend-yield and board independence and negatively by high leverage. The results suggest that managers of firms exhibiting greater compliance with mandatory regulations have a greater propensity to make voluntary risk disclosures. When we distinguish between high- and low-risk firms, we find that high-risk firms appear to be more sensitive to underlying risk levels, resulting in more disclosure of both voluntary and mandatory risk information than in the case of low-risk firms. The results generally support the present UK emphasis on encouraging rather than mandating risk disclosure. Nevertheless, under this regime, the voluntary risk disclosures of some firms, e.g., those characterised by higher-volatility market returns, do not reflect their underlying risk levels.

Heavy menstrual bleeding (HMB) seriously impacts physical and mental well-being of many women during their lifetimes. Many women turn to primary care providers or gynecologists seeking relief and resort to invasive surgical procedures such as endometrial ablation and/or hysterectomy. Pharmaceutical agents (e.g., progestogens, combined oral contraceptives, nonsteroidal anti-inflammatory drugs, hormone-releasing intrauterine devices and hemostatic agents) are all options for women who wish to avoid risks inherent to surgery, maintain fertility and limit the potential for early onset of menopausal symptoms. The response to these agents can be unpredictable and may depend on clinical- and patient-related factors. Agents with a contraceptive effect are not appropriate for women wishing to conceive. Tranexamic acid, an antifibrinolytic, has been used worldwide for over 50 years to effectively treat HMB, but a modified immediate-release formulation was only recently approved in the USA as the only approved treat...

Historically, the terminology used for abnormal uterine bleeding has been inconsistent and confusing. The Federation Internationale de Gynecologie et d'Obstetrique (FIGO) has recently approved new definitions and a standardized classification system for menstrual disorders and other contributors to the problem of abnormal uterine bleeding. This article describes the need for these changes and aims to encourage their use in routine clinical practice, medical education and scientific research, with the hope that they will lead to improved reproductive healthcare for women.

The original inserter of the contraceptive implant, Implanon®, resulted in very deep insertion in some cases, sometimes in close proximity to neurovascular structures. This occasionally resulted in removal complications. We successfully adopted a hook-wire marker method used in breast tumor surgery to safely and simply remove these deep-lying, non-palpable implants.

This study demonstrates a robust and thorough trial design leading to accurate and objective data collection. We recommend that future studies investigating heavy menstrual bleeding (HMB) should follow, and improve upon, this rigorous approach to menstrual trial data collection, not only to validate clinical results but also to improve the techniques used to acquire these results. We propose that the state-of-the-art methodology described here be used as the basis for new guidelines for the implementation of clinical trials in the area of HMB.

Endometriosis is a common, benign gynecological disease affecting 10 - 15% of reproductively aged women. It is characterized by the presence of endometrial-like tissue at sites outside the uterus. The most widely accepted theory of endometriosis pathogenesis proposes that shed menstrual endometrium can reach the peritoneum, implant and grow as endometriotic lesions. Angiogenesis, lymphangiogenesis and neurogenesis are implicated in successful ectopic establishment and the generation of endometriosis-associated symptoms. This review considers these processes as they occur in the eutopic endometrium and ectopic endometriotic lesions of women with endometriosis. Their regulation is inter-connected and complex. Dysregulation in endometriosis occurs on a background of accumulating evidence that endometriosis is an endometrial disease with underlying genetic influences and cross talk with endometriotic lesions. Understanding the roles of angiogenesis, lymphangiogenesis and neurogenesis in endometriosis pathophysiology is essential for the development of novel therapeutic approaches.

The aim of the study was to explore Australian women's experiences of menstruation and effect on quality of life (QoL).A representative sample of women recruited through a commercial social research sampling organisation completed a detailed online questionnaire about menstruation. Specific detailed questions were asked about perceptions of heavy menstrual bleeding (HMB) and menstrual pain.The questionnaire was completed by 1575 women aged 20-39 years. Most perceived their bleeding to be light (11.6%) or moderate (60.5%); 363 (22.5%) perceived it to be heavy and 86 (5.3%) very heavy. Women who experienced severe or very severe menstrual pain were significantly more likely to report periods as heavy or very heavy (p .001). The prevalence ratios for being confined to bed during menstruation for women experiencing severe or very severe menstrual pain were 12.02 (95% CI: 5.71-25.31) and 15.93 (95% CI: 7.51-33.78), respectively, compared with women experiencing no pain. The prevalence ratios for being confined to bed were 1.58 (95% CI: 1.11-2.24) and 1.53 (95% CI: 1.04-2.25) for women with heavy or very heavy bleeding, respectively. Women who experienced severe or very severe menstrual pain associated with their HMB were12 times more likely to be confined to bed for 0.5-1 day during menstruation than if they reported HMB without pain.Severe menstrual pain with HMB has a much more profound effect on all aspects of women's QoL than HMB alone; it accounts for more days in bed and for loss of productivity.

Iron deficiency (ID) is the most common micronutrient deficiency worldwide with >20% of women experiencing it during their reproductive lives. Hepcidin, a peptide hormone mostly produced by the liver, controls the absorption and regulation of iron. Understanding iron metabolism is pivotal in the successful management of ID and iron deficiency anaemia (IDA) using oral preparations, parenteral iron or blood transfusion. Oral preparations vary in their iron content and can result in gastrointestinal side effects. Parenteral iron is indicated when there are compliance/tolerance issues with oral iron, comorbidities which may affect absorption or ongoing iron losses that exceed absorptive capacity. It may also be the preferred option when rapid iron repletion is required to prevent physiological decompensation or given preoperatively for non-deferrable surgery. As gynaecologists, we focus on managing women's heavy menstrual bleeding (HMB) and assume that primary care clinicians are treating the associated ID/IDA. We now need to take the lead in diagnosing, managing and initiating treatment for ID/IDA and treating HMB simultaneously. This dual management will significantly improve their quality of life. In this chapter we will summarise the importance of iron in cellular functioning, describe how to diagnose ID/IDA and help clinicians choose between the available treatment options.

Background About 10% of reproductive-aged women suffer from endometriosis, which is a costly, chronic disease that causes pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but it is expensive and carries surgical risks. Currently, there are no non-invasive tests available in clinical practice that accurately diagnose endometriosis. This is the first diagnostic test accuracy review of endometrial biomarkers for endometriosis that utilises Cochrane methodologies, providing an update on the rapidly expanding literature in this field. Objectives To determine the diagnostic accuracy of the endometrial biomarkers for pelvic endometriosis, using a surgical diagnosis as the reference standard. We evaluated the tests as replacement tests for diagnostic surgery and as triage tests to inform decisions to undertake surgery for endometriosis. Search methods We did not restrict the searches to particular study designs, language or publication dates. To identify trials, we searched the following databases: CENTRAL (2015, July), MEDLINE (inception to May 2015), EMBASE (inception to May 2015), CINAHL (inception to April 2015), PsycINFO (inception to April 2015), Web of Science (inception to April 2015), LILACS (inception to April 2015), OAIster (inception to April 2015), TRIP (inception to April 2015) and ClinicalTrials.gov (inception to April 2015). We searched DARE and PubMed databases up to April 2015 to identify reviews and guidelines as sources of references to potentially relevant studies. We also performed searches for papers recently published and not yet indexed in the major databases. The search strategies incorporated words in the title, abstract, text words across the record and the medical subject headings (MeSH). Selection criteria We considered published peer-reviewed, randomised controlled or cross-sectional studies of any size that included prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). Data collection and analysis Two authors independently extracted data from each study and performed a quality assessment. For each endometrial diagnostic test, we classified the data as positive or negative for the surgical detection of endometriosis and calculated the estimates of sensitivity and specificity. We considered two or more tests evaluated in the same cohort as separate data sets. We used the bivariate model to obtain pooled estimates of sensitivity and specificity whenever sufficient data were available. The predetermined criteria for a clinically useful test to replace diagnostic surgery was one with a sensitivity of 94% and a specificity of 79%. The criteria for triage tests were set at sensitivity at or above 95% and specificity at or above 50%, which in case of negative results rules out the diagnosis (SnOUT test) or sensitivity at or above 50% with specificity at or above 95%, which in case of positive result rules in the diagnosis (SpIN test). Main results We included 54 studies involving 2729 participants, most of which were of poor methodological quality. The studies evaluated endometrial biomarkers either in specific phases of the menstrual cycle or outside of it, and the studies tested the biomarkers either in menstrual fluid, in whole endometrial tissue or in separate endometrial components. Twenty-seven studies evaluated the diagnostic performance of 22 endometrial biomarkers for endometriosis. These were angiogenesis and growth factors (PROK-1), cell-adhesion molecules (integrins α3β1, α4β1, β1 and α6), DNA-repair molecules (hTERT), endometrial and mitochondrial proteome, hormonal markers (CYP19, 17βHSD2, ER-α, ER-β), inflammatory markers (IL-1R2), myogenic markers (caldesmon, CALD-1), neural markers (PGP 9.5, VIP, CGRP, SP, NPY, NF) and tumour markers (CA-125). Most of these biomarkers were assessed in single studies, whilst only data for PGP 9.5 and CYP19 were available for meta-analysis. These two biomarkers demonstrated significant diversity for the diagnostic estimates between the studies; however, the data were too limited to reliably determine the sources of heterogeneity. The mean sensitivities and specificities of PGP 9.5 (7 studies, 361 women) were 0.96 (95% confidence interval (CI) 0.91 to 1.00) and 0.86 (95% CI 0.70 to 1.00), after excluding one outlier study, and for CYP19 (8 studies, 444 women), they were were 0.77 (95% CI 0.70 to 0.85) and 0.74 (95% CI 0.65 to 84), respectively. We could not statistically evaluate other biomarkers in a meaningful way. An additional 31 studies evaluated 77 biomarkers that showed no evidence of differences in expression levels between the groups of women with and without endometriosis. Authors' conclusions We could not statistically evaluate most of the biomarkers assessed in this review in a meaningful way. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Although PGP 9.5 met the criteria for a replacement test, it demonstrated considerable inter study heterogeneity in diagnostic estimates, the source of which could not be determined. Several endometrial biomarkers, such as endometrial proteome, 17βHSD2, IL-1R2, caldesmon and other neural markers (VIP, CGRP, SP, NPY and combination of VIP, PGP 9.5 and SP) showed promising evidence of diagnostic accuracy, but there was insufficient or poor quality evidence for any clinical recommendations. Laparoscopy remains the gold standard for the diagnosis of endometriosis, and using any non-invasive tests should only be undertaken in a research setting. We have also identified a number of biomarkers that demonstrated no diagnostic value for endometriosis. We recommend that researchers direct future studies towards biomarkers with high diagnostic potential in good quality diagnostic studies.

sUMMArY Endometriosis is increasingly being recognised as a disease which commonly affects women through the reproductive years. It is the commonest cause of chronic pelvic pain in developed countries, and frequently begins in adolescence. Endometriosis is a highly variable condition, and diagnosis can be difficult. Confirmation of diagnosis still requires laparoscopy in most situations, but successful therapy of many, especially milder, cases can be based on a presumptive diagnosis. A careful history needs to be taken to try and exclude other common causes of pelvic pain. Medical management requires treatment of pain with analgesics, and suppression of disease activity mainly with hormonal preparations. This needs to be integrated with the potential need for surgery.

BACKGROUND: The study was conducted to assess the efficacy of estradiol valerate/dienogest (E(2)V/DNG) administered using an estrogen step-down and progestogen step-up approach in a 28-day regimen in the treatment of heavy menstrual bleeding (HMB) using clinical end points allowing E(2)V/DNG to be compared with other available medical therapies. STUDY DESIGN: This was a pooled analysis of data from two identically designed randomized placebo-controlled multiple center studies conducted in Europe Australia and North America that assessed the effectiveness of E(2)V/DNG in reducing menstrual blood loss (MBL) in women with HMB. Women aged >/= 18 years with objectively confirmed HMB were randomized to E(2)V/DNG (n=220) or placebo (n=135) for seven treatment cycles. Outcomes analyzed included absolute reduction in MBL from baseline proportion of women successfully treated (defined as MBL below 80 mL and >/= 50% reduction in MBL) proportion with MBL below 80 mL and proportion with >/= 50% reduction in MBL from baseline. RESULTS: At study end 63.6% and 11.9% of patients were successfully treated with E(2)V/DNG and placebo respectively with 68.2% and 15.6% of women with MBL below 80 mL and 70.0% and 17.0% with MBL reduction >/= 50% (all p

PurposeThe paper aims to explore the social origins of Scottish chartered accountants and the accounting stereotype as portrayed in popular fiction.Design/methodology/approachThe detective novels of the Scottish chartered accountant Alexander Clark Smith are used as a lens through which to explore the social origins of accountants and the changing popular representations of the accountant.FindingsThe novels contribute to our understanding of the construction of accounting stereotypes and of the social origins of Scottish accountants. They suggest that, while working class access to the profession was a reality, so was class division within it. In addition, Smith was ahead of contemporary professional discourse in creating a protagonist who combines the positive aspects of the traditional stereotype with qualities of a private‐eye action‐hero, and who uses accounting skills to uncover corruption and address (social) wrongs. However, this unconventional portrayal may have been incongruent with the image the profession wished to portray. The public image (or stereotype) portrayed by its members would have been as important in signalling and maintaining the profession's collective status as the recruitment of its leadership from social elites.Originality/valueSmith's portrayal of accountants in personal and societal settings at a time of profound social change, as well as his background in the Scottish profession, provide a rich source for the study of social origins of Scottish chartered accountancy during the first half of the twentieth century. Further, Smith's novels are of a popular genre, and innovative in the construction of their hero and of accounting itself; as such they merit attention because of their potential to influence the construction of the accounting stereotype(s) within the popular imagination.

Objective: To determine whether older women with a poor response to follicular stimulation achieve pregnancy results that are comparable to those of younger poor responders. Methods: Two hundred five women undergoing in vitro fertilization treatment at the Fertility Unit in the Royal Prince Alfred Hospital in Sydney, Australia were selected for retrospective cohort analysis. The outcomes in women > 38 years of age with < 5 oocytes retrieved were compared with those in women ≤ 38 years who also had < 5 oocytes retrieved. Clinical and ongoing pregnancy rates were compared. Results: Implantation rates (21.01 ± 0.38 % vs. 12.82 ± 0.27%, P = 0.11) and clinical pregnancy rates (25.71 ± 0.44% vs. 20.21 ± 0.40%, P = 0.41) were similar in the two groups following cleavage stage embryo transfer. The same was true for blastocyst stage embryo transfer (implantation rates 16.67 ± 0.33% vs. 13.89 ± 0.33%, P = 0.80, and clinical pregnancy rates 23.81 ± 0.44% vs. 16.67 ± 0.38%, P = 0.59). Ongoing pregnancies beyond the 12th week of gestation were also comparable between cleavage stage (24.28 ± 0.43% vs. 16.84 ± 0.34%, P = 0.24) and blastocyst stage embryo transfers (23.81 ± 0.44% vs. 11.11 ± 0.32%, P = 0.32). Conclusion: If older poor responders reach the stage of embryo transfer, they can achieve pregnancy rates similar to those of younger poor responders when matched numbers of embryos are transferred. Objectif : Déterminer si les femmes âgées qui réagissent faiblement à la stimulation folliculaire obtiennent des résultats de grossesse comparables à ceux des femmes qui réagissent tout aussi faiblement à cette stimulation, mais qui sont plus jeunes. Méthodes : Deux cent cinq femmes subissant un traitement de fécondation in vitro au sein de la Fertility Unit du Royal Prince Alfred Hospital à Sydney, en Australie, ont été sélectionnées en vue d’une analyse de cohorte rétrospective. Les issues chez des femmes de plus de 38 ans comptant moins de cinq ovocytes récupérés ont été comparées à celles qui ont été constatées chez des femmes de 38 ans ou moins qui comptaient également moins de cinq ovocytes récupérés. Les taux de grossesse clinique et en cours ont été comparés. Résultats : Les taux d’implantation (21,01 ± 0,38 % vs 12,82 ± 0,27 %, P = 0,11) et les taux de grossesse clinique (25,71 ± 0,44 % vs 20,21 ± 0,40 %, P = 0,41) étaient semblables dans les deux groupes à la suite du transfert d’embryons en étant au stade de la segmentation. Cela était également vrai pour ce qui est du transfert d’embryons en étant au stade du blastocyste (taux d’implantation 16,67 ± 0,33 % vs 13,89 ± 0,33 %, P = 0,80, et taux de grossesse clinique 23,81 ± 0,44 % vs 16,67 ± 0,38 %, P = 0,59). Les grossesses en cours se situant au-delà de la 12e semaine de gestation étaient également similaires lorsque l’on a comparé les transferts d’embryons en étant au stade de la segmentation (24,28 ± 0,43 % vs 16,84 ± 0,34 %, P = 0,24) et les transferts d’embryons en étant au stade du blastocyste (23,81 ± 0,44 % vs 11,11 ± 0,32 %, P = 0,32). Conclusion : Lorsque le nombre d’embryons transférés est le même et que les femmes âgées qui réagissent faiblement à la stimulation folliculaire atteignent l’étape du transfert d’embryons, ces femmes peuvent obtenir des taux de grossesse semblables à ceux que l’on constate chez les femmes qui réagissent tout aussi faiblement à cette stimulation, mais qui sont plus jeunes

Background About 10% of reproductive-aged women suffer from endometriosis which is a costly chronic disease that causes pelvic pain and subfertility. Laparoscopy is the 'gold standard' diagnostic test for endometriosis, but it is expensive and carries surgical risks. Currently, there are no simple non-invasive or minimally-invasive tests available in clinical practice that accurately diagnoses endometriosis. Objectives 1. To provide summary estimates of the diagnostic accuracy of urinary biomarkers for the diagnosis of pelvic endometriosis compared to surgical diagnosis as a reference standard. 2. To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses. Urinary biomarkers were evaluated as replacement tests for surgical diagnosis and as triage tests to inform decisions to undertake surgery for endometriosis. Search methods The searches were not restricted to particular study design, language or publication dates. We searched the following databases to 20 April - 31 July 2015: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP and ClinicalTrials.gov (trial register). MEDION, DARE, and PubMed were also searched to identify reviews and guidelines as reference sources of potentially relevant studies. Recently published papers not yet indexed in the major databases were also sought. The search strategy incorporated words in the title, abstract, text words across the record and the medical subject headings (MeSH) and was modified for each database. Selection criteria Published peer-reviewed, randomised controlled or cross-sectional studies of any size were considered, which included prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of one or more urinary biomarkers with surgical visualisation of endometriotic lesions. Data collection and analysis Two authors independently collected and performed a quality assessment of the data from each study. For each diagnostic test, the data were classified as positive or negative for the surgical detection of endometriosis and sensitivity and specificity estimates were calculated. If two or more tests were evaluated in the same cohort, each was considered as a separate data set. The bivariate model was used to obtain pooled estimates of sensitivity and specificity whenever sufficient data sets were available. The predetermined criteria for a clinically useful urine test to replace diagnostic surgery was one with a sensitivity of 94% and a specificity of 79% to detect endometriosis. The criteria for triage tests were set at sensitivity of equal or greater than 95% and specificity of equal or greater than 50%, which in case of negative result rules out the diagnosis (SnOUT test) or sensitivity of equal or greater than 50% with specificity of equal or greater than 95%, which in case of positive result rules the diagnosis in (SpIN test). Main results We included eight studies involving 646 participants, most of which were of poor methodological quality. The urinary biomarkers were evaluated either in a specific phase of menstrual cycle or irrespective of the cycle phase. Five studies evaluated the diagnostic performance of four urinary biomarkers for endometriosis, including three biomarkers distinguishing women with and without endometriosis (enolase 1 (NNE); vitamin D binding protein (VDBP); and urinary peptide profiling); and one biomarker (cytokeratin 19 (CK 19)) showing no significant difference between the two groups. All of these biomarkers were assessed in small individual studies and could not be statistically evaluated in a meaningful way. None of the biomarkers met the criteria for a replacement test or a triage test. Three studies evaluated three biomarkers that did not differentiate women with endometriosis from disease-free controls. Authors' conclusions There was insufficient evidence to recommend any urinary biomarker for use as a replacement or triage test in clinical practice for the diagnosis of endometriosis. Several urinary biomarkers may have diagnostic potential, but require further evaluation before being introduced into routine clinical practice. Laparoscopy remains the gold standard for the diagnosis of endometriosis, and diagnosis of endometriosis using urinary biomarkers should only be undertaken in a research setting.

We examine the effect of family control on IFRS mandatory disclosure levels, and the valuation implications of these disclosure levels, for Malaysian companies. We find that family control is related negatively to disclosure and that compliance levels are not value relevant. These findings suggest that agency theory predictions and theories linking common law legal systems to high quality financial reporting require refining in certain national contexts. Where Type 2 agency problems dominate, institutional arrangements intended to enhance financial reporting quality aimed at mitigating Type 1 problems in developed markets may have limited effect in less developed jurisdictions.