Caesarean section operation is not associated with myometrial hypertrophy-a prospective cohort study.

Maternity statistics of England in 2020 showed rise in Caesarean Section (CS) rate to 31%. Some studies correlated adverse gynaecological symptoms e.g. menstrual irregularities and pelvic pain to 'niche' formation at CS scar site. Niche formation was speculated to cause myometrial hypertrophy aggravating these symptoms. This was a prospective comparative histological study including 52 consecutive benign hysterectomy specimens which were categorised into 2 groups: (i) specimens with CS scar (n = 22), (ii) specimens with no CS scar (n = 30). Median (IQ range) uteri weight was 97.2grms (43.5-226) and 91.7grms (35.7-201.7) in study and control groups, respectively (p = .991). Mean (±SD) thickness of anterior myometrial wall was 18.7 mm (±3.6) and 19.4 mm (±4.5) in study and control groups, respectively (p = .58). Mean (±SD) thickness of posterior myometrial wall was 19.1 mm (±3.7) and 18.7 mm (±3.9) in study and control groups, respectively (p = .78). The assumption that CS scar causes myometrial hypertrophy was not demonstrated in this study.IMPACT STATEMENTWhat is already known on this subject? Maternity statistics world-wide show a continuous rise in the rate of Caesarean Section (CS) operation. The CS scar is assumed to be related to adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the mechanism of this association is not clear. Further, little is known about the effects of CS scar on uterine wall morphology and function.What do the results of this study add? This study was the first prospective series in the literature to compare the uteri with scar with those without in respect of weight and myometrial wall thickness. It was not able to demonstrate the association between having CS scar and myometrial hypertrophy which was hypothesised to be the cause of adverse gynaecological symptoms. However, the microscopic examination of the CS scar revealed adenomyosis, haemorrhage and/or chronic inflammation in most cases.What are the implications of these findings for clinical practice and/or future research? The clinical implication of the histological changes shown in the CS scar requires large comparative clinical studies.

Is routine adnexal scanning for postmenopausal bleeding of value? Observational study of 2101 women.

Our objective is to assess the merits of adnexal scanning during the investigation of women with postmenopausal bleeding (PMB) in terms of adnexal cancer diagnosis. This observational study was designed utilising an institutional PMB database in a teaching hospital, analysing a sample of 2101 consecutive women with PMB seen between 16th February 2012 and 12th August 2014 looking at the prevalence of cancer in adnexal masses identified on Trans-vaginal ultrasound scanning (TVS) in these PMB women. This study suggests that routine adnexal scanning in women with PMB may provide no benefit. It could be exposing women to unnecessary surgery or surveillance with the associated risks and cost implications. Most of the women who underwent surgery presented with palpable masses. Those with negative clinical examination had either benign masses which may have remained inconsequential or non-suspicious scan findings. A well-designed randomised controlled trial is needed to confirm the findings. Impact statement Trans-vaginal ultrasound scanning (TVS) is the standard first line investigation for women presenting with postmenopausal bleeding (PMB) primarily to assess the endometrial thickness. This has led to a widespread practice of opportunistic adnexal scanning, which generated a debate amongst gynaecologists about the value of such practice. This observational study, assessing the merits of routine adnexal scanning in these women in terms of adnexal cancer diagnosis, suggests that this practice may provide no benefit to women with isolated self-limiting PMB and unremarkable bimanual examination. It could be exposing women to unnecessary surgery or surveillance with the associated risks and cost implications when insignificant adnexal masses are identified on the scan. A well-designed randomised controlled trial is needed to elucidate if clinical examination in combination with endometrial scanning only is more effective and cost-effective than clinical examination followed by systematic pelvic scanning to detect cases of ovarian cancer in women with PMB.

The optimal endometrial thickness threshold for prediction of endometrial cancer in postmenopausal women without bleeding remains uncertain-Systematic review and meta-analysis.

The incidental finding of endometrial thickness (ET) >4 mm in the absence of postmenopausal bleeding (PMB) is a common cause of referring women to secondary care. However, there is lack of consensus amongst gynecologists as regards the management. It is estimated that up to 15 % of endometrial cancers occur in women without PMB. The aim this study was to determine the optimal ET threshold, on trans-vaginal ultrasound scan, that discriminates normal endometrium from endometrial hyperplasia and cancer in this cohort. On using a thorough search strategy, a total 16 studies including 4088 women were deemed eligible. However, the data were not amenable to meta-analysis. There were wide variations in the thresholds reported with potential bias given the retrospective nature of the majority of the studies. Despite contacting authors, we could not obtain the primary data to generate a Receiver Operating Characteristic (ROC) Curve. No linear or curvilinear association was found between ET thresholds and the percentage of women diagnosed with endometrial hyperplasia and cancer using either Pearson's correlation, linear or curvilinear regression, or a simple visual scan/scatter diagram. The result of this study reveals the lack of evidence to inform clinical practice in this area, and there is a need for a well-designed multi-center prospective study.

Folic acid supplementation may cure hot flushes in postmenopausal women: a prospective cohort study.

BACKGROUND: Neurotransmitter norepinephrine seems to be involved in the pathophysiology of hot flushes in postmenopausal women, and folic acid was found to interact with its receptors. OBJECTIVES: To examine the effect of folic acid supplementation on the occurrence of hot flushes and the plasma level of 3-methoxy 4-hydroxy phenyl glycol (MHPG, the main metabolite of brain norepinephrine). METHOD: Forty-six postmenopausal women were allocated (by alternation) into 2 groups (n = 23 each); Group 1 received folic acid 5mg tablets daily for 4 weeks and group 2 received placebo tablets. Four women in group 2 discontinued the study. RESULTS: The number of women who reported improvement in hot flushes was significantly higher in the treatment group. On comparing the mean plasma levels of MHPG before and after treatment, a significant lowering was found in the treatment group (mean % change = -24.1 +/- 17.9, p < 0.001) when compared with the placebo-control group (mean % change = -5.59 +/- 16.4, p = 0.10). In the treatment group, there was a significant negative correlation between improvement in hot flushes and the plasma level of MHPG (r = -0.453, p = 0.03). CONCLUSION: Folic acid supplementation may cause subjective improvement of hot flushes by lowering the increased central noradrenergic activity.

The first-line investigation of postmenopausal bleeding: transvaginal ultrasound scanning and endometrial biopsy may be enough.

Postmenopausal bleeding is a common problem in clinical practice with significant implications; however, the diagnostic strategies often vary among different centers. In the recent years, there was a trend to adopt less invasive procedures without compromising efficacy and safety. There is continuous debate about the different available modalities for investigation, and a large number of studies were conducted to define their roles. Some authors recommended that hysteroscopy should be the standard investigation procedure for women with postmenopausal bleeding. Nonetheless, there is a strong evidence to suggest that transvaginal ultrasound scanning, with or without endometrial biopsy, is a safe and more cost-effective initial tool in investigating these women. This commentary highlights this important issue and discusses the role of these different modalities.

Levonorgestrel-releasing intrauterine system--the discontinuing story.

Levonorgestrel-releasing Intrauterine System (LNG-IUS) is licensed for use as a contraceptive, for the treatment of heavy menstrual bleeding and during estrogen replacement therapy. It is publicized as a local source of progestogen with minimal systemic adverse effects. However, there is overwhelming evidence of elevated serum and tissue levels of levonorgestrel, and high discontinuation and dissatisfaction rates amongst users. The guidelines of The National Institute for Health and Clinical Excellence (NICE), United Kingdom recommended that the healthcare professionals should be aware that upto 60% of women discontinue using LNG-IUS within 5 years because of unscheduled bleeding, pain, and/or systemic progestogenic adverse effects. This article highlights these issues to healthcare professionals to ensure that the rates of adverse effects are not underestimated, and full information are made available to women to enable them making an informed choice.

Changes in transcription profile and cytoskeleton morphology in pelvic ligament fibroblasts in response to stretch: the effects of estradiol and levormeloxifene.

Failure of ligamentous support of the genital tract to resist intra-abdominal pressure is a plausible underlying mechanism for the development of pelvic organ prolapse, but the nature of the molecular response of pelvic tissue support remains unknown. We hypothesized that the expression of genes coding for proteins involved in maintaining the cellular and extracellular integrity would be altered as a result of mechanical stretch. Therefore, cDNA microarrays were used to examine the difference in transcriptional profile in RNA of primary culture fibroblasts subjected to mechanical stretch and those that remained static. Out of 34 mechano-responsive genes identified (P < 0.05), four were coding for regulation of actin cytoskeleton remodelling, and its interaction with the extracellular matrix proteins; these are phosphatidyl inositol-4-phosphate 5-kinase (PIP5K1C), the human signal-induced proliferation associated gene-1 (SIPA-1), TNFRSF1A-associated via death domain (TRADD) and deoxyribonuclease 1-like 1 (DNase 1-L1). The transcriptosomal changes led us to investigate the phenotypic consequences of stretch, levormeloxifene and estradiol (E(2)) on the cytoskeleton of cultured fibroblasts. The percentage of cells with abnormal F-actin configuration was significantly higher in fibroblasts subjected to stretch compared with the static model (P < 0.0001). Levormeloxifene caused similar significant alterations in actin morphology of the static fibroblasts. The use of E(2) did not reverse the process or protect the cells from the effect of stretch, but significantly increased the rate of fibroblast proliferation, suggestive of a role in healing process. Mechanical stretch and/or levormeloxifene disturb the fibroblasts ability to maintain the cytoskeleton architecture and we speculate that they may disrupt ligamentous integrity and result in clinical prolapse.

Levonorgestrel-releasing intrauterine system: why do some women dislike it?

BACKGROUND: There is growing evidence of women's dissatisfaction with the levonorgestrel-releasing intrauterine system (LNG-IUS) because of a high incidence of adverse effects. OBJECTIVE: To quantify the continuation rate and users' satisfaction, and identify symptoms associated with early removal before the 5-years effective life-time. METHOD: A questionnaire was sent to 212 women, who had LNG-IUS inserted from 1 January 1998 to 31 December 2003 at The Ipswich Hospital, UK. RESULTS: The response rate was 76% (n = 161), 16 of the respondents were excluded and the data of 145 are presented. The continuation rate was 85%, 70%, 59%, 56%, 50% and 50% at 6 months, 1, 2, 3, 4 and 5 years, respectively. The total number of women who had the LNG-IUS removed before 5 years was 72 (50%), and the median duration of use was 270 days (range 4-1460). The reasons for early removal were unscheduled bleeding, progestogenic adverse effects, abdominal pain and others in 40 (28%), 32 (22%), 19 (13%) and 19 (13%) women, respectively. Only 73 (50%) women were satisfied with LNG-IUS. CONCLUSIONS: Our findings are similar to recent reports, and this information should be readily available to women to enable them to make an informed choice.

Caesarean section scar causes myometrial hypertrophy with subsequent heavy menstrual flow and dysmenorrhoea.

In the recent years, maternity statistics world-wide show a continuous rise in the rate of Caesarean Section (CS) operation. Many CS deliveries are conducted despite having no clear obstetric indications. The CS scar is assumed to be related to many adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the mechanism of this relation is not clear. Further, little is known about the effects of CS scar on uterine wall morphology, function or patho-physiology. We hypothesize that: (i) the CS scar causes myometrial hypertrophy (myohypertrophy) of the anterior uterine wall above the scar, and (ii) the scar-induced morphological changes in the uterine wall causes adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain. This article discusses the hypothesis and its clinical implications, as well as presents supportive preliminary data and the emerging research to prove it.

Ovarian Mature Cystic Teratoma: Challenges of Surgical Management.

Although ovarian mature cystic teratomas are the commonest adnexal masses occurring in premenopausal women, there are many challenges faced by gynecologists on deciding upon the best surgical management. There is uncertainty, lack of consensus, and variation in surgical practices. This paper critically analyzes various surgical approaches and techniques used to treat these cysts in an attempt to outline a unified guidance. MEDLINE and EMBASE databases were searched in January 2015 with no date limit using the key words "ovarian teratoma" and "ovarian dermoid." The search was limited to articles in English language, humans, and female. The two authors conducted the search independently. The laparoscopic approach is generally considered to be the gold standard for the management. Oophorectomy should be the standard operation except in younger women with a single small cyst. The risk of chemical peritonitis after contents spillage is extremely rare and can certainly be overcome with thorough peritoneal lavage using warmed fluid. There is a place for surveillance in some selected cases.

Cattle Uterus: A Novel Animal Laboratory Model for Advanced Hysteroscopic Surgery Training.

In recent years, due to reduced training opportunities, the major shift in surgical training is towards the use of simulation and animal laboratories. Despite the merits of Virtual Reality Simulators, they are far from representing the real challenges encountered in theatres. We introduce the "Cattle Uterus Model" in the hope that it will be adopted in training courses as a low cost and easy-to-set-up tool. It adds new dimensions to the advanced hysteroscopic surgery training experience by providing tactile sensation and simulating intraoperative difficulties. It complements conventional surgical training, aiming to maximise clinical exposure and minimise patients' harm.

Phytoestrogens in the management of the menopause: up-to-date.

UNLABELLED: Despite the benefits of conventional hormone replacement therapy, some women are not candidates for this treatment and many others choose not to take it. As a result, there is growing interest among patients about natural alternatives. There is some evidence that phytoestrogens may offer protection against a wide range of human conditions, including breast cancer, cardiovascular disease, brain dysfunction, osteoporosis, and menopausal symptoms. The literature on the possible health benefits of phytoestrogens has expanded exponentially since the 1980s, mainly in response to funding initiatives by the U.S. government and soybean industries, and more lately by European and UK Ministries of Food. The physiological effects of phytoestrogens also have created a marketing opportunity that has been used by industry, particularly in soybean-producing countries such as the U.S. and Australia. Nevertheless, clinical applications for phytoestrogens are still in their infancy, and more interventional trials are required to reach definitive conclusions regarding their efficacy and safety, although they appear to represent a promising group of compounds, which may be useful in the future for the treatment of the menopausal syndrome. Also, the lack of clinical data presently available must signal caution in relation to the possible risk of adverse effects. TARGET AUDIENCE: Obstetricians and Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to identify the various types of phytoestrogens, list the sources of phytoestrogens, and summarize the various effects of phytoestrogens.

Endometrial biopsy in women with abnormal uterine bleeding: inadequate and unassessable categorisation is not clinically relevant.

AIMS: Inadequate endometrial biopsy comprises a dilemma for gynaecologists and histopathologists alike. This study was conducted to assess the clinical merit of classifying scant endometrial biopsy into inadequate and unassessable using McCluggage criteria. METHODS: We retrospectively classified 268 endometrial biopsies, initially reported as inadequate, into inadequate (n=74) and unassessable (n=174) using McCluggage criteria after excluding 20 cases; all taken from patients aged ≥50 years with abnormal uterine bleeding attending Sandwell and West Birmingham Hospitals, UK from 1 January 2007 until 30 September 2012. The electronic clinical records were reviewed to find out the consequent clinical decisions and final outcomes. The follow-up period was 15 months after including the last patient. RESULTS: The median age was 57 years (range: 50-97), and the median number of visits to hospital till the diagnosis was achieved was 2 (range: 1-4). The final diagnosis of endometrial hyperplasia or cancer was reported in 9 cases; 5 (7.1%) with an initial finding of inadequate and 4 with unassessable (2.4%); the difference was statistically insignificant (p=0.13). More patients in the inadequate category (82.4%) underwent further investigations when compared with the unassessable category (68.4%); the difference was statistically significant (p=0.029). There was no statistically significant difference in the inadequate to unassessable ratio when the endometrial thickness was ≥5 mm or <5 mm within the Pipelle group (p=0.46) or the curettage group (p=0.34). CONCLUSIONS: Our findings suggest that categorising scant endometrial specimens into inadequate or unassessable has no clinical implications. The gynaecologist should interpret the histopathology report in the light of clinical scenario.

Use of levonorgestrel-releasing intrauterine system in the prevention and treatment of endometrial hyperplasia.

Endometrial hyperplasia is a commonly seen gynecological condition that affects women of all age groups. Whereas hysterectomy is the most preferred treatment option for complex endometrial hyperplasia with atypia, there is no consensus regarding the first-line management of women with hyperplasia without cytological atypia. Oral progestogen therapy was used with some success. Nonetheless, it may be plausible to argue that women with endometrial hyperplasia need continuous treatment and high level of compliance to ensure complete regression, which may not be guaranteed with oral therapy. Observational studies suggested that levonorgestrel-releasing intrauterine system (LNG-IUS) has been successfully used to treat endometrial hyperplasia without cytological atypia and selected cases of atypical endometrial hyperplasia. Furthermore, there is strong evidence from randomized controlled trials that LNG-IUS prevents the development of endometrial hyperplasia in exogenous estrogen users; however, its protective role and safety in tamoxifen-treated breast cancer survivors remain uncertain. This article evaluates the current evidence for the use of LNG-IUS, releasing 20 µg of LNG per day, in the prevention and treatment of endometrial hyperplasia.