Altered Differential Expression of Genes and microRNAs Related to Adhesion and Apoptosis Pathways in Patients with Different Phenotypes of Endometriosis.

We aim to investigate the expression of genes (MAPK1 and CAPN2) and microRNAs (miR-30a-5p, miR-7-5p, miR-143-3p, and miR-93-5p) involved in adhesion and apoptosis pathways in superficial peritoneal endometriosis (SE), deep infiltrating endometriosis (DE), and ovarian endometrioma (OE), and to evaluate whether these lesions share the same pathophysiological mechanisms. We used samples of SE (n = 10), DE (n = 10), and OE (n = 10), and endometrial biopsies of these respective patients affected with endometriosis under treatment at a tertiary University Hospital. Endometrial biopsies collected in the tubal ligation procedure from women without endometriosis comprised the control group (n = 10). Quantitative real-time polymerase chain reaction was performed. The expression of MAPK1 (p < 0.0001), miR-93-5p (p = 0.0168), and miR-7-5p (p = 0.0006) was significantly lower in the SE group than in the DE and OE groups. The expression of miR-30a (p = 0.0018) and miR-93 (p = 0.0052) was significantly upregulated in the eutopic endometrium of women with endometriosis compared to the controls. MiR-143 (p = 0.0225) expression also showed a statistical difference between the eutopic endometrium of women with endometriosis and the control group. In summary, SE showed lower pro-survival gene expression and miRNAs involved in this pathway, indicating that this phenotype has a different pathophysiological mechanism compared to DE and OE.

Misoprostol Administration Before Hysteroscopy Procedures - A Retrospective Analysis / O uso do misoprostol prévio aos procedimentos histeroscópicos - Um estudo retrospectivo

Abstract Objective To evaluate the use of misoprostol prior to hysteroscopy procedures regarding technical ease, the presence of side effects, and the occurrence of complications. Methods This is a retrospective, observational, analytical, case-control study, with the review of medical records of 266 patients followed-up at the Gynecological Videoendoscopy Sector of the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto of the Universidade de São Paulo (HCFMRP - USP, in the Portuguese acronym) from 2014 to 2019, comparing 133 patients who used the drug before the procedure with 133 patients who did not. Results The occurrence of postmenopausal uterine bleeding was the main indication for hysteroscopy and revealed a statistical difference between groups (p < 0.001), being present in 93.23% of the patients in the study group and in 69.7% of the patients in the control group. Only 2 patients (1.5%) in the study group reported adverse effects. Although no statistical differences were observed regarding the occurrence of complications during the procedure (p = 0.0662), a higher total number of complications was noted in the group that used misoprostol (n = 7; 5.26%) compared with the group that did not use the drug (n = 1; 0.75%), a fact that is clinically relevant. When evaluating the ease of the technique (measured by the complete performance of all steps of the hysteroscopy procedure), it was verified that although there was no difference between groups (p = 0.0586), the control group had more than twice as many incompletely performed procedures (n = 17) when compared with the group that used misoprostol previously (n = 8), which is also clinically relevant. Conclusion The use of misoprostol prior to hysteroscopy in our service indicated that the drug can facilitate the performance of the procedure, but not without side effects and presenting higher complication rates.

Resumo Objetivo Avaliação do misoprostol prévio à histeroscopia quanto à facilidade técnica, efeitos colaterais e a ocorrência de complicações durante o procedimento. Métodos Estudo analítico observacional retrospectivo tipo caso controle com revisão de prontuários de 266 pacientes do Setor de Videoendoscopia Ginecológica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo (HCFMRP - USP), de 2014 a 2019, sendo comparadas 133 pacientes que utilizaram o medicamento prévio ao procedimento com 133 pacientes que não o utilizaram. Resultados Sangramento uterino após a menopausa foi a principal indicação de histeroscopia, apresentando diferença estatística (p < 0,001), estando presente em 93,23% das pacientes do grupo de estudo e em 69,17% das pacientes do grupo controle. Apenas 2 pacientes (1,5%) do grupo de estudo relataram efeitos adversos. Não foram observadas diferenças quanto à presença de complicações durante o procedimento (p = 0,0662), mas observamos um número total de complicações maior no grupo de estudo (n = 7; 5,26%) do que no grupo controle (n = 1; 0,75%), o que é clinicamente relevante. Não houve diferença entre os grupos quanto à facilidade técnica (p = 0,0586), mas o grupo controle apresentou mais do que o dobro de procedimentos não completamente realizados (n = 17) quando comparado com o grupo de estudo (n = 8), o que é clinicamente relevante. Conclusão O uso de misoprostol prévio à histeroscopia no nosso serviço demonstrou que ele pode facilitar a realização do procedimento, mas não é isento de efeitos colaterais e apresenta maiores taxas de complicações.

Prevalence of chronic pelvic pain and primary dysmenorrhea in women of reproductive age in Ecuador.

BACKGROUND: Chronic pelvic pain (CPP) and primary dysmenorrhoea are debilitating conditions that can impair the quality of life of affected women. These conditions are frequently neglected, delaying proper diagnosis and healthcare provision. This study aimed to estimate the prevalence of CPP and primary dysmenorrhoea in Ecuador and identify potential variables associated with their occurrence. METHODS: We conducted a cross-sectional survey in an urban neighbourhood of Quito, the capital of Ecuador. A total of 2397 participants of 14-49 years of age were included. The data were collected through questionnaires administered by trained interviewers.The crude and adjusted prevalence ratios were calculated using a log-binomial regression model. The correlation between pain intensity catastrophising of symptoms were statistically analysed. RESULTS: The prevalence of CPP and primary dysmenorrhoea was 9.8% and 8.9%, respectively. Irritative urinary symptoms, primary dysmenorrhoea, and underlying mental disorders were associated with CPP, while smoking, irritable bowel syndrome, sleep disturbance, dyspareunia, and mental disorders were associated with primary dysmenorrhoea. CONCLUSIONS: The prevalence of CPP and primary dysmenorrhoea in Ecuador was similar to that in other Latin American countries. Primary dysmenorrhoea is a risk factor of CPP, and less than a quarter of women are undergoing treatment for the condition. Our findings reinforce the importance of healthcare interventions in anticipating the diagnosis of these conditions in women of reproductive age.

Misoprostol Administration Before Hysteroscopy Procedures - A Retrospective Analysis.

OBJECTIVE: To evaluate the use of misoprostol prior to hysteroscopy procedures regarding technical ease, the presence of side effects, and the occurrence of complications. METHODS: This is a retrospective, observational, analytical, case-control study, with the review of medical records of 266 patients followed-up at the Gynecological Videoendoscopy Sector of the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto of the Universidade de São Paulo (HCFMRP - USP, in the Portuguese acronym) from 2014 to 2019, comparing 133 patients who used the drug before the procedure with 133 patients who did not. RESULTS: The occurrence of postmenopausal uterine bleeding was the main indication for hysteroscopy and revealed a statistical difference between groups (p < 0.001), being present in 93.23% of the patients in the study group and in 69.7% of the patients in the control group.: Only 2 patients (1.5%) in the study group reported adverse effects. Although no statistical differences were observed regarding the occurrence of complications during the procedure (p = 0.0662), a higher total number of complications was noted in the group that used misoprostol (n = 7; 5.26%) compared with the group that did not use the drug (n = 1; 0.75%), a fact that is clinically relevant. When evaluating the ease of the technique (measured by the complete performance of all steps of the hysteroscopy procedure), it was verified that although there was no difference between groups (p = 0.0586), the control group had more than twice as many incompletely performed procedures (n = 17) when compared with the group that used misoprostol previously (n = 8), which is also clinically relevant. CONCLUSION: The use of misoprostol prior to hysteroscopy in our service indicated that the drug can facilitate the performance of the procedure, but not without side effects and presenting higher complication rates.

OBJETIVO: Avaliação do misoprostol prévio à histeroscopia quanto à facilidade técnica, efeitos colaterais e a ocorrência de complicações durante o procedimento. MéTODOS: Estudo analítico observacional retrospectivo tipo caso controle com revisão de prontuários de 266 pacientes do Setor de Videoendoscopia Ginecológica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo (HCFMRP ­ USP), de 2014 a 2019, sendo comparadas 133 pacientes que utilizaram o medicamento prévio ao procedimento com 133 pacientes que não o utilizaram. RESULTADOS: Sangramento uterino após a menopausa foi a principal indicação de histeroscopia, apresentando diferença estatística (p < 0,001), estando presente em 93,23% das pacientes do grupo de estudo e em 69,17% das pacientes do grupo controle. Apenas 2 pacientes (1,5%) do grupo de estudo relataram efeitos adversos. Não foram observadas diferenças quanto à presença de complicações durante o procedimento (p = 0,0662), mas observamos um número total de complicações maior no grupo de estudo (n = 7; 5,26%) do que no grupo controle (n = 1; 0,75%), o que é clinicamente relevante. Não houve diferença entre os grupos quanto à facilidade técnica (p = 0,0586), mas o grupo controle apresentou mais do que o dobro de procedimentos não completamente realizados (n = 17) quando comparado com o grupo de estudo (n = 8), o que é clinicamente relevante. CONCLUSãO: O uso de misoprostol prévio à histeroscopia no nosso serviço demonstrou que ele pode facilitar a realização do procedimento, mas não é isento de efeitos colaterais e apresenta maiores taxas de complicações.

Impact of Bevacizumab on Experimentally Induced Endometriotic Lesions: Angiogenesis, Invasion, Apoptosis, and Cell Proliferation.

Endometriosis is responsible for pain symptoms with great impact on the patient's quality of life. Several medication lines have been studied aiming at its definitive treatment. Among them, angiogenesis inhibitor factors may be effective given that angiogenesis has fundamental role in the establishment and growth of endometriotic lesions. In this study, we investigated the influence of bevacizumab, anti-factor drug of endothelial growth (anti-VEGF), used at two different dosages, in experimental endometriosis induced in rats. After the induction of endometriosis lesions in rats, they were divided in 3 groups: control group, no treatment, and two other groups were treated with different dosages of the same medication for 4 weeks. At the end of the treatment, endometriotic lesions were removed and evaluated regarding area of lesions, presence of endometrial tissue in microscopy, positivity for anti-VEGF antibody in immunohistochemistry, and gene expression of Pcna, Mmp9, Tp63, and Vegfa. Bevacizumab acted by reducing the area of lesions in the groups that received medication (p = 0.002) and reducing gene expression to Tp63 in lesions (p = 0.04). There was no significant result in other evaluations. We observed that there was significant reduction of the area of lesions among groups, suggesting that bevacizumab has a positive effect on disease control. The gene expression of Tp63 was significantly lower in the group that received high dose of the drug when compared with the other two groups; therefore, we concluded that bevacizumab acts by reducing cell proliferation and differentiation in lesions, constituting a real option for treating endometriosis.

Analysis of body composition and pain intensity in women with chronic pelvic pain secondary to endometriosis / Análise da composição corporal e intensidade de dor em mulheres com dor pélvica crônica secundária a endometriose

Abstract Objective To determine the average body composition (percentage of body fat), the anthropometric markers, and the intensity of clinical pain in women with a clinical diagnosis of chronic pelvic pain (CPP) secondary to endometriosis. Methods A case-control study performed with 91 women, 46 of whom with CPP secondary to endometriosis and 45 of whom with CPP secondary to other causes. They underwent an evaluation of the anthropometric parameters by means of the body mass index (BMI), the perimeters (waist, abdomen, hip), and the percentage of body fat (%BF), which were assessed on a body composition monitor by bioimpedance; the intensity of the clinical pain was evaluated using the visual analog scale (VAS), and the symptoms of anxiety and depression, using the hospital's anxiety and depression scale (HAD). Results The groups did not differ in terms of mean age, BMI, %BF or regarding the available waist-to-hip ratio (WHR). The mean intensity of the clinical pain by the VAS was of 7.2 ± 2.06 in the group with CPP secondary to endometriosis, and of 5.93 ± 2.64 in the group with CPP secondary to other causes (p = 0.03), revealing significant differences between the groups. Conclusion We concluded that, despite the difference in the pain score assessed between the two groups, there was no difference regarding body composition and anthropometry.

Resumo Objetivo Determinar a composição corporal média (porcentagem de gordura corporal), os marcadores antropométricos, e a intensidade de dor clínica em mulheres com diagnóstico clínico de dor pélvica crônica (DPC) secundária a endometriose. Métodos Um estudo de caso-controle realizado com 91 mulheres, 46 das quais com DPC secundária a endometriose, e 45 das quais com DPC secundária a outras causas. As pacientes foram submetidas à avaliação dos parâmetros antropométricos por meio do índice de massa corporal (IMC), dos perímetros (cintura, abdômen, quadril), e do percentual de gordura corporal (%GC), que foram avaliados emmonitor de composição corporal por bioimpedância; a intensidade clínica da dor foi avaliada usando-se a escala visual analógica (EVA), e os sintomas de ansiedade e depressão, usando a escala de ansiedade e depressão do hospital (EADH). Resultados Os grupos não diferiram quanto à idade média, ao IMC, ao %GC, nem quanto à relação da cintura-quadril (RCQ) disponível. Amédia da intensidade clínica da dor pela EVA foi de 7,2 ± 2,06 no grupo com DPC secundária a endometriose, e de 5,93 ± 2,64 no grupo com DPC secundária a outras causas (p = 0,03), revelando diferenças significativas entre os grupos. Emrelação à EADH, ambos os grupos estavam acima da média de corte. Conclusão Concluímos que, apesar da diferença no escore de dor avaliado entre os dois grupos, não houve diferença com relação à composição corporal e à antropometria.

Thalidomide Reduces Cell Proliferation in Endometriosis Experimentally Induced in Rats.

OBJECTIVE: To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium. METHODS: Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells. RESULTS: Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2 mm2, a significantly higher value compared with Group II (49.4 mm2, p = 0.023) and Group III (48.6 mm2, p = 0.006). No significant difference was observed between Groups II and III. CONCLUSION: Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1 mg/kg/day and at the dose of 10 mg/kg/day.

OBJETIVO: Analisar o efeito da talidomida na progressão de lesões endometrióticas induzidas experimentalmente em ratas e caracterizar o padrão de proliferação celular pela marcação imunohistoquímica de Antígeno Nuclear de Célula Proliferativa (PCNA) no endométrio eutópico e ectópico. MéTODOS: Quinze ratas Wistar foram submetidas a laparotomia para indução de endometriose por ressecção de um corno uterino, isolamento do endométrio e fixação de um segmento do tecido ao peritônio pélvico. Após quatro semanas, os animais foram divididos em 3 grupos: controle (I), 10 mg/kg/dia (II) e 1 mg/kg/dia (III) de talidomida intraperitoneal por um período de 10 dias. As lesões foram resseccionadas juntamente com o corno uterino oposto para análise da glândula endometrial e do estroma. O tecido endometrial eutópico e ectópico foi submetido à imunohistoquímica para análise da proliferação celular por marcação com PCNA e o índice de proliferação celular (CPI) foi calculado como o número de células marcadas por 1.000 células. RESULTADOS: O grupo I apresentou média de CPI de 0,248 ± 0,0513 na glândula e de 0,178 ± 0,046 no estroma. Em contraste, os grupos II e III apresentaram CPI significativamente menor, isto é, 0,088 ± 0,009 e 0,080 ± 0,021 para a glândula (p < 0,001) e 0,0945 ± 0,0066 e 0,075 ± 0,018 para o estroma (p < 0,001), respectivamente. Além disso, a área de lesão média do Grupo I foi de 69,2 mm2, valor significativamente maior em relação ao Grupo II (49,4 mm2, p = 0,023) e Grupo III (48,6 mm2, p = 0,006). Não houve diferença estatisticamente significante entre os Grupos II e III. CONCLUSãO: A talidomida mostrou-se eficaz na redução da área da lesão e CPI dos implantes de endometriose experimental tanto na dose de 1 mg/kg/dia quanto na dose de 10 mg/kg/dia.

Thalidomide reduces cell proliferation in endometriosis experimentally induced in rats / A talidomida induz diminuição da proliferação celular em endometriose experimentalmente induzida em ratas

Abstract Objective To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium. Methods Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells. Results Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2mm2, a significantly higher value compared with Group II (49.4mm2, p = 0.023) and Group III (48.6mm2, p = 0.006). No significant difference was observed between Groups II and III. Conclusion Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1mg/kg/day and at the dose of 10 mg/kg/day.

Resumo Objetivo Analisar o efeito da talidomida na progressão de lesões endometrióticas induzidas experimentalmente em ratas e caracterizar o padrão de proliferação celular pela marcação imunohistoquímica de Antígeno Nuclear de Célula Proliferativa (PCNA) no endométrio eutópico e ectópico. Métodos Quinze ratas Wistar foram submetidas a laparotomia para indução de endometriose por ressecção de um corno uterino, isolamento do endométrio e fixação de um segmento do tecido ao peritônio pélvico. Após quatro semanas, os animais foram divididos em 3 grupos: controle (I), 10 mg/kg/dia (II) e 1 mg/kg/dia (III) de talidomida intraperitoneal por um período de 10 dias. As lesões foram resseccionadas juntamente com o corno uterino oposto para análise da glândula endometrial e do estroma. O tecido endometrial eutópico e ectópico foi submetido à imunohistoquímica para análise da proliferação celular por marcação com PCNA e o índice de proliferação celular (CPI) foi calculado como o número de células marcadas por 1.000 células. Resultados O grupo I apresentou média de CPI de 0,248 ± 0,0513 na glândula e de 0,178 ± 0,046 no estroma. Em contraste, os grupos II e III apresentaram CPI significativamentemenor, isto é, 0,088 ± 0,009 e 0,080 ± 0,021 para a glândula (p < 0,001) e 0,0945 ± 0,0066 e 0,075 ± 0,018 para o estroma (p < 0,001), respectivamente. Além disso, a área de lesãomédia do Grupo I foi de 69,2mm2, valor significativamentemaior em relação ao Grupo II (49,4mm2, p = 0,023) e Grupo III (48,6mm2, p = 0,006). Não houve diferença estatisticamente significante entre os Grupos II e III. Conclusão A talidomida mostrou-se eficaz na redução da área da lesão e CPI dos implantes de endometriose experimental tanto na dose de 1mg/kg/dia quanto na dose de 10 mg/kg/dia.

Current usage of qualitative research in female pelvic pain: a systematic review.

PURPOSE: Qualitative research has received growing attention in the multidisciplinary investigation of patients' perceptions about chronic diseases. The purpose of this systematic review was to characterize the usage of qualitative research in women with chronic pelvic pain (CPP). METHODS: We performed a structured search in Web of Science, Pubmed, and EMBASE platforms until June 2019. The search combined the keywords: "pelvic pain", "endometriosis", "dyspareunia", "dysmenorrhea", "vaginismus", "focus groups", "qualitative research", "hermeneutics", "grounded theory", and "women". Qualitative studies on female CPP were included and the main findings combined using thematic synthesis. RESULTS: We found 1211 citations, of which 52 were included in this review. The majority of included studies were based on phenomenological design. The main method for data collection was semi-structured interviews. Endometriosis was the theme of 23 studies, chronic pelvic pain of eight, dysmenorrhea of eight, dyspareunia of four, interstitial cystitis of two, vaginismus of two, vulvodynia of two, and pelvic inflammatory disease of one study. We found a wide variety of contributions. Among them, the impact of the disease on women's lives was the commonest. CONCLUSION: Qualitative research has the potential to reveal and explain several aspects of CPP in women. The medical community may better accept knowledge gained from these studies if the methods are described more transparently in published articles.

Increased Expression Levels of Metalloprotease, Tissue Inhibitor of Metalloprotease, Metallothionein, and p63 in Ectopic Endometrium: An Animal Experimental Study.

OBJECTIVE: To characterize the patterns of cell differentiation, proliferation, and tissue invasion in eutopic and ectopic endometrium of rabbits with induced endometriotic lesions via a well- known experimental model, 4 and 8 weeks after the endometrial implantation procedure. METHODS: Twenty-nine female New Zealand rabbits underwent laparotomy for endometriosis induction through the resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of animals (one with 14 animals, and the other with15) were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised along with the opposite uterine horn for endometrial gland and stroma determination. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissues for analysis of the following markers: metalloprotease (MMP-9) and tissue inhibitor of metalloprotease (TIMP-2), which are involved in the invasive capacity of the endometrial tissue; and metallothionein (MT) and p63, which are involved in cell differentiation and proliferation. RESULTS: The intensity of the immunostaining for MMP9, TIMP-2, MT, and p63 was higher in ectopic endometria than in eutopic endometria. However, when the ectopic lesions were compared at 4 and 8 weeks, no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue. CONCLUSION: Ectopic endometrial lesions seem to express greater power for cell differentiation and tissue invasion, compared with eutopic endometria, demonstrating a potentially invasive, progressive, and heterogeneous presentation of endometriosis.

OBJETIVO: Caracterizar o padrão de diferenciação celular, proliferação e invasão tecidual em endométrio eutópico e ectópico de coelhas com lesões de endometriose induzidas por um modelo experimental 4 e 8 semanas após o procedimento de implantação endometrial. MéTODOS: Vinte e nove coelhas fêmeas Nova Zelândia foram submetidas a laparotomia para indução de endometriose através da ressecção de um dos cornos uterinos, isolamento do endométrio e fixação do tecido no peritônio pélvico. Dois grupos de animais (14 animais em um grupo e 15 animais no outro) foram sacrificados 4 e 8 semanas após a indução da endometriose. A lesão foi excisada junto com o corno uterino contralateral para determinação da presença de glândulas e de estroma endometrial. Reações de imunohistoquímica foram realizadas no tecido endometrial eutópico e ectópico para análise dos seguintes marcadores: metaloprotease (MMP9) e inibidor tecidual da metaloprotease 2 (TIMP-2), os quais estão envolvidos na capacidade de invasão do tecido endometrial; e metalotioneina (MT) e p63, os quais estão envolvidos na diferenciação e proliferação celular. RESULTADOS: A intensidade da imunomarcação para MMP9, TIMP-2, MT e p63 foi mais alta nos endométrios ectópicos do que nos endométrios eutópicos. Contudo, quando as lesões foram comparadas entre 4 e 8 semanas, nenhuma diferença foi observada, com exceção do marcador p63, o qual foi mais evidente depois de 8 semanas de evolução do tecido endometrial ectópico. CONCLUSãO: Lesões endometriais ectópicas parecem expressar maior poder de diferenciação celular e de invasão tecidual comparadas com endométrios eutópicos, demonstrando o potencial de invasão, de progressão e de apresentação heterogênea da endometriose.

Increased expression levels of metalloprotease, tissue inhibitor of metalloprotease, metallothionein, and p63 in ectopic endometrium: an animal experimental study / Aumento nos níveis de expressão de metaloprotease, inibidor tecidual das metaloproteases, metalotioneina e p63 em endométrio ectópico: um estudo experimental animal

Abstract Objective To characterize the patterns of cell differentiation, proliferation, and tissue invasion in eutopic and ectopic endometrium of rabbits with induced endometriotic lesions via a well- known experimental model, 4 and 8 weeks after the endometrial implantation procedure. Methods Twenty-nine female New Zealand rabbits underwent laparotomy for endometriosis induction through the resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of animals (one with 14 animals, and the other with15) were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised along with the opposite uterine horn for endometrial gland and stroma determination. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissues for analysis of the following markers: metalloprotease (MMP-9) and tissue inhibitor of metalloprotease (TIMP-2), which are involved in the invasive capacity of the endometrial tissue; and metallothionein (MT) and p63, which are involved in cell differentiation and proliferation. Results The intensity of the immunostaining for MMP9, TIMP-2, MT, and p63 was higher in ectopic endometria than in eutopic endometria. However, when the ectopic lesions were compared at 4 and 8 weeks, no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue. Conclusion Ectopic endometrial lesions seem to express greater power for cell differentiation and tissue invasion, compared with eutopic endometria, demonstrating a potentially invasive, progressive, and heterogeneous presentation of endometriosis.

Resumo Objetivo Caracterizar o padrão de diferenciação celular, proliferação e invasão tecidual em endométrio eutópico e ectópico de coelhas com lesões de endometriose induzidas por um modelo experimental 4 e 8 semanas após o procedimento de implantação endometrial. Métodos Vinte e nove coelhas fêmeas Nova Zelândia foram submetidas a laparotomia para indução de endometriose através da ressecção de um dos cornos uterinos, isolamento do endométrio e fixação do tecido no peritônio pélvico. Dois grupos de animais (14 animais em um grupo e 15 animais no outro) foram sacrificados 4 e 8 semanas após a indução da endometriose. A lesão foi excisada junto com o corno uterino contralateral para determinação da presença de glândulas e de estroma endometrial. Reações de imunohistoquímica foram realizadas no tecido endometrial eutópico e ectópico para análise dos seguintes marcadores: metaloprotease (MMP9) e inibidor tecidual da metaloprotease 2 (TIMP-2), os quais estão envolvidos na capacidade de invasão do tecido endometrial; e metalotioneina (MT) e p63, os quais estão envolvidos na diferenciação e proliferação celular. Resultados A intensidade da imunomarcação para MMP9, TIMP-2, MT e p63 foi mais alta nos endométrios ectópicos do que nos endométrios eutópicos. Contudo, quando as lesões foram comparadas entre 4 e 8 semanas, nenhuma diferença foi observada, com exceção do marcador p63, o qual foi mais evidente depois de 8 semanas de evolução do tecido endometrial ectópico. Conclusão Lesões endometriais ectópicas parecem expressar maior poder de diferenciação celular e de invasão tecidual comparadas com endométrios eutópicos, demonstrando o potencial de invasão, de progressão e de apresentação heterogênea da endometriose.

Translation and validation of the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire for the Brazilian Portuguese language / Tradução e validação do questionário Uterine Fibroid Symptom and Quality of Life (UFS-QOL) para a língua portuguesa brasileira

ABSTRACT CONTEXT AND OBJECTIVE: Uterine fibroids (UF), also known as leiomyomas, are the most prevalent gynecological tumors. The Uterine Fibroid Symptoms and Quality of Life (UFS-QOL) is the only specific questionnaire that assesses symptom intensity and quality-of-life issues for women with symptomatic UF; however, it only exists in the English language. Thus, we aimed to translate and culturally validate the UFS-QOL questionnaire for the Brazilian Portuguese language. DESIGN AND SETTING: Cross-sectional study, Department of Gynecology and Obstetrics, FMRP-USP. METHODS: 113 patients with UF (case group) and 55 patients without UF (control group) were interviewed using the UFS-QOL questionnaire after translation and cultural adaptation. The Short Form-36 questionnaire was used as a control. Demographic and psychometric variables were analyzed. RESULTS: Women with UF presented higher mean age, body mass index, weight, parity and comorbidities than the control group (P < 0.05). The most prevalent complaints were abnormal uterine bleeding (93.8%), pelvic pain (36.3%) and extrinsic compression (10.6%) and these presented adequate construct validity regarding UFS-QOL severity (P < 0.05). The UFS-QOL questionnaire presented good internal consistency regarding symptom severity and quality-of-life-related domains (intraclass correlation coefficient, ICC = 0.82/0.88). Structural validity presented correlation coefficients ranging from 0.59 to 0.91. Test-retest comparison did not show differences among the UFS-QOL subscales. After treatment, women with UF presented improvements on all subscales. CONCLUSION: The UFS-QOL questionnaire presented adequate translation to the Brazilian Portuguese language, with good internal consistency, discriminant validity, construct validity, structural validity and responsiveness, along with adequate test-retest results.

RESUMO CONTEXTO E OBJETIVO: O leiomioma uterino (LU) é o tumor ginecológico mais comum. Existe apenas um questionário específico que avalia a intensidade de sintomas e qualidade de vida de mulheres com LU sintomático, o Uterine Fibroid Symptom and Quality of Life (UFS-QOL), porém somente na língua inglesa. Dessa forma, objetivamos traduzir e validar culturalmente o questionário UFS-QOL para a língua portuguesa brasileira. TIPO DE ESTUDO E LOCAL: Estudo transversal, Departamento de Ginecologia e Obstetrícia da FMRP-USP. MÉTODOS: 113 pacientes portadoras de LU (grupo caso) e 55 pacientes-controle foram entrevistadas com o questionário UFS-QOL após tradução e adaptação cultural. O questionário Short Form-36 foi utilizado para controle. Variáveis demográficas e psicométricas foram analisadas. RESULTADOS: As mulheres com LU apresentaram maior média de idade, índice de massa corporal, peso, paridade e comorbidades do que o grupo controle (P < 0,05). As queixas mais prevalentes foram sangramento uterino anormal (93,8%), dor pélvica (36,3%) e compressão extrínseca (10,6%) e estas apresentaram adequada validade de constructo com a gravidade indicada pelo UFS-QOL (P < 0,05). O questionário UFS-QOL apresentou boa consistência interna com a gravidade dos sintomas e com os domínios relacionados a qualidade de vida (coeficiente de correlação intraclasse, CCI = 0,82/0,88). A validade estrutural mostrou coeficientes de correlação variando de 0,59 até 0,91. A comparação teste-reteste não mostrou diferença entre as subscalas do UFS-QOL. Depois do tratamento, as mulheres com LU apresentaram melhora em todas as subscalas. CONCLUSÃO: O questionário UFS-QOL apresentou adequada tradução para a língua portuguesa brasileira, com boa consistência interna, validade de constructo/discriminatória, estrutural e responsividade, assim como adequados resultados teste-reteste.

Translation and validation of the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire for the Brazilian Portuguese language.

CONTEXT AND OBJECTIVE:: Uterine fibroids (UF), also known as leiomyomas, are the most prevalent gynecological tumors. The Uterine Fibroid Symptoms and Quality of Life (UFS-QOL) is the only specific questionnaire that assesses symptom intensity and quality-of-life issues for women with symptomatic UF; however, it only exists in the English language. Thus, we aimed to translate and culturally validate the UFS-QOL questionnaire for the Brazilian Portuguese language. DESIGN AND SETTING:: Cross-sectional study, Department of Gynecology and Obstetrics, FMRP-USP. METHODS:: 113 patients with UF (case group) and 55 patients without UF (control group) were interviewed using the UFS-QOL questionnaire after translation and cultural adaptation. The Short Form-36 questionnaire was used as a control. Demographic and psychometric variables were analyzed. RESULTS:: Women with UF presented higher mean age, body mass index, weight, parity and comorbidities than the control group (P < 0.05). The most prevalent complaints were abnormal uterine bleeding (93.8%), pelvic pain (36.3%) and extrinsic compression (10.6%) and these presented adequate construct validity regarding UFS-QOL severity (P < 0.05). The UFS-QOL questionnaire presented good internal consistency regarding symptom severity and quality-of-life-related domains (intraclass correlation coefficient, ICC = 0.82/0.88). Structural validity presented correlation coefficients ranging from 0.59 to 0.91. Test-retest comparison did not show differences among the UFS-QOL subscales. After treatment, women with UF presented improvements on all subscales. CONCLUSION:: The UFS-QOL questionnaire presented adequate translation to the Brazilian Portuguese language, with good internal consistency, discriminant validity, construct validity, structural validity and responsiveness, along with adequate test-retest results.

Cultural Adaptation of the Patient Satisfaction Questionnaire and Validation of Its Use in the Portuguese Language for Women with Chronic Pelvic Pain / Transculturação e validação do questionário de satisfação do paciente para a língua portuguesa para mulheres com dor pélvica crônica

Abstract Objectives to translate and adapt the Patient Satisfaction Questionnaire (PSQ) to Portuguese and to assess its psychometric properties based on internal consistency, test-retest, factor analysis and divergent and convergent construct validities. Methods The study involved 218 participants and was approved by the local Research Ethics Committee. All participants gave written informed consent and their anonymity was ensured. The instrument was translated and culturally adapted for use in the Portuguese language. The internal consistency and factorial analysis were assessed by patients and physicians. Convergent and divergent validities were also assessed specifically for the patient group, as well as test-retest reliability. The Portuguese versions of the Patient Health Questionnaire (PHQ-9) and State-Trait Anxiety Inventory (STAI) were used for the analysis of the convergent validity. In addition, we applied a questionnaire of clinical and demographic data for the analysis of the divergent validity. Results The adapted version of the PSQ showed good Cronbach’s α and test-retest values, and the results of the convergent construct validity between the PSQ and the PHQ-9 (r = 0.34; p = 0.02) and the STAI (r = 0.47; p = 0.001) were negative, significant and moderate correlations. Divergent validity showed significant correlations only with race and education. The Brazilian Portuguese versionof the PSQ proved to be a valid and reliable instrument, with psychometric properties suitable for the assessment of satisfaction among patients with chronic pelvic pain and their physicians in Brazil. The questionnairemay allow the homogenization of reports on this topic in the international literature.

Resumo Objetivo traduzir e adaptar o Patient Satisfaction Questionnaire (PSQ) para o Português e avaliar suas propriedades psicométricas com base na consistência interna, teste-reteste, análise fatorial e validades de construto divergente e convergente. Métodos O estudo incluiu 218 participantes e foi aprovado pelo Comitê de Ética em Pesquisa local. Todos os participantes assinaram o termo de consentimento livre e esclarecido, e o anonimato dos participantes foi assegurado. O instrumento foi traduzido e adaptado culturalmente para uso em Português. A consistência interna e análise fatorial foram avaliadas por pacientes e médicos. As validades convergente e divergente também foram avaliadas especificamente para o grupo de pacientes, bem como a confiabilidade teste-reteste. O Questionário de Saúde do Paciente (PHQ-9) e o Inventário de Ansiedade Traço-Estado (STAI) foram utilizados para a análise da validade convergente. Além disso, foi aplicado um questionário de dados clínicos e demográficos para análise da validade divergente. Resultados A versão adaptada do PSQ apresentou bons valores alfa de Cronbach e teste-reteste, e a validade de construto convergente entre o PSQ e o PHQ-9 (r = 0 ,34; p = 0,02) e o STAI (r = 0,47; p = 0,001) foram negativas, significativas e com correlação moderada. A validade divergente mostrou correlações significativas com raça e educação. Conclusão: a versão brasileira do PSQ provou ser um instrumento válido e confiável, com propriedades psicométricas adequadas para a avaliação da satisfação entre os pacientes com dor pélvica crônica e seus médicos no Brasil. O questionário pode permitir a homogeneização dos relatórios sobre este tema na literatura internacional.

The Influence of Education and Depression on Autonomy of Women with Chronic Pelvic Pain: A Cross-sectional Study / A influência da educação e depressão sobre a autonomia de mulheres com dor pélvica crônica: um estudo transversal

Objective Patient autonomy has great importance for a valid informed consent in clinical practice. Our objectives were to quantify thedomains of patient autonomy and to evaluate the variables that can affect patient autonomy in women with chronic pelvic pain. Methods This study is a cross sectional survey performed in a tertiary care University Hospital. Fifty-two consecutive women scheduled for laparoscopic management of chronic pelvic were included. Three major components of autonomy (competence, information or freedom) were evaluated using a Likert scale with 24 validated affirmatives. Results Competence scores (0.85 vs 0.92; p = 0.006) and information scores (0.90 vs 0.93; p = 0.02) were low for women with less than eight years of school attendance. Information scores were low in the presence of anxiety (0.91 vs 0.93; p = 0.05) or depression (0.90 vs 0.93; p = 0.01). Conclusions Our data show that systematic evaluation of patient autonomy can provide clinical relevant information in gynecology. Low educational level, anxiety and depression might reduce the patient autonomy in women with chronic pelvic pain.

Objetivo A autonomia da paciente é de grande importância para que o consentimento informado seja válido na prática clínica. Nossos objetivos foram quantificar os domínios da autonomia e avaliar variáveis que modificam a autonomia em mulheres com dor pélvica crônica. Métodos Este é um estudo transversal realizado em um Hospital Universitário terciário. Foram incluídas consecutivamente 52 mulheres com dor pélvica crônica agendadas para videolaparoscopia. Foi utilizada uma escala Likert com 24 afirmativas validadas para quantificar os três principais componentes da autonomia (competência, informação e liberdade). Resultados Os escores de competência (0,85 vs 0,92; p = 0,006) e informação (0,90 vs 0,93; p = 0,02) foram menores para mulheres com ensino fundamental incompleto. Os escores de informação foram menores em mulheres com sintomas de ansiedade (0,91 vs 0,93; p = 0,05) ou depressão (0,90 vs 0,93; p = 0,01). Conclusões Nossos dados mostram que a quantificação da autonomia pode produzir informações relevantes para a prática clínica em ginecologia. O nível educacional e a presença de ansiedade e depressão podem afetar a autonomia de mulheres com dor pélvica crônica.

Low-dose progestin-releasing contraceptives are associated with a higher pain threshold in healthy women.

OBJECTIVE: To determine the pain thresholds of women taking different formulations of hormonal contraceptives. DESIGN: Cross-sectional study. SETTING: Basic health care unit. PATIENT(S): Eighty-nine healthy nonusers and 188 users of hormonal contraceptives. INTERVENTION(S): Subject interviews were followed by the application of a semistructured questionnaire, including a psychometric assessment with the Beck Depression Inventory and the State-Trait Anxiety Inventory. After the interview, a 10-mL peripheral blood sample was collected. Pain thresholds were obtained by performing pressure algometry. MAIN OUTCOME MEASURE(S): Serum concentrations of E2, P, and T (free fraction) were determined via chemoluminescence. The menstrual cycle phase was determined according to hormonal level and identification of an LH surge in urine. Pain threshold was evaluated with a dynamometer applied to the forearm skin of the nondominant limb and abdominal wall. RESULT(S): Progestin-only contraceptive users showed a higher pain pressure threshold in the forearm (2.94 ± 0.96 vs. 2.74 ± 0.89 vs. 2.62 ± 0.92) and right (2.11 ± 0.87 vs. 1.83 ± 0.81 vs. 1.78 ± 0.77) and left abdomen (2.12 ± 0.88 vs. 1.79 ± 0.76 vs. 1.73 ± 0.70) than did combined hormonal contraceptive users and nonusers of hormonal contraceptives, respectively. Users of contraceptives that continuously release etonogestrel (subcutaneous implant, vaginal ring) or levonorgestrel (intrauterine devices) had higher pain thresholds. CONCLUSION(S): Women who used hormonal contraceptives enabling continuous release of etonogestrel or levonorgestrel tended to have higher pain thresholds than did nonusers of hormonal contraceptives.

Presentation and treatment of uterine leiomyoma in adolescence: a systematic review.

BACKGROUND: Uterine leiomyoma is the most common gynecological tumor in the reproductive years. However, it is extremely rare in adolescence (<1%), with few reports found in the literature. The biological behavior of such tumors in this age group is unknown, as well as the best possible treatment for this population. We aimed to analyze all available reports of uterine leiomyoma in adolescence. METHODS: A systematic review was performed at PubMed/MEDLINE and EMBASE. Between 1965 and 2014, 19 reports were found on uterine leiomyoma in patients under 18 years. The following parameters were discussed: age, tumor diameter, symptoms, clinical treatments, surgical treatments, hemodynamic changes. RESULTS: Mean age was 15.35 (14-17) years. Mean tumor diameter was 12.28 cm (3-30) and median diameter was 10 cm. Most patients presented with symptoms (87.5%), including abnormal uterine bleeding (10/18) and pelvic/abdominal pain (6/18). A pelvic mass was the most common finding. Two patients required transfusion due to anemia. One patient underwent abdominal hysterectomy, and the others underwent myomectomy. Mean follow-up was 1 year and 8 months, and only case recurred, after 6 months. CONCLUSION: Leiomyomas' biologic behavior in adolescents may be different from that of older women, but their molecular characteristics still haven't been analyzed. Optimal treatment is still not defined, but myomectomy has several advantages in this population. Leiomyomas must be remembered as an important differential diagnosis of pelvic mass in adolescents.