Menopausia quirúrgica en pacientes con mutación BRCA, el papel de la terapia hormonal / Surgical Menopause in Patients with BRCA Mutation, the Role of Hormone Therapy

Introducción: las mujeres con mutación BRCA1/2 (mBRCA) tienen un riesgo aumentado de desarrollar cáncer de mama (CM) y ovario (CO). La salpingo-oforectomía bilateral (SOB) se asocia con la reducción del riesgo del 80% para CO y un 50% para CM. Se recomienda realizarla entre los 35 y 40 años. Como consecuencia se produce una menopausia prematura, con un impacto negativo sobre la calidad de vida por la presencia de síntomas climatéricos, aumento del riesgo de enfermedad cardiovascular, osteoporosis y riesgo de alteración cognitiva. La terapia hormonal (THM) es el tratamiento más eficaz para la prevención de estos síntomas. Estado del arte: distintos estudios han demostrado un mayor riesgo de CM en mujeres posmenopáusicas que reciben THM en particular con terapia combinada, estrógeno + progesterona (E+P). Según el metanálisis de Marchetti y cols., en las mujeres portadoras de mBRCA que recibieron THM, no hubo diferencias en el riesgo de CM comparando E solo con E+P. En el estudio de Kotsopoulos, incluso se encontró un posible efecto protector en aquellas que usaron E solo. Otro estudio en portadoras sanas demostró que, en las mujeres menores de 45 años al momento de la SOB, la THM no afectó las tasas de CM. Sin embargo, en las mujeres mayores de 45 años, las tasas de CM fueron más altas. Como el esquema de E+P se asocia con un mayor riesgo relativo (RR) de CM, las dosis de progestágenos utilizados se deberían limitar, eligiendo derivados naturales de progesterona, de uso intermitente para disminuir la exposición sistémica. Según diferentes guías internacionales, a las portadoras de mBRCA sanas que se someten a una SOB se les debe ofrecer THM hasta la edad promedio de la menopausia. Conclusión: la menopausia prematura disminuye la expectativa de vida; es por ello que una de las herramientas para mejorar y prevenir el deterioro de la calidad de vida es la THM. El uso de THM a corto plazo parece seguro para las mujeres portadoras de mBRCA que se someten a una SOB antes de los 45 años, al no contrarrestar la reducción del riesgo de CM obtenida gracias a la cirugía. (AU)

Introduction: women with BRCA1/2 (mBRCA) mutation have an increased risk of developing breast (BC) and ovarian (OC) cancer. Bilateral salpingo-oophorectomy (BSO) is associated with an 80% risk reduction for OC and 50% for BC. The recommended age for this procedure is 35 to 40 years. The consequence is premature menopause, which hurts the quality of life due to the presence of climacteric symptoms, increased risk of cardiovascular disease, osteoporosis, and a higher risk of cognitive impairment. Hormone therapy (MHT) is the most effective treatment for preventing these symptoms. State of the art: different studies have shown an increased risk of BC in postmenopausal women receiving MHT, particularly with combined therapy, estrogen + progesterone (E+P). According to the meta-analysis by Marchetti et al., in women carrying mBRCA who received MHT, there was no difference in the risk of BC compared to E alone with E+P. In the Kostopoulos study, there was also a possible protective effect in those who used E alone. Another study in healthy carriers showed that in women younger than 45 years at the time of BSO, MHT did not affect BC rates. However, in women older than 45 years, BC rates were higher. As the E+P scheme is associated with a higher RR of BC, the doses of progestogens should be limited, choosing natural progesterone byproducts of intermittent use to decrease systemic exposure. According to various international guidelines, healthy mBRCA carriers undergoing BSO should be offered MHT until the average age of menopause. Conclusion: premature menopause decreases life expectancy, which is why one of the tools to improve and prevent deterioration of quality of life is MHT. Short-term use of MHT appears safe for women with mBRCA who undergo BSO before age 45 as it does not counteract the reduction in the risk of MC obtained by surgery. (AU)

Bone effects of epidural and intra-articular glucocorticoids: a systematic literature review / Efectos óseos de los glucocorticoides epidurales e intraarticulares: revisión sistemática de la literatura

Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)

La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)

Progestinas y cáncer de mama en terapia de reemplazo hormonal: cómo actúan y qué alternativas son más seguras / Progestins and breast cancer in hormone replacement therapy: how do they work, and what alternatives are safer

En algunos estudios se ha asociado a la terapia de reemplazo hormonal (TRH) con estrógenos y progestinas a un mayor riesgo de cáncer de mama que la terapia con estrógenos solos. Sin embargo, dependiendo de su naturaleza algunas progestinas serían más seguras que otras. Se buscaron y analizaron artículos atingentes al tema en las bases de datos Google Scholar, PubMed, Science, SciELO y Cochrane, introduciendo los siguientes términos: terapia de reemplazo hormonal y cáncer de mama, progestinas y cáncer de mama, receptor de progesterona. Específicamente se ha asociado a las progestinas sintéticas acetato de medroxiprogesterona, noretisterona y levonorgestrel con un mayor riesgo de cáncer de mama, no así a la progesterona natural, a la progesterona oral micronizada ni a la didrogesterona. La progesterona natural, progesterona micronizada y didrogesterona serían más seguras en TRH para evitar el desarrollo de cáncer de mama, lo que estaría dado por la mayor especificidad en su acción.

In some studies, hormone replacement therapy (HRT) with estrogens and progestins has been associated with a higher risk of breast cancer than therapy with estrogens alone. However, depending on their nature, some progestins may be safer than others. This article analyzes the mode of action of progesterone in breast tissue and also the role of some progestins in the development of this pathology. Articles related to the subject were searched for and analyzed in Google Scholar, PubMed, Science, SciELO and Cochrane databases, introducing the following terms: hormone replacement therapy and breast cancer, progestins and breast cancer, progesterone receptor. Specifically, synthetic progestins medroxyprogesterone acetate, norethisterone, and levonorgestrel have been associated with an increased risk of breast cancer, but not natural progesterone, micronized oral progesterone, or dydrogesterone. Natural progesterone, micronized progesterone and dydrogesterone would be safer in HRT to prevent the development of breast cancer, which would be due to the greater specificity of their action.

Analysis of Estrogen Effects on Eruption of Rat Molars / Análisis de los Efectos del Estrógeno en la Erupción de Molares de Rata

ABSTRACT: Tooth eruption requires resorption of the alveolar bone interposed between the tooth germ and the oral mucosa (coronal bone). The cells responsible for bone resorption are the osteoclasts and their activity can be reduced or inactivated by estrogen hormone. We aimed to investigate the effects of estrogen on the process of tooth eruption in rats. Thirty-three Wistar rats, aged two-to-17-days, were divided into control, sham and estrogen-treated groups. After daily injections with estrogen, the animals were euthanized and the jaws removed and processed for histological analysis. We performed clinical examination, morphological analysis, quantification of the number of osteoclasts on the surface of the coronal bone and immunohistochemical analysis of estrogen receptor type alpha (ERα). Estrogen therapy was effective, which could be confirmed by the higher estrogen plasma levels on treated animals. However, it had no effect on tooth development or tooth eruption. Progressive bone resorption was observed and the number of osteoclasts on coronal bone was not affected on hormoneinjected animals, allowing tooth to erupt at the same time observed in untreated animals. Immunohistochemistry for ERα confirmed the presence of this type of receptor in osteoclasts, osteoblasts and osteocytes. Taken together, our results showed that estrogen stimulation was not sufficient to decrease the number of osteoclasts on the coronal bone, supporting the idea that, although estrogen may have a protective activity on bone resorption, this may not apply to the alveolar bone that is meant to be resorbed during eruptive process.

RESUMEN: La erupción dental requiere la resorción del hueso alveolar interpuesto entre el germen dental y la mucosa oral (hueso coronal). Las células responsables de la resorción ósea son los osteoclastos y su actividad puede reducirse o inactivarse por la hormona del estrógeno. Objetivos: apuntamos a investigar los efectos del estrógeno en el proceso de la erupción dental en ratas. Treinta y tres ratas Wistar, de dos a 17 días de edad, se dividieron en grupos de control, Sham y se trataron con estrógenos. Los animales fueron eutanizados después del tratamento con estrógeno y se procesaron las mandíbulas para el análisis histológico. Se realizó el examen clínico, el análisis morfológico, la cuantificación del número de osteoclastos en la superficie del hueso coronal y el análisis inmunohistoquímico del tipo de receptor de estrógeno alfa (ERα). La terapia de estrógeno fue eficaz, lo que podría ser confirmado por los niveles plasmáticos más altos de estrógeno en los animales tratados. Sin embargo, no se observó ningún efecto sobre el desarrollo de los dientes o la erupción dental. Se observó una resorción ósea progresiva y el número de osteoclastos en el hueso coronal no se vio afectado en los animales inyectados con hormonas, permitiendo que el diente erupcionó durante el mismo período de tiempo observado en animales no tratados. La inmunohistoquímica para el ERα confirmó la presencia de este tipo de receptor en los osteoclastos, osteoblastos y osteocitos. Nuestros resultados mostraron que la estimulación del estrógeno no fue suficiente para reducir el número de osteoclastos en el hueso coronal confirmando que, si bien el estrógeno puede tener una actividad protectora en la resorción ósea, esto puede no se aplica al hueso alveolar que está destinado a ser rerecurrido durante el proceso eruptivo.

Distribución de esteroides estrogénicos en plantas de tratamiento de aguas residuales municipales / Distribution of estrogenic steroids in municipal wastewater treatment plants

En la actualidad, existe una preocupación creciente por la presencia de estrógenos en el medio acuático, donde pueden ser introducidos a partir de aguas residuales después de su eliminación incompleta en las plantas de tratamiento. Las aguas residuales sistemáticamente reciben estrógenos naturales y sintéticos, y por lo tanto una comprensión más profunda de la suerte de ellos en el medio ambiente es necesaria. Se evaluaron los niveles de estrógenos en los efluentes de las Plantas de Tratamiento de Aguas Residuales (PTARs) Penha e Ilha do Governador, ambos de tipo convencional de flujo continuo de lodo activado con aireación prolongada. Fue utilizado como el parámetro de determinación de algunos compuestos de interés como estrógenos naturales [estrona (E1), 17β-estradiol (E2), estriol (E3)) y sintéticos (17α-etinilestradiol (EE2)]. Las muestras individuales se recogieron posteriormente al tratamiento de cada PTAR y después de los procedimientos de laboratorio se realizó la determinación de estrógenos basado en la extracción en fase sólida (SPE) y la cromatografía líquida de alta resolución con detector de arreglo de diodos (HPLC-DAD). Las concentraciones fueron de: 0,7 a 5,2 μg/l y de 0,5 a 5,6 de E1; 0,9 a 7,7 y 1,2 a 9,2 μg/l para E2; 2,01 a 6,09 y 1,07 a 4,08 μg/l para EE2 en PTAR Penha y PTAR Ilha do Governador, respectivamente. La capacidad de eliminación de estrógenos fue eficaz, pero denota que la eliminación sistemática de la población es en la actualidad alta. Se recomienda instalar mecanismos para mitigar el consumo exagerado de estas sustancias o implementar una eliminación completa más eficaz.

Currently, there is a growing concern over the presence of estrogens in the aquatic environment, where they can be introduced from wastewater after their incomplete elimination in the treatment plants. Wastewater systematically receives natural and synthetic estrogens, and thus a deeper understanding of the fate of them in the environment is extremely necessary. It was evaluated estrogen levels in the effluent from the Sludge Wastewater Treatment Plants (SWTPs) Penha and Ilha do Governador, both of type conventional continuous-flow activated sludge with extended aeration. The determination of some target compounds as natural estrogens was used as the evaluation parameter [estrone (E1), 17β-estradiol (E2), estriol (E3) and synthetic (17α-ethinylestradiol (EE2)]. Individual samples were collected posterior treatment of each SWTP, and after laboratory procedures, the determination of estrogens was performed by a method based on solid phase extraction (SPE) and high performance liquid chromatography-diode array detector (HPLC-DAD). Concentrations ranged from 0.7 to 5.2 μg/l and from 0.5 to 5.6 for E1; 0.9 to 7.7 and 1.2 to 9.2 μg/l for E2; 2.1 to 6.9 and 1.7 to 4.8 μg/l for EE2 at SWTPs Penha and Ilha do Governador, respectively. The removal capacity of estrogens despite its effectiveness denotes that the systematic elimination by the population is high nowadays and urging mechanisms to mitigate the exaggerated consumption or to implement most effective complete removal.

Androgênios e mama / Androgens and breast

O câncer de mama (BCA) é uma das neoplasias mais frequentes em mulheres de vários países, a exposição excessiva aos estrogênios é um dos principais fatores de risco. Os ovários são as principais fontes de produção estrogênica endógena; porém, na menopausa essa produção cessa e a síntese extragonadal, sobretudo nas células mesenquimais do tecido adiposo, passa a ser a principal fonte de produção estrogênica, pois essas células apresentam aromatase, enzima que converte androgênios em estrogênios. Apoiada por fortes evidências clínicas, a reposição androgênica tem sido recomendada para o alívio de sintomas decorrentes da síndrome da insuficiência androgênica feminina, tais como fadiga, alterações do humor e quadros de depressão; além disso, estudos experimentais têm sugerido a possibilidade de uma plausível proteção da reposição androgênica contra o BCA. Nesses estudos, em que atuou por meio de seus receptores, a testosterona apresentou efeitos antiproliferativos, pró­apoptóticos e inibiu a atividade dos receptores estrogênicos e do crescimento de tumores mamários; evidências clínicas também apoiam o papel protetor dos androgênios na mama. Entretanto, outros estudos indicam que esse papel protetor depende do nível de atividade da aromatase; assim, a testosterona pode exercer um efeito inibidor direto no crescimento tumoral ao ligar­se ao seu receptor, porém ter um efeito estimulador indireto através de sua conversão para estrogênios pela aromatase. A obesidade e a insulina, além de múltiplos outros fatores, alguns dos quais são fatores de risco independentes para BCA, podem resultar na superexpressão da aromatase e ter como resultado aumento na produção localizada de estrogênios, os quais são fatores estimulantes do BCA. Estudos sobre a administração de testosterona em mulheres são escassos e controversos e não existem estudos que forneçam dados em termos de segurança desse uso em longo prazo. Assim, nesta revisão pretendemos mostrar como os androgênios atuam na mama. Frente às evidências atuais, o uso de androgênios em mulheres com fatores de risco para câncer de mama não é recomendado.(AU)

Breast cancer (BCAA) is one of the most frequent malignancies in women in several countries, which excessive exposure to oestrogens is one of the main risk factors. The ovaries are the main source of endogenous estrogen production; however, at menopause this production sessate and extra­gonadal synthesis, especially in ectomesenchymal cells from adipose tissue, turns the main source of estrogen production, since these cells express aromatase, an enzyme that converts androgens to estrogens. Supported by strong clinical evidence androgen replacement has been recommended for the relief of symptoms caused by female syndrome of androgen insufficiency, such as fatigue, mood swings and depression; Furthermore, experimental studies have suggested the possibility of protection of androgen replacement against BCA. In these studies, acting through their receptors, testosterone showed antiproliferative, proapoptotic and inhibited the activity of estrogen receptors and growth of mammary tumors; Clinical evidence also support the protective role of androgens in the breast. However, studies indicate that this protective role depends on the level of aromatase activity; for instance, testosterone can exert a direct inhibitory effect on tumor growth by binding to its receptor, but have an indirect effect by stimulating its conversion to oestrogens by aromatase. Obesity and insulin, as well as multiple other factors, some of which are independent risk factors for BCA, may result in overexpression of aromatase, resulting in increased localized production of estrogens, which are inducible factors of BCA. Studies on the administration of testosterone in women are scarce and controversial, and there are no studies that provide data in terms of long­term use of safety. Thus, in this review we intend to show how androgens act in the breast. Given the current evidence, the use of androgens in women with risk factors for breast cancer is not recommended.(AU)

Anticoncepção na paciente com lúpus eritematoso sistêmico / Contraception in patients with lupus erythematosus

Introdução: O lúpus eritematoso sistêmico (LES) é uma doença grave, crônica, de origem autoimune, mais prevalente entre as mulheres. Devido à melhora da terapêutica, crianças e adolescentes têm se beneficiado de maior sobrevida, devendo-se orientar sobre contracepção, evitando assim uma possível gravidez, em uso de terapia com risco de teratogenicidade. Objetivo: Avaliar o tipo de contracepção mais adequada em portadoras de LES, de acordo com a fase da doença. Métodos: Esta revisão sistematizada utilizou as bases de dados: Medline (PubMed), SciELO, LILACS e Google Acadêmico, usando como estratégia de busca "Systemic lupus erythematosus" AND "Contraception". Resultados: Sete estudos foram selecionados para avaliação da anticoncepção hormonal em pacientes portadoras de LES. As pacientes com anticorpo antifosfolipídeo positivo (aPL+) ou desconhecido apresentam restrição aos métodos hormonais, sendo o DIU de cobre o único método indicado. Em pacientes com trombocitopenia severa, qualquer método pode ser usado, apenas o início da contracepção com injetável ou DIU de cobre são considerados categoria 3. O uso de anticoncepcionais só de progestagênio ou DIU de levonorgestrel reduz o volume do sangramento vaginal nestas pacientes. No caso de uso de imunossupressores, pode-se utilizar qualquer método, desde que não apresentem aPL+. Conclusão: Métodos hormonais não devem ser utilizados em pacientes com aPL+. É importante rastrear a presença desses anticorpos, antes de iniciar a contracepção na paciente lúpica, além de adequar os diversos tipos de anticoncepção individualmente, de acordo com a forma de administração que melhor se adapte a aquele momento de vida.(AU)

Introduction: The Systemic Lupus Erythematosus (SLE) is a serious and chronic disease with an autoimmune origin, more prevalent among women. Due to improvement of the therapeutic, children and adolescents have been benefited with greater survival and must be guided on contraception, thus avoiding a possible pregnancy, in use of therapy with risk of teratogenicity. Objective: To evaluate the most appropriate type of contraception in women with SLE, according to the stage of the disease. Methods: This critical review has used the databases of: Medline (via PubMed), SciELO, LILACS and Google Scholar, using as search strategy "Systemic lupus erythematosus" AND "Contraception". Results: Seven studies were selected for the evaluation of hormonal contraception in women with SLE. Patients with positive antiphospholipid antibody (aPL+) or unknown present restriction on hormonal methods, being the copper IUD, the only suitable method. In patients with severe thrombocytopenia, any method can be used, only the beginning of contraception with injectable or copper IUDs are considered category 3. Only progestogen contraceptives or levonorgestrel IUD reduce the amount of vaginal bleeding in these patients. In the case of use of immunosuppressants may be used any method, provided they do not exhibit aPL+. Conclusion: Hormonals methods should not be used in patients with aPL+. It is important to track the presence of these antibodies before starting contraception in lupus patients, in addition to adjust different types of contraception for each patient according to the form of administration which best suits the moment of their lives.(AU)

Histopathological and immunohistochemical changes induced by contraceptive pills in the cervix of female rabbits

Oral contraceptive pills [OCPs] are the most popular form of hormonal contraception in young women. The present study focused on evaluating the effects of two different contraceptive pills including combined pills [estrogen and progesterone] and mini pills [progesterone only] on the cervix of female rabbit. After three months of daily oral administration of these contraceptive pills the animals were sacrificed. The excised organs were dissected, processed and stained with H and E, PAS reaction and Masson's trichrome stain and orcein stain. This was followed by morphometric measurements and statistical study. This study revealed that contraceptive pills administration - specially the combined one - caused marked alterations in the form of hyperplastic cervical mucosal cells and hypertrophied muscular layer. Also, there was a significant increase in collagenous and elastic fibres content in the muscular layer of the cervix. There was also a statistically significant increase in PAS positive materials in the lumina of the mucosal glands of the cervix. All these changes were less marked in the case of mini pill treatment. Pills of progesterone only showed marked histopathological change, in the cervix as a contraceptive mean, but in less manner than the combined pills [estrogen and progesterone]

Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients / Fatores precipitantes na porfiria cutanea tardia no Brasil com enfase nas mutacoes do gene (HFE) da hemocromatose. Estudo de 60 casos

BACKGROUND: Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. OBJECTIVES: Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations. METHODS: An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR. RESULTS: Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors. CONCLUSIONS: Alcohol abuse, hepatitis C and ...

FUNDAMENTOS: A porfiria cutânea tardia é a forma mais comum das porfirias e caracteriza-se pela diminuição da atividade da enzima uroporfirinogênio descarboxilase. Há vários relatos da associação das mutações do gene HFE da hemocromatose hereditária com porfiria cutânea tardia no mundo, mas até hoje apenas um estudo foi realizado no Brasil. OBJETIVOS: Estudar a associação da porfiria cutânea tardia com as mutações C282Y e H63D do gene HFE. Identificar os fatores precipitantes (hepatite C, HIV, etilismo e estrógeno) e sua relação com as mutações HFE. MÉTODOS: Estudo ambispectivo de 60 pacientes com porfiria cutânea tardia no período de 2003 a 2012. Investigou-se as sorologias para hepatite C, anti-HIV, histórico de etilismo e ingestão de estrógenos. As mutações HFE foram identificadas com PCR em tempo real. RESULTADOS: A porfiria cutânea tardia predominou no sexo masculino e o etilismo foi o principal fator precipitante. A ingestão de estrógenos foi o único fator precipitante em 25% das mulheres. A hepatite C estava presente em 41,7%. Todos os pacientes com HIV (15,3%) apresentavam etilismo associado. A frequência dos alelos C282Y (p=0,0001) e H63D (p=0,0004) do gene HFE foi significativamente mais elevada nos pacientes com porfiria cutânea tardia em relação à população controle. ...

Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats / Dano oxidativo ao tecido cerebral como possível mecanismo de efeito deletério da alta dose crônica de estradiol no aprendizado e memória de ratas ooforectomizadas

In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg) for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p≪0.01 and p≪0.001). In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p≪0.05 and p≪0.001). In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA) concentrations were higher than in the Sham and OVX groups (p≪0.05 and p≪0.001). It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.

Além dos efeitos antioxidantes, os estrógenos também têm ação pró-oxidativa. Foi investigado o efeito da administração crônica de alta dose de valereato de estradiol no desempenho do labirinto aquático de Morris e o dano oxidativo ao tecido cerebral. Os grupos Sham-Est e OVX-Est foram tratados com valereato de estradiol (4 mg/kg) por 12 semanas. O tempo de latência para escapada e o caminho percorrido foram significativamente maiores nos grupos Sham-Est e OVX-Est em relação aos grupos Sham e OVX (p≪0,01 e p≪0,001). No estudo probe, os animais dos grupos Sham-Est e OVX-Est levaram menos tempo no Q1 em comparação aos grupos Sham e OVX (p≪0,05 e p≪0,001). Nos grupos Sham-Est e OVX-Est, a concentração total de tiol foi significativamente menor, enquanto a concentração de malondialdehydo (MDA) for maior do que aquela dos grupos Sham e OVX (p≪0,05 e p≪0,001). Concluiu-se que a administração de altas doses de estradiol exógeno compromete o desempenho e aumenta o estresse oxidativo naqueles animais.

Predisposición genética para el cáncer de mama: genes BRCA1 y BRCA2 / Genetic predisposition for breast cancer: BRCA1 and BRCA2 genes

El descubrimiento de los genes BRCA1 y BRCA2 ha llevado a la introducción de pruebas genéticas cada vez más sofisticadas para medir el riesgo de cáncer de mama de origen hereditario, entre otras cosas. En el presente artículo exploramos los criterios a seguir para realizar pruebas para estos genes, así como las implicaciones en el tratamiento para los pacientes en caso de identificarlos.

The discovery of genes BRCA1 and BRCA2 has led to the introduction of genetic tests more complex every time for the evaluation ofthehereditarycancerrisk,amongothers.In the present paper we explore the criteria to decide when to run the testing for the genes, as well as the implications for the treatment of patients who are identified with them.

Perfil neuropsicológico en transexuales: efecto del tratamiento de reasignación de sexo / Neuropsychological profile in transsexuals: effect of sex reassignment treatment

Las funciones cognitivas, como el aprendizaje, la memoria y las funciones ejecutivas, son afectadas por las hormonas esteroides sexuales. El objetivo fue evaluar el perfil cognoscitivo en personas transexuales hombre a mujer (TH-M) en presencia y ausencia de tratamiento hormonal con estrógenos. Participaron un total de 54 sujetos. El grupo experimental fue de 22 pacientes TH-M, dividido en dos grupos: con tratamiento hormonal (n=9) y sin tratamiento hormonal (n=13). El grupo control fue conformado por hombres (n=16) y mujeres (n=16), pareados en edad y escolaridad. Evaluados con la batería NEUROPSI: Atención y Memoria (Ostrosky-Solís, Gómez, Matute, Roselli, Ardila & Pineda, 2003). Los grupos transexuales tuvieron mejores puntajes que los controles en atención inmediata y en formación de categorías, pero mostraron menores puntajes que los controles en codificación de material visoespacial y de caras, en memoria verbal inmediata y evocada. Se encontraron correlaciones negativas entre meses de tratamiento y la codificación visoespacial, memoria para caras y memoria verbal. Los resultados sugieren que las hormonas sexuales tienen efectos organizadores y activadores sobre la cognición.

Mental functions, including learning, executive functions and memory, are susceptible to be affected by sexual steroids hormones. The objective was to evaluate the cognitive profile of transsexual’s male to female (TM-F) in presence and absence of hormonal treatment with estrogens. A total of 54 subjects participated. The experimental group was conformed by 22 patients in condition transsexual male to female, divided in two groups: with hormonal treatment (n=9) and without hormonal treatment (n=13). The control group was conformed by heterosexual men (n=16) and women (n=16) paired in age and schooling to the experimental group. Subjects were evaluated by a comprehensive neuropsychological battery, NEUROPSI: Attention and Memory (Ostrosky-Solís, Gómez, Matute, Roselli, Ardila & Pineda, 2003). Transsexual’s groups performed better than controls in immediate attention, category formation, but worse than controls in visuospatial codification, faces, recall and immediate verbal memory. Negative correlations were founded between treatment months in visuospatial codification, faces, and verbal memory.

Porfiria cutânea tardia esporádica associada ao uso de estrógenos: relato de caso e revisão de literatura / Sporadic late cutaneous porphyria associated estrogen use: a case report and literature review

Porfiria é a designação de um grupo de doenças enzimáticas que afetam a síntese do heme. São sete os tipos de porfiria, que se diferenciam pela enzima afetada. A porfiria cutânea tardia é acarretada pela deficiência da enzima uroporfirinogênio descarboxilase, gerando manifestações cutâneas e hepáticas aos portadores. Fatores como estrógenos, álcool, HIV, HCV, juntamente com o ferro podem desencadear a doença que é diagnosticada principalmente por análise urinária. O tratamento se dá por flebotomia e administração de cloroquina. No caso relatado a paciente, 54 anos, apresentou bolha na mão esquerda e após alguns meses foi diagnosticada porfiria cutânea tardia, por análise histopatológica alterada e eliminação anormal de uroporfirinas urinárias. O provável fator desencadeante foi o estrógeno, devido à eliminação de possível causa por outros fatores. Após tratamento com cloroquina e eliminação do fator causal, houve remissão da doença.

Porphyria is the designate of an enzyme group of diseases that affect the synthesis of heme. There are seven types of porphyria, which differ by the enzyme affected. Porphyria cutanea tarda is caused for the deficiency of the enzyme uroporphyrinogen descarboxylase, generating skin expression disorders and liver patients. Factors such as estrogens, alcohol, HIV, HCV, getting together with iron can cause the disease is mainly diagnosed by urinalysis. The treatment is done by phlebotomy and administration of chloroquine. In that case related the patient, 54 years old, presented blister on his left hand and after a some months was diagnosed tarda cutaneous porphyria, through histopathology and altered abnormal urinary elimination uroporphyrin. The probable factor precipitating was estrogen, due to elimination of possible causes for other factors. After treatment with chloroquine and elimination of the causal factor, there was remission of the disease.

Role of estrogen, progesterone and prolactin in the etiopathogenesis of melasma in females

Melasma is a commonly acquired hypermelanosis of facial skin due to various etiological factors including hormonal imbalance. To find out the relationship between hormonal imbalance and melasma in females. One hundred and fifty female patients suffering from melasma, between the ages of 17-45 years, were enrolled in the study. They were examined by Wood's lamp to see the type of melasma whether epidermal, dermal or mixed [dermoepidermal]. Patients were investigated for levels of estrogen, progesterone and prolactin in two consecutive follicular and luteal phases on 9[th] and 18[th] day of cycle, respectively. Forty control cases were also investigated for the aforementioned hormonal levels in their follicular and luteal phases. Out of 150 patients, 138 completed the study while 12 patients were lost to follow up. Amongst the 138 evaluable patients, there were only 4 patients who had normal values for all the three hormones i.e. estrogen, progesterone and prolactin in all four phases. Fifteen patients [10.9%] had normal values of estrogen in both follicular [Fl and F2] and luteal phases [LI and L2] while the remaining 123 patients [89.1%] had deranged values of estrogen [mostly increased] in any of the four phases. The values of progesterone were normal in 62 [44.9%] patients while they were deranged in 76 [55.1%] patients in all four phases. The levels of prolactin were normal in 134 [97.1%] patients while deranged in 4 [2.9%]. Out of 40 controls, only 3 [7.5%] had increased values of estrogen in both follicular and luteal phases. Estrogen is found to be the causative agent of melasma

Doenças pulmonares interticiais: linfangioliomiomatose em questão / Intertitial pulmonary diseases: lymphangioleiomyomatosis in question

As doenças pulmonares intersticiais (DPIs) são conceituadas como distúrbios que acometem o parênquima pulmonar - o endotélio cailar, os alvéolos, o epitélio alveolar e os espaços entreestas estruturas, bem como os tecidos perivasculares e linfáticos - , podendo ser classificadas segundo critérios histopatológicos, distinguindo-se dois grandes grupos: 1. das associadas à inflamação e fibrose; e 2. daquelas com reação granulomatosa predominante na área intersticial u vasculas. A linfangioliomiomatose (LAM) é uma rara DPI, idiópática, e com altas taxas de morbimortalidade, sendo caracterizada por uma multiplicação acelerada de células musculares lisas imaturas em qualquer estrutura pulmonar. No presente artigo apresentar-se-á uma revisão da literatura enfocando a etiopatogenia, a epidemiologia, o quadro clínico, o diagnóstico - procedimentos, critérios e diagnóstico diferencial - o tratamento e o prognóstico da LAM.

The interstitial pulmonary diseases (IPDs) are a range of disorders that affect the pulmonary parenchyma - the capillary endothelium, alveoli, alveolar epithelium and the spaces between thesestructures, as well as the perivascular and lymphatic tissues. The IPDs may be classified according to histopathologic criteria, and are divided into two large groups: 1. those associated with inflammation and fibrosis; and 2. those associated with granulomatous reactions predominantly in the interstitial or vascular area. Lymphangioleiomyomatosis (LAM) ia a rare, idiopathic IPD with high morbimortality rates, which is characterized by an accelerated multiplication of immature smooth muscle cellsin any pulmonary structure. In this article, we present a review of the literature onthe etiopathogenesis, epidemiology, clinical picture, diagnosis and differential diagnosos, treatment, and prognosis of this condition.

Proliferation of the superficial epithelium of ovaries in senile female rats following oral administration of conjugated equine estrogens

OBJECTIVE: To evaluate the effect of different concentrations of estrogen on the ovarian superficial epithelium in senile female rats. Design: Fifty female rats at 15 months of age and with irregular estrous cycles were selected and randomly divided into five experimental groups containing equal numbers of animals in each: GPROP, control group receiving vehicle only; GE0.05mg, group receiving conjugated equine estrogens (CEE) at a dose of 50 µg/kg; GE0.5mg, group receiving CEE at 500 µg/kg; GE1mg, group receiving CEE at 1 mg/kg; and GE2mg, receiving CEE at 2 mg/kg. The length of treatment was 21 days. After this period, the animals were anesthetized and the ovaries were fixed in 10 percent formaldehyde and processed for routine histology. Histomorphology was analyzed by light microscopy, and histomorphometrics were evaluated using the Imagelab program. RESULTS: In the GPROP and GE0.05mg groups, the superficial epithelium of the ovary had a simple cuboidal shape, and as the estrogen dose increased, the epithelium thickened, with pseudo-stratified or stratified epithelium appearing in the GE2mg group. The animals in the group given the highest estrogen dose (GE2mg) showed the thickest ovarian epithelium and the largest perimeter and surface area of the surface ovarian epithelium (P < 0.01). However, the difference in epithelium thickness between the GE0.5mg and GE1mg groups was only slight. CONCLUSION: Our data suggest that CEE at a dose of 2 mg/kg may induce marked proliferation of rat ovarian epithelium.