Abnormal Endometrial Histology Research Articles

Non-Sex Cord-Stromal Ovarian Tumors Frequently Produce and Secrete Estrogen in Postmenopausal Women: Impact on Bone Metabolism and Abnormal Endometrial Histology

We investigated whether the estrogen released from non-sex cord-stromal ovarian tumors has biological effects on bone and endometrial tissue in postmenopausal women. A total of 132 patients with malignant (n = 112) or benign (n = 20) gynecological disease with normal postmenopausal ovaries were recruited as a control group (group C). The 75 patients with ovarian tumors were divided into 2 groups: group L (serum estradiol [E2] level of < 20 pg/ml; n = 42) and group H (serum E2 level of > 20 pg/ml; n = 33). The subjects' serum E2 levels, bone mineral density, urinary levels of the N-telopeptide of type I collagen, and serum levels of bone-specific alkaline phosphatase were measured before and after surgery. Histological examinations of the endometrium were carried out in the 75 patients with non-sex cord-stromal ovarian tumors. High serum E2 levels were detected in 33 (44%) of 75 patients with ovarian tumors. The serum E2 levels of group H were significantly decreased after surgery. In the other subjects, there were no significant differences between the serum E2 levels observed before and after surgery. The mean preoperative N-telopeptide of type I collagen and bone-specific alkaline phosphatase levels of group H were significantly lower than those of group C. The bone mineral density values of groups L and H were significantly decreased after surgery. Five (6.7%) of 75 patients with non-sex cord-stromal ovarian tumors displayed abnormal endometrial histology, including 4 patients with grade 1 endometrioid cancer. The E2 released from ovarian tumors might have biological effects on bone metabolism and the incidence of abnormal endometrial histology.

Mifepristone for uterine fibroids.

Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU-486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre-menopausal women. We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre-menopausal women with confirmed uterine fibroids were included. Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta-analyses were performed using the fixed-effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I(2) = 0%). Three studies (Bagaria 2009; Engman 2009; Fiscella 2006) were included in the meta-analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) -0.02; 95% CI -0.38 to 0.41; 99 women).Two studies (Bagaria 2009; Fiscella 2006) were included in the meta-analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) -77.24; 95% CI -240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I(2) = 0%). Only one study (Bagaria 2009) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03).One study (Fiscella 2006) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid-specific quality of life. However, it was not found to reduce fibroid volume. Further well-designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids.

Endometrial Effects of Tibolone

The Tibolone Histology of the Endometrium and Breast Endpoints Study is a multicenter, randomized, double-blind study designed to address the conflicting reports in the literature about the endometrial safety of tibolone (1.25 or 2.5 mg/d). Tibolone was compared with continuous combined conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) (0.625 + 2.5 mg/d). Subjects were randomized in a 1:1:2 ratio to tibolone 1.25 mg/d, 2.5 mg/d, and CEE/MPA, respectively. The one-sided 95% confidence interval (CI) has been evaluated for the incidence of abnormal endometrial histology (hyperplasia or carcinoma) and hyperplasia and carcinoma separately for each of the two treatment groups and the treatment groups combined after 1 and 2 yr of treatment with tibolone, compared with CEE/MPA. A total of 3240 women were randomized, with 3224 receiving at least one dose of study medication. The incidence and upper one-sided 95% CI for the incidence of abnormal endometrium (hyperplasia or carcinoma), and hyperplasia and carcinoma separately, were calculated at end point, yr 1, and yr 2. The incidence (upper one-sided 95% CI) of abnormal endometrium at end point was 0.0 (0.5), 0.0 (0.4), and 0.2 (0.5) in the tibolone 1.25 mg, 2.5 mg, and CEE/MPA groups, respectively. During the entire treatment period, amenorrhea was reported more frequently with tibolone 1.25 mg (78.7%) and 2.5 mg (71.4%) than CEE/MPA (44.9%). The Tibolone Histology of the Endometrium and Breast Endpoints Study results confirm previous findings that tibolone does not induce endometrial hyperplasia or carcinoma in postmenopausal women, and it is associated with a better vaginal bleeding profile than CEE/MPA.

Endometrial evaluation with transvaginal ultrasound during hormone therapy: a prospective multicenter study

Objective To assess the value of endometrial thickness as a marker of endometrial abnormality risk during hormone therapy (HT) and to study the correlation between abnormal bleeding and abnormal endometrial histology in patients with thick endometrium. Design Prospective multicenter study. Setting University and general hospitals outpatient centers. Patient(s) Postmenopausal women (702) on HT. Intervention(s) Biendometrial thickness was measured by transvaginal sonography (TVS) between day 5 and day 10 after the last P intake and, when present, after the end of the menstrual-like bleeding. Main outcome measure(s) Hysteroscopy and biopsy were performed within 5 days from TVS on all patients with an endometrial thickness >4.5 mm (precision scale 0.5 mm). Result(s) Endometrial thickness >4.5 mm was observed in 20.5% of patients. One hundred sixteen hysteroscopies and biopsies were performed. Hyperplasia, polyps, and endocavitary fibroids were detected in 15%, 24%, and 8% of cases, respectively. The positive predictive value of TVS examination was 47%. Endometrial thickness was the only variable significantly and independently associated with histologic abnormalities and endocavitary fibroids. Abnormal bleeding occurred in 17.1% of patients. Among 17 patients detected with thick endometrium and hyperplasia, 8 cases showed abnormal bleeding. Conclusion(s) Sonographic endometrial thickness of 4.5 mm provides a sensitive tool to select HT patients who might benefit from hysteroscopy and biopsy. Abnormal bleeding is not a sensitive sign of hyperplasia in patients with thick endometrium.

Significant increase of benign endometrial cells on Papanicolaou smears in women using hormone replacement therapy

OBJECTIVE: To determine the prevalence of benign endometrial cells on Papanicolaou smears from postmenopausal women and to compare the prevalence and histologic diagnosis in women who use hormone replacement therapy (HRT) with those who do not. METHODS: Papanicolaou smear diagnoses from postmenopausal women and women over age 50 between April 1995 and December 1998 were retrieved and linked with follow-up smears and biopsies. Hormone status of women with benign endometrial cells smears was obtained from requisition forms or phone conversation with primary care providers. All surgical pathology material as well as Papanicolaou smears from women subsequently diagnosed with endometrial adenocarcinoma were reviewed. Relative prevalence with 95% confidence intervals was determined. RESULTS: A total of 589 of 52,662 Papanicolaou smears from postmenopausal women were diagnosed with benign endometrial cells, a prevalence of 1.1%. Also, HRT was reported in 16,073 (31%), no HRT was reported in 33,170 (63%), and hormone status was unknown in 3379 (6%). Smears from 245 HRT users, 324 nonusers, and 20 with unknown hormone status were diagnosed with benign endometrial cells. There was a significant increased prevalence of benign endometrial cells in women on HRT compared with nonusers (relative prevalence 1.56, 95% confidence interval 1.32, 1.84, P < .001). Among 436 women with known hormonal status and follow-up, 12 (2.7%) had endometrial carcinoma, three (1.5%) in HRT users and nine (3.7%) in nonusers ( P = .175). In addition, HRT users had significantly less abnormal endometrial histology than non-HRT users (2.6% versus 7.4%, P = .025). CONCLUSION: We found that HRT is significantly associated with an increased prevalence of benign endometrial cells on Papanicolaou smears. Women on HRT who have benign endometrial cells on their Papanicolaou smears, however, have less abnormal endometrial histology compared with women not using HRT who have benign endometrial cells on their Papanicolaou smears.

Exclusion of abnormal endometrial histology before balloon endometrial ablation: lessons to be learnt

Exclusion of abnormal endometrial histology before balloon endometrial ablation: lessons to be learnt

Risk Categories for Abnormal Endometrial Biopsy in Dysfunctional Uterine Bleeding

Objective: this study was designed to examine the clinical utility of risk factors for postmenopausal endometrial adenocarcinoma in predicting abnormal endometrial biopsy in premenopausal women diagnosed with dysfunctional uterine bleeding (DUB). The second purpose was to develop risk categories for abnormal endometrial biopsy in women with DUB.Design: prospective observational study.Setting: gynaecology department of a large teaching hospital.Population: women complaining of premenopausal abnormal gynaecological bleeding.Methods: women were included in the study if they experienced abnormal gynaecological bleeding due to either DUB or small fibroids. The risk factors for endometrial cancer that were tested included menstrual cycle irregularity, diabetes, nulliparity, hypertension, obesity (weight ≥ 100 kilograms or Body Mass Index > 33) and age ≥ 40 years. Logistic regression was used to investigate the relative importance of each risk factor.Main outcome measures : the correlation of abnormal endometrial histology with risk factors for endometrial cancer.Results: six hundred women were studied. Sixty-nine patients were excluded. The results from 531 patients with either DUB alone (467) or bleeding associated with small fibroids (64) were analysed. Thirty-four (6.4%) patients had abnormal endometrial biopsies. Menstrual cycle irregularity was the only statistically significant independent risk factor for an abnormal biopsy. No specific subtype of irregular menstrual pattern predicted an increased prevalence of abnormal endometrial biopsy.Conclusions: premenopausal women diagnosed with DUB whose menstrual cycles are regular have a negligible risk of developing endometrial hyperplasia, and can safely be spared the discomfort and risk of complications associated with endometrial biopsy.

Intravascular endometrial tissue in an ovary of a patient with abnormal endometrial histology

A case of ovarian intravascular endometrial tissue in a 46 yr old woman with a strong family history of endometrial carcinoma and abnormal endometrial histology is presented. The diagnosis was supported by histological and immunohistochemical findings. Although recognized at other sites, intravascular endometrial tissue has not been described previously in the ovary.

The diagnostic value and patient acceptability of outpatient endometrial sampling with Gynoscann.

Endometrial sampling with Gynoscann was performed in the outpatient department in 70 women with abnormal vaginal bleeding prior to dilatation and curettage (D&C). Successful endometrial sampling was achieved in 62 (89%) patients; Of the samples obtained 44 (71.0%) were adequate for cytological assessment and 46 (74.2%) for histological assessment, compared to 80% of D&C samples being adequate for histological examination. In those patients in whom outpatient endometrial sampling was adequate, both the cytological and histological diagnosis agreed with the D&C. The outpatient endometrial sampling was well tolerated by the patients since the majority (89%) experienced either no or little pain. Vaginal bleeding following the procedure was minimal in all except 1 patient. Endometrial sampling with Gynoscann may be useful for endometrial assessment prior to commencement of hormonal therapy and hysterectomy. It is a potentially useful screening test for early detection of endometrial cancer in patients at risk.

Endometrial histology after first trimester spontaneous abortion

The endometrial histology after spontaneous abortion was investigated by performing an endometrial biopsy in the two menstrual cycles subsequent to miscarriage in 12 women. In the first cycle, 66% (8/12) of the biopsies had the following abnormalities: (1) proliferative endometrium (n = 4), (2) proliferative glands and decidualized stroma (n = 1), (3) endometritis (n = 1), and (4) luteal insufficiency (n = 2). In the second cycle, 20% (2/10) of the biopsies demonstrated luteal insufficiency. Forty-five percent (10/22) of the first two cycles after spontaneous abortion demonstrated abnormal endometrial histology, with the first appearing more abnormal than the second (P = 0.06). Two conceptions occurred during the study period; both were uneventful term pregnancies. These findings suggest that a large proportion of the first two menstrual cycles after spontaneous abortion and curettage are abnormal, with the first cycle being more frequently abnormal than the second.

Endometrial inadequacy after treatment with human menopausal gonadotropin/human chorionic gonadotropin

The incidence of abnormal endometrial histology in patients undergoing human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) treatment during cycles of in vitro fertilization (IVF) or gamete intrafallopian transfer has been reported to be 52% to 91%. The incidence of endometrial inadequacy, as judged by a single late luteal endometrial biopsy, has not been studied in hMG/hCG non-IVF cycles. In the current study, 30 patients (30 cycles) undergoing hMG/hCG treatment were evaluated by an endometrial biopsy. The incidence of endometrial inadequacy was found to be 27%. No preovulatory predictors for endometrial inadequacy could be identified. Therefore, luteal support for patients undergoing non-IVF hMG/hCG cycles should be considered.

In vitro fertilization: the degree of endometrial insufficiency varies with the type of ovarian stimulation

Fifty-eight patients in an in vitro fertilization program who did not have embryo transfers had endometrial biopsies performed on the second day after ovulation. The patients had been stimulated with clomiphene citrate (CC) and human chorionic gonadotropin (hCG) (group I); with CC, human menopausal gonadotropin (hMG), and hCG (group II), or with hMG and hCG (group III). Only 17 patients (30%) showed a normal luteal phase histology. The remaining 41 patients (70%) showed variety of endometrial abnormalities. Patients stimulated with hMG and hCG (group III) had a normal luteal phase at a significantly higher rate (48% versus 16%). Women below the age of 35 had a significantly higher rate of normal luteal phase histology than women older than 35 years. The study establishes abnormal endometrial histology as a possible cause of the low pregnancy rate of in vitro fertilization. The degree of endometrial histologic abnormality varies considerably with the type of ovarian stimulation used.

Malignant Brenner tumour presenting with lower motor neurone paralysis

SummaryBrenner tumours form only 1•5 to 2•5 per cent of ovarian tumours and are rarely malignant. Their origin is uncertain although the concensus is that they arise from coelomic surface ovarian epithelium. Malignancy may be defined by criteria laid down by Hull and Campbell (1973). Benign tumours often present as a silent mass, most frequently in the fourth, fifth and sixth decades (Fox, 1972). An association with oestrogen production has been postulated, in relation to the coincidental finding of abnormal endometrial histology (Idelson, 1963). Mucinous and serous cystadenomas occur more often when a Brenner tumour is present (Silverberg, 1971). Extensive calcification has been seen in up to 50 per cent of cases.