Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mês
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=9980902 https://hdl.handle.net/11600/64814 |
Resumo: | Introduction: Oral combined contraceptives (OCC) have been used since 1957 and currently estimates that approximately one billion women worldwide use OCC to treat some gynecological disorders and primarily as a contraceptive method. Due to their systemic actions, OCC have benefits and harms. However it is the increased risk of breast cancer its most controversial adverse effect and the most feared by women. The mechanisms by which contraceptives would act on the breast parenchyma leading to its increased incidence, are not yet well known. Objectives: To calculate and compare α estrogen receptor (ERα) and progesterone receptor (PR) expression in the mammary epithelium in the first, second, third and fourth weeks of patients who do not use OCC (natural cycle) and those who use one cycle of OCC composed of 30 μg ethinyl estradiol (EE) and 150 μg levonorgestrel (L). Casuistic and Methods: A retrospective study with paraffin blocks of 118 women from February 2001 to February 2004. At the time, women were included in the menacme who had a breast lump with the triple diagnosis of positive benignity and eumenorrheic during the last six months. The study project was analyzed and approved by the Research Ethics Committee of UNIFESP-EPM. The patients underwent excision of the breast lumps and adjacent normal breast tissue fragments which were fixed in 10% buffered formalin. 31 patients were excluded and 87 patients were analyzed. The patients were divided into two groups: group A (with OCC) consisted of 42 women who used an OCC cycle composed of 30 μg of EE and 150 μg of L, group B (without OCC) consisted of 45 women with natural cycles. The immunohistochemical reaction was performed in an automation device and the following antibodies were used: ERα antibody clone SP1 titer 1:500 and PR antibody clone PgR636 titer 1:400. The histological slides were read using conventional optical microscopy. After identifying the epithelial areas, 7 fields with 40X magnification were evaluated. Statistical analysis for parity was performed using Fisher's exact test. At age the Students t-Test was applied. ERα and PR counts were evaluated in the Generalized Estimation Equation (EEG) model. In order to compare the total ERα and PR counts by evaluation and group moments, we used the Analysis of Variance (ANOVA) and the Kolmogorov-Smirnov test. Statistical analyzes were performed using the programs SPSS 20.0 and STATA 12. For all statistical tests the significance level of 5% (p ≤ 0.05) was adopted. Results: The control group (without OCC) had a higher mean age of 23.7 ± 5.9 years compared to the study group (with OCC) with a mean age of 20.5 ± 5.1 years. Regarding parity, the study group (with COC) had 83.9% of nulligesta versus 73.3% in the control group (without OCC). From the EEG model a statistically significant mean difference in ERα expression was observed in the fourth week in the study group (with COC) compared to the control group (without OCC) with p <0.001. The comparison of PR expressions in the control group (without OCC) in the fourth week or in the late luteal phase (LLP) with the ERα expressions, also in the fourth week (LLP) of the control group (without OCC) the mean PR expression was higher and statistically significant than ERα expression with p <0.001. The group of women using OCC showed higher average percentages of ERα (p <0.001) and PR (p <0.001) when compared to women in the control group (without OCC). Conclusions: The expressions of ERα and PR in users of an OCC cycle composed of 30 μg EE and 150 μg L higher percentages of ERα (p <0.001) and PR (p <0.001) media when compared to women from the control group (without OCC). The ERα expression in the study group (with OCC) in the fourth week (pause) was higher than the ERα expression in the fourth week (LLP) of the control group (without OCC), a statistically significant difference (p <0.001). The expression PR in the fourth week of the control group (without OCC) or LLP was higher than the ERα and this difference was statistically 5 significant (p <0.001). This difference was not observed at another three weeks in the control group (without OCC) and in the four weeks of the study group (with OCC). |
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Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mêsOral Combined Contraceptiveα Estrogen ReceptorsProgesterone ReceptorsBreastAnticoncepcional Hormonal Combinado OralReceptores De Estrogênio αReceptores De ProgesteronaMamaIntroduction: Oral combined contraceptives (OCC) have been used since 1957 and currently estimates that approximately one billion women worldwide use OCC to treat some gynecological disorders and primarily as a contraceptive method. Due to their systemic actions, OCC have benefits and harms. However it is the increased risk of breast cancer its most controversial adverse effect and the most feared by women. The mechanisms by which contraceptives would act on the breast parenchyma leading to its increased incidence, are not yet well known. Objectives: To calculate and compare α estrogen receptor (ERα) and progesterone receptor (PR) expression in the mammary epithelium in the first, second, third and fourth weeks of patients who do not use OCC (natural cycle) and those who use one cycle of OCC composed of 30 μg ethinyl estradiol (EE) and 150 μg levonorgestrel (L). Casuistic and Methods: A retrospective study with paraffin blocks of 118 women from February 2001 to February 2004. At the time, women were included in the menacme who had a breast lump with the triple diagnosis of positive benignity and eumenorrheic during the last six months. The study project was analyzed and approved by the Research Ethics Committee of UNIFESP-EPM. The patients underwent excision of the breast lumps and adjacent normal breast tissue fragments which were fixed in 10% buffered formalin. 31 patients were excluded and 87 patients were analyzed. The patients were divided into two groups: group A (with OCC) consisted of 42 women who used an OCC cycle composed of 30 μg of EE and 150 μg of L, group B (without OCC) consisted of 45 women with natural cycles. The immunohistochemical reaction was performed in an automation device and the following antibodies were used: ERα antibody clone SP1 titer 1:500 and PR antibody clone PgR636 titer 1:400. The histological slides were read using conventional optical microscopy. After identifying the epithelial areas, 7 fields with 40X magnification were evaluated. Statistical analysis for parity was performed using Fisher's exact test. At age the Students t-Test was applied. ERα and PR counts were evaluated in the Generalized Estimation Equation (EEG) model. In order to compare the total ERα and PR counts by evaluation and group moments, we used the Analysis of Variance (ANOVA) and the Kolmogorov-Smirnov test. Statistical analyzes were performed using the programs SPSS 20.0 and STATA 12. For all statistical tests the significance level of 5% (p ≤ 0.05) was adopted. Results: The control group (without OCC) had a higher mean age of 23.7 ± 5.9 years compared to the study group (with OCC) with a mean age of 20.5 ± 5.1 years. Regarding parity, the study group (with COC) had 83.9% of nulligesta versus 73.3% in the control group (without OCC). From the EEG model a statistically significant mean difference in ERα expression was observed in the fourth week in the study group (with COC) compared to the control group (without OCC) with p <0.001. The comparison of PR expressions in the control group (without OCC) in the fourth week or in the late luteal phase (LLP) with the ERα expressions, also in the fourth week (LLP) of the control group (without OCC) the mean PR expression was higher and statistically significant than ERα expression with p <0.001. The group of women using OCC showed higher average percentages of ERα (p <0.001) and PR (p <0.001) when compared to women in the control group (without OCC). Conclusions: The expressions of ERα and PR in users of an OCC cycle composed of 30 μg EE and 150 μg L higher percentages of ERα (p <0.001) and PR (p <0.001) media when compared to women from the control group (without OCC). The ERα expression in the study group (with OCC) in the fourth week (pause) was higher than the ERα expression in the fourth week (LLP) of the control group (without OCC), a statistically significant difference (p <0.001). The expression PR in the fourth week of the control group (without OCC) or LLP was higher than the ERα and this difference was statistically 5 significant (p <0.001). This difference was not observed at another three weeks in the control group (without OCC) and in the four weeks of the study group (with OCC).Introdução: Os anticoncepcionais hormonais combinados orais (AHCO) são usados desde 1957 e atualmente estima que aproximadamente um bilhão de mulheres em todo mundo usam AHCO para tratamento de algumas afecções ginecológicas e principalmente como método contraceptivo. Devido as suas ações sistêmicas, os AHCO têm benefícios e malefícios; no entanto, é o aumento do risco do câncer de mama, o seu efeito adverso mais controverso e o mais temido pelas mulheres; ainda não são bem conhecidos os mecanismos pelos quais os contraceptivos agiriam no parênquima mamário, levando a um provável aumento da sua incidência. Objetivos: Calcular e comparar as expressões dos receptores de estrogênio α (REα) e dos receptores de progesterona (RP) no epitélio mamário na primeira, segunda, terceira e quarta semanas das pacientes não usuárias de AHCO (ciclo natural) com as usuárias de um ciclo de AHCO composto por 30mg de etinilestradiol (EE) e 150 mg de levonorgestrel (L). Casuística e Métodos: Estudo retrospectivo realizado com 118 mulheres no período de fevereiro de 2001 a fevereiro de 2004. Na ocasião foram incluídas mulheres na menacme, que apresentavam nódulo mamário com o tríplice diagnóstico de benignidade positivo, eumenorréicas durante os seis últimos meses. O projeto de estudo foi analisado e aprovado pelo Comitê de Ética em Pesquisa da UNIFESP-EPM. As pacientes foram submetidas às exéreses dos nódulos mamários e dos fragmentos de tecidos mamários normais adjacentes, que foram fixados em formol tamponado a 10%. Foram excluídas 31 pacientes; assim, foram analisadas 87 pacientes. As pacientes foram divididas em dois grupos: o grupo A (com AHCO) foi constituído por 42 mulheres que utilizaram um ciclo de AHCO composto de 30 mg de EE 150 mg de L e o grupo B (sem AHCO) foi formado por 45 mulheres com ciclos naturais. A reação de imuno-histoquímico (IHQ) foi realiza em aparelho de automação e foram usados os seguintes anticorpos: anticorpo do REα, clone SP1, título 1:500 e anticorpo do RP, clone PgR636, título 1:400. A leitura das lâminas foi realizada em microscopia óptica convencional, após a identificação das áreas epiteliais foram avaliados 7 campos com aumento de 40X. Na análise estatística para a paridade e a idade, empregou-se o Teste exato de Fisher e o Teste t de Students, respectivamente. A avaliação das contagens dos REα e RP foi no modelo de Equação de Estimação Generalizadas (EEG); visando comparar as contagens de REα e RP totais por momentos de avaliação e grupo, foram empregadas a Análise de Variância (ANOVA) e teste de Kolmogorov-Smirnov. As análises estatísticas foram realizadas utilizando-se os programas SPSS 20.0 e o STATA 12. Para todos os testes estatísticos foi adotado o nível 2 de significância de 5% (p ≤ 0,05). Resultados: O grupo controle (sem AHCO) apresentou média de idade superior com 23,7 ± 5,9 anos em relação ao grupo estudo (com AHCO) com média de idade de 20,5 ± 5,1 anos. No que se refere à paridade, o grupo de estudo (com AHCO) apresentou 83,9% de nuligestas versus 73,3% no grupo controle (sem AHCO). A partir do modelo EEG observou-se na quarta semana, diferença de média estatisticamente significativa na expressão do REα no grupo estudo (com AHCO) em comparação ao grupo controle (sem AHCO) com p < 0,001; a comparação das expressões dos RP no grupo controle (sem AHCO) na quarta semana, ou seja, na fase lútea tardia (FLT) com as expressões dos REα, também na quarta semana (FLT) do grupo controle (sem AHCO) a média de expressão dos RP foi superior e estatisticamente significativo às expressões dos REα com p<0,001. O grupo de mulheres usuárias de AHCO apresentou maiores porcentagens médias de REα (p<0,001) e RP (p<0,001), quando se compara às mulheres do grupo controle (sem AHCO). Conclusões: As expressões dos REα e RP nas usuárias de um ciclo de AHCO composto por 30mg de EE e 150 mg de L apresentaram maiores porcentagens médias de REα (p < 0,001) e RP (p < 0,001), quando comparadas às mulheres do grupo controle (sem AHCO). A expressão do REα no grupo estudo (com AHCO) na quarta semana (pausa), foi maior que a expressão dos REα na quarta semana (FLT) do grupo controle (sem AHCO), diferença estatisticamente significativa (p < 0,001). A expressão do RP na quarta semana do grupo controle (sem AHCO), isto é, na FLT, foi maior que a do REα e essa diferença foi estatisticamente significativa (p < 0,001); diferença essa que não é observada nas outras três semanas no grupo controle (sem AHCO) e nas quatro semanas do grupo de estudo (com AHCO).Dados abertos - Sucupira - Teses e dissertações (2020)Universidade Federal de São Paulo (UNIFESP)Nazario, Afonso Celso Pinto [UNIFESP]Universidade Federal de São PauloAraujo Neto, Joaquim Teodoro De [UNIFESP]2022-07-22T17:29:00Z2022-07-22T17:29:00Z2020-07-30info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion69 p.application/pdfhttps://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=9980902JOAQUIM TEODORO DE ARAUJO NETO.pdfhttps://hdl.handle.net/11600/64814porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-07-27T03:46:25Zoai:repositorio.unifesp.br/:11600/64814Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-07-27T03:46:25Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mês |
title |
Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mês |
spellingShingle |
Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mês Araujo Neto, Joaquim Teodoro De [UNIFESP] Oral Combined Contraceptive α Estrogen Receptors Progesterone Receptors Breast Anticoncepcional Hormonal Combinado Oral Receptores De Estrogênio α Receptores De Progesterona Mama |
title_short |
Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mês |
title_full |
Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mês |
title_fullStr |
Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mês |
title_full_unstemmed |
Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mês |
title_sort |
Avaliação semanal dos receptores de estrogênio α e progesterona no epitéllio mamário de mulheres após o uso de anticoncepcional hormonal combinado oral por um mês |
author |
Araujo Neto, Joaquim Teodoro De [UNIFESP] |
author_facet |
Araujo Neto, Joaquim Teodoro De [UNIFESP] |
author_role |
author |
dc.contributor.none.fl_str_mv |
Nazario, Afonso Celso Pinto [UNIFESP] Universidade Federal de São Paulo |
dc.contributor.author.fl_str_mv |
Araujo Neto, Joaquim Teodoro De [UNIFESP] |
dc.subject.por.fl_str_mv |
Oral Combined Contraceptive α Estrogen Receptors Progesterone Receptors Breast Anticoncepcional Hormonal Combinado Oral Receptores De Estrogênio α Receptores De Progesterona Mama |
topic |
Oral Combined Contraceptive α Estrogen Receptors Progesterone Receptors Breast Anticoncepcional Hormonal Combinado Oral Receptores De Estrogênio α Receptores De Progesterona Mama |
description |
Introduction: Oral combined contraceptives (OCC) have been used since 1957 and currently estimates that approximately one billion women worldwide use OCC to treat some gynecological disorders and primarily as a contraceptive method. Due to their systemic actions, OCC have benefits and harms. However it is the increased risk of breast cancer its most controversial adverse effect and the most feared by women. The mechanisms by which contraceptives would act on the breast parenchyma leading to its increased incidence, are not yet well known. Objectives: To calculate and compare α estrogen receptor (ERα) and progesterone receptor (PR) expression in the mammary epithelium in the first, second, third and fourth weeks of patients who do not use OCC (natural cycle) and those who use one cycle of OCC composed of 30 μg ethinyl estradiol (EE) and 150 μg levonorgestrel (L). Casuistic and Methods: A retrospective study with paraffin blocks of 118 women from February 2001 to February 2004. At the time, women were included in the menacme who had a breast lump with the triple diagnosis of positive benignity and eumenorrheic during the last six months. The study project was analyzed and approved by the Research Ethics Committee of UNIFESP-EPM. The patients underwent excision of the breast lumps and adjacent normal breast tissue fragments which were fixed in 10% buffered formalin. 31 patients were excluded and 87 patients were analyzed. The patients were divided into two groups: group A (with OCC) consisted of 42 women who used an OCC cycle composed of 30 μg of EE and 150 μg of L, group B (without OCC) consisted of 45 women with natural cycles. The immunohistochemical reaction was performed in an automation device and the following antibodies were used: ERα antibody clone SP1 titer 1:500 and PR antibody clone PgR636 titer 1:400. The histological slides were read using conventional optical microscopy. After identifying the epithelial areas, 7 fields with 40X magnification were evaluated. Statistical analysis for parity was performed using Fisher's exact test. At age the Students t-Test was applied. ERα and PR counts were evaluated in the Generalized Estimation Equation (EEG) model. In order to compare the total ERα and PR counts by evaluation and group moments, we used the Analysis of Variance (ANOVA) and the Kolmogorov-Smirnov test. Statistical analyzes were performed using the programs SPSS 20.0 and STATA 12. For all statistical tests the significance level of 5% (p ≤ 0.05) was adopted. Results: The control group (without OCC) had a higher mean age of 23.7 ± 5.9 years compared to the study group (with OCC) with a mean age of 20.5 ± 5.1 years. Regarding parity, the study group (with COC) had 83.9% of nulligesta versus 73.3% in the control group (without OCC). From the EEG model a statistically significant mean difference in ERα expression was observed in the fourth week in the study group (with COC) compared to the control group (without OCC) with p <0.001. The comparison of PR expressions in the control group (without OCC) in the fourth week or in the late luteal phase (LLP) with the ERα expressions, also in the fourth week (LLP) of the control group (without OCC) the mean PR expression was higher and statistically significant than ERα expression with p <0.001. The group of women using OCC showed higher average percentages of ERα (p <0.001) and PR (p <0.001) when compared to women in the control group (without OCC). Conclusions: The expressions of ERα and PR in users of an OCC cycle composed of 30 μg EE and 150 μg L higher percentages of ERα (p <0.001) and PR (p <0.001) media when compared to women from the control group (without OCC). The ERα expression in the study group (with OCC) in the fourth week (pause) was higher than the ERα expression in the fourth week (LLP) of the control group (without OCC), a statistically significant difference (p <0.001). The expression PR in the fourth week of the control group (without OCC) or LLP was higher than the ERα and this difference was statistically 5 significant (p <0.001). This difference was not observed at another three weeks in the control group (without OCC) and in the four weeks of the study group (with OCC). |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-07-30 2022-07-22T17:29:00Z 2022-07-22T17:29:00Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=9980902 JOAQUIM TEODORO DE ARAUJO NETO.pdf https://hdl.handle.net/11600/64814 |
url |
https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=9980902 https://hdl.handle.net/11600/64814 |
identifier_str_mv |
JOAQUIM TEODORO DE ARAUJO NETO.pdf |
dc.language.iso.fl_str_mv |
por |
language |
por |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
69 p. application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
publisher.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP |
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Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
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1814268346172964864 |