Effects of clinical and metabolic variables and hormones on the expression of immune protein biomarkers in the endometrium of women with polycystic ovary syndrome and normal-cycling controls.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are at an elevated risk of endometrial cancer, which may be associated with the continuous proliferative state caused by the interaction between hormones and metabolic factors. OBJECTIVE: To investigate the impact of hormones and metabolic factors in the proliferation and death of endometrium during the proliferative phase. METHODS: Cross-sectional study with 11 women with PCOS and eight normal-cycling non-PCOS controls at the Federal University of the State of Rio de Janeiro from February 2011 to June 2019. Clinical, biochemical, and hormonal data were collected to analyze their influence on the expression of biomarkers related to the endometrial tissue breakdown. Hysteroscopy and endometrial biopsies were conducted, and the endometrial samples underwent immunohistochemistry for markers of apoptosis B-cell lymphoma 2 (BCL2), cleaved caspase-3 (CASP3), fas cell surface death receptor (FAS), FAS ligand (FASLG), BCL2 associated X (BAX), marker of proliferation Ki-67 (MKI67), and cell death using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL). RESULTS: CASP3 and TUNEL expressions were lower in both stroma and endometrium gland of PCOS women than in controls. MKI67 and homeostasis indexes (BCL2/BAX; FASLG/FAS) in the endometrium of the PCOS group were significantly higher. Body mass index (BMI) values were positively correlated with the expression of MKI67 and MKI67/TUNEL ratio in the endometrial stroma compartment. Fasting insulin levels were positively correlated with the expression of BCL2, and DHEA-S levels were negatively correlated with the expression of CASP3 of women with PCOS. CONCLUSION: BMI, insulin, and DHEA-S influence the endometrial homeostasis breakdown in PCOS in the endometrium stroma.

Does obesity modify the expression of cyclin D1 and pten in endometrial polyps in postmenopausal women?

OBJECTIVE: To assess cyclin D1 and PTEN immunoexpression in benign endometrial polyps (EPs) in asymptomatic postmenopausal women and its correlation with obesity. Methods: This was a cross-sectional study based on data from a sample of 52 patients diagnosed with EP between February 2018 and January 2019. The women included in this study were amenorrheal for at least 1 year and were asymptomatic (no postmenopausal bleeding). Obesity defined by body mass index (BMI) was investigated for correlation with Cyclin-D1 and PTEN gene expression (immunohistochemistry) in glandular and stromal compartments of polyps. Results: No significant differences among groups were identified in any clinical and epidemiological parameter (age, age of menopause, time since menopause, number of gestations, polyp size, leucocyte count, fasting blood glucose and basic pathologies), except for BMI. Body mass index did not alter PTEN or Cyclin D1 immunoexpression. Conclusion: Our study shows that obesity does not appear to be a relevant factor in the immunoexpression of PTEN and Cyclin D1 in benign EP, in either the stromal or glandular compartments.

Expression levels of BCL2 and MKI67 in endometrial polyps in postmenopausal women and their correlation with obesity.

Obesity is associated with numerous diseases, including endometrial disorders in postmenopausal women, such as adenocarcinoma, hyperplasias and endometrial polyps, and the risk of malignant transformation of these structures. The present study evaluated the influence of body mass index (BMI) on cell proliferation (BCL2 and MKI67) in endometrial polyps in postmenopausal women. A prospective cross-sectional study using immunohistochemical analysis of the expression of a cell proliferation marker (MKI67) and an anti-apoptotic gene (BCL2) in endometrial polyps in postmenopausal women was performed. The patients were divided into three groups depending on BMI: i) <24.9 kg/m2 (normal); ii) >25 and <29.9 kg/m2 (overweight); and iii) >30 kg/m2 (obese). The present study analyzed the expression of these markers in relation to polyp size, histological type and time since menopause in 38 patients. The interpretation of MKI67 and BCL2 expression accounted for the percentage of positive cells (scores): 1 (weak), <5% of cells showed expression; 2 (moderate), between 5 and 50%; and 3 (intense), >50%. Statistical analysis was performed using GraphPad InStat version 3.00 software. ANOVA was used to analyze BCL2 and MKI67 expression. A significance level of P<0.05 was adopted for rejecting the null hypothesis. There was greater glandular expression of MKI67 in obese women than in normal weight women (P=0.02) and greater expression of BCL2 in the stroma of polyps >2 cm (P=0.03). Hyperplastic polyps exhibited hyperexpression of MKI67 (P=0.04) compared with atrophic polyps. No difference in MKI67 and BCL2 expression was identified in the glands and stroma of polyps when comparing overweight and obese postmenopausal patients. The present findings suggest that BMI has an influence on proliferation markers (MKI67) in the polyps of postmenopausal women and that polyps >2 cm exhibit hyperexpression of BCL2 in the stroma.

How long is the ovary relevant for synthesis of steroids after menopause?

This study aimed to determine whether the ovaries synthesize estradiol (E2), testosterone (T), and androstenedione (A) after menopause. The first group (30 patients) underwent surgical menopause (SM) - their ovaries were removed due to a benign condition around the time of menopause. The second group (30 patients) consisted of patients with natural menopause (NM). The E2 median level was 10.0 pg/ml (CI ± 2.18) and 9.5 pg/ml (CI ± 1.63) in the NM and SM groups (p = .69), respectively. The median level of total T was 0.12 ng/ml (CI ± 0.01) and 0.11 ng/ml (CI ± 0.03) in NM and SM, respectively (p = .96). The median level of A was 783.85 pg/ml (CI ± 154.39) and 883.48 pg/dl (CI ± 201.03) in NM and SM, respectively (p = .57). The FAI (free androgen index) was 1.06 (CI ± 0.24) and 1.35 (CI ± 0.68) for NM and SM, respectively (p = .98). We concluded that 5-10 years after menopause the ovaries are no longer relevant for sex steroid synthesis.

The evaluation of endometrial sulfate glycosaminoglycans in women with polycystic ovary syndrome.

The aim of this study was to quantify the sulfated glycosaminoglycans in the endometria of women with polycystic ovary syndrome (PCOS). Of the 18 patients recruited for this study, 10 patients with PCOS comprised the PCOS group (PCOSG), and eight patients with regular and ovulatory menstrual cycles comprised the control group (CG). The clinical, biochemical, morphological and endometrial data from both groups were analyzed. Biopsies were performed during the proliferative phase of the menstrual cycle for the CG and during the persistent proliferative phase for the PCOSG (all women were amenorrheic). In the PCOSG, there was a significant increase in the endometrial concentration levels of heparan sulfate (p = 0.03), but no difference in the concentrations of chondroitin sulfate was determined between the two groups (p = 0.77). Period of time without menstruation (p = 0.001) and body mass index (BMI) (p = 0.04) correlated directly and positively with heparan sulfate concentration. There was no association between heparan sulfate levels and basal insulin values (p = 0.08). High levels of endometrial heparan sulfate in women with PCOS indicate an interference with maternal-fetal recognition, which contributes to infertility; thus, endometrial heparan sulfate may be a predictive marker of future neoplasia risk.

Sexualidade e hormônios na transição menopausal e na pós-menopausa / Sexuality and hormones in menopausal transition and after the menopause

A síntese dos esteróides segue seqüência consagrada. Dois sistemas enzimáticos são importantes para a biotransformação das diversas substâncias: hidrogenases e citocromo P450. Tanto os estrogênios como os androgênios são relevantes para o desenvolvimento e manutenção da troficidade das estruturas genitais, além de muitas outras ações metabólicas em todo o organismo. Há queda na síntese dos androgênios a partir da terceira década da vida da mulher, podendo agravar-se em situações especiais. Algumas mulheres têm manifestações clínicas, impondo-se a suplementação terapêutica. É também inegável a ação dos esteróides sexuais no sistema nervoso central. Experiências em aves e animais comprovaram essas influências. Malgrado outros estímulos na atividade sexual - olfato, visão, tato - e de várias substâncias - vasopressina, ocitocina, dopamina, é inegável o fator preponderante dos esteróides sexuais. A insuficiência androgênica (IA) pode manifestar-se com sinais e sintomas peculiares. A reposição androgênica poderá melhorar tanto a sexualidade quanto o bem-estar das pacientes.

The steroid biosynthesis follows a time-honored sequence. Two enzymatic groups are important in this action: hydrogenases and cytochrome P450. Both estrogens and androgens act on the development and trophicity of genital organs besides other metabolic actions. Female androgen secretion declines, starting in the thirties, with aggravation in particular clinical situations needing therapeutic supplementation. The action of sexual steroids on the Central Nervous System is well established. Experiments with birds and animals prove this action. Despite the influence of smell, vision, tact and substances such as vasopressin, oxytocin, and dopamine, it is indisputable that the sexual steroids play the major role in sexual activity. Androgen insufficiency (AI) may exhibit signs and symptoms in particular clinical situations. Replacement therapy (androgens) may improve well-being and sexual activity.

Síndrome metabólica/policistose ovariana: condições relacionadas? / Metabolic syndrome/polycystic ovaries: related diseases?

A policistose ovariana (PCO) é entidade clínica muito frequente na ginecologia e bem conhecida pelos especialistas. Descrita há mais de dois séculos, tem ainda muitas características clínicas indefinidas. A síndrome metabólica (SM) é outra condição patogênica com roupagem clínica superponível à PCO. A SM teve identificação e descrição mais recente, apesar de já ser abordada há muito na prática clínica. A importância das duas condições mórbidas está relacionada aos distúrbios associados graves que, se não identificados e prontamente tratados, encurtarão a vida e comprometerão a qualidade de vida das portadoras. Diversos critérios foram elaborados para diagnóstico das duas condições patogênicas e o diagnóstico diferencial se impõe para exclusão de outras doenças. O ginecologista está em posição de destaque para identificação, tratamento ou envio das pacientes para outros especialistas quando requerido pelas condições clínicas das pacientes.

Cognição, demência e hormônios: tratamento / Cognition, dementia and hormones: treatment

Não há como contestar a inequívoca importância dos E para a higidez e funcionalidade dos diversos setores cerebrais seja por ações genômicas seja por mecanismos não genômicos, como ativação da circulação cerebral entre outros. Decorre, pois, que os E têm primazia quando se cogita administrar algum fármaco para controle e possível tratamento da DA. Okhura et al., 1995, avaliaram a circulação cerebral em grupo restrito de 14 mulheres no pós-menopausa. Nove pacientes usaram estrogênios conjugados eqüinos por três semanas e as cinco restantes usaram placebo. Verificaram aumento da circulação sanguínea cerebral e cerebelar, de modo significativo, entre as usuárias de E. O pequeno número de pacientes e a mensuração global da circulação cerebral não permitiram inferências particularizadas embora inequívocos foram os benefícios observados. O estudo de Baltimore em idosas (Resnick et al., 1998) analisou grupo de 15 mulheres usuárias de E, isolado ou associado a Pg, por até 20 anos. Grupo de 17 mulheres serviu de controle. Testes de avaliação cognitiva, a MRI, o PET foram instrumentos utilizados para análise dos dados. A MRI não evidenciou diferenças no volume cerebral ou dos ventrículos. Houve incremento da circulação em áreas específicas do SNC entre as usuárias de E. Estas, também, melhor se saíram nos testes neuropsíquicos de memória verbal e espacial. Contudo, como concluem os autores, os mecanismos e a avaliação cognitiva demandam mais estudos para melhor esclarecimento dos dados obtidos

Biópsia de fragmento guiada por ultra-sonografia mamária com agulha de 18 gauge / Ultrassonography-guided core breast biopsy with 18 gauge needle

Foi realizado estudo prospectivo que teve como objetivo determinar a sensibilidade e a especificidade da biópsia por fragmentos com agulha de 18 gauge, de menor calibre, abordando a validade da ultra-sonografia como guia do procedimento e a menor quantidade de material necessário ao diagnóstico do nódulo sólido da mama. Foram estudados 39 casos em 37 mamas femininas, diagnosticados nos exames de rastreio ou diagnóstico, em acordo com o sistema Bi-Rads. No total, 110 fragmentos de 22 nódulos malignos e 17 benignos. O padrão-ouro foi a peça cirúrgica. Resultados: A sensibilidade, a especificidade e a exatidão foram de, respectivamente, 100%, 94%, 97%. Conclui-se que o nódulo sólido de mama pode ser biopsiado com agulha de menor calibre, obtendose de 1 a 4 fragmentos para o estudo histopatológico, quando a punção for guiada por ultra-sonografia.

If was done a prospective study of ultrasonography-guided core breast biopsy, in which was used the 18 gauge needle as choice, to find the minimum number of specimens to the diagnostic of the tumor. There have been studied 39 cases in 37 patients with breast tumor seen on screening or diagnostic examination according to Bi-Rads. A number of 110 core-biopsies were realized, 22 malignant and 17 benigns. The gold standard was the histopathology on surgery. Results: The sensitivity, especificity and accuracy were, respectively, 100%, 94% and 97%. It was concluded that ultrasound guided core breast biopsy may be done with 18 gauge needle, getting from 1 to 4 specimens to histopathologic study.

Adipocitocinas e hormônios relevantes em ginecologia / Adipocytokines and important hormones in gynecology

Atualmente o tecido gorduroso é considerado um compartimento dinâmico, que produz várias substâncias. Os hormônios sintetizados e liberados neste tecido são relevantes no controle de funções metabólicas e reprodutivas. A leptina, a adiponectina e a resistina estão entre estes hormônios, e vêm mostrando importância crescente no controle de várias atividades orgânicas e em eventuais disfunções ginecológicas

Carcinoma adenóide cístico da mama / Adenoid cystic carcinoma of the breast

Carcinoma adenóide cístico da mama é uma neoplasia rara. Tem seu curso biológico com progressão lenta e ausência de metástases para linfonodos axilares. Ao contrário do carcinoma adenóide cístico extramamário, o prognóstico do carcinoma adenóide cístico da mama é excelente. É importante diferençar esse tipo de câncer de outros tipos de neoplasias da mama pelo excelente prognóstico.

Adenoid cystic carcinoma of the breast is a rare neoplasm. It has a biological course of slow progression and near absence of axillary lymph node metastasis. In contrast to extramammary adenoid cystic carcinoma, the prognosis of adenoid cystic carcinoma of the breast is excellent. It is important to distinguish this cancer from other forms of breast cancer because of its excellent prognosis.

Aspectos ginecológicos da neurofibromatose / Gynecological aspects of neurofibromatosis

A neurofibromatose é uma doença genética que afeta uma parcela da população sem que haja correlação com sexo, raça ou idade. É incluída no grupo das facomatoses ou síndromes neurocutâneas. Manifesta-se com quadro clínico variável com alterações vulvares, pélvicas e mamárias entre outras. É uma doença hereditária autossômica dominante. Contudo, em cerca de 50 porcento dos casos não há história prévia familiar. Na doença de von Recklinghausen podem estar presentes alterações ginecológicas como puberdade precoce, tumores no complexo aréolo-papilar, neurofibromas vulvares e tumorações pélvicas ou retroperitoneais. O ginecologista deve conhecer as principais manifestações clínicas da doença, a identificação e pronto encaminhamento das portadoras para especialistas