Sangrado y terapia hormonal en la menopausia (THM) / Bleeding during menopause hormone therapy (MHT)

La definición de sangrado ginecológico anormal durante terapia hormonal de la menopausia es aquel sangrado no programado durante el uso de la terapia. Este artículo es un pauteo que describe: 1) cuándo diagnosticar unsangrado anormal, ya que difiere según el tipo de esquema hormonal utilizado; 2) eldiagnóstico diferencial del origen del sangrado anormal; 3) los métodos de evaluación para diagnosticar el origen del sangrado. Se destacan los aspectos principales para el diagnóstico diferencial entre patología orgánica versus disrupción endometrial debida al tratamiento hormonal. Además, se describen los ajustes posibles para resolver el sangrado cuando éste se debe a disrupción del endometrio.

Abnormal bleeding related to menopausal hormone therapy is defined as unscheduled bleeding during the use of the therapy. This article outlines when to diagnose an abnormal bleeding -as this differs according to the type of hormonal scheme used-, the differential diagnosis of the origin of abnormal bleeding, and the methods of evaluation to assess the origin of the bleeding. The main aspects are highlighted on the differentiation of organic pathology versus disruption of the endometrium due to treatment. Also, treatment adjustments to resolve bleeding when it is due to disruption of the endometrium are outlined.

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice

To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. METHODS: BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. RESULTS: Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. CONCLUSION: There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.(AU)

[Incidence of endometrial cancer in patients with biopsy specimens of endometrial hyperplasia]. / Incidencia de cáncer de endometrio en pacientes con biopsia preoperatoria de hiperplasia endometrial.

BACKGROUND: According to the Histopathological Registry of Malignant Neoplasms in Mexico, endometrial cancer ranks third gynecological cancers after cervical cancer and ovarian cancer. In 2003 represented 2.16% of all female cancers and in 2007 was the cause of 2.8% of hospital discharges nationwide cancer. OBJECTIVE: To determine the possibility of coincidence of endometrial cancer in biopsy specimens of patients with endometrial hyperplasia. MATERIAL AND METHODS: We analyzed patients who underwent hysterectomy for hyperplasia preoperative biopsy between January 2007 and October 2008. RESULTS: We found 86 patients with biopsy specimens of hyperplasia who underwent hysterectomy, hyperplasia was confirmed in 70 (group A) and endometrioid endometrial cancer reported in 16 (group B). We found cancer in 2 of 61 patients with simple hyperplasia without atypia (3.2%), none of the 6 patients with atypical hyperplasia was found simple cAncer (0%) and 19 patients with complex hyperplasia with atypia was documented EC 14 (73.68%). Patients in group B are older vs 51.3 44.4 years, have a lower number of pregnancies 2.6 vs 3.1 and have a higher body mass index 34.71 vs 29.05 than group A. CONCLUSION: The percentage of agreement between complex endometrial hyperplasiaand endometrial cancer is the highest reported in the literature. Endometrial biopsy in our hospital has low sensitivity for predicting coexistence between complex endometrial hyperplasia and CE. Patients with endometrial biopsy complex endometrial hyperplasia associated with BMI greater than 30 and age over 50 years are at high risk for having coexistence with endometrial cancer. For the high frequency of coexistence with cancer, patients with preoperative biopsy complex endometrial hyperplasia should undergo hysterectomy with frozen section of the uterus to avoid reoperation in case of malignancy.

Validation of hysteroscopic view in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding.

STUDY OBJECTIVE: To validate hysteroscopic view with histology in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding (AUB) DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: University teaching hospitals in Rio de Janeiro and São Paulo, and private office in Rio de Janeiro. PATIENTS: Four thousand and fifty-four patients with AUB in whom hysteroscopic views were complete and the histologic result was conclusive. INTERVENTION: Four thousand and fifty-four office hysteroscopies with complete views and conclusive histologic results. The material for histologic examination was obtained through biopsy of the lesion in an outpatient unit or through the resection of the entire lesion in patients who underwent surgery. Histology was considered the "gold standard" and compared with the hysteroscopic view. MEASUREMENTS AND MAIN RESULTS: In the histology of the 4054 examinations, 613 (15.2%) were endometrial hyperplasia, and 105 (2.6%) were endometrial cancer. The most frequent hysteroscopic finding was endometrial polyps (31.2%). In endometrial hyperplasia, the sensitivity of the hysteroscopic view was 56.3% (95% CI 52.2%-60.2%), specificity was 89.1% (95% CI 88.0%-90.1%), positive predictive value (PPV) was 48.0% (95% CI 44.3%-51.7%), negative predictive value (NPV) was 92.0% (95% CI 90.1%-92.9%), and accuracy was 72.7% (95% CI 70.7%-74.7%). Accuracy was defined as the proportion of correct results among the hysteroscopic examinations. In endometrial cancer, the sensitivity of the hysteroscopic view was 80.0% (95% CI 71.1%-87.2%), specificity was 99.5% (95% CI 99.2%-99.7%), PPV was 81.5% (95% CI 72.7%-88.5%), NPV was 99.5% (95% CI 99.2%-99.7%), and accuracy was 89.8% (95% CI, 85.9%-93.6%). In the 814 patients (20.0%) in whom the hysteroscopic view was normal, there were no false negatives for endometrial cancer; however, there were 37 (4.5%) false negatives for endometrial hyperplasia. In the histologic cases of endometrial cancer, 101 (96.2%) hysteroscopic views were compatible with cancer or hyperplasia (80.0% and 16.2%, respectively). Ninety-seven out of 103 hysteroscopic views with cancer findings (94.2%) had histologic diagnosis of cancer or hyperplasia (81.5% and 12.6%, respectively). CONCLUSION: It seems that even in face of good validity of hysteroscopic view for endometrial hyperplasia and cancer, histologic study is mandatory in the presence of any lesion as the hysteroscopic view cannot completely replace the histologic study in patients with AUB.

Androgen and estrogen receptors and co-regulators levels in endometria from patients with polycystic ovarian syndrome with and without endometrial hyperplasia.

OBJECTIVE: To study if the endocrinological status of PCOS women affects the endometrial sensitivity to steroids by evaluating the expression of androgen receptor (AR), estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), co-activators AIB1 and ARA70, and co-repressor NCoR. METHODS: Gene and/or protein expression of steroid receptors and co-regulators was measured in 17 samples of normal endometrium (NE), 23 PCOS endometrium without treatment (PCOSE), 11 endometria from PCOS women and with endometrial hyperplasia (HPCOSE), and 10 endometria from patients with endometrial hyperplasia (HE), using RT-PCR and/or immunohistochemistry and Western blot. RESULTS: Gene and protein expression of AR was relatively elevated in PCOSE and HPCOSE compared with NE. A significant increase in ERalpha protein expression was observed in PCOSE, preferentially in the nucleus of endometrial cells, whereas ERbeta gene and protein expression increased gradually from PCOSE to HPCOSE and HE, mainly in the epithelial compartment. Importantly, we found a gradual increase in the ERbeta/ERalpha gene and protein expression ratio in endometria from the four groups of women. AIB1 showed increased nuclear protein expression in PCOSE compared to NE, in the presence of a high expression of ARA70 in all groups. High expression of ARA70 together with a normal expression level of AIB1 was observed in HPCOSE. The cytoplasmic immunostaining of NCoR was similar between the four groups of patients. CONCLUSION: The PCOS endometrium exhibits a higher sensitivity to steroid action. We can inferred that these alterations could deregulate the transcription of genes involved in the cell cycle, which may lead to the development of endometrial hyperplasia in PCOS women.

Sangramento na pós menopausa: avaliaçäo clínica e histopatológica / Clinical and hystopatological findings in women with postmenopausal bleeding

OBJETIVO: Avaliaçäo clínica e análise histopatológica do endométrio em pacientes com sangramento na pós-menopausa. PACIENTES E MÉTODOS: Foram analisadas, retrospectivamente, 268 pacientes com sangramento uterino na pós-menopausa, submetidas e curetagem uterina diagnóstica. De acordo com o achado histopatológico, foram separadas as pacientes com lesöes endometriais benignas, pré-malignas e malignas. RESULTADOS: A análise histopatológica mostrou que 79,1 por cento destas mulheres apresentam lesöes endometriais benignas e 20,9 por cento pré-malignas e malignas, correspondendo a hiperplasia atípica e adenocarcinoma de endométrio. Endométrio atrófico (28,7 por cento) foi o achado endometrial mais freqüentemente associado ao sangramento na pós-menopausa, seguido de material insuficiente (18,3 por cento), pólipo endometrial (17,2 por cento), adenocarcinoma (16,4 por cento), hiperplasia sem atipia (10,4 por cento), com atipia (4,5 por cento), proliferativo (3,3 por cento), endometrite (0,4 por cento), secretor (0,4 por cento). Verificou-se que a média de idade das pacientes com hiperplasia atípica e adenocarcinoma foi de 63,2ñ9,6 anos contra 58,5ñ8,0 anos daquelas com lesöes endometriais benignas. A obesidade, diabetes mellitus, hipertensäo arterial, nuliparidade, menopausa tardia e ciclos anovulatórios ocorreram respectivamente, na freqüencia de 49,0 por cento, 16,6 por cento, 49,8 por cento, 6,8 por cento, 25,9 por cento e 11,8 por cento nas lesöes benignas e 39,6 por cento, 33,9 por cento, 58,9 por cento, 28,5 por cento, 32,1 por cento e 12,9 por cento nas pré-malignas e malignas, sendo que a idade, nuliparidade e o diabetes mellitus apresentaram diferença estatisticamente significativa (p<0,05). CONCLUSÕES: O sangramento pós menopausa representa sinal de alerta, necessitando de avaliaçäo histopatológica do endométrio mesmo nas pacientes näo consideradas de risco para o desenvolvimento de câncer de endométrio

[Diagnostic evaluation of endouterine manual aspiration for the detection of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding]. / Validación diagnóstica de la aspiración manual endouterina para la detección de hiperplasia y cáncer de endometrio en pacientes con sangrado uterino anormal.

The objective was to determinate the diagnostic value of manual vacuum aspiration with Karman cannula (MVA) for the detection of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding. Fifty patients with abnormal uterine bleeding were evaluated with MVA prior to dilatation and curettage (D&C). The needing of cervical dilatation was noted. A matched analysis of the histological reports with Wilcoxon contrast test was performed. In order to calculate the diagnostic value, the histological examination of the tissue recollected by D&C was defined as gold-standard. Sensitivity, specificity, pre-test probability (prevalence), post-test probabilities (predictive values) and likelihood-ratios were calculated. No significant difference between either histological reports in matched analysis and the insufficient samples proportion was detected. Cervical dilatation was performed more frequently to D&C (p = 0.0002). The pre-test probability (prevalence) of endometrial hyperplasia/cancer was 20%. Two cases of hyperplasia were not detected by MVA (negative false 20%). The endometrial biopsy for MVA showed a sensitivity of 71% and specificity 93%. The post-test probabilities for an abnormal and normal biopsy (positive and negative predictive values) were 62.5% and 95.2%, respectively. The corresponding likelihood-ratios were 10.23 and 0.3, respectively. The endometrial biopsy for MVA has a high diagnostic value, similar to D&C, in the detection of endometrial hyperplasia/cancer in patients with abnormal uterine bleeding with the advantage to be an office procedure without either risks and costs of D&C.

Evaluation of the endometrial cavity during menopause.

OBJECTIVE: To compare transvaginal sonography (TVS), hysteroscopy and suction curettage in the evaluation of uterine bleeding during the menopause. METHODS: Forty-seven patients who presented with either postmenopausal bleeding (31 cases) or sonographic endometrial abnormalities at menopause (16 cases) were evaluated using TVS, hysteroscopy, and curettage with a Karman curette. RESULTS: When endometrial thickness measured by TVS was < 4 mm, there was no endometrial pathology. However TVS could not differentiate accurately between hyperplasia, polyps or endometrial carcinoma. In these cases, endometrial thickness was invariably greater than 5 mm. CONCLUSIONS: Hysteroscopy proved superior to curettage in the diagnosis of endometrial polyps.

Nódulo o placa de sitio placentario / Nodule or plaque of placental site

Se presenta el primer caso en nuestro medio de Nodulo placentario con la idea de que se reconozca histologicamente y que se diferencie de otras condiciones, para el manejo adecuado de los pacientes, dado que la condicion es poco conocida y solo hay reportados 20 casos en la literatura americana

Adenomiose: variaçöes do quadro clínico e associaçäo a outras patologias ginecológicas / Adenomiosis: variation in clinical feature and association with other gynecological pathologies

Diante do quadro clínico näo-caracterfstico e da dificuldade do diagnóstico pré-operatório de adenomiose, o objetivo deste estudo foi avaliar os vários parâmetros clínicos encontrados em pacientes, que tiveram o diagnóstico de adenomiose comprovado através de estudo anatomopatológico da peça cirúrgica pós-histerectomia. A adenomiose esteve presente em 118 das 717 histerectomias, realizadas no Hospital das Clínicas da FMRP-USP, durante o período de 1983 a 1986. O diagnóstico pré-operatório foi feito em apenas 15,3 por cento dos casos. A maioria das pacientes era constituída de multíparas na pré-menopausa e apresentavam sangramento uterino anormal e/ou dor pélvica. A adenomiose estava associada a outras patologias pélvicas em 75 pacientes (63,6 por cento), sendo a mais freqüente o leiomioma, seguida de endometriose, hiperplasia do endométrio e pólipo endometrial. A freqüente associaçäo com patologias pélvicas mais comuns, que ela própria e de quadro-clínico semelhante, dificulta o diagnóstico de adenomiose, que, assim, perde a importância clínica, frente a maior exuberância do quadro clínico da entidade mórbida associada.

Lesiones premalignas del endometrio / Endometrium pre-malignant injuries

Se presenta el estudio de 550 pacientes mayores de 30 años, portadores de patología endometrial que fueron sometidas a Biopsia de Endometrio entre los años 1981 a 1985. Los hallazgos histopatológico de endometrios hiperplásicos se encuentran notoriamente agrupados en los grupos de edad correspondiente a pacientes por encima de los 30 años, destacando las hiperplasias quísticas glandulares y iatrogénicas. La hiperplasia adenomatosa tiene una mayor concentración de casos en los grupos etáreos de 40 a 59 años (77.77 por ciento). El 5.92 por ciento cursaron metrorragia y presentaron hiperplasias quísticas. El 3.95 por ciento con el mismo síntoma, tuvieron hiperplasias glándulo-quísticas. El 3.16 por ciento de mujeres con metrorragia, el estudio histopatógico reveló hiperplasia adenomatosa. Cuando el síntoma principal fue menorragia, el hallazgo histopatológico mayor fue el de hiperplasia endometrial simple, quística o iatrogénica (48 por 100) e hiperplasia adenomatosa sólo en 1.34 por 100. En pacientes cuyo síntoma principal fue oligomenorrea, el hallazgo histopatológico arrojó endometrio de tipo proliferativo (18.25 por 100) e hiperplásicos (18.25 por 100).El 53.49 por 100 de pacientes con amenorrea tuvieron endometrios de tipo proliferativo e hiperplásicos. El síntoma metrorragia se asocia preferentemente con adenocarcinoma y pólipo endometrial. La menorragia es síntoma principal de endometrios hiperplásicos adenomatosos, en pacientes por encima de 45 años. En mujeres mayores de 40 años que cursaron con metrorragia, el hallazgo histopatológico fue en el 66 por 100 de endometrios de tipo proliferativo

Perspectivas de manejo en la hiperplasia endometrial. Informe preliminar / The outlook for the management of endometrial hyperplasia. a preliminary report

Con el propósito de encontrar un tratamiento menos traumático y unificar criterios en nuestro medio en el menejo de la Hiperplasia Endometrial (HE) realizamos una prueba farmacológica en siete mujeres con HE y hemorragia uterina en edad fértil (n=3) y perimenopaútisicas (n=4). Se les prescribió noretindrona (NET) 5 mg/45d. No se observaron efectos colaterales indesables. Las siete pacientes mostraron regresión endometrial, dos de las tres jóvenes lograron embarazo a término y las cuatro perimenopaúsicas no volvieron a menstruar. En estas observaciones preliminares no hubo ningún fenómeno de asociación entre hormonas esteroides gonadales (Estradiol E-2, estrona E-1, Progesterona P-4) con la histología endometrial