Reactional changes in short-term levonorgestrel-releasing intrauterine system (lng-ius) use

SUMMARY OBJECTIVE: To evaluate endocervical and vaginal environment changes in women using a levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: A quasi-experimental study included sixty women who had an LNG-IUS inserted in the Family Planning Clinic of UNICAMP between April and November of 2016. Women in reproductive age, non-pregnant, without the use of antibiotics and contraceptives seeking for LNG-IUS insertion were selected for this study. All women were evaluated with regard to vaginal and endocervical pH, vaginal and endocervical Gram-stained bacterioscopy, and Pap-smear before and two months after LNG-IUS insertion. Clinical aspects such as cervical mucus, vaginal discharge, and cervical ectopy were also observed. RESULTS: After LNG-IUS insertion, there was an increase in the following parameters: endocervical pH>4.5 (p=0.02), endocervical neutrophil amount (p<0.0001), vaginal cytolysis (p=0.04). There was a decrease in vaginal discharge (p=0.01). No statistically significant changes were found in vaginal pH, neutrophils amount in the vaginal mucosa, vaginal discharge appearance, vaginal candidiasis, bacterial vaginosis, vaginal coccobacillary microbiota, cervical mucus appearance, or cervical ectopy size. CONCLUSIONS: Short-term LNG-IUS use did not increase vulvovaginal candidiasis or bacterial vaginosis, and led to diminished vaginal discharge. Notwithstanding, this device promoted reactional changes in the vaginal and endocervical environment, without modification on cervical ectopy size.

RESUMO OBJETIVO: Avaliar as alterações do ambiente endocervical e vaginal em mulheres usuárias de sistema intrauterino liberador de levonorgestrel (SIU-LNG). MÉTODOS: Um estudo quase-experimental incluiu 60 mulheres que inseriram o SIU-LNG na Clínica de Planejamento Familiar da UNICAMP entre abril e novembro de 2016. Mulheres em idade reprodutiva, não gestantes, sem uso de antibióticos e contraceptivos, em busca pela inserção do SIU-LNG, foram selecionadas para este estudo. Todas as mulheres foram avaliadas quanto ao pH vaginal e endocervical, bacterioscopia vaginal e endocervical por coloração de Gram, exame de Papanicolau antes e dois meses após a inserção de SIU-LNG. Aspectos clínicos como muco cervical, corrimento vaginal e ectopia cervical também foram observados. RESULTADOS: Após a inserção do SIU-LNG houve aumento nos seguintes parâmetros: pH endocervical >4,5 (p=0,02), quantidade de neutrófilos endocervicais (p<0,0001), citolise vaginal (p=0,04). Houve diminuição do conteúdo vaginal (p=0,01). Não foram encontradas alterações estatisticamente significativas no pH vaginal, na quantidade de neutrófilos na mucosa vaginal, apecto do corrimento vaginal, candidíase vaginal, vaginose bacteriana, microbiota cocobacilar vaginal, aparência de muco cervical ou tamanho da ectopia cervical. CONCLUSÃO: O uso do SIU-LNG em curto prazo não aumentou a candidíase vulvovaginal ou a vaginose bacteriana, levou à diminuição do conteúdo vaginal. No entanto, este dispositivo promoveu mudanças reacionais no ambiente vaginal e endocervical, sem modificação no tamanho da ectopia cervical.

Efeito do tamoxifeno sobre o endométrio em pacientes com câncer de mama na pós-menopausa / Effect of tamoxifen on the endometrium in post-menopausal patients with breast cancer

O trabalho tem como objetivo discutir, através de uma revisão da literatura, as influências do tamoxifeno sobre as alterações do padrão endometrial em pacientes com câncer de mama na pós-menopausa. Além de caracterizar os principais padrões endometriais e relacioná-los ao câncer de endométrio, são descritas também as recomendações da literatura vigente para a monitorização e seguimento destas pacientes. A literatura especializada demonstra claramente a relevância do acompanhamento clínico rigoroso destas mulheres pelo risco aumentado de câncer endometrial; no entanto, ainda não há consenso sobre qual o melhor exame de rastreio ou a periodicidade de realização do mesmo. Conclui-se que a prioridade é o exame clínico anual e orientação das pacientes quanto à sintomatologia, principalmente quanto à presença de sangramento vaginal. A partir destes sintomas, dá-se prosseguimento com investigação mais detalhada.(AU)

The present work aims to discuss, through a literature review, the influence of tamoxifen use in endometrial pattern changes in postmenopausal patients with breast cancer. In addition, to characterize the main endometrial patterns and relate them to endometrial cancer was a secondary objective. This review describes the recommendations of the current literature for endometrial monitoring of these patients. The literature clearly demonstrated to be relevant the clinical monitoring of these patients, because the increased risk of endometrial cancer. However, there is no consensus about which is the best tracking exam or the timing of completion of it. It was concluded that the priority is an annual clinical checkup for symptoms, especially the presence of vaginal bleeding; further, detailed investigation will depend on which symptoms are presented.(AU)

Evaluation of peritoneal endometriosis treatment using intralesional acetylsalicylic acid injection in rabbits

PURPOSE: To investigate the efficacy of intralesional 20% aspirin injection for treatment of experimental peritoneal endometriosis. Methods: Peritoneal endometriosis was experimentally induced in forty adult nulligravid female rabbits. On day 30 post-endometriosis induction, rabbits were randomly divided to assess early (10 days) and late (20 days) effects of intralesional injection of physiological saline solution (control groups) in comparison to intralesional injection of 20% bicarbonate aspirin solution (experimental groups) as follows: control group 1 (10 days, n=10); control group 2 (20 days, n=10); experimental group 3 (10 days, n=10); experimental group 4 (20 days, n=10). Resected tissues, including endometriosis foci, were qualitatively (general morphology and signs of inflammatory cells infiltrate, necrosis and apoptosis) and quantitatively (remaining endometriosis area) assessed by histopathological analysis. Results: Extensive necrosis, hemorrhage, apoptosis, and fibrosis were observed in the experimental groups 3 and 4. Groups 1 and 2 presented typical endometrial tissue cysts, respectively. Groups 3 and 4 showed sparse endometrial tissue foci and no endometrial tissue, respectively. Quantitative analysis revealed that aspirin-treated groups 3 and 4 had significantly (p<0.05) smaller remaining endometriosis area, compared to control groups 1 and 2. Conclusion: Intralesional 20% aspirin injection caused total destruction of peritoneal endometriosis foci in rabbits.

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

PURPOSE: 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.

Effect of prenatal exposure to Bisphenol A on the endometrium of albino rats: a histological and an immuno-histochemical study

Aim of the work: bisphenol A [BPA] is a synthetic monomer that is polymerized to manufacture polycarbonate plastic products and resins, including those used in food packaging and dental sealants. It is used in the manufacture of a great variety of products including: compact disks, food can linings, plastic windows, car parts, adhesives, protective coatings and powder paints. This work aimed to study the effect of prenatal exposure to BPA on the endometrium of female rats

Materials and methods: thirty adult female albino rats were divided into three groups: rats in group 1 served as a control [G1] and received an equal amount of sesame oil to those of the treated groups; those in group 2 [G2] were administered by gavage 5.0 microg BPA/kg/day [low-dose group]; the third group [G3] received 50 microg BPA/kg/day [high-dose group]. The female offspring of each group were weaned at day 21 and maintained until 3 months old. The uteri were dissected for the histological and immuno-histochemical examination

Results: low-dose group showed degeneration of the epithelial lining of the endometrium with focal patches of increased epithelial cell layers. The high dose group revealed cytoplasmic hydropic degeneration and pyknotic nuclei of the epithelial cells. Estrogen receptors showed a significant decrease of positive cells in low dose treated group and this decrease markedly accentuated in the high dose one. Positive nuclei for Ki-67 were markedly increased with increasing doses of BPA

Conclusion: BPA showed obvious endometrial degenerative and proliferative histological changes. Therefore, the use of this substance in food packaging materials and in the manufacture of substances liable to come into contact with food and drink should be phased out

Tamoxifeno y afecciones endometriales en pacientes con cáncer de mama / Tamoxifen and endometrial disease in patients with breast cancer

Los objetivos fueron evaluar la prevalencia de afecciones endometriales en pacientes tratadas con tamoxifeno (TAM) y analizar los aspectos epidemiológicos, ecográficos, histeroscópicos e histopatológicos. Desde enero de 1999 a diciembre 2008 se estudiaron 152 pacientes con cáncer de mama tratadas con TAM (20 mg/día), sintomáticas (con sangrado) o asintomáticas, pre y postmenopáusicas, incluidas en forma consecutiva. El diseño fue prospectivo y observacional. Los métodos diagnósticos usados fueron ecografía transvaginal, histeroscopía y biopsia. Las pacientes fueron seguidas durante 5 años con ecografía cada 12 meses e histeroscopia con biopsia en casos que lo justificaran. Edad: 62.76 ± 10.24 años y tiempo de tratamiento: 36.2 ± 19.9 meses. El adenocarcinoma se observó en 3/87 (3.45%) pacientes con factores de riesgo y en 1/65 (1.54%) sin ellos (RA: 1.91, IC 95% 1.88 a 1.94). Las afecciones benignas se hallaron en 148 pacientes (97.37% y los adenocarcinomas en 4 (2.63%),1 en un pólipo de aspecto benigno. Los 4 se observaron en mujeres postmenopáusicas (2 asintomáticas) con grosor endometrial igual o mayor a 16 mm. El riesgo de cáncer fue significativamente mayor en sintomáticas (2.36 versus 0.42 en asintomáticas). Tres adenocarcinomas se detectaron entre 24 y 48 meses del tratamiento. Recomendamos un seguimiento con ecografía transvaginal de las pacientes asintomáticas, resección de los pólipos evaluando factores de riesgo y tiempo de exposición, en especial luego de los 24 meses. Consideramos aceptable un cut-off = 10 mm en el grosor del endometrio en postmenopáusicas asintomáticas para realizar histeroscopía y biopsia.

The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre- and postmenopausal, were included consecutively in a prospective and observational follow-up study Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients´ age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45%) with risk factors and in 1/65 (1.54%) without them (RA 1.91, IC 95% 1.88-1.94). We found benign disease in 148 patients (97.37%) and adenocarcinomas in 4 (2.63%), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considerin risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.

Low doses of celecoxib stimulate human endometrium growth in a three-dimensional culture model

The endometrium plays a pivotal role in implantation and pregnancy. Cyclooxygenase II [COX-2] has an important function in biological processes such as cell proliferation and inflammation. Celecoxib is a selective inhibitor of COX-2 with numerous pharmacologic functions. The aim of present study is to investigate the effects of celecoxib on the human endometrium in a three-dimensional [3D] culture model. In this experimental study, normal human endometria [n=10] obtained from reproductive age women were cut into 1x1 mm sections. Endometrial explants were placed between two layers of fibrin gel. To create the fibrin gel, we poured a thin layer of fibrinogen solution [3 mg/ml in medium 199 [M199]] into each well of a 24-well culture dish and added thrombin enzyme. Endometrial fragments were placed in the center of each well and covered with a second layer of fibrinogen solution. M199 supplemented with L-glutamine, fetal bovine serum [FBS, 5%] and antibiotics were added to each well. The media in each experimental well contained either1, 10 or 50 micro M of celecoxib. At the end of the study, we calculated endometrial tissue growth changes by scoring methods and determined the percentage of angiogenesis. Data were analyzed by the Kruskal-Wallis method. P<0.05 was considered significant. The growth scores were as follows: control [1.37 +/- 0.16], 1 micro M [1.96 +/- 0.28], 10 micro M [2.01 +/- 0.25], and 50 micro M [1.17 +/- 0.14] celecoxib, all of which were significantly different. The angiogenesis percentages were: 25.56 +/- 6.72% [control], 31.98 +/- 6.18% [1 micro M], 42.67 +/- 7.27% [10 micro M] and 23.44 +/- 4.03% [50 micro M], which were not significantly different from each other. Lower celecoxib concentrations had stimulatory effects on the growth of normal endometrium

Efeitos das isoflavonas em altas doses sobre o útero da rata / Effects of high-dose isoflavones on rat uterus

OBJETIVO: Avaliar o efeito de altas doses de isoflavonas no útero de ratas adultas castradas. MÉTODOS: Ratas virgens ovariectomizadas (n = 40) foram tratadas por 30 dias consecutivos com veículo (GCtrl) ou genisteína nas concentrações 42 (GES42), 125 (GES125) e 250 (GES250) µg/g de peso corporal ao dia. O extrato de soja e o veículo (propilenoglicol) foram administrados por gavagem. Ao final do experimento, foi realizada dosagem sérica de 17 β-estradiol e progesterona, avaliou-se o peso dos animais e dos úteros e foi feito exame colpocitológico. Fragmentos do terço médio dos cornos uterinos foram fixados em formol a 10 por cento e processados para inclusão em parafina para estudo histológico. Cortes de 5 µm de espessura foram corados pelo HE e destinados a estudo em microscopia de luz. Analisou-se a histomorfologia do endométrio, área endometrial, número e área ocupada pelas glândulas, assim como a concentração de eosinófilos presentes na lâmina própria. Os dados numéricos obtidos foram submetidos à análise de variância complementada pelo teste de Tukey-Kramer (p < 0,05). RESULTADOS: Verificou-se que o peso do útero, as áreas endometrial e glandular e o número de glândulas e de eosinófilos foram maiores nos animais dos grupos GES250 > GES125 do que nos outros grupos (GES250 > GES125 > GES42 = GCtrl; p < 0,05). Os dados morfológicos mostraram proliferação endometrial nos grupos ES125 e ES250, que apresentavam endométrio mais desenvolvido que outros grupos. Em todos os animais do grupo ES250 notou-se a presença de metaplasia escamosa. CONCLUSÃO: A administração de isoflavonas em altas doses promove metaplasia escamosa no endométrio.

OBJECTIVE: To evaluate the effects of high-dose isoflavones on the uterus of castrated adult rats. METHODS: Adult, ovariectomized virgin rats (n = 40) were treated by gavage during 30 consecutive days with vehicle (propylene glycol, group GCtrl) or different doses of genistein: 42 (group GES42), 125 (GES125), or 250 (GES250) µg/g body weight per day. Animals were killed, weighed, vaginal and uterine samples were taken for cytologic evaluation, and serum levels of 17 β-estradiol and progesterone were determined. The middle third of the uterine horns was dissected, fixed in 10 percent formaldehyde and processed for paraffin inclusion; 5-µm thick sections were obtained and stained with HE for further histological study under light microscopy. The endometrial morphology and area, number and area of glands, and number of eosinophils in the lamina propria were analyzed. ANOVA and the Tukey-Kramer test were used for statistical analyses. RESULTS: Uterine weight, endometrial glandular area, and number of glands and eosinophils were all higher in GES250 > G125 than in the other groups (GES250 > GES125 > GES42 = GCtrl; p < 0.05). Morphological data showed signs of endometrial proliferation upon treatment with genistein, especially in animals in GES125 and GES250 compared to other groups. In all animals in GES250, signs of uterine squamous metaplasia were observed. CONCLUSION: A short treatment period with high daily doses of isoflavones can promote endometrial squamous metaplasia in ovariectomized rats.

Efeito do anti-TNF-α em implantes endometriais no peritônio de ratas / Effect of anti-TNF-α on peritoneal endometrial implants of rats

OBJETIVO: Avaliar o efeito da terapia anti-TNF-α no tratamento de implantes endometriais no peritônio de ratas. MÉTODOS: Os implantes endometrióticos foram induzidos cirurgicamente em 120 ratas Wistar-Albino. Os animais foram aleatoriamente distribuídos em 4 grupos. O grupo C (n=36) recebeu uma injeção intraperitoneal de 0,2ml de solução salina. O grupo L (n=41) recebeu uma injeção subcutânea de 1mg/kg de leuprolide. O grupo I5 (n=20) recebeu uma injeção subcutânea de 5mg/kg de anticorpo monoclonal anti-fator de necrose tumoral (TNF) a (infliximab). O grupo I10 (n=20) recebeu uma injeção subcutânea de 10mg/kg de infliximab. As ratas foram sacrificadas após 21 dias para se avaliar o tamanho dos implantes e a expressão do TNF-α. RESULTADOS: O tratamento com leuprolide promoveu uma redução absoluta na área de superfície do implante comparado com o grupo C (+14mm vs. 0mm; p=0,013) e com o grupo I10 (+14mm vs. +5mm; p=0,018). Da mesma forma, uma redução percentual da area de superfície do implante foi observada comparando o grupo L com o grupo C (+33,3 por cento vs. 0 por cento; p=0,005) e com o grupo I10 (+33,3 por cento vs. +18,3 por cento; p=0,027). O tratamento com infliximab não foi capaz de diminuir a área de superfície do implante comparado com o grupo C. A expressão de TNF-α reduziu nos grupos L, I5 e I10 comparado com o grupo C (505,6µm² vs. 660,5µm² vs. 317,2µm² vs. 2519,3µm², respectivamente; p<0,001). CONCLUSÃO: A terapia anti-TNF-α reduziu a expressão de TNF-α nos implantes endometrióticos mas não reduziu a área de superfície da lesão.

OBJECTIVE: To evaluate the effect of anti-TNF-α in the treatment of endometrial implants in the peritoneum of rats. METHODS: Endometrial implants were surgically induced in 120 female Wistar-Albino rats. The animals were randomly divided into four groups. Group C (n = 36) received an intraperitoneal injection of 0.2 ml of saline. Group L (n = 41) received a subcutaneous injection of 1mg/kg of leuprolide. Group I5 (n = 20) received a subcutaneous injection of 5mg/kg of monoclonal anti-tumor necrosis factor (TNF) a (infliximab). Group I10 (n = 20) received a subcutaneous injection of 10mg/kg of infliximab. The rats were sacrificed after 21 days to assess the size of the implants and the expression of TNF. RESULTS: Treatment with leuprolide (group L) promoted an absolute reduction in the surface area of the implant when compared with group C (+14 mm vs. 0mm, p = 0.013) and group I10 (+14 mm vs. +5 Mm, p = 0.018). Likewise, a percentage reduction of surface area of the implant was observed comparing group L with group C (+33.3 percent vs. 0 percent, p = 0.005) and group I10 (+33.3 percent vs. +18.3 percent, p = 0.027). Treatment with infliximab was not able to decrease the surface area of the implants when compared with group C. The expression of TNF-α in groups L, I5 and I10 was lower than in group C (505.6 mm² vs. 660.5 mm² vs. 317.2 mm² vs. 2519.3 mm², respectively; p <0.001). CONCLUSION: The anti-TNF-α therapy reduced the expression of TNF-α in endometriotic implants, but did not reduce the surface area of the lesion.

Efeito da tibolona sobre o endométrio de ratas castradas / Effect of tibolone on endometrium of castrated rats

OBJETIVO: avaliar o efeito do uso prolongado de alta dose de tibolona na morfologia do endométrio em ratascastradas. MÉTODOS: foram utilizadas 15 ratas Wistar, fêmeas, com idade de oito semanas e peso médio de 250 g.Todas as ratas foram submetidas à ooforectomia bilateral e 30 dias depois foi coletada citologia vaginal, verificandose o status de menopausa. As ratas foram divididas aleatoriamente em dois grupos: o tratado (n=9) recebeu via oral 1 mg tibolona/dia; o controle (n=6) recebeu apenas solução do veículo carboximetilcelulose. Após 20 semanas de tratamento, todos os animais foram sedados e sacrificados por deslocamento cervical. Os úteros foram retirados e fixados em formol 10% tamponado. Ambos os cornos uterinos foram clivados em três regiões (proximal, medial, distal) e processados para inclusão em parafina. Cortes histológicos corados com hematoxilina-eosina foram submetidos à análise morfológica e morfométrica. Foram avaliados os seguintes parâmetros: espessura do epitélio superficialendometrial, espessura do estroma endometrial, área endometrial, número absoluto de glândulas endometriais e número de glândulas/área endometrial. Os dados obtidos foram comparados mediante o teste t de Student. RESULTADOS: no Grupo Tibolona os úteros se apresentaram bem desenvolvidos e houve aumento significativo (p��0,01) de todos osparâmetros histomorfométricos. Por vezes, o epitélio cilíndrico tornava-se estratificado pavimentoso e recobria porções internas das glândulas bem como a cavidade endometrial. As ratas do Grupo Controle apresentaram útero atrofiado. Havia poucas glândulas de padrão tubular e escassa substância intercelular. As glândulas eram revestidas de epitélio cúbico que se estendia à cavidade endometrial...

PURPOSE: to evaluate the effect of long-term use of a high dose of tibolone on the morphology of the endometriumof castrated female rats. METHODS: fifteen female Wistar rats, aged eight weeks and weighting about 250 g wereused. All the female rats were submitted to bilateral oophorectomy and 30 days afterwards, vaginal cytology was collected, to verify the menopause status. The female rats were randomly divided in two groups. The Treatment Group (n=9) received 1 mg of tibolone/day orally; the Control Group (n=6) received a solution of carboxymethylcellulose vehicle. After 20 weeks of treatment, all the animals were sedated and sacrificed by cervical dislocation. The uterus was removed and fixated in 10% buffer formaldehyde. Both uterine horns were divided in three regions (proximal,medial and distal) and processed to be included in paraffin. Histological sections, stained with hematoxylin-eosin were submitted to morphological and morphometrical analysis. The following parameters have been analyzed: thickness of the endometrial superficial epithelium, thickness of the endometrium stroma, endometrial area, absolute number of endometrial glands and number of glands/endometrial area. The data obtained were compared by the t-Student test. RESULTS: in the Tibolone Group, the uteri were well developed and there was a significant increase (p<0.01) of all the histomorphometric parameters. In some cases, the cylindrical epithelium became stratified, pavimentous and coveredthe internal portions of the glands, as well as of the endometrium cavity. Rats from the Control Group presented uterineatrophy. There were few tubular-like glands and scarce intercellular substance. Glands were covered by cubic epithelium which extended itself to the endometrial cavity...

Focal adhesion kinase [FAK] involvement in human endometrial remodeling during the menstrual cycle

Endometrial remodeling occurs during each menstrual cycle in women. Reports have shown that, in a variety of cell types, processes such as proliferation, signaling complex formation and extra cellular matrix remodeling require a cytoplasmic tyrosine kinase, focal adhesion kinase [FAK]. The present study has focused on the expression pattern of FAK in human endometrium during the menstrual cycle. The purpose of this study was to ascertain the probable function of FAK in menstrual cycle changes and the role of FAK in tissue repair and tissue remodeling in vivo. Formalin-fixed paraffin-embedded endometrial samples were obtained from 400 pre-menopausal, non-pregnant women, who underwent hysterectomy and biopsy for benign diseases. Forty six samples with no tissue abnormalities were studied and ABC staining method of immuno-histochemistry methods was applied. Positive staining of FAK by different cell types of human endometrium was scaled and compared with each other by using histologic score method. All different cell types of endometrium showed various patterns of FAK expression in different stages of menstruation. FAK in glandular and luminal epithelial cells is up-regulated during the early proliferative [EP] to mid-secretory [MS] phases. FAK in stromal cells is up-regulated during the EP, early and MS phases in comparison to the late secretory [LS] phase. FAK expression in endothelial cells is up-regulated during the EP and MS phases in comparison to LS phase. This study showed that endometrial FAK expression is a phase-dependent manner during the menstrual cycle. It appears that up-regulation of FAK during the proliferative phases is responsible for endometrial regeneration and high expression of FAK in the EP and MS phases may associate with the implantation. Down-regulation of FAK during the LS phase may facilitate apoptosis in human endometrium. It seems that FAK as a key kinase plays a critical role in endometrial remodeling that it may regulate by steroid hormones

O tratamento com isoflavonas mimetiza a ação do estradiol no acúmulo de gordura em ratas ovariectomizadas / Treatment with isoflavones replaces estradiol effect on the tissue fat accumulation from ovariectomized rats

OBJETIVO: As isoflavonas (ISO) presentes na soja são consideradas fitoestrógenos. A administração de fitoestrógenos tem efeito benéfico nos distúrbios da pós-menopausa que são caracterizados pela suspensão da função ovariana com declínio da secreção de estrogênio e conseqüentes desajustes histomorfológicos e metabólicos. O objetivo do presente estudo foi investigar o efeito da suplementação com ISO sobre a espessura do endométrio uterino, o acúmulo de gordura tecidual, o colesterol HDL e a glicose plasmática de ratas ovariectomizadas (OVX). MÉTODOS: Ratas Wistar com 60 dias de vida sofreram cirurgia bilateral para retirada dos ovários. Após o período de 8 dias de recuperação foram divididas em três grupos: falso operada (GC), OVX não-tratadas com ISO (GI) e as OVX suplementadas com ISO (GII). Foram retirados e pesados o útero, as gorduras uterinas e retroperitoneais. Também foram coletadas amostras de sangue para dosagem da concentração de HDL e glicose. RESULTADOS: A OVX promoveu atrofia do endométrio, diminuição do peso do útero e diminuição do HDL. O tratamento com ISO promoveu diminuição dos estoques de gorduras uterina e retroperitoneal, aumento de HDL e redução da glicemia, porém não teve efeito uterotrófico. CONCLUSÕES: Os dados do presente estudo mostram que o tratamento com ISO promove redução da adiposidade, o que pode estar relacionado à redução da lipogênese e ao aumento da lipólise.

OBJECTIVE: Isoflavones (ISO) present in soybean are named phytoestrogens because they show estrogen effect. The use of isoflavones has beneficial effect in disturbance of post-menopause, which is characterized by ovarian function suppression. Decreasing of estrogen secretion and consequent morphologic and metabolic disarrangements are observed in female hormonal decline. The aim of present work was to investigate the effect of ISO on the fat accretion of uterin endometric tissue, and HDL and glucose blood concentration from ovariectomized rats (OVX). METHODS: Female Wistar rats with 60 days-old were submitted a surgery to remove bilaterally the ovarium. After 8-day recovery period the animals were distributed into three groups: sham operate (GC); OVX ISO untreated (GI) and OVX supplemented with ISO (G II). Total uterus mass, uterus fat and retroperitoneal fat pad, were removed, washed and weighted. Samples of uterus were histological processed to measure endometrium thickness. Blood samples were also collected to analyze the concentration of HDL and glucose. The OVX caused endometric atrophy, decrease of uterus weight and HDL reduction. The treatment with ISO provoked decrease of uterin and retroperitoneal fat pad. HDL increase and glycemia reduction were also observed. However, there was no uterotrophic effect. CONCLUSIONS: ISO treatment causes decrease in tissue fat accretion from ovariectomized rats.

Efficacy of etoricoxib for pain relief during endometrial biopsy; a double blind randomized controlled trial.

OBJECTIVE: To compare the efficacy of oral etoricoxib and placebo for pain relief during endometrial biopsy. MATERIAL AND METHOD: A double-blind, randomized controlled trial that included 80 women who underwent endometrial biopsy was done at Thammasat University Hospital between 1 September 2005 and 30 June 2006. Forty women were randomly allocated to the etoricoxib group (120 mg, tablet) and 40 to the placebo group. The main outcome was the patient's assessment of intensity of pain measured by visual analog scale (VAS) before speculum insertion, during endometrial biopsy, immediately after endometrial biopsy, and 30 minutes after endometrial biopsy. Satisfactory score was also evaluated. RESULTS: Demographic data including age, BMI, previous vaginal deliveries, previous pelvic surgery and history of curettage were not significantly different between the etoricoxib group and the placebo group. Mean pain score in the etoricoxib group was not significantly lower when compared with the placebo group during endometrial biopsy (5.0 +/- 1.7 versus 5.25 +/- 2.2, p = 0.7) and immediately after endometrial biopsy (2.1 +/- 2.2 versus 2.8 +/- 1.7, p = 0.1) but significantly lower at 30 minutes after endometrial biopsy (0.2 +/- 0.5 versus 0.6 +/- 0.8, p = 0.01). Mean satisfactory score was significantly higher in the etoricoxib group (6.9 +/- 1.8 versus 5.1 +/- 2.3, p = 0.001). CONCLUSION: A single oral dose of etoricoxib for reduction of pain during endometrial biopsy had not significantly lower the pain score during the procedure compared with the placebo. However mean satisfactory score in the etoricoxib group was higher with statistically significant difference. Also the authors found no serious adverse effects of this drug.

[ effects of lead on the ultrastructure of uterine endometrium of immature Balb/c mice]

Study of the effects of lead on the ultrastructure of uterine endometrium. In this study 40 female Balb/c mice with the age of one week were divided into two control and experimental groups. The experimental group were daily injected intraperitoneally 75 microgram per gram of lead nitrate dissolved in physiological serum for two weeks. The mice of control group were received only physiological serum. After the end of the injection period, the mice were anesthetized and dissected, then their uterus were removed and divided into small pieces and transferred into karnovsky solution, After ward they were processed for electron microscope and prepared semithin and ultrathin sections, morphometry on electron micrographs were carried out by point counting and also the number of stromal cells in 50 fields of light microscope were counted too, the data was analyzed with SPSS software and student's T-Test. The endometrium epithelial cells in experimental group in comparison to control one had vacuoles inside the cytoplasm and volume fractions of nucleus to cell and mitochondria to cell were statistically different P<0.05 and also the mean number of the stromal cells had increased [P<0.05]. The entrance of the lead to the body from living environment in different ways can have adverse effects on the uterine endometrium

The salivary ferning test and ovulation in clomiphene citrate-stimulated cycles.

OBJECTIVE: To determine the day of ovulation by the salivary ferning test in clomiphene citrate-treated women. DESIGN: A descriptive study. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. SUBJECT: Seventy-five infertile women with regular menstrual cycles. MATERIAL AND METHOD: Infertile women were given 100 mg of clomiphene citrate for five days and collected their saliva samples daily until seven days after ovulation. Transvaginal ultrasound was performed daily to detect ovulation. The salivary ferning formation was examined by a normal light microscope and graded from 1-3, according to its extent and intensity. MAIN OUTCOME MEASURE: The salivary ferning score, the peak salivary ferning day, and the day of ovulation detected by ultrasound. RESULTS: The patients' age and cycle length (mean +/- SD) were 32.9 +/- 3.7 years and 28.4 +/- 1.3 days. The peak salivary ferning day corresponded with the ultrasound ovulation day in only 7.1%. There were two peaks of median salivary ferning scores; one was two days prior ovulation and the other was five days post ovulation. There was no correlation between the peak salivary ferning day and day of ovulation detected by ultrasound (r = 0.102, p > 0.05). CONCLUSION: In clomiphene citrate-stimulated cycles, the saliva ferning test does not seem to associate with ovulation.

Effect of GnRH on guinea pig endometrium at preimplantation stage.

Endometrium of GnRH treated group resembled with pregnant group and endometrial thickness in these groups significantly increased in comparison with non-pregnant group. In GnRH treated animals, most of histomorphological changes in epithelial cells, glands and stroma of uterus was similar to pregnant group. The results revealed that mammalian form of GnRH exerted endometrial change in guinea pig almost similar to those occur in normal pregnant animals and its administration prior to implantation may improve pregnancy rate following embryo transfer.

Effect of matrigel on function and morphology of human endometrial epithelial cell in vitro

The importance of extra cellular matrix [ECM] in development and function of different cells has been reported but little is known about its role in human endometrial epithelial cells. The aim of the present study was to examine effects of artificial ECM [Matrigel] and progesterone on the function and morphology of human endometrial epithelial cells in vitro. Endometrial samples were removed, with informed patients consent and Ethics Committee approval, from 17 previously fertile women undergoing total abdominal hysterectomy. The tissue was dissociated and centrifuged to provide an epithelial rich suspension which was cultured either on plastic or seeded into Matrigel to produce polarized cells and then supplemented with or without progesterone [10-6 M]. The amount of nucleic acid content of the cells in both in vitro model systems was examined by DNA, RNA extraction methods. The DNA and RNA content were later measured by spectrophotometry. The amount of total RNA in cells grown on Matrigel [23 +/- 1.5 pg/cell] was more than double that in cells grown on pl1astic [9.1 +/- 1.4 pg/cell]. Cells cultured on both in vitro model systems had RNA induced by steroid hormones, but the extent of induction was greater in cells grown on Matrigel [30 +/- 2 pg/cell] than those on plastic [12 +/- 1.9 pg/cell]. Cells cultured on Matrigel were differentiated and became polarized but cells grown on plastic proliferated to full confluency. Cells grown on Matrigel with progesterone supplementation were highly polarized, euchromatic and had greater mitochondria and accumulation of glycogen, when compared to unsupplemented cultures. These results suggest that ECM plays an important role in gene expression, polarization and differentiation of human endometrial epithelial cells in vitro. Endometrial cells grown on ECM responded to steroid hormone in a manner to that reported in endometrial cells in vivo

Avaliação do endométrio em menopausadas após uso de isoflavonas / Endometrial evaluation in menopausal women after six months of isoflavones

OBJETIVO: Este estudo descritivo e prospectivo teve como objetivo avaliar o endométrio de mulheres menopausadas antes e após seis meses de uso de isoflavonas totais. MÉTODOS: Foi realizado um ensaio clínico não controlado, do tipo antes e depois, em 32 mulheres na pós-menopausa, com idade entre 40 e 60 anos, que receberam 80 mg por dia de isoflavonas totais (Trifolium pratense-Climadil®) durante seis meses. Foram avaliadas no início e no final do tratamento por meio de ultra-sonografia pélvica transvaginal, histeroscopia e biópsia endometrial. Os dados coletados foram registrados no programa Epi Info, versão 6,04b e a análise dos dados foi realizada pelo programa estatístico SAS versão 8,2, considerando um nível de significância (alfa) de 0,05 e um poder (1-beta) de 0,80. As variações médias da espessura endometrial, dos achados histeroscópicos e histológicos, entre os instantes iniciais e após seis meses, foram avaliadas pelo teste t de Student para dados pareados. RESULTADOS: Dentre as 32 mulheres que participaram do estudo, seis apresentaram sangramento vaginal e três, alterações endometriais. Duas mulheres desenvolveram proliferação endometrial e uma, hiperplasia endometrial. Não houve alterações significativas em relação ao espessamento endometrial ao ultra-som. CONCLUSÃO: Neste estudo, três mulheres que utilizaram isoflavonas durante seis meses apresentaram modificações endometriais que sugeriram estímulo endometrial.

OBJETIVE: To evaluate the endometrium of menopausal women before and after six months use of total isoflavone. METHODS: A non-controlled clinical, type "before and after" trial was carried out with 32 post-menopause women, between 40 and 60 years of age. They received 80mg/day of total isoflavones obtained from Trifolium pratense (Climadilâ) during six months. They were evaluated at the beginning and end of treatment by transvaginal pelvic ecography, hysteroscopy and endometrial biopsy. DATA ANALYSIS: Data collected were registered by means of the Epi info, version 6.04b software, data analysis was made using the SAS version 8.2 statistics program, considering a significance level (alpha) of 0.05 and a 0.80 power (1-beta). In order to study the average variation of endometrial thickness and variation of the hysteroscopic and hystologic findings the t Student test for paired data was used. RESULTS: Among the 32 participant women, six presented vaginal bleeding and three presented endometrial alteration when compared to the initial exams. Two of the women developed endometrial cell proliferation and one of them endometrial hiperplasia. There were no significant alterations in relation to endometrial thickness. CONCLUSION: In this study, three women who used isoflavones during the six month period presented endometrial activity.

Evaluation of endometrial changes and p53 expression in tamoxifen treated women: comparison of various methods.

OBJECTIVE: To compare transvaginal sonography (TVS), sonohysterography (SHG), hysteroscopy and endometrial aspiration (EA) and p53 expression in assessing endometrial abnormalities in women on tamoxifen. METHODS: In a cross sectional study of 50 pre- and post-menopausal women receiving tamoxifen for > 2 years, all participants underwent TVS and EA. Those with endometrial thickness > 4 mm on TVS underwent hysteroscopy and SHG. Serum p53 antibody and p53 immunohistochemistry were tested in all women. RESULTS: The sensitivity and specificity when compared with histopathology as the reference standard were as follows: TVS 100% and 33.3%, SHG 85.7% and 50%, hysteroscopy 92.8% and 80.8%, serum p53 50% and 83.3%, and p53 immunohistochemistry 57.1% and 61.1%. Prevalence of endometrial abnormalities was not significantly different in asymptomatic and symptomatic women. CONCLUSION: Tamoxifen-users require routine testing for endometrial evaluation. TVS followed by hysteroscopy and biopsy is an effective option. p53 expression correlates with histological abnormalities.

Clomiphene citrate for ovulation inducation in patients with polycystic ovarian sndrome

To provide fertility assistance and to determine the response of clomiphene citrate in polycystic ovarian syndrome. Observational study. Department of Obstetrics and Gynecology Lady Willingdon Hospital Lahore. Eighty-four patients of polycystic ovarian syndrome who required fertility assistance were subjected to clomiphene citrate therapy for duration of 12 months from February 2005 to January 2006. Clomiphene citrate [50-150mg] was administered from second to sixth day of menstrual cycle and TVS performed on 12th and 16th day of cycle for follicular growth, ovulation, endometerial thickness and echogenic pattern. Ovulation, conception rate, miscarriage rate and ovarian hyperstimulation rate were assessed. In addition the thickness and echogenic pattern of the endometrium was observed in conceived group. Forty-six patients [54.76%] ovulated in six cycles while twenty-seven [32.14%] remained anovulatory. Sixteen women [34.79%] conceived during the study period. Out of which ten women [62.5%] miscarried. Endometerial thickness did not differ [P>.50] between the conceived and non-conceived group but echogenic grade A pattern [75%] was observed during the conceived cycles [P<. 001]. Clomiphene citrate [CC] is a successful drug for ovulation induction in patients with polycystic ovarian syndrome. But the discrepancy in ovulation and pregnancy rate s upport that clomiphene citrate therapy has antiestrogenic effect at the endometrium, which interferes with implantation of pregnancy. The high miscarriage rate in these patients demand some other forms of therapies. These include weight reduction, use of insulin sensitizing drugs, gonadotrophin therapy and ovarian drilling to reduce high LH levels, thus correcting disturbed hormonal milieu, ovulation resumption and pregnancy outcome