Estrógeno potenciado en el tratamiento homeopático del dolor pélvico asociado a endometriosis: un estudio aleatorizado, doble ciego, controlado con placebo, de 24 semanas / Potentiated estrogen in the homeopathic treatment of pelvic pain associated with endometriosis: a 24-week randomized, double-blind, placebo-controlled study

Evaluar la eficacia y seguridad del estrógeno potenciado en comparación con el placebo en el tratamiento homeopático del dolor pélvico asociado a endometriosis (EAPP, por sus siglas en inglés). Diseño del estudio: El presente fue un estudio clínico aleatorizado, doble ciego, controlado con placebo, de 24 semanas, el cual incluyó a 50 mujeres de entre 18 y 45 años de edad con diagnóstico de endometriosis infiltrante profunda con base en ultrasonido transvaginal o imágenes de resonancia magnética después de preparación intestinal, así como puntaje ≥ 5 en una escala visual analógica (VAS: rango de 0 a 10 puntos) para el dolor pélvico asociado con la endometriosis. Se administró estrógeno potenciado (12cH, 18cH y 24cH) o placebo dos veces al día por vía oral. La medida principal de resultado fue el cambio en la severidad de los puntajes parcial y global de EAPP (VAS) de la línea basal a la semana 24, determinada como la diferencia en el puntaje medio de cinco modalidades de dolor pélvico crónico (dismenorrea, dispareunia profunda, dolor pélvico no cíclico, dolor intestinal cíclico y/o dolor urinario cíclico). Las medidas secundarias de resultado fueron la diferencia media de puntaje para la calidad de vida evaluada con el Cuestionario de Salud SF-36, los síntomas de depresión en el Inventario de la Depresión de Beck (BDI) y los síntomas de ansiedad en el Inventario de Ansiedad de Beck (BAI). Resultados: El puntaje global de EAPP (VAS: rango de 0 a 50 puntos) se redujo en 12.82 (p < 0.001) en el grupo tratado con estrógeno potenciado de la línea basal a la semana 24. El grupo que utilizó estrógeno potenciado también presentó una reducción en el puntaje parcial (VAS: rango de 0 a 10 puntos) en tres modalidades de EAPP: dismenorrea (3.28; p < 0.001), dolor pélvico no cíclico (2.71; p = 0.009) y dolor intestinal cíclico (3.40; p < 0.001). El grupo de placebo no mostró cambio significativo alguno en los puntajes global o parcial de EAPP. Además, el grupo de estrógeno potenciado mostró un mejoramiento significativo en tres de ocho ámbitos de SF-36 (dolor de cuerpo, vitalidad y salud mental) y síntomas de depresión (BDI). El grupo de placebo no mostró un mejoramiento significativo a este respecto. Estos resultados demuestran la superioridad del estrógeno potenciado sobre el placebo. Se asociaron pocos eventos adversos con el estrógeno potenciado. Conclusiones: El estrógeno potenciado (12cH, 18cH y 24cH) en dosis de 3 gotas dos veces al día durante 24 semanas fue significativamente más efectivo que el placebo para reducir el dolor pélvico asociado con la endometriosis. Registro del estudio clínico: ClinicalTrials.gov Identificador: https://clinicaltrials.gov/show/NCT02427386.

To evaluate the efficacy and safety of potentized estrogen compared to placebo in homeopathic treatment of endometriosis-associated pelvic pain (EAPP). Study design: The present was a 24-week, randomized, doubleblind, placebocontrolled trial that included 50 women aged 18-45 years old with diagnosis of deeply infiltrating endometriosis based on magnetic resonance imaging or transvaginal ultrasound after bowel preparation, and score ≥ 5 on a visual analogue scale (VAS: range 0 to 10 points) for endometriosis-associated pelvic pain. Potentized estrogen (12cH, 18cH and 24cH) or placebo was administered twice daily per oral route. The primary outcome measure was change in the severity of EAPP global and partial scores (VAS) from baseline to week 24, determined as the difference in the mean score of five modalities of chronic pelvic pain (dysmenorrhea, deep dyspareunia, non-cyclic pelvic pain, cyclic bowel pain and/or cyclic urinary pain). The secondary outcome measures were mean score difference for quality of life assessed with SF-36 Health Survey Questionnaire, depression symptoms on Beck Depression Inventory (BDI), and anxiety symptoms on Beck Anxiety Inventory (BAI). Results: The EAPP global score (VAS: range 0 to 50 points) decreased by 12.82 (p < 0.001) in the group treated with potentized estrogen from baseline to week 24. Group that used potentized estrogen also exhibited partial score (VAS: range 0 to 10 points) reduction in three EAPP modalities: dysmenorrhea (3.28; p < 0.001), non-cyclic pelvic pain (2.71; p = 0.009), and cyclic bowel pain (3.40; p < 0.001). Placebo group did not show any significant changes in EAPP global or partial scores. In addition, the potentized estrogen group showed significant improvement in three of eight SF-36 domains (bodily pain, vitality and mental health) and depression symptoms (BDI). Placebo group showed no significant improvement in this regard. These results demonstrate superiority of potentized estrogen over placebo. Few adverse events were associated with potentized estrogen. Conclusions: Potentized estrogen (12cH, 18cH and 24cH) at a dose of 3 drops twice daily for 24 weeks was significantly more effective than placebo for reducing endometriosis-associated pelvic pain.

Breast cancer molecular diagnostics in Rwanda: a cost-minimization study of immunohistochemistry versus a novel GeneXpert® mRNA expression assay

Objective To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in subSaharan African laboratories, leading to improved treatment selection and better clinical outcomes.

Usos não contraceptivos dos fármacos anticoncepcionais orais hormonais: uma revisão / Non-contraceptive uses of hormonal oral contraceptive drugs: a review

Introdução: os anticoncepcionais orais hormonais são fármacos constituídos por hormônios, geralmente combinados, estrogênio e progestogênio, ou apenas progestogênio. Devido às propriedades características desses hormônios, são também responsáveis por diversos efeitos colaterais, o que tem levado a uma evolução contínua das formulações e tem-se observado vários benefícios não contraceptivos à saúde da mulher. Objetivo: o objetivo dessa revisão foi analisar os usos não contraceptivos dos anticoncepcionais orais hormonais, evidenciando sua eficácia e segurança. Metodologia: A pesquisa foi realizada em bases de dados eletrônicos e portais de busca, priorizando materiais publicados na faixa anual de 2008 a 2018, sendo encontrados 332 e utilizados 148 materiais de estudo. Resultados: esses fármacos tem sido uma alternativa eficaz de tratamento da síndrome do ovário policístico, uma vez que reduzem os androgênios circulantes e induzem a melhora dos sintomas como acne, irregularidade menstrual e dismenorreia. Estão associados ao tratamento da endometriose e à menor incidência de câncer de ovário. Neste último, exercem um efeito protetor durante anos, até mesmo após a interrupção. Conclusão: assim, os anticoncepcionais orais hormonais têm representado uma nova proposta terapêutica simples, segura e eficaz, para diversas utilidades não contraceptivas, e seus benefícios ultrapassam os riscos associados, proporcionando uma terapia adequada e individualizada para cada mulher.

Introduction: hormonal oral contraceptives are drugs consisted by hormones, usually combined, estrogen and progestogen, or just progestins. Due to the characteristic properties of these hormones, they are also responsible for several side effects, which has led to a continuous evolution of the formulations and various non-contraceptive benefits to women's health have been observed. Objective:the objective of this review was to analyze the non-contraceptive uses of hormonal oral contraceptives, showing their effectiveness and safety. Methodology: the research was conducted in electronic databases and search portals, prioritizing materials published in the annual range from 2008 to 2018, with 332 found and 148 study materials used. Results: these drugs have been an effective alternative for the treatment of polycystic ovary syndrome, since they reduce circulating androgens and induce improvement in symptoms such as acne, menstrual irregularity and dysmenorrhea. They are associated with the treatment of endometriosis and a lower incidence of ovarian cancer. In the latter, they have a protective effect for years, even after the interruption. Conclusion: thus, hormonal oral contraceptives have represented a new simple, safe and effective therapeutic proposal, for several non-contraceptive uses, and their benefits outweigh the associated risks, providing an adequate and individualized therapy for each woman

Alternativas aos antibióticos na profilaxia das infecções urinárias recorrentes não complicadas na mulher / Alternatives to antibiotics in the prophylaxis of recurrent uncomplicated infections in women

A infecção do trato urinário (ITU) é a doença bacteriana mais comum no sexo feminino, e cerca de 25% a 30% das mulheres apresentam ITUs recorrentes ao longo da vida. Os antibióticos são muito utilizados para o tratamento e prevenção dessas infecções. Entretanto, o uso excessivo e indevido desses medicamentos, além dos efeitos adversos, está relacionado ao surgimento de uropatógenos multirresistentes. Há um interesse crescente na comunidade científica para encontrar alternativas ao uso de antibióticos para tratamento e/ou prevenção das infecções bacterianas. Esta revisão tem por objetivo discutir algumas dessas alternativas.(AU)

Urinary tract infection (UTI) is the most common bacterial disease in females, and about 25% to 30% of women experience recurrent UTIs throughout their lives. Antibiotics are widely used standard for treating and preventing these infections. However, the excessive and improper use of these drugs, in addition to the adverse effects, is related to the emergence of multidrug-resistant uropathogens. There is a growing interest in the scientific community to find alternatives to the use of antibiotics for the treatment and/or prevention of bacterial infections. This review aims to discuss some of these alternatives.(AU)

Parâmetros clínicos, periodontais, nutricionais e imaginológicos em pacientes em uso de inibidores de aromatase / Clinical, periodontal, nutritional and imaginological parameters in patients using aromatase inhibitors

A osteoporose é uma doença sistêmica multifatorial, caracterizada pela redução da massa óssea. A osteoporose pode ser primária ou secundária ao uso de medicamentos como os inibidores de aromatase. Estes medicamentos interferem com a conversão de andrógenos a estrogênios, reduzindo a produção destes e sendo indicados para tratamento do câncer de mama dependente de estrógeno. O diagnóstico da osteoporose é baseado em critérios densitométricos da Organização Mundial de Saúde com referência na classificação do T-score, realizada pela técnica de absorciometria de energia dupla de raios X (DXA). Por se tratar de uma doença sistêmica, a osteoporose também afeta os ossos maxilares. Entretanto, a ocorrência e extensão de perda de estrutura do osso alveolar na osteoporose, bem como o risco destes pacientes à doença periodontal e perdas dentárias não estão claramente definidos. Este estudo teve como objetivo identificar os parâmetros clínicos, periodontais, nutricionais e bioquímicos envolvidos na perda óssea em pacientes em uso de inibidores de aromatase. A perda óssea foi avaliada por absorciometria dupla de raios-X (DXA). Foram coletados dados sobre estado nutricional, antropométrico, bucal e periodontal e qualidade de vida relacionada à saúde bucal (OHRQoL). Citocinas e adipocinas foram quantificadas na saliva e soro. Foi realizado um estudo transversal do tipo caso-controle, com um grupo de comparação, no serviço de densitometria óssea do Hospital Mater Dei, no período de 2018 a 2021. A amostra foi constituída por 72 mulheres divididas em dois grupos: em uso de inibidores de aromatase (IAs) (n=40) e pacientes sem uso de inibidores de aromatase (controle) (n=32). Do total da amostra, 39 pacientes (57,4%) foram diagnosticados com perda de massa óssea. Os resultados mostraram que as mulheres idosas em uso de inibidores de aromatase (p=0,009) e fumantes (p=0,034) apresentaram maior perda óssea. Não houve diferença significativa entre os grupos considerando-se as comorbidades analisadas. A análise antropométrica demonstrou que os indivíduos em uso de inibidores de aromatase com perda óssea apresentaram menor peso (p=0,028). O modelo de regressão revelou que a única variável que explica a perda óssea é o uso de antirreabsortivos sendo a perda óssea significativamente reduzida nos indivíduos que usaram esse medicamento (p=0,022). Embora a frequência de periodontite tenha sido semelhante comparando todos os grupos, maiores valores de IL-6 (p=0,004); IL-1ß (p=0,002) e IL-33 (p=0,006) na saliva foram relacionados à pior condição periodontal. Indivíduos que usaram inibidores de aromatase foram 1,18 mais propensos a relatar uma melhor qualidade de vida relacionada à saúde bucal (OHRQoL) do que os controles. Conclusão: Enquanto idade avançada, tabagismo e menor peso são fatores associados à perda óssea, o uso de antirreabsortivos foi fator protetor em indivíduos em uso de inibidores de aromatase.

Osteoporosis is a multifactorial systemic disease characterized by reduced bone mass. Osteoporosis can be primary or secondary to the use of drugs such as aromatase inhibitors. These drugs interfere with the conversion of androgens to estrogens, reducing their production and are indicated for the treatment of estrogen-dependent breast cancer. The diagnosis of osteoporosis is based on densitometric criteria of the World Health Organization with reference to the T-score classification, performed by the technique of dual energy x-ray absorptiometry (DXA). Because it is a systemic disease, osteoporosis also affects the jaw bones. However, the occurrence and extent of loss of alveolar bone structure in osteoporosis, as well as the risk of these patients for periodontal disease and tooth loss, are not clearly defined. This study aimed to identify clinical, periodontal, nutritional and biochemical determinants involved with bone loss in patients using aromatase inhibitors. Bone loss was assessed by dual X- ray absorptiometry (DXA). Data on nutritional, anthropometric, oral and periodontal status and oral health-related quality of life (OHRQoL) were collected. Cytokines and adipokines were quantified in saliva and serum. A cross-sectional case-control type study, with a comparison group, was conducted at the bone densitometry service of Hospital Mater Dei from 2018 to 2021. The sample consisted of 72 women divided into two groups: using aromatase inhibitors (AIs) (n=40) and patients not using aromatase inhibitors (control) (n=32). Of the total sample, 39 patients (57.4%) were diagnosed with bone loss. The results showed that elderly women using aromatase inhibitors (p=0.009) and smokers (p=0.034) had greater bone loss. There was no significant difference between the groups considering the analyzed comorbidities. Anthropometric analysis showed that individuals using aromatase inhibitors with bone loss had lower weight (p=0.028). The regression model revealed that the only variable that explains bone loss is the use of antiresorptive drugs, with bone loss significantly reduced in individuals who used this medication (p=0.022). Although the frequency of periodontitis was similar comparing all groups, higher values of IL-6 (p=0.004); IL-1ß (p=0.002) and IL-33 (p=0.006) in saliva were related to worse periodontal status. Subjects who used aromatase inhibitors were 1.18 times more likely to report a better oral health-related quality of life (OHRQoL) than controls. Conclusion: While advanced age, smoking and lower weight are factors associated with bone loss, the use of antiresorptives was a protective factor in individuals using aromatase inhibitors.

Estradiol inhibits differentiation of mouse macrophage into a pro-inflammatory phenotype by upregulating the IRE1α-XBP1 signaling axis / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which estradiol modulates the immunophenotype of macrophages through the endoplasmic reticulum stress pathway.@*METHODS@#Peritoneal macrophages isolated from C57 mice were cultured in the presence of 60 ng/mL interferon-γ (IFN-γ) followed by treatment with estradiol (1.0 nmol/L) alone, estradiol with estrogen receptor antagonist (Acolbifene, 4 nmol/L), estradiol with IRE1α inhibitor (4 μ 8 C), or estradiol with IRE1α agonist. After the treatments, the expression levels of MHC-Ⅱ, iNOS and endoplasmic reticulum stress marker proteins IRE1α, eIF2α and ATF6 in the macrophages were detected with Western blotting, and the mRNA levels of TGF-β, IL-6, IL-10 and TNF-α were detected with RT-PCR.@*RESULTS@#Estrogen treatment of the macrophages significantly decreased the expressions of M1-related proteins MHC-Ⅱ (P=0.021) and iNOS (P < 0.001) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.004), increased the mRNA expression of TGF-β (P=0.002) and IL-10 (P=0.008), and up-regulated the protein expressions of IRE1α (P < 0.001) and its downstream transcription factor XBP-1 (P < 0.001). Addition of the estrogen inhibitor obviously blocked the effect of estrogen. Compared with estrogen treatment alone, combined treatment of the macrophages with estrogen and the IRE1α inhibitor 4 μ 8 C significantly up-regulated the protein expressions of MHC-Ⅱ (P=0.002) and iNOS (P=0.003) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.024), and obviously down-regulated the mRNA expression of TGF-β (P < 0.001) and IL-10 (P < 0.001); these changes were not observed in cells treated with estrogen and the IRE1α agonist.@*CONCLUSION@#Estrogen can inhibit the differentiation of murine macrophages into a pro-inflammatory phenotype by up-regulating the IRE1α-XBP-1 signaling axis, thereby producing an inhibitory effect on inflammatory response.

Cross-sectional analysis of gonadal hormone expression and relevant factors in female centenarians in Hainan, China / 中南大学学报(医学版)

OBJECTIVES@#Gonadal hormone is essential for the health of postmenopausal women, however, few studies have focused on the epidemiological distribution of gonadal hormones in postmenopausal women in very late postmenopausal women. This study aims to investigate and analyze the differences of serum gonadal hormone content and its influential factors among female centenarians in Hainan, China.@*METHODS@#The questionnaire and physical examination data of 741 female centenarians and 401 elderly females in Hainan Province were collected, and venous blood samples were taken to detect the indexes of lipid metabolism, bone metabolism, and gonadal hormone. The differences of gonadal hormones and relavant factors in female centenarians were analyzed and compared.@*RESULTS@#The serum levels of estradiol and progesterone of female centenarians were significantly higher than those of the elderly females (both P<0.001). The serum levels of estradiol and testosterone of ethnic minority centenarians were higher than those in Han nationality (P<0.001), and the serum estradiol and testosterone concentrations were relatively higher when the daily activities were more than 10 min (both P<0.05). Serum estradiol concentration was negatively correlated with apolipoprotein A-I, high density lipoprotein, triglyceride and bone formation markers such as calcium, inorganic phosphorus and vitamin D3, and was positively correlated with the special sequence of β-collagen (markers of bone resorption) (all P<0.01).@*CONCLUSIONS@#For the extremely late postmenopausal women (such as centenarians), there may be characteristic expressions of gonadal hormones, especially estradiol. There is an unprotective correlation of serum estradiol with lipid metabolism index and bone metabolism index in female centenarians, so it is necessary to evaluate the estrogen content and the use of estrogen therapy in postmenopausal women.

Relações entre a Redução de Estrogênio, Obesidade e Insuficiência Cardíaca com Fração de Ejeção Preservada / Crossroads between Estrogen Loss, Obesity, and Heart Failure with Preserved Ejection Fraction

Resumo A prevalência de obesidade e insuficiência cardíaca com fração de ejeção preservada (ICFEP) aumenta significativamente em mulheres na pós-menopausa. Embora a obesidade seja um fator de risco para disfunção diastólica do ventrículo esquerdo (DDFVE), o mecanismo que liga a interrupção da produção de hormônios ovarianos, especialmente o estrogênio, ao desenvolvimento da obesidade, DDFVE, e ICFEP em mulheres em processo de envelhecimento não é claro. Estudos clínicos e epidemiológicos demonstram que mulheres na pós-menopausa com obesidade abdominal (definida pela circunferência de cintura) têm risco maior de desenvolver a ICFEP do que homens ou mulheres sem obesidade abdominal. Este estudo analisa dados clínicos que corroboram a existência de uma ligação de mecanismo entre a perda de estrogênio mais obesidade e o remodelamento ventricular esquerdo com ICFEP. Ele também discute os possíveis mecanismos celulares e moleculares para a proteção mediada por estrogênio contra tipos de células, depósitos de tecidos, função e metabolismo de adipócitos negativos que podem contribuir para a DDFVE e a ICFEP.

Abstract The prevalence of obesity and heart failure with preserved ejection fraction (HFpEF) increases significantly in postmenopausal women. Although obesity is a risk factor for left ventricular diastolic dysfunction (LVDD), the mechanisms that link the cessation of ovarian hormone production, and particularly estrogens, to the development of obesity, LVDD, and HFpEF in aging females are unclear. Clinical, and epidemiologic studies show that postmenopausal women with abdominal obesity (defined by waist circumference) are at greater risk for developing HFpEF than men or women without abdominal obesity. The study presents a review of clinical data that support a mechanistic link between estrogen loss plus obesity and left ventricular remodeling with LVDD. It also seeks to discuss potential cell and molecular mechanisms for estrogen-mediated protection against adverse adipocyte cell types, tissue depots, function, and metabolism that may contribute to LVDD and HFpEF.

Resultados de Covid-19 en mujeres posmenopáusicas y perimenopausicas: ¿Se atribuye a los estrógenos las diferencias? / COVID-19 outcomes in postmenopausal and perimenopausal women: are the diferences ascribed to estrogens ?

Antecedentes: A nivel mundial, la tasa de letalidad es mayor en hombres que en mujeres. Algunos estudios lo han sugerido. Se plantea la hipótesis de que la hormona estrogénica, puede disminuir la susceptibilidad al síndrome respiratorio agudo severo coronavirus 2. Objetivo: El objetivo del estudio fue evaluar las diferencias de género en los resultados del SARS CoV-2 y analizar si existen diferencias en los resultados en mujeres premenopáusicas en comparación con posmenopáusicas. Materiales y métodos: Se incluyeron en el estudio 720 pacientes que dieron positivo (+) para SARS CoV-2 a través de la reacción en cadena de la polimerasa (PCR) con transcripción inversa en tiempo real, mediante el ensayo Thermo Fischer Taqpath, aprobado por el Consejo Indio de Investigación Médica. Los datos obtenidos fueron analizados por las características epidemiológicas, clínicas y de laboratorio de sus historias clínicas. Resultados: La tasa de mortalidad en las mujeres fue del 12,6%, mientras que la mortalidad en los hombres fue del 19,4%. En el análisis entre grupos, el 8,6% (16/185) de las mujeres murieron en el grupo de edad premenopáusica frente al 12,8% (27/211) en el grupo posmenopáusico. La proporción de mujeres que fallecieron debido a COVID difiere significativamente según la edad y el estado posmenopáusico X2 (1, n = 293) = 7,2, el valor de p es 0,007. La diferencia es estadísticamente significativa a P<0,05. Las mujeres posmenopáusicas tenían más probabilidades de fallecer debido a la infección por COVID-19 en comparación con las mujeres premenopáusicas

Disparidad global por sexo de Covid-19: una revisión descriptiva de las hormonas sexuales y consideración del uso terapéutico potencial de la terapia de reemplazo hormonal en adultos mayores / COVID-19 global gender disparity: a descriptive review of sex hormones and consideration of the potential therapeutic use of hormone replacement therapy in older adults

La pandemia de coronavirus-2 (SARS-CoV-2) relacionada con el SARS 2019-2020 ha traído desafíos sin precedentes a los sectores de la salud en todo el mundo. Hasta noviembre de 2020, ha habido más de 64 millones de casos confirmados y se acercan a 2 millones de muertes en todo el mundo. A pesar de la gran cantidad de casos positivos, existen muy pocos estándares establecidos de atención y opciones terapéuticas disponibles. Hasta la fecha, (Diciembre 2020) todavía no existe una vacuna aprobada por la Administración de Alimentos y Medicamentos (FDA) para COVID-19, aunque existen varias ensayos clínicos en diferentes. etapas de desarrollo. En este documento, hemos realizado una revisión global que evalúa los roles de la edad y el sexo en las hospitalizaciones por COVID-19, las admisiones a la UCI, las muertes en hospitales y las muertes en hogares de ancianos. Hemos identificado una tendencia en la que las personas mayores y los pacientes masculinos se ven afectados significativamente por los resultados adversos.

Linear and Nonlinear Heart Rate Variability Analysis in Gonadal Dysgenesis (Swyer Syndrome): A Case Report

Abstract Swyer syndrome is one of the disorders of sexual differentiation. Previous studies have demonstrated increased sympathetic activity with heart rate variability (HRV) analysis with decreasing estradiol levels. One patient presented a pure 46, XY gonadal dysgenesis with female phenotype. Cardiac autonomic modulation was assessed through HRV analysis while at rest. This research analyzed linear and nonlinear indexes. HRV analysis showed reduced parasympathetic and global modulation with an apparent increase in sympathetic tone and a loss of HR fractal dynamics toward correlated behavior, characterized by low entropy and high determinism of time series.

Tratamiento del síndrome genitourinario de la menopausia con láser CO2 en pacientes de Clínica Estrella / Treatment for genitourinary syndrome of menopause with CO2 laser in Clinica Estrella patients

El síndrome genitourinario de la menopausia se refiere a los signos y síntomas relacionados a la disminución estrogénica dando como resultado una atrofia vaginal, esto ocasiona un gran impacto negativo en las actividades cotidianas de las mujeres, existen varios tratamientos para aliviar y resolver los síntomas, siendo los más frecuentes la incontinencia urinaria por esfuerzo y resequedad vaginal. Dentro de los distintos tratamientos, el láser tiene como objetivo la restauración de la mucosa vaginal, estimulando los fibroblastos para obtener la neo colagenogenesis y vascularización, recuperando su funcionalidad y obteniendo mejoría de los síntomas junto con la calidad de vida de las pacientes

Genitourinary syndrome of menopause refers to a group of signs and symptoms related to the decreased estrogen and as a result, the vaginal atrophy, this has a great negative impact on the daily activities of women, there are several treatments to alleviate and resolve the symptoms, the most frequent being stress urinary incontinence and vaginal dryness. Among the different treatments, the laser aims to restore the aavaginal mucosa, stimulating fibroblasts to obtain neo-collagen oogenesis and revascularization, recovering their functionality and obtaining an improvement in symptoms along with the quality of life of patients

Terapia de reemplazo hormonal después del cáncer de mama: ¿sí, no o quizás? / Hormone replacement therapy after breast cancer: yes, no, or maybe?

Más de nueve millones de sobrevivientes de cáncer de mama en todo el mundo sufren un deterioro en la calidad de vida atribuible a los síntomas de la menopausia relacionados con el déficit de los estrógenos y con los efectos secundarios de la terapia contra el cáncer. La terapia de reemplazo hormonal (TRH) es muy eficaz para controlar estos síntomas en la población general y en las sobrevivientes de cáncer de mama. Sin embargo, la preocupación de la recurrencia del cáncer de mama como resultado del uso de TRH impide que muchos oncólogos utilicen este enfoque en el tratamiento de los síntomas menopáusicos. La evidencia de ensayos aleatorizados, estudios observacionales y meta-nálisis sobre el impacto del uso de TRH en la recurrencia y supervivencia del cáncer de mama sigue siendo controvertida.

More than nine million breast cancer survivors in everyone suffers a deterioration in the quality of life attributable to the symptoms of menopause related to the deficiency of the estrogens and with the side effects of anti-estrogen therapy Cancer. Hormone replacement therapy (HRT) is very effective in controlling these symptoms in the general population and in survivors of breast cancer. However, the concern of recurrence of breast cancer as a result of the use of HRT prevents many oncologists use this approach in the treatment of menopausal symptoms. Evidence from randomized trials, observational studies, and meta-analysis on the impact of the use of HRT on recurrence and Breast cancer survival remains controversial

Use of cooled buffalo semen as a strategy to increase conception rates in fixed-time artificial insemination programs during unfavorable reproductive periods / [Uso de sêmen resfriado de búfalo como estratégia para aumentar as taxas de concepção em programas de inseminação artificial em tempo fixo, durante períodos reprodutivos desfavoráveis]

The objective of this study was to compare the reproductive efficiency of dairy buffaloes undergoing fixed-time artificial insemination (FTAI) protocols based on progesterone/estrogen (P4/E2) and eCG during unfavorable breeding season using cooled (CS) and frozen semen (FS). A total of 446 buffaloes (> 40 days postpartum) were randomly distributed into four blocks (years): B1-2014 (n = 143), B2-2015 (n = 34), B3-2016 (n = 90), and B4-2017 (n = 179). Each block was subdivided into two (AI with CS and FS using the same ejaculate of each bull). Thus, the block subdivision was as follows: B1 (CS = 71 and FS = 72); B2 (CS = 18 and FS = 16); B3 (CS = 47 and FS = 43); and B4 (CS = 90 and FS = 89). The ejaculates of eight Murrah bulls collected using an artificial vagina were divided into two aliquots: one aliquot was diluted in Botu-Bov® commercial extender and cooled (BB-CS), and the other was diluted in the same extender and frozen (BB-FS). BB-CS aliquots were cooled at 5 °C/24 h using a refrigerator. BB-FS group aliquots were also cooled, and after equilibrating at 5 °C for 4 h, were placed in a 21-L Styrofoam box, 5 cm above the surface of liquid nitrogen. In the afternoon (A) on D0 (2:00 p.m.) the animals received EB 2.0 mg IM (Estrogin®) and an ear implant (CRESTAR® 3.0 mg P4). At D9 (A), the implant was removed, and the animals received eCG 400 IU IM (Folligon® 5000) + Cloprostenol PGF2α 0.530 mg IM (Sincrocio®). At D10 (A), the animals received EB 1.0 mg IM (Estrogin®), and at D12 (8:00 a.m.), AI was performed. At D42, pregnancy was diagnosed via ultrasonography. Total CRs were 48.2% CS and 34.6% FS for years 2014 to 2017, with a significant difference of 13.7% (P<0.05). In conclusion, cooled semen resulted in higher CR than frozen semen in dairy buffaloes under the P4/E2 and eCG FTAI during the unfavorable reproductive season.(AU)

O objetivo deste estudo foi comparar a eficiência reprodutiva de búfalas leiteiras submetidas a protocolos de inseminação artificial em tempo fixo (IATF) à base de progesterona/estrogênio (P4/E2) e eCG, durante a estação reprodutiva desfavorável, usando-se sêmen resfriado (SR) e congelado (SC) Um total de 446 búfalas (> 40 dias após o parto) foi distribuído aleatoriamente em quatro blocos (anos): B1-2014 (n = 143), B2-2015 (n = 34), B3-2016 (n = 90) e B4-2017 (n = 179). Cada bloco foi subdividido em dois (IA com SR e SC utilizando-se a mesma ejaculação de cada touro). Assim, a subdivisão do bloco foi a seguinte: B1 (SR = 71 e SC = 72); B2 (SR = 18 e SC = 16); B3 (SR = 47 e SC = 43); e B4 (SR = 90 e SC = 89). Os ejaculados de oito touros Murrah coletados com vagina artificial foram divididos em duas alíquotas: uma alíquota diluída em diluente comercial Botu-Bov® e resfriada (BB-SR), e a outra diluída no mesmo diluente e congelada (BB-SC). As alíquotas de BB-SR foram resfriados a 5°C/24h usando-se um refrigerador. As alíquotas do grupo BB-SC também foram resfriadas e, após equilíbrio a 5°C por 4h, foram colocadas em uma caixa de isopor de 21L, 5 cm acima da superfície do nitrogênio líquido. À tarde (A), no D0 (14h), os animais receberam BE 2,0 mg IM (Estrogin®) e um implante auricular (Crestar® 3,0 mg P4). No D9 (A), o implante foi retirado e os animais receberam eCG 400 UI IM (Folligon® 5000) + cloprostenol PGF2α 0,530 mg IM (Sincrocio®). No D10 (A), os animais receberam BE 1,0mg IM (Estrogin®), e, no D12 (8h da manhã), foram realizadas as IAs. No D42, a gestação foi diagnosticada por ultrassonografia. As taxas de concepção (TC) totais foram 48,2% SR e 34,6% SC para os anos de 2014 a 2017, com uma diferença significativa de 13,7% (P<0,05). Em conclusão, o sêmen resfriado resultou em maior TC do que o sêmen congelado em bubalinos leiteiros sob P4/E2 e eCG FTAI durante a estação reprodutiva desfavorável.(AU)

Long-term lung inflammation is reduced by estradiol treatment in brain dead female rats

OBJECTIVES: Lung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17β-estradiol on the lungs. Here, we aimed to investigate the effect of estradiol on the long-lasting lung inflammatory state to understand a possible therapeutic application in lung donors with BD. METHODS: Female Wistar rats were separated into 3 groups: BD, subjected to brain death (6h); E2-T0, treated with 17β-estradiol (50 μg/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17β-estradiol (50 μg/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-α, IL-1β, IL-10, and IL-6 gene expression (RT-PCR) and levels in 24h lung culture medium were quantified. Finally, analysis of caspase-3 gene and protein expression in the lung was performed. RESULTS: Estradiol reduced complement C3 protein and gene expression. The presence of lung macrophages was not modified by estradiol, but the release of inflammatory mediators was reduced and TNF-α and IL-1β gene expression were reduced in the E2-T3 group. In addition, caspase-3 protein expression was reduced by estradiol in the same group. CONCLUSIONS: Brain death-induced lung inflammation in females is modulated by estradiol treatment. Study data suggest that estradiol can control the inflammatory response by modulating the release of mediators after brain death in the long term. These results strengthen the idea of estradiol as a therapy for donor lungs and improving transplant outcomes.

Influence of CYP19A1 gene expression levels in women with breast cancer: a systematic review of the literature

Breast cancer is the most frequently diagnosed malignant neoplasm in women and is considered a multifactorial disease of unknown etiology. One of the major risk factors is genetic alteration. Changes in CYP19A1 gene expression levels have been associated with increased risk and increased aggressiveness of breast cancer. Increased CYP19A1 gene expression and/or aromatase activity are among the major regulatory events for intratumoral production of estrogens in breast malignant tissues. This systematic review aimed to investigate the influence of CYP19A1 gene expression levels in women with breast cancer. The research was carried out using the PubMed, Scopus, and Web of Science databases. Searches were conducted between February 2 and May 15, 2019. Inclusion criteria were studies published between 2009 and 2019, English language publications, and human studies addressing the gene expression of CYP19A1 in breast cancer. A total of 6.068 studies were identified through PubMed (n=773), Scopus (n=2,927), and the Web of Science (n=2,368). After selecting and applying the inclusion and exclusion criteria, six articles were included in this systematic review. This systematic review provides evidence that increased or decreased levels of CYP19A1 gene expression may be related to pathological clinical factors of disease, MFS, OS, DFS, WATi, markers of metabolic function, concentrations of E1, FSH, and in the use of multiple exons 1 of the CYP19A1 gene in breast cancer.

Terapia hormonal de la menopausia en el año 2021 / Menopause hormone therapy in 2021

En enero de 2021 la Asociación Colombiana de Menopausia realizó el simposio "Terapia hormonal de la menopausia" contando con la participación de respetados profesores de la especialidad y a cada uno se le asignó un tema para ser revisado y presentado de acuerdo a la evidencia actual. En noviembre del año 2020 el Instituto de Vigilancia de Medicamentos y Alimentos (INVIMA) había lanzado una alerta sobre "Riesgo de desarrollar cáncer de mama en mujeres postmenopáusicas en manejo con terapia de reemplazo hormonal", apoyándose en una decisión del Reino Unido. Dentro de las afirmaciones de INVIMA se encontró que el uso prolongado por más de un año incrementa el riesgo de cáncer de mama sin que sea claro su soporte científico para tal afirmación. El pronunciamiento del Reino Unido se soportó en el estudio "Tipo y momento de la terapia hormonal de la menopausia y el riesgo de cáncer de mama: Meta-análisis de participantes individuales de la evidencia epidemiológica mundial, del Grupo de colaboración sobre factores hormonales en el cáncer de mama, publicado en la revista médica The Lancet el 29 de agosto de 2019. Varias asociaciones científicas se manifestaron en contra de lo enunciado y por ende la Asociación Colombiana de Menopausia consideró apropiado hacer una revisión exhaustiva del papel de la terapia hormonal en la actualidad. El resultado de dicho trabajo es presentado en esta revisión.

On January 2021 de Colombian Menopause Association did a symposium "Menopause hormonal therapy" with participation of respectable professors of the specialty, to each one previously a topic had been assigned for its review and presentation according to actual evidence. On November 2020 the Colombian Institute for Drugs and Foods Vigilance (INVIMA) had issued an alert about the "Risk of developing breast cancer in postmenopausal women under treatment with hormone replacement therapy", having support in a decision taken in the United Kingdom. One of the things affirmed by INVIMA was that prolonged use, greater than one year, increases the risk of breast cancer, without clear scientifically supporting this issue. In the United Kingdom the pronunciation was supported on the study, "Type and moment of menopausal hormone therapy and risk of breast cancer: Metanalisis of individual participants of worldwide epidemiological evidence, from the Collaborative group on hormonal factors in breast cancer published in The Lancet on August 29, 2019. Various scientific associations manifested against what was expressed and the Colombian Menopause Association considered appropriate to do an exhaustive review of the role of hormonal therapy today. The result of such work is presented in this paper.

Parâmetros imaginológicos em pacientes com alteração de massa óssea / Imaginological parameters in patients with bone mass alteration

Os inibidores de aromatase (IAs) são medicamentos mais comumente utilizados para tratamento para pacientes com câncer de mama. Os IAs atuam inibindo a enzima aromatase, que é responsável pela conversão de hormônios esteroidais. Vários estudos mostram a importância do estrógeno para a formação óssea. Acredita-se que a privação do estrógeno possa ter um efeito deletério no osso causando o aumento da reabsorção óssea, diminuição da densidade mineral óssea (DMO) e com isso o aumento do risco de osteoporose e fraturas. A osteoporose é uma doença sistêmica multifatorial caracterizada pela redução da massa óssea e desorganização estrutural do tecido ósseo. O diagnóstico da osteoporose é baseado em critérios densitométricos da Organização Mundial de Saúde (OMS) com referência na classificação do T-score, realizada pela técnica de absorciometria de energia dupla de raios X (DXA), cujo valor avalia a DMO. Por se tratar de uma doença sistêmica, a osteoporose também afeta os ossos maxilares. Desta forma, o trabalho tem como objetivo avaliar parâmetros imaginológicos em pacientes mulheres que fazem tratamento com; IAs e encaminhadas para investigação de perda de massa óssea em um hospital de referência no tratamento dessas pacientes. Foram avaliadas 40 mulheres sob terapia com IAs. Foram avaliados índices radiomorfométricos (IR) de tomografia computadorizada de feixe cônico (TCFC) e análise fractal (AF) para algumas regiões de interesse (RI), espessura da cortical mandibular (ECM) e índice cortical mandibular (ICM) em radiografias panorâmicas digitais (RPD). Todas as pacientes foram submetidas ao exame DXA para avaliar a condição de DMO e divididas nos grupos: normal e baixa DMO. Para cada IR e para as RI da dimensão fractal, foram estabelecidas a curva característica de operação do receptor (ROC), a área sob a curva (AUC), a sensibilidade e a especificidade com seus receptivos intervalos de confiança. Os valores de AUC para os índices de RPD variaram de 52,6%-75,8%. O índice com a maior AUC foi a ECM, apresentando sensibilidade de 38,1%-100,0% e especificidade de 36,8%-84,2%. Para a AF, a RI do trabeculado total teve a maior sensibilidade, enquanto a RI anterior ao forame mentual teve a maior especificidade. Na análise da TCFC, os valores de AUC variaram de 51,8%-62,0%. Os índices com a AUC mais elevada foram o índice molar (M), com sensibilidade 18,1%-61,6% e especificidade de 66,9%-98,7% e o índice anterior (A) com sensibidade de 25,7%- 70,2% e especificidade de 48,8%-90,9%. O índice da sínfise (S) apresentou a maior sensibilidade e o índice posterior (P) apreentou a maior especificidade. Os índices de tomografia computadorizada inferior (ITC I) apresentou sensibilidade e especificidade razoáveis. Assim a ECM, a AF das RI do ângulo da mandíbula e do trabeculado total da RPD, bem como os índices ITC (I), M, P e A na TCFC mostraram-se úteis para identificar mulheres na pós-menopausa que usavam AI com baixa DMO.

Aromatase inhibitors (AIs) are the most commonly used drugs to treat breast cancer patients. AIs work by inhibiting the aromatase enzyme, which is responsible for converting steroid hormones. Several studies show the importance of estrogen for bone formation. It is believed that estrogen deprivation can have a deleterious effect on bone, causing increased bone resorption, decreased bone mineral density (BMD) and thus an increased risk of osteoporosis and fractures. Osteoporosis is a multifactorial systemic disease characterized by reduced bone mass and structural disorganization of bone tissue. The diagnosis of osteoporosis is based on densitometric criteria of the World Health Organization (WHO) with reference to the T- score classification, performed by the dual energy X-ray absorptiometry (DXA) technique, whose value assesses the BMD. As it is a systemic disease, osteoporosis also affects the maxillary bones. Thus, the study aims to evaluate imaging parameters in female patients undergoing treatment with AIs and referred for investigation of bone mass loss in a reference hospital in the treatment of these patients. Forty women undergoing therapy with AIs were evaluated. Radiomorphometric indices (RI) of cone beam computed tomography (CBCT) and fractal dimension (FD) were evaluated for some regions of interest (ROI), mandibular cortical width (MCW) and mandibular cortical index (MCI) in digital panoramic radiographs (DPR). All patients underwent the DXA exam to assess the status of BMD and divided into groups: normal and low BMD. The AUC values for the DPR indices ranged from 52.6%-75.8%. The index with the highest AUC was the mandibular cortical width ([MCW]; sensitivity: 38.1%-100.0%; specificity: 36.8%-84.2%). For FD, the total trabecular index had the greatest sensitivity, while the index anterior to the mental foramen (MF) had the highest specificity. In CBCT analysis, the values of AUC ranged from 51.8%-62.0%. The indices with the highest AUC were the molar index (M, sensitivity: 18.1%-61.6% and specificity: 66.9%-98.7%) and anterior (A, sensitivity: 25.7%-70.2% and specificity 48.8%-90.9%). The symphysis (S) index had the highest sensitivity, and the posterior (P) index presented the highest specificity. Sensitivity and specificity reasonable were obtained to computed tomography index (Inferior) [CTI (I)]. The MCW, FD of ROI of the mandible angle and total mandibular in the DPR, as well as the CTI (I), M, P, and A indices in the CBCT are useful to identify postmenopausal women who were using AI with low BMD.