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.

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.

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.

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.

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.

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.

Endometrial hyperplasia - the dilemma of management remains: a retrospective observational study of 280 women.

OBJECTIVE: To quantify the rate of inconsistency in histopathological reporting between endometrial biopsy specimens (obtained by Pipelle endometrial sampler or curettage) and hysterectomy specimens using the World Health Organization classification criteria. STUDY DESIGN: A retrospective review of the records of 280 women with a histopathological diagnosis of endometrial hyperplasia treated in Ipswich Hospital NHS Trust, UK from 1 January 1998 to 31 May 2009. RESULTS: Discrepancy was found between the histopathological results of endometrial samples and hysterectomy specimens. The discrepancy was doubled for specimens obtained using a Pipelle endometrial sampler, with false-positive (i.e. overdiagnosis when the hysterectomy specimen showed a better diagnosis) and false-negative (i.e. underdiagnosis when the hysterectomy specimen showed a worse diagnosis) rates of 5.3% and 22.6%, respectively. For curettage specimens, the false-positive and false-negative rates were 1.8% and 13.2%, respectively. All cases of curettage were performed under general or regional anaesthesia, and were preceded by hysteroscopy. Apart from age, no risk factors were associated with a worse diagnosis. The association of age differed between types of endometrial hyperplasia and cancer; the strongest association was seen for cancer and the weakest association was seen for simple hyperplasia. CONCLUSION: Hysteroscopy and curettage may be considered when simple or complex hyperplasia is diagnosed from a specimen obtained with a Pipelle endometrial sampler. When a diagnosis of atypical hyperplasia is made, irrespective of the method of endometrial sampling, the gynaecologist must be concerned that endometrial carcinoma exists concomitantly within the uterus.

Managing postmenopausal bleeding revisited: what is the best first line investigation and who should be seen within 2 weeks? A cross-sectional study of 326 women.

OBJECTIVES: The management strategies of postmenopausal bleeding (PMB) vary between different centres. This study was conducted to (1) evaluate the performance of a "One Stop PMB Clinic" that uses trans-vaginal ultrasound scanning (TVS) ± Pipelle(®) endometrial biopsy (EB) as the first line investigation, and (2) identify the risk factors for endometrial cancer to help setting criteria to prioritize clinic slots. STUDY DESIGN: A retrospective data review of 326 women seen in the period from 1 August 2005 until 31 August 2009 at Ipswich Hospital, UK. RESULTS: The median primary referral interval was 30 days. The prevalence of endometrial cancer and atypical hyperplasia was 5.5% (n = 18) and 1.8% (n = 6), respectively. One case with endometrial thickness (ET) of < 5mm and negative Pipelle(®) EB was found to have cancer on a curettage specimen taken for persistent bleeding. Statistical analysis revealed an association between endometrial cancer and increased ET (p < 0.0001), increased age (p = 0.004) and multiple episodes of bleeding (p=0.04). There was no evidence of an association with parity (p = 0.64) or severity of bleeding (p = 0.46). There was no case of endometrial cancer in HRT users. CONCLUSION: TVS ± Pipelle(®) EB may be a safe first line investigation in managing PMB. Accepting that all investigations have a false negative rate, women with persistent bleeding should be re-investigated. Given the ever-increasing workload, the priority for urgent appointments may be given to the older women, non-users of HRT and those with multiple episodes rather than heavy bleeding.

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.

Women with asymptomatic cervical polyps may not need to see a gynaecologist or have them removed: an observational retrospective study of 1126 cases.

OBJECTIVES: (1) To determine the prevalence of pathology in cervical polyps and whether referring and/or removing them is justified, (2) to assess the frequency of associated endometrial pathology and whether investigating the uterine cavity is warranted, and (3) to estimate the financial costs of processing cervical polyps. STUDY DESIGN: Retrospective review of the histopathology database and case notes of women who had cervical polyps examined at the pathology department of Ipswich Hospital, UK, over a seven-year period from 01/01/2002 to 31/12/2008. RESULTS: The number of cervical polyps removed from 988 women was 1126. Each case of polyps was considered as a separate episode. The recurrence rate was 15%. All polyps were benign except two (0.2%) symptomatic polyps that showed high grade cervical intraepithelial neoplasia. The cost of referring women with cervical polyps (excluding women aged >45 years with abnormal bleeding and those with abnormal smear) to see a gynaecologist and of examining polyps histologically was estimated to be pound 94816.40. Further investigations to assess the cervix and/or uterine cavity which were performed for 133 women (14.3%), because of the cervical polyps and for no other clinical indication, showed no significant pathology at cost of pound 41195.54. CONCLUSION: Our data do not justify referring women with asymptomatic cervical polyps to see a gynaecologist. Further, removing these polyps and investigating the uterine cavity is not warranted. A policy of removing polyps from only symptomatic women or those with abnormal smear and limiting histological examination to these polyps would result in significant savings.

Premenopausal bleeding: When should the endometrium be investigated?--A retrospective non-comparative study of 3006 women.

OBJECTIVE: There is lack of consensus amongst professional organizations as regards the cut-off age for endometrial sampling of premenopausal women presenting with abnormal uterine bleeding (AUB) to exclude endometrial hyperplasia or carcinoma. Therefore we conducted this study to quantify the prevalence of hyperplasia and carcinoma in different age categories in premenopausal women with AUB to identify the appropriate cut-off age for endometrial sampling. STUDY DESIGN: A retrospective review of the histopathology reports of endometrial samples taken from 3006 women presenting with AUB and aged from > or =30 to < or =50 years at Ipswich Hospital, UK, from 1 January 1998 to 31 December 2007. Women were divided into three subgroups according to age; group 1: 30 to < or =40 (n=862), group 2: 40 to < or =45 (n=1035) and group 3: 45 to < or =50 (n=1109). RESULTS: Logistic regression revealed that the prevalence of atypical hyperplasia (OR: 3.85; 95% CI: 1.75, 8.49; p=0.01) and carcinoma (OR: 4.03; 95% CI: 1.54, 10.5; p=0.04) was significantly higher in women in group 3 when compared to younger women. There was no statistically significant difference as regards simple and complex hyperplasia in the different age categories. All but one of the women (n=23) who had complex atypical hyperplasia or carcinoma under the age of 45 years, presented with irregular rather than cyclical heavy menstrual bleeding. CONCLUSION: Our study, the largest in the literature, suggests using the age 45 years as a cut-off for sampling the endometrium in all women with AUB. However, irregular menstrual bleeding justifies investigating women regardless of their age.

Folic acid supplementation cures hot flushes in postmenopausal women.

Over the past four decades, it was found that folic acid supplementation produced an antidepressant-like effect mediated by interaction with the brain noradrenergic receptors (inhibitory effect) and serotonergic receptors (stimulatory effect). Hot flushes occur in postmenopausal women because of disturbances in the thermoregulatory centre, most likely as a result of estrogen deficiency-related increase in central noradrenergic activity and reduced serotonergic activity. Therefore, we hypothesize that folic acid supplementation may ameliorate hot flushes by the same mechanism as estrogen replacement, i.e., by interacting with monoamine neurotransmitters in the brain; namely norepinephrine and serotonin. This article discusses the hypothesis and presents supportive preliminary data.