Aromatase inhibitor “letrozole” versus progestin “norethisterone” in women with simple endometrial hyperplasia without atypia: A prospective cohort trial

ObjectiveTo evaluate the effectiveness of the aromataze inhibitor “letrozole” to progestin “norethisterone” for women with simple endometrial hyperplasia without atypia.Subjects and methodsOne hundred women with a histo-pathological diagnosis of simple endometrial hyperplasia without atypia were divided into two groups: Groups A and B. Group A included 50 patients who received a daily 5 mg dose of letrozole for three successive months. Group B included the other 50 patients who received norethisterone 10 mg daily by non-stop regimen for 3 months. All patients in both groups were reevaluated after treatment. Women diagnosed with progressive or persistent endometrial hyperplasia at the second curettage were asked to continue on the same medication for another 3 months. Transvaginal sonography as well as serum estradiol level measurement were performed before the start of treatment and 3 months after treatment.ResultsDespite that there was no statistically significant difference between the two groups as regards the proportion of women whose endometrial sample revealed resolution, regressing or persistence after 3 months of treatment. However, endometrial thickness was significantly thinner in women who received letrazole than in women who received norethisterone (mean difference 0.12 mm, 95% CI: 0.22–0.01, P = 0.02). Serum E2 level was significantly lower in the Group A compared to Group B (mean difference 9.1 pg, 95% CI: 13.74–4.45, P < 0.001).ConclusionLetrozole is as effective as norethisterone for women with abnormal uterine bleeding due to endometrial hyperplasia without atypia.     

Endometrial hyperplasia with secretory changes

OBJECTIVE: Secretory changes in endometrial hyperplasia are uncommon. The aim of this study is to review the morphologic and clinical findings of 24 cases of endometrial hyperplasia with secretory changes. METHODS: In 24 patients diagnosed with endometrial hyperplasia with secretory changes during 6 years, clinical characteristics such as menopausal status and hormone treatment were correlated with morphological features. A matched age control group of 24 women with conventional endometrial hyperplasia was used to compare the hormonal effect. RESULTS: Nineteen patients were premenopausal. Nine women showed simple hyperplasia without atypia and 15 complex hyperplasia, 7 of them with atypia. Seventeen women were under hormonal treatment at the time of diagnosis, 10 of them with progestins. In 7 patients endometrial adenocarcinoma could be seen, 5 coexisting with endometrial hyperplasia with secretory changes and in 2 appearing after 1 and 4 months. In control group only 2 patients were undergoing progestin hormonal treatment. CONCLUSIONS: Secretory changes can be found in hyperplastic endometrium, particularly in premenopausal women under hormonal treatment with progestins, with the risk of misdiagnosis.     

Serum and tissue angiogenin in patients with endometrial hyperplasia

ObjectiveTo evaluate angiogenin levels in both tissue and serum of patients with endometrial hyperplasia with and without atypia.MethodsSixty women were classified according to the histopathological findings of endometrium into three groups. The control group consisted of 20 women with normal non-hyper plastic endometrium. The second group included 20 women diagnosed as complex endometrial hyperplasia without atypia. The third group included 20 women diagnosed as complex endometrial hyperplasia with atypia. Serum and tissue angiogenin were measured by enzyme immunoassay (EIA) technique and confirmed in tissues with Western Blotting (WB) technique.ResultsThere was a statistically significant increase in serum and tissue angiogenin levels of endometrial hyperplasia groups compared to those of control group (P<0.001). Serum and tissue angiogenin levels were with a statistically significant higher (P<0.001) in group III compared to group II. The sensitivity of serum angiogenin to detect the potential possibility of endometrial hyperplasia with atypia in endometrial hyperplasia patients was 100%, specificity 85%, positive predictive value 86.9%, negative predictive value 100%, positive likelihood ratio 6.6%, negative likelihood ratio 0% and accuracy 91.7%.ConclusionElevated levels of serum angiogenin in endometrial hyperplasia could assist in determining which patients are at high risk for atypical change requiring aggressive treatment.     

不孕症合并子宫内膜非典型增生患者助孕治疗的临床分析

目的探讨不孕症合并子宫内膜非典型增生患者经保守治疗后助孕治疗的疗效和安全性。方法回顾性分析8例不孕症合并子宫内膜非典型增生患者，经孕激素或促性腺激素释放激素激动剂（GnRHa）治疗子宫内膜非典型增生缓解后，采用助孕治疗，观察助孕治疗的疗效及其对子宫内膜的影响。结果经孕激素或GnRHa治疗后，8例患者子宫内膜非典型增生全部缓解。共进行单纯促排卵治疗7个周期，促排卵联合人工授精2个周期，体外受精-胚胎移植（IVF—ET）7个周期，冻融胚胎移植2个周期。单纯促排卵周期均未妊娠，人工授精1个周期双胎妊娠；7个IVF—ET周期中，胚胎移植6个周期，3个周期获得临床妊娠；冻融胚胎移植1个周期获得临床妊娠。现足月分娩6活婴。1例未妊娠患者在促排卵后4个月发现子宫内膜癌变。结论不孕症合并子宫内膜非典型增生的患者经孕激素或GnRHa治疗缓解后，及时助孕治疗能提高妊娠率，但需严密观察，注意子宫内膜癌发生的可能。     

Implementation of assisted reproductive technologies following conservative management of FIGO grade I endometrial adenocarcinoma and/or complex hyperplasia with atypia

OBJECTIVE: The objective was to report a series of infertility therapy outcomes following conservative management of endometrial adenocarcinoma and/or complex hyperplasia with atypia. METHODS: A retrospective review of the University of Iowa assisted reproductive technology database was performed. All women presenting with International Federation of Obstetrics and Gynecology (FIGO) grade I uterine adenocarcinoma and/or complex hyperplasia with atypia were assessed for type and duration of medical management, initial, interim treatment, and preinfertility treatment endometrial biopsy (BX) findings. Assessment of infertility treatment outcomes and postinfertility endometrial biopsy findings were performed. All of the pathology samples were re-reviewed at the Gynecologic Oncology Tumor Board to confirm the diagnosis by a pathologist with a particular expertise in gynecologic pathology. RESULTS: Four infertile women, three nulligravid and one primigravid, were evaluated with the diagnosis of FIGO grade 1 endometrial adenocarcinoma and/or complex hyperplasia with atypia desiring to preserve fertility. Two women with FIGO grade 1 endometrial adenocarcinoma were successfully treated with high-dose progestational agents resulting in normal proliferative endometrium. In addition, both women with complex hyperplasia with atypia were successfully treated with progestins and/or ovulation induction. Successful pregnancy outcomes were achieved for three of the four women with assisted reproductive technology. A total of five successful pregnancies and eight healthy live-born infants were achieved among three women. One of the four women was unable to conceive despite three cycles of in vitro fertilization. Hysterectomy was performed for recurrent complex hyperplasia with atypia. In our series, we found it can take 3-10 months (mean, 6.25 months; median, 6 months) to obtain benign endometrium preceding infertility therapy. CONCLUSION: This report demonstrates that conservative management of well-differentiated endometrial adenocarcinoma and/or complex hyperplasia with atypia followed by aggressive assisted reproduction is an option to highly motivated and carefully selected women.     

Risk factors for atypical endometrial hyperplasia in infertile women:possible association with polycystic ovarv syndrome

Objective：Endometrial hyperplasia is considered as a precursor of endometrial carcinoma, in which oncogenic potential is low in hyperplasia without atypia, but high in atypical hyperplasia. The objective of this study was to identify the risk factors for atypical endometrial hyperplasia in infertile women. Methods：Fifty four infertile women with endometrial hyperplasia,which were selected from a large cohort of 2 098 women who desired for the future childbearing in our center, were diagnosed by hysteroscopy with directed biopsies or dilation and curettage （D＆C）, including 44 with hyperplasia without atypia, 10 with atypical hyperplasia. Clinical characteristics were recorded in terms of age, body mass index （BMI）, parity, insulin resistance, polycystic ovary syndrome （PCOS）. Statistical comparison was made between women with hyperplasia without atypia and atypical hyperplasia. Logistic regression analysis was employed to assess the contribution of PCOS, obesity and insulin resistance to atypical hyperplasia. Results：The incidence of endometrial hyperplasia in infertile women was 2.57 % （54/2098） , which included 10 women （0.48%） were diagnosed as atypical hyperplasia. PCOS in women with atypical hyperplasia （70% ,7/10） was significantly higher than those of hyperplasia without atypia （27.27% , 12/44 ）. Stepwise regression analysis showed that PCOS contributed maximally to atypical endometrial hyperplasia in infertile women. Conclusion：PCOS is an independent risk factor for atypical endometrial hyperplasia in women with infertility. The infertile women with PCOS are at an increased risk for atypical endometrial hyperplasia and endometrial cancer.     

Resectoscopic surgery in 10 women with abnormal uterine bleeding and atypical endometrial hyperplasia

STUDY OBJECTIVE: To evaluate the role of the resectoscope in the diagnosis and treatment of women with abnormal uterine bleeding (AUB) and atypical endometrial hyperplasia. DESIGN: Retrospective case series (Canadian Task Force classification III-3). SETTING: University-affiliated teaching hospital. PATIENTS: Ten women. Intervention. Hysteroscopic evaluation after preoperative endometrial biopsy indicated simple hyperplasia without atypia, complex hyperplasia with atypia, or inadequate specimen. MEASUREMENTS AND MAIN RESULTS: Atypical hyperplasia was confirmed in eight patients after total endomyometrial resection. Hysterectomy was offered to all patients but accepted by only two: one for bilateral ovarian serous cystadenomas and the second for a granulosa cell ovarian tumor. No residual endometrium was found in hysterectomy specimens. Seven women were amenorrheic and well 1 to 9 years after resection. An additional patient with amenorrhea died from colon cancer 2 years after resection. CONCLUSION: Resectoscopic surgery confirmed or detected atypical endometrial hyperplasia in eight women and excluded it in two patients with AUB and a previous diagnosis of simple hyperplasia, atypical hyperplasia, or inadequate specimen. Skillful resectoscopic surgery may be an alternative to hysterectomy in selected patients with atypical hyperplasia who are compliant with regular and long-term follow-up.     

Descriptive epidemiology of endometrial hyperplasia in patients with abnormal uterine bleeding

PURPOSE OF INVESTIGATION: To evaluate the prevalence and epidemiologic characteristics of endometrial hyperplasias in women with abnormal uterine bleeding. METHODS: We performed a retrospective analysis on data gained from 294 patients with histologically documented endometrial hyperplasia (with or without atypia), detected among 1,469 women who underwent fractional dilatation and curettage in our department due to abnormal uterine bleeding from 1986 to 1998. Epidemiologic characteristics were abstracted from the patients' medical charts. RESULTS: 294/1469 women were found with endometrial hyperplasia (258 without atypia and 36 atypical hyperplasias). Thirty-six of them were under 40 years of age. Four of the detected endometrial hyperplasias progressed to endometrial carcinoma (one with simple hyperplasia, two with complex and one with atypical hyperplasia). Obesity and hypertension were justified as risk factors in our study population. CONCLUSIONS: The prevalence of endometrial hyperplasia according to our data was 20%. There were statistically significant differences in most epidemiologic parameters between the two types of hyperplasia. The progression of four endometrial hyperplasias to endometrial adenocarcinoma indicates the need for intense follow-up even in cases where patients undergo conservative therapy.     

Endometrial hyperplasia: a review

Endometrial hyperplasia is a precursor to the most common gynecologic cancer diagnosed in women: endometrial cancer of endometrioid histology. It is most often diagnosed in postmenopausal women, but women at any age with unopposed estrogen from any source are at an increased risk for developing endometrial hyperplasia. Hyperplasia with cytologic atypia represents the greatest risk for progression to endometrial carcinoma and the presence of concomitant carcinoma in women with endometrial hyperplasia. Abnormal uterine bleeding is the most common presenting symptom of endometrial hyperplasia. Specific Pap smear findings and endometrial thickness per ultrasound could also suggest the diagnosis. Unopposed estrogen in women taking hormone replacement therapy increases the risk of endometrial hyperplasia. Tamoxifen has demonstrated its efficacy in treating women at risk for breast cancer, but it increases the risk of endometrial hyperplasia. The choice of treatment for endometrial hyperplasia is dependent on patient age, the presence of cytologic atypia, the desire for future childbearing, and surgical risk. Endometrial hyperplasia without atypia responds well to progestins. However, women with atypical hyperplasia should be treated with hysterectomy unless other factors preclude surgery. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe the definition and classification of endometrial hyperplasia, to outline the clinical features of a patient with endometrial hyperplasia, to point out the natural history of endometrial hyperplasia, and to summarize the diagnostic options for patients with endometrial hyperplasia.     

Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women

The endometrial histology and endocrinologic and demographic characteristics of 556 asymptomatic postmenopausal women ,who attended the menopause outpatient clinic at Ankara Numune Education and Research Hospital were studied before initiating estrogen replacement therapy. Of these women ,486 (87.4%) had atrophic endometrium ,37 (6.65%) had proliferative endometrium ,27 (4.86%) had endometrial hyperplasia without atypia ,three (0.54%) had endometrial hyperplasia with atypia and three (0.54%) had endometrial adenocarcinoma on their biopsy specimens. When demographic characteristics of the patients were considered, we found that the patients with endometrial adenocarcinoma and endometrial hyperplasia with atypia had potential risk factors for endometrial pathology such as chronic anovulation ,diabetes or hypertension. This study confirms that routine endometrial sampling in asymptomatic postmenopausal women is not warranted ,but patients with associated risk factors should be screened for endometrial pathology before starting estrogen replacement therapy.     

Endometrial patterns and endocrinologic characteristics of asymptomatic menopausal women.

The endometrial histology and endocrinologic and demographic characteristics of 556 asymptomatic postmenopausal women, who attended the menopause outpatient clinic at Ankara Numune Education and Research Hospital were studied before initiating estrogen replacement therapy. Of these women, 486 (87.4%) had atrophic endometrium, 37 (6.65%) had proliferative endometrium, 27 (4.86%) had endometrial hyperplasia without atypia, three (0.54%) had endometrial hyperplasia with atypia and three (0.54%) had endometrial adenocarcinoma on their biopsy specimens. When demographic characteristics of the patients were considered, we found that the patients with endometrial adenocarcinoma and endometrial hyperplasia with atypia had potential risk factors for endometrial pathology such as chronic anovulation, diabetes or hypertension. This study confirms that routine endometrial sampling in asymptomatic postmenopausal women is not warranted, but patients with associated risk factors should be screened for endometrial pathology before starting estrogen replacement therapy.     

Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects

OBJECTIVE: To investigate the short-term hormonal and clinical effects of the aromatase inhibitor letrozole (Femara) in patients with endometrial cancer. MATERIALS AND METHODS: Ten previously untreated, post-menopausal patients (mean age 59 years) with endometrial cancer, predominantly stage I disease, received letrozole 2.5mg per day for 14 days before surgery. Clinical, sonographic, morphologic, cytologic, and hormonal-metabolic parameters (blood estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and cholesterol by radioimmunoassay, enzyme immune assay, or enzyme-colorimetric methods; tumor progesterone receptors by ligand-binding assay; and aromatase activity by 3H-water release assay) were evaluated before and after treatment. RESULTS: Treatment was well-tolerated in all patients. In two patients, pain relief in the lower part of the belly and/or decrease in intensity of uterine discharge was reported. In the three cases, substantial decreases in endometrial M-echo (ultrasound) signal were noted; the mean value of this parameter after treatment was 31.1% lower than before treatment. Blood estradiol concentration decreased by an average of 37.8% after letrozole therapy, and tumor progesterone receptor levels and aromatase activity decreased by 34.4 and 17.5%, respectively. Treatment with letrozole did not influence surgery. CONCLUSIONS: These data show that short-term treatment with letrozole in the neoadjuvant setting resulted in some positive clinical changes. Longer-term and larger-scale trials of neoadjuvant letrozole in endometrial cancer are warranted.     

The management of endometrial hyperplasia: an evaluation of current practice

OBJECTIVE: To identify current management practices and evaluate subsequent outcomes of treatment for women diagnosed with endometrial hyperplasia. STUDY DESIGN: All women with a histological diagnosis of endometrial hyperplasia at the Birmingham Women's Hospital were identified between October 1998 and September 2000. A retrospective case note review was performed for each woman using a standardised data abstraction sheet. Baseline characteristics including clinical presentation and treatment strategy were obtained. Results of subsequent endometrial tissue examinations were used to assess histological response to treatment and the need and indication for hysterectomy was used to assess clinical response. RESULTS: There were 351 women diagnosed with endometrial hyperplasia during the study period of which 84% presented with symptoms of abnormal uterine bleeding and 54% were postmenopausal. Complex endometrial hyperplasia was the most common diagnosis accounting for 60% of all cases. Eighty percent of women with atypical endometrial hyperplasia were treated by hysterectomy compared with 30% without evidence of cytological atypia (relative hysterectomy rate of 2.6, 95% CI 2.0-3.3). Hysterectomy was avoided in 138/172 (80%, 95% CI 74-86%) women managed conservatively during the study period. Overall 35/108 (36%, 95% CI 27-46%) of women managed conservatively had persistent or progressive disease identified (mean follow up 36 months). 20/143 (14%) women initially diagnosed with endometrial hyperplasia who subsequently underwent hysterectomy were found to have endometrial cancer, the majority of whom had been diagnosed with atypical disease (14/20, 70%). CONCLUSION(S): The majority of women with atypical endometrial hyperplasia were managed by hysterectomy and the substantial risk of diagnostic under-call supports this approach to treatment. In contrast, there is no consensus regarding the initial management of women with endometrial hyperplasia without cytological atypia.     

A comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on superovulation in Asian women with normal ovulatory cycles

OBJECTIVE: To compare the effect of the aromatase inhibitor letrozole and clomiphene citrate (CC) on superovulation in women with normal ovulation. METHODS: A cross-over randomized study of 22 women with normal ovulation, divided randomly into two equal cohorts, was carried out. Each group of 11 women was randomly allocated to take letrozole or CC for one cycle. After washing out for one cycle, the alternative drug was administered in the subsequent cycle. The number and size of mature follicles, endometrial thickness, and estradiol and progesterone levels were monitored. RESULTS: The number of mature follicles and estradiol levels on ovulation day were significantly lower in the letrozole group than the CC group (p < 0.05 for both). However, no differences between the two groups in endometrial thickness and pattern were observed. Progesterone levels showed ovulation in all cycles. CONCLUSIONS: The administration of 50 mg CC on days 3-5 was superior to 2.5 mg letrozole for superovulation induction in women with normal ovulation.     

The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a,and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/β-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100?mg CC or 5?mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.     

Endometrial abnormalities in infertile women

OBJECTIVE: To analyze retrospectively the frequency, long-term prognosis and pregnancy rate in infertile women diagnosed with endometrial hyperplasia or carcinoma by endometrial biopsy. STUDY DESIGN: From 1989 to 2000, endometrial biopsies were performed on 2,573 patients to investigate the cause of infertility. The main outcome measures were frequency, long-term prognosis and pregnancy rate for patients with each type of endometrial abnormality. RESULTS: Twenty-four patients (0.93%) were diagnosed with an endometrial abnormality. Of them, 10 were diagnosed with simple hyperplasia, 7 with complex hyperplasia, 3 with complex hyperplasia with atypia and 4 with endometrial carcinoma. All 4 patients (0.16%) with endometrial carcinoma were infertile as a result of complications arising from polycystic ovary syndrome. Two of them underwent hysterectomies. High-dose medroxyprogesterone acetate therapy combined with assisted reproductive technology resulted in pregnancy in 1 of the 2 patients with endometrial carcinoma. CONCLUSION: Of infertile women, 0.93% have endometrial abnormalities, and those with polycystic ovary syndrome have a high risk of endometrial carcinoma. Assisted reproductive technology combined with high-dose medroxyprogesterone acetate may be effective means of overcoming infertility, allowing women with endometrial carcinoma to readily achieve pregnancy.     

Successful pregnancy in an infertile woman with endometrial hyperplasia and embryo transfer. A case report

BACKGROUND: Successful pregnancy in a woman with complex endometrial hyperplasia with atypia was treated conservatively with gestagens. CASE: The patient was initially diagnosed with complex hyperplasia of the endometrium with atypia by endometrial curettage and treated with several cycles of different gestagens. After repeated endometrial curettage, in vitro fertilization and embryo transfer were introduced for immediate treatment of the patient's infertility in order to avoid the risk of recurrent hyperplasia of the endometrium from estrogens. A single pregnancy was achieved after transfer of embryos obtained from intracytoplasmic sperm injection. This was performed due to poor semen characteristics. The patient delivered a normal, healthy male infant at term. CONCLUSION: Conservative treatment of complex endometrial hyperplasia with atypia in young women wishing to preserve fertility should be considered in carefully selected cases.     

Resectoscopic surgery in women with abnormal uterine bleeding and nonatypical endometrial hyperplasia

STUDY OBJECTIVE: To evaluate the role of resectoscopic surgery in the diagnosis and treatment of women with abnormal uterine bleeding and endometrial hyperplasia without atypia. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated teaching hospital. PATIENTS: Twenty-five women with simple and seven with complex hyperplasia. INTERVENTION: Hysteroscopic endometrial ablation. MEASUREMENTS AND MAIN RESULTS: In patients with simple hyperplasia, average age, parity, body mass index, and mean arterial pressure were 53.2 years, 2.4 pregnancies, 30 kg/m2, and 99.5 mm Hg, respectively; in those with complex hyperplasia corresponding figures were 48 years, 2 pregnancies, 36 kg/m2, and 100 mm Hg. Nineteen of 32 women had postmenopausal bleeding, 9 of whom were taking combined hormone replacement therapy. Two had subsequent hysterectomies, one for pain and the other for incomplete resection due to an enlarged uterus. Resection could not be completed in one morbidly obese woman. One patient died from heart disease. During the follow-up of 1 to 8 years (mean 4 yrs) all patients remained amenorrheic with no evidence of recurrent disease or progression to cancer. CONCLUSION: Resectoscopic surgery by experienced hysteroscopists may be effective therapy for endometrial hyperplasia without atypia, especially in women at high risk for medical therapy or hysterectomy. Patient surveillance is mandatory for early detection and management of recurrent disease and progression to cancer.     

Histopathologic correlation of dilatation and currettage and hysterectomy specimens in patients with postmenopausal bleeding

PURPOSE OF INVESTIGATION: To evaluate the consistency of preoperative and postoperative histopathological findings in postmenopausal patients with abnormal bleeding. METHODS: Pathologic diagnoses of 42 postmenopausal women with abnormal bleeding or increased endometrial thickness who underwent both dilatation and curettage (D and C), and hysterectomy for proper indications were retrospectively examined. RESULTS: The most common diagnosis was irregular proliferative endometrium in both the pre- and postoperative groups with 16 patients each (38%). After subgroup analysis, 50% of the patients with a preoperative diagnosis of complex hyperplasia without atypia, had complex atypical hyperplasia, and two-thirds of the patients with a preoperative diagnosis of complex atypical hyperplasia had endometrial cancer as the final diagnoses. CONCLUSION: Preoperative D and C endometrial pathology findings positively correlated with postoperative hysterectomy pathology results. However, as the real pathology gets worse , D and C seems to under-diagnose the real pathology. In cases with complex hyperplasia with or without atypia , a second D and C or hysteroscopic evaluation may be recommended.     

Unopposed estradiol therapy in postmenopausal women: results from two randomized trials

OBJECTIVE: To estimate the rates of endometrial hyperplasia, bleeding episodes, and interventions among menopausal women receiving unopposed oral estradiol or placebo therapy with ultrasound monitoring over 3 years. METHODS: Two-hundred eighteen healthy women with intact uteri enrolled in the Estrogen in the Prevention of Atherosclerosis Trial (EPAT) or the Women's Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial (WELL-HART) were randomly assigned to either 1 mg of micronized 17beta-estradiol (n=96) or placebo (n=122) daily for up to 3 years in a double-blind fashion. Patients were followed with annual measurement of endometrial thickness using transvaginal ultrasonography. Logistic regression was used to identify predictors of uterine bleeding and endometrial biopsy. RESULTS: Over the study periods, nine women (9.4% of patients, 95% confidence interval [CI] 3.6-15.2%) in the estradiol group developed hyperplasia. Eight of the nine cases (88.9%) of hyperplasia were simple without atypia. Women receiving estradiol were more likely than those receiving placebo to have at least one episode of uterine bleeding (67% versus 11% at 3 years, respectively, P<.001). Women in the estradiol group were also more likely to have an endometrial biopsy (48% versus 4% at 3 years, P<.001). Among women on estradiol, obesity (body mass index [BMI] greater than 30 kg/m(2)) significantly increased the odds of uterine bleeding compared with normal-weight patients (BMI 25 or less) (OR 3.7, 95% CI 1.2-11.8). CONCLUSION: Short-term, unopposed estradiol therapy with gynecologic monitoring may be an option for the treatment of menopausal symptoms. Menopausal women choosing estradiol therapy, especially if obese, should anticipate uterine bleeding and the possibility of an endometrial biopsy. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, www.clinicaltrials.gov, NCT 00000559 and NCT 00115024. LEVEL OF EVIDENCE: I.