Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/332513
Type: DISSERTAÇÃO DIGITAL
Degree Level: Mestrado
Title: Avaliação de biomarcadores em mulheres com endometriose e dor usuárias do implante liberador de etonogestrel ou sistema intrauterino liberador de levonorgestrel = Assessment of biomarkers among women with endometriosis-associated pain users of the etonogestrel-releasing contraceptive implant or 52-mg levonorgestrel releasing intrauterine system: randomized clinical trial : ensaio clínico randomizado
Title Alternative: Assessment of biomarkers among women with endometriosis-associated pain users of the etonogestrel-releasing contraceptive implant or 52-mg levonorgestrel releasing intrauterine system : randomized clinical trial
Author: Gonçalves, Deborah Margatho Ramos, 1975-
Advisor: Bahamondes, Luis Guillermo, 1946-
Abstract: Resumo: Está descrito que a prevalência da endometriose ocorre entre 2 a 10% das mulheres em idade reprodutiva sendo que dor pélvica crônica, infertilidade, dismenorréia e dispareunia de profundidade estão entre os principais sintomas. O diagnóstico padrão ouro é cirúrgico, no entanto, a dificuldade de se obter informações de infiltração retroperitonial das lesões na cirurgia, levou a propor uma classificação por métodos de imagem, como ressonância nuclear magnética (RNM) de pelve e ultrassonografia (US) para pesquisa de endometriose profunda, que contribuem conjuntamente para diagnóstico. O tratamento pode ser cirúrgico, e medicamentoso, indicado isoladamente e ou complementarmente. O objetivo do tratamento clínico é reduzir a produção estrogênica e com isto a inflamação. Os contraceptivos hormonais são efetivos no tratamento e com baixo custo. Entre as opções de somente progestogenio estão disponíveis o sistema intrauterino liberador de levonorgestrel (SIU-LNG) com 52 mg o qual tem sido estudado em mulheres com endometriose e dor, com resultados positivos, porém há poucos estudos com o implante liberador de etonogestrel (ENG) para essa finalidade. O objetivo deste estudo foi o de comparar os níveis séricos dos marcadores CA-125 e CD 23 e densidade de fibras nervosas em mulheres com dor associada à endometriose antes e após 6 meses do uso do SIU-LNG ou do implante de ENG. O estudo foi um ensaio clinico, aberto, randomizado, conduzido no Departamento de Tocoginecologia da Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brasil, no período de outubro de 2016 a outubro de 2017. Foram incluídas 103 mulheres com diagnóstico cirúrgico ou de imagem (US ou RNM) de endometriose que apresentavam dor pélvica. Foram alocadas 52 mulheres para o implante com ENG e 51 para o uso de SIU-LNG. As avaliações dos escores de dor pélvica, dismenorreia e dos marcadores foram realizadas ao inicio do estudo e após 180 dias do uso do método alocado. O CA-125 e o CD-23 solúvel foram analisados no soro pelo método de enzima-imunoensaio (ELISA). As amostras de endométrio foram colhidas com cureta aspirativa (Pipelle de Cornier) e a densidade das fibras nervosas foi observada através de reação imuno-histoquímica para o anticorpo PGP9.5. Os resultados mostraram que não houve diferença significativa intergrupos em relação às características sócio-demográficas (p>0,05). Verificou-se no grupo do SIU-LNG, redução significativa (p<0,001) entre a avaliação inicial dos escores de dor pélvica crônica (média ± desvio padrão [DP]) (7,4 ± 1,7 [IC 95% 6,92; 7,90]) e após 180 dias (1,9 ± 1,7 [IC 95% 1,38; 2,45]), dismenorreia inicial (7,4 ± 1,8 [IC 95% 6,92; 7,90]) e após 180 dias (1,9 ± 2,2 [IC 95% 1,19; 2,65]) das concentrações de CD-23 solúvel iniciais (35,6 ± 75,7 [IC 9,05; 61,88]) e após 180 dias (6,2 ± 14,5 [IC 95%1,18; 11,31]), e densidade de fibras nervosas inicial (7,4 ± 8,3 [IC 95% 4,30; 10,50]) e após 180 dias (2,1 ± 3,1 [IC 95% 0,93; 3,26]). No grupo do implante de ENG (p<0.001), houve redução dos escores de dor pélvica crônica iniciais (7,6 ± 1,7 [IC 95% 7.11; 8.04]) e após 180 dias (2,0 ± 2,4 [IC 95%1.23; 2.68]), dismenorreia inicial (7,6 ± 1,7 [IC 95% 7.11; 8.04]) e após 180 dias (2,2 ± 3,2 [IC 95% 1.15; 3.21]) do CD-23 solúvel inicial ( 59,6 ± 124,2 [IC 95%18.75; 100.41]) e após 180 dias ( 6,5 ± 13,2 [IC 95% 2.15; 10.84]), densidade de fibras nervosas inicial (6,7 ± 8,4 [IC 95% 3,50; 9.92]) e após 180 dias (2,7 ± 4,1 [IC 95% 1.17; 4.26]), como também dos níveis de CA-125 inicial (45,4 ± 63,8 [IC 95% 24,14; 66.69]) e após 180 dias (26,7 ± 41,6 [IC 95%12.88; 40.61]). Em conclusão ambos contraceptivos foram similares na redução dos três biomarcadores avaliados em mulheres com endometriose e dor, por pelo menos 180 dias. Entretanto, a redução dos níveis de CA 125 ocorreu apenas no grupo de usuárias de implante de ENG, provavelmente por bloqueio da ovulação

Abstract: INTRODUCTION: Endometriosis is a chronic, benign, inflammatory, estrogen-dependent disease that affects women of reproductive age. It is characterized by the presence of endometrial tissue, with glandular or stromal pattern, outside the uterine cavity inducing a local inflammatory response. The prevalence is uncertain, occurring between 2 and 10% of the women in menacme. The symptomatology of pelvic pain is the factor that most leads the woman in search of medical assistance. In addition, infertility, dysmenorrhea and dyspareunia of depth are among the main symptoms that lead the gynecologist to suspect the disease. The gold standard diagnosis is surgical, however, the difficulty of obtaining information of retroperitoneal infiltration of the lesions in the surgery has been proposed a classification by imaging methods, such as nuclear magnetic resonance of the pelvis and ultrasonography for find deep endometriosis, that contribute together for diagnosis. The most affected sites are ovaries, uterossacral ligaments, posterior pouch of Douglas and gastrointestinal tract. The treatment may be surgical, reserved for specific cases, and medicated, indicated alone and or complementarily. The goal of clinical treatment is to reduce estrogen production and thereby inflammation. Hormonal contraceptives are effective and inexpensive. The hormonal options containing progestogen have few side effects and long-acting methods are available with maintenance of stable serum hormone levels during its use. This contributes to neuromodulation of pain and perception. Of the long-acting contraceptives, there is a 52 mg levonorgestrel-releasing intrauterine system (SIU-LNG), which has been extensively studied in women with endometriosis and pain, with positive results, but few studies with the etonogestrel-releasing implant (ENG) for this purpose. OBJECTIVES: The purpose of this study was to compare CA-125, CD23 soluble serum levels and fiber nerve density in women with pain associated with endometriosis before and after 6 months of use of the IUS-LNG or the ENG implant. MATERIALS AND METHODS: An open, randomized clinical trial conducted at the Department of Tocoginecology of the State University of Campinas, UNICAMP, Campinas, SP, Brazil, from October 2016 to October 2017. A total of 103 women with a surgical or (USG) or magnetic resonance imaging (MRI) of endometriosis presenting pelvic pain, who met the criteria for inclusion and signed the informed consent form. Fifty-two women were allocated to the implant with ENG and 51 for the use of IUS-LNG. The chronic pelvic pain and dysmenorrhea scores and biomarkers evaluations were performed in two moments, at the beginning of the study and 180 days after of the use of the allocated method. CA-125 and soluble CD-23 was analyzed in serum by the enzyme-immunoassay (ELISA) method. Endometrial biopsy was performed with aspirate curette (Pipelle de Cornier) and the fiber nerve density was observed by immunohistochemical reaction to the antibody to PGP9.5, which stained nerve fibers. RESULTS: The results showed that there was no significant intergroup difference in relation to the socio-demographic characteristics (p> 0.05, exact Fischer and Chi square test), 81% of the population studied were white, 49% were between 30 and 39 years; 95% with more than 8 years of schooling; 49% never got pregnant; mean age of menarche of 12.41 years ± 1.77 (SD); BMI 27.45 kg / m2 ± 5.24 (DP); 93% never smoked and 72% reported never having drunk alcohol. There was a significant reduction (p <0.001) in the LNG-SIU group between the initial assessment of chronic pain scores (7.41 ± 1.75 [CI 95% 6.92; 7.90]) and 180 days after (1.92 ± 1.66 [CI 95% 1.38; 2.45]), dysmenorrhea score at baseline (7.41 ± 1.75 [CI 95% 6.92;7.90]) and 180 days after (1.92 ± 2.22 [CI 95% 1.19;2.65]), CD-23 soluble level (35.6 ± 75.7 [CI 9.05;61.88]) and 180 days after (6.2 ± 14.5 [CI 95%1.18;11.31]), and fiber nerve density at baseline (7.40 ± 8.30 [CI 4.30; 10.50]) and 180 days after (2.10 ± 3.11DP [CI 0.93; 3.26]). In the ENG implant group, there was a reduction (p <0.001) of chronic pelvic pain scores (7.58 ± 1.66[CI 95% 7.11; 8.04]) and 180 days after (1.96 ± 2.36 [CI 95%1.23;2.68]), dysmenorrhea at baseline (7.58 ± 1.66[CI 95% 7.11; 8.04]) and 180 days after (2.18 ± 3.23[CI 95% 1.15; 3.21]) and CD-23 serum level at baseline (59.6 ± 124.22 [CI 95%18.75;100.41]) and 180 days after ( 6.5 ± 13.2 [CI 95% 2.15;10.84]), fiber nerve density at baseline (6.71 ± 8.43DP [CI 3.50; 9.92]) and 180 days after (2.72 ± 4.06 [CI1.17; 4.26]) as well as CA-125 levels at baseline (45.42 ± 63.82 [CI 24.14; 66.69]) and 180 days after (26.75 ± 41.59 SD [CI 12.88; 40.61]). However, we didn¿t note directly correlation with pain scores and biomarkers decrease. CONCLUSION: This study showed that long-acting contraceptives, such as the LNG-SIU and the ENG implant, are great options for pain and dysmenorrhea management in women with pain associated with endometriosis for at least 180 days, associated with the reduction of endometrial fiber nerve density and CD23 soluble concentration. Only in the ENG implant group did CA-125 levels decrease, probably by blocking ovulation
Subject: Endometriose
Dor pélvica
Marcadores biológicos
Dispositivos intrauterinos medicados
Anticoncepcionais
Etonogestrel
Language: Português
Editor: [s.n.]
Date Issue: 2018
Appears in Collections:FCM - Tese e Dissertação

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