Gonadotrophin-releasing hormone agonist (GnRHa) has been commonly used for the medical treatment of prostate cancer, precocious puberty, endometriosis, adenomyosis and uterine leiomyomas. GnRHa therapy in cases of symptomatic uterine leiomyomas aims for the reduction of their size and remission of symptoms such as menometrorrhagia, causing a state of hypoestrogenemia. This is considered to be a helpful preoperative strategy in cases of large myomas, or anemia because of abnormal vaginal bleeding. The aim of this retrospective study was to examine the clinicopathological changes in uterine leiomyomas exposed to preoperative GnRHa therapy for two up to six months.The study group consisted of 10 premenopausal patients who were treated with GnRHa prior to surgery.In all cases the size of leiomyomas was reduced after GnRHa therapy. A microscopic review of the surgical specimens showed increased cellularity and ischemic type of necrosis.Morphological changes of uterine leiomyomas are often associated with preoperative GnRH agonist therapy. The differential diagnosis from uterine leiomyosarcomas includes absence of mitotic activity.

Up to 14 percent of women experience irregular or excessively heavy menstrual bleeding. This abnormal uterine bleeding generally can be divided into anovulatory and ovulatory patterns. Chronic anovulation can lead to irregular bleeding, prolonged unopposed estrogen stimulation of the endometrium, and increased risk of endometrial cancer. Causes include polycystic ovary syndrome, uncontrolled diabetes mellitus, thyroid dysfunction, hyperprolactinemia, and use of antipsychotics or antiepileptics. Women 35 years or older with recurrent anovulation, women younger than 35 years with risk factors for endometrial cancer, and women with excessive bleeding unresponsive to medical therapy should undergo endometrial biopsy. Treatment with combination oral contraceptives or progestins may regulate menstrual cycles. Histologic findings of hyperplasia without atypia may be treated with cyclic or continuous progestin. Women who have hyperplasia with atypia or adenocarcinoma should be referred to a gynecologist or gynecologic oncologist, respectively. Ovulatory abnormal uterine bleeding, or menorrhagia, may be caused by thyroid dysfunction, coagulation defects (most commonly von Willebrand disease), endometrial polyps, and submucosal fibroids. Transvaginal ultrasonography or saline infusion sonohysterography may be used to evaluate menorrhagia. The levonorgestrel-releasing intrauterine system is an effective treatment for menorrhagia. Oral progesterone for 21 days per month and nonsteroidal anti-inflammatory drugs are also effective. Tranexamic acid is approved by the U.S. Food and Drug Administration for the treatment of ovulatory bleeding, but is expensive. When clear structural causes are identified or medical management is ineffective, polypectomy, fibroidectomy, uterine artery embolization, and endometrial ablation may be considered. Hysterectomy is the most definitive treatment.

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.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).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.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.

To estimate the prevalence of endometrial polyps and to investigate associated abnormal uterine bleeding in a Danish population aged 20-74 years.This was a study of a random selection of women from the Danish Civil Registration System: 1660 women were invited of whom 686 were included (429 pre- and 257 postmenopausal). AUB was assessed by a validated questionnaire. The women underwent transvaginal sonography (TVS) and saline contrast sonohysterography (SCSH). Hysteroscopic resection was performed in cases with suspected focal intrauterine pathology. Full evaluation was performed in 619 women (two failures of TVS and 60 failures of SCSH, in two women SCSH was contraindicated (endometrial cancer), in two women hysteroscopy was contraindicated, and one polyp was lost before histology). World Health Organization histopathological criteria were used for diagnosing true endometrial polyps.On final diagnosis there were 48 women with polyps, eight with submucosal myomas, four with other benign findings and one with polypoidal growing endometrial cancer. Complex hyperplasia without atypia was diagnosed in two women with polyps. The prevalence of endometrial polyps was 7.8% (48/619; 95% CI, 5.6-9.9%). The prevalence was influenced significantly by age (P<0.005); in women below the age of 30 years, the prevalence was 0.9%. Polyps were diagnosed in 5.8% of pre- and 11.8% of postmenopausal women (P<0.01). Thirty-nine (82%) of the women who had histopathologically verified polyps were asymptomatic. In asymptomatic premenopausal women the prevalence of polyps was 7.6%, while it was 13% in asymptomatic postmenopausal women. AUB, in particular intermenstrual bleeding, was more frequent among women without polyps (38%). By ultrasound examination, submucosal myomas were diagnosed in 4.2% (26/622; 95% CI, 2.6-5.8%) and intramural myomas in 11.1% (76/684; 95% CI, 8.8-13.5%) of women. Polyps were diagnosed in 2% of oral-contraceptive and 25% of hormone-therapy users.The overall prevalence of endometrial polyps was 7.8% and the prevalence increased with age. Polyps were rare (0.9%) in women below the age of 30 years. Surprisingly, AUB was less frequent among women with polyps than among those without polyps.

The purpose of this study was to estimate the influence of alternatives to hysterectomy for abnormal uterine bleeding (AUB) on hysterectomy rates.Retrospective cohort study. Canadian Task Force II-2.University hospital.Premenopausal patients with AUB.Medical records of all premenopausal patients treated for AUB in our university clinic between January 1, 1995, and December 31, 2004, were reviewed. Patients were identified based on (specific) diagnostic and therapy codes used in the registry system of the hospital. The total number of placements of levonorgestrel-releasing intrauterine device (LNG-IUD), hysteroscopic surgery, and hysterectomies performed/year was estimated. In addition, the course of treatment of each patient was assessed.A total of 640 patients received surgery and 246 LNG-IUDs were placed. The proportion of endometrial ablations decreased significantly over time (p <.001), whereas hysteroscopic polyp or myoma removal (p =.030) and insertion of LNG-IUD (p <.001) both increased. The proportion of patients receiving hysterectomy for AUB as their first therapy decreased significantly (p =.005) from 40.6% to 31.4%, although the total number of patients receiving hysterectomy remained similar (p =.449). The 5-year intervention-free percentage for LNG-IUD was 70.6% (SD = 3.3%), for hysteroscopic polyp or myoma removal 75.5% (SD = 3.3%), and for endometrial ablation 78.0% (SD = 4.3%; p =.067).Despite the introduction of alternative therapies, the total hysterectomy rate in the management of AUB did not decrease in our clinic.

To evaluate diagnostic accuracy and timing of abnormal transvaginal ultrasonography for the recommendation of endometrial biopsy among premenopausal patients with abnormal uterine bleeding.Two-hundred and thirteen transvaginal ultrasonograms of premenopausal women with abnormal uterine bleeding were retrospectively evaluated.'Abnormal' ultrasonography was defined as either non-three-layer appearance during the proliferative phase or thickening > or =15 mm during the secretory/unknown phase. Findings were assessed on the basis of the histological diagnosis of the biopsies taken as the reference standard. Accuracy of the defined criteria with their likelihood ratio for detection of an endometrial disease was calculated.Abnormal histopathologic findings were detected in 147 (69%) of 213 patients. 'Abnormal' transvaginal ultrasonography criteria could detect disease states in 90.3% of patients with a sensitivity of 94.6% and a specificity of 77.2% (p<0.01). Sensitivity and specificity increased to 97.1 and 84.4% for ultrasonography conducted during the proliferative phase and were 60 and 61.9% for the secretory/unknown phase, respectively. Better results were clearly found for ultrasonograms obtained during the proliferative phase (p<0.01). The inclusion of post-biopsy proliferative phase transvaginal ultrasonography data of the following cycle resulted in a sensitivity of 95.2% and a specificity of 89.4%.The application of transvaginal ultrasonography using non-three-layer criteria is a highly accurate first step for the selection of premenopausal patients with abnormal uterine bleeding, which may reduce the number of unnecessary endometrial biopsies by approximately 25%. Proliferative phase evaluation is preferable.

To evaluate the efficacy, indication, and complication of microwave endometrial ablation (MEA) in treating abnormal uterine bleeding (AUB).One hundred and sixty-eight women with AUB due to benign causes received MEA treatment. Pre-operative endometrial thinning was carried out using uterine curettage. Then, the applicator radiating microwaves was moved by progressive withdrawal as well as "W" shape motion inside uterine cavity. All the patients were followed-up. The change of menstrual cycle, the amount of flow, dysmenorrhoea, anemia after treatment at 1, 3, 6, 12 and 24 months was recorded.The mean operating time was (286 +/- 75) seconds. Average follow-up time was (22 +/- 6, range 6-36) months. Of these patients, 156 women (92.9%) were premenopausal, 97 cases (62.2%) were amenorrhea, 56 cases (35.9%) were hypomenorrhoea or eumenorroea, and 3 cases (1.9%) had irregular bleeding. The overall satisfaction of this treatment reached 98.1% (153/156). The follow-up of 119 cases was up to 24 months after operation. The concentration of hemoglobin in 107 women with anemia increased significantly from (83 +/- 24) g/L to (117 +/- 18) g/L 3 months after operation (P < 0.01). Dysmenorrhoea was relieved in 74.5% (35/47) patients. No bleeding occurred in any one of 12 postmenopausal patients after MEA. There was no intraoperative complication in any case. The procedure was successful in all of 47 patients with severe medical disorders. After operation, 12 cases were complicated with endometritis, 2 with hematometra, and one case was performed with hysterectomy due to postablation tubal sterilization syndrome.MEA is a simple, safe and effective treatment of patients with abnormal uterine bleeding, especially suitable for those women associated with severe medical complications. Complete endometrial ablation is one of the most important determinants of treatment success. Stringent selection of patients may reduce the rate of complications.

To identify changes in expression of stimulatory and inhibitory factors when normal endometrium becomes menorrhagic.Retrospective blinded immunohistologic study.Private research center.Premenopausal and postmenopausal women with non-menorrhagic and menorrhagic endometrium undergoing curettage or hysterectomy were selected.Samples of endometrium were obtained from all patients.Expression of angiopoietins 1 and 2, and vascular receptors Tie-1 and Tie-2 and endothelial nitric oxide synthase (eNOS).Angiopoietin 1 (ANG-1) expression was similar in non-menorrhagic and menorrhagic endometrium. However, there was a significant increase in expression of ANG-2 and its receptor Tie-2 in menorrhagic tissues, which may be important in destabilizing the endometrial vasculature. Tie-1, responsible for endothelial integrity, was also increased in menorrhagic tissues, and is a likely compensatory mechanism for the existing vascular pathology. Expression of eNOS was also increased in menorrhagic women.Differences in the expression of ANG-2, Tie-2, Tie-1, and eNOS were found in menorrhagic endometrium, which may represent a new target for therapeutic intervention to correct menorrhagic conditions.

The aim of this observational clinical study was to evaluate the feasibility and diagnostic accuracy of outpatient diagnostic hysteroscopy in premenopausal patients suffering from abnormal uterine bleeding. Between September 1996 and September 1999, 819 patients were referred to our outpatient hysteroscopy clinic, 317 of which were premenopausal, and presenting with menstrual symptoms. All hysteroscopies were performed using a standard 30 degrees 5-mm hysteroscope, and the uterine cavity was generally distended with normal saline. Hysteroscopy was completed successfully in 305 cases (96.2%), but since the routine use of lidocaine spray in 1998 this figure increased up to 98.9%. Intrauterine pathology was diagnosed in almost 34% of patients, the most frequent being submucous myomas (14%) and endometrial polyps (14%); there was no case of endometrial cancer in this subset of patients. Moreover, there was an age-related distribution of intrauterine pathology, with the highest incidence in patients aged 41-50 years. Diagnostic hysteroscopy is a simple and safe technique, well accepted by the vast majority of patients; due to its excellent diagnostic accuracy, and its high success rate as an outpatient procedure, we wonder why inpatient D&C under general anesthesia is still regarded a diagnostic or even therapeutic option for patients with abnormal uterine bleeding.

To compare the diagnostic accuracy of transvaginal sonography (TVS) and saline infusion sonography (SIS) for detecting intracavitary abnormalities in premenopausal women with abnormal uterine bleeding.Consecutive premenopausal women who underwent hysterectomy for abnormal uterine bleeding were included. All women underwent TVS and SIS before their hysterectomy. The findings at TVS and SIS were compared with the findings of the hysterectomy specimen. Sensitivity, specificity, and likelihood ratios were calculated.The results of 50 patients with abnormal uterine bleeding were evaluated. Histological examination revealed normal endometrial histology in 27 patients, submucous myomas in 13 patients and intracavitary polyps in 10 patients. The sensitivity of TVS in directly visualizing intracavitary abnormalities was 61% for a specificity of 96%. The likelihood ratio of presence of an intracavitary abnormality was 16 and the likelihood ratio of absence of such a finding was 0.41. When defining abnormality at TVS as direct visualization of an intracavitary abnormality or an increased endometrial thickness (cut-off level 5 mm), the sensitivity of TVS was 87% for a specificity of 56%, with corresponding likelihood ratios of 2 and 0.23, respectively. The sensitivity and specificity of SIS was 100% and 85% with likelihood ratios of 6 and 0.0, respectively. No intracavitary abnormality was missed by SIS.The diagnostic accuracy of SIS is higher than the accuracy of TVS. A combined approach using endometrial thickness measurement by TVS and, reserving SIS for patients with increased (> 5 mm) endometrial thickness, or endometrium inadequately visualized on TVS, is the optimal method of reducing the hysteroscopy rate.