Gene expression profile in experimental frozen-thawed ovarian grafts treated with scaffold-base delivery of adipose tissue-derived stem cells

Abstract Purpose: Gelfoam scaffold is a feasible and safe non-invasive technique for Adipose tissue-derived Stem Cell (ASC)-delivery in the treatment of frozen-thawed ovarian autografts. This study seeks to analyze the genes expression profile of rat frozen-thawed ovarian autografts treated with scaffold-based delivery of adipose tissue-derived stem cells. Methods: Eighteen adult Wistar rats were distributed into three groups: Control (frozen-thawed only); Group 1 (Gl) and Group 2 (G2) (frozen-thawed ovaries treated with culture medium or ASC, respectively). Both treatments were performed immediately after autologous retroperitoneal transplant with scaffold-based delivery. The ovarian grafts were retrieved 30 days after transplantation. Quantitative gene expression (qPCR) for apoptosis, angiogenesis, and inflammatory cytokines (84 genes in each pathway) were evaluated by RT-PCR. Graft morphology (HE), apoptosis (cleaved-caspase-3), neoangiogenesis (VEGF), and cellular proliferation (Ki-67) were assessed. Results: In grafts treated with ASC, the apoptosis pathway showed the highest number of genes over-regulated — 49 genes — compared to inflammation cytokines and angiogenesis pathway — 36 and 23 genes respectively, compared to grafts treated with culture medium. Serpinb5 family was highlighted in the angiogenesis pathway and Cxcl6 in the inflammation cytokines pathway. In the apoptosis pathway, the most over-regulated gene was Cap-sasel4. ASC treatment promoted the reduction of cleaved caspase-3 in the theca internal layer and increased cell proliferation by Ki-67 in the granulosa layer without altering VEGF. A mild inflammatory infiltrate was observed in both groups. Conclusion: ASC therapy in rat frozen-thawed ovarian autografts promoted an abundance of genes involved with apoptosis and inflammatory cytokines without compromising the ovary graft morphology and viability for short time. Further studies are necessary to evaluate the repercussion of apoptosis and inflammation on the graft in the long term. HIGHLIGHTS The scaffold-based delivery therapy with adipose tissue-derived stem cells in the rat ovarian autografts seems to be the best option when compared to direct injection or systemic route. Ovarian grafts treated with adipose tissue-derived stem cells showed the highest number of genes over-regulated in the apoptosis pathway, compared to inflammation cytokines and angiogenesis pathway. Capsase14 was the most over-regulated gene in the apoptosis pathway. The treatment with adipose tissue-derived stem cells in ovarian grafts treated didn't compromise the ovary graft morphology and viability for short time.

Invariant Natural Killer T-cells and their subtypes may play a role in the pathogenesis of endometriosis

Abstract Objective To evaluate the frequencies of iNKT cells and their subsets in patients with deep endometriosis. Methods A case-control study was conducted between 2013 and 2015, with 73 patients distributed into two groups: 47 women with a histological diagnosis of endometriosis and 26 controls. Peripheral blood, endometriosis lesions, and healthy peritoneal samples were collected on the day of surgery to determine the frequencies of iNKT cells and subtypes via flow cytometry analysis. Results The authors observed a lower number of iNKT (p= 0.01) and Double-Negative (DN) iNKT cells (p= 0.02) in the blood of patients with endometriosis than in the control group. The number of DN iNKT IL-17+ cells in the secretory phase was lower in the endometriosis group (p= 0.049). There was an increase in the secretion of IL-17 by CD4+ iNKT cells in the blood of patients with endometriosis and severe dysmenorrhea (p= 0.038), and severe acyclic pelvic pain (p= 0.048). Patients with severe dysmenorrhea also had a decreased number of CD4+ CCR7+ cells (p= 0.022). Conclusion The decreased number of total iNKT and DN iNKT cells in patients with endometriosis suggests that iNKT cells play a role in the pathogenesis of endometriosis and can be used to develop new diagnostic and therapeutic agents.

Coronavirus disease 2019 and human reproduction: a changing perspective

Since the outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 has had a wide range of effects on human health. This paper summarizes the data related to the effects of the SARS-CoV-2 infection on human reproduction. Both the male and female reproductive tract express high levels of receptors and proteins needed for viral cell entry. There is presently no evidence that gametes are affected by the infection. Male fertility may be temporarily reduced due to inflammatory responses following infection. The endometrium is highly susceptible to SARS-CoV-2 cell entry; however, it remains unclear whether this could alter receptivity and embryo implantation. Menstrual cycle changes were reported in women who experienced severe infection; however, they tended to be reversible. For couples undergoing assisted reproduction treatment, the pandemic led to a significant psychological burden, with changes in lifestyle that could directly affect the success of the treatment. Human reproduction societies recommend screening all patients prior to cycle initiation and avoiding treatment of women with severe comorbidities until the pandemic is under control. Finally, for pregnant women, it is expected that the infection is more severe in women in the third trimester and in those with comorbidities. Those who are symptomatic for SARS-CoV-2 are more likely to have increased rates of prematurity and intrapartum fetal distress than those who are asymptomatic. Vertical transmission cannot be completely ruled out, but neonatal infection rates are low. Vaccination appears to be safe and is indicated for use in pregnant and lactating women because the benefits outweigh the risks.

Laparoscopic surgery and coronavirus disease: What do we know now?

Questions regarding the transmissibility of the novel coronavirus disease (COVID-19) remain unanswered. It is known that the transmission of the severe acute respiratory syndrome coronavirus (SARS-CoV) occurs predominantly through droplets and contact. However, aerosols can be generated in some situations, such as orotracheal intubation, ventilation, and the use of electric or ultrasonic scalpels, and can therefore potentially contaminate the care team if adequate protection is not used. It is therefore necessary to assess issues of transmissibility of COVID-19 during surgery in infected patients. This review gathers the recent research pertaining to this topic. A search of the literature was performed using the PubMed and UpToDate databases with the search terms "surgery" and "covid-2019," in addition to other MeSH variants of these terms. We do not have consistent evidence on the exposure of healthcare professionals assisting patients with COVID-19 undergoing laparoscopy or the impact of such exposure. In view of the evidence obtained and drawing parallels with other infectious and contagious diseases, medical personnel must wear complete protective attire for proper protection against the generated aerosol. Further studies are required to assess the impact of such surgeries on healthcare professionals conducing or assisting with these procedures.

Repercussions of melatonin on the risk of breast cancer: a systematic review and meta-analysis

SUMMARY Breast Cancer is common in women, but its etiology is not yet fully understood. Several factors may contribute to its genesis, such as genetics, lifestyle, and the environment. Melatonin may be involved in the process of breast cancer. Therefore, the aim of this study is to evaluate the influence of the levels of melatonin on breast cancer through a systematic review and meta-analysis. We performed a systematic review according to PRISMA recommendations. The primary databases MEDLINE, Embase, and Cochrane were consulted. There was no restriction on the year of publication and language. Data of systematic reviews from April 2017 to September to 2017 were analyzed. The meta-analysis was conducted using RevMan 5.3 software provided by the Cochrane Collaboration. From a total of 570 articles, 9 manuscripts were included in this review. They analy onzed women with breast cancer and control patients, of which 10% and 90% were in the reproductive period and after menopause, respectively. The lowest level of melatonin was found in approximately 55% of studies with breast cancer in post-menopause. The metanalyses of the studies demonstrated low levels of melatonin in breast cancer patients (n=963) compared with control patients (n= 1332), with a mean difference between the studies of 8722;3.54 (CI8722;6.01,8722;1.06). Another difference found was in the comparison between smoking patients, with an average difference between 1.80 [0.97-2.63]. Our data suggest that low levels of melatonin might be a risk factor for breast cancer.

RESUMO O câncer de mama é comum em mulheres, mas sua etiologia ainda não é totalmente compreendida. Vários fatores podem contribuir para sua gênese, genética, estilo de vida e meio ambiente. A melatonina pode estar envolvida no processo de câncer de mama. Portanto, o objetivo deste estudo é avaliar a influência dos níveis de melatonina no câncer de mama por meio de uma revisão sistemática e meta-análise. Realizamos uma revisão sistemática de acordo com as recomendações do Prisma. Os principais bancos de dados, Medline, Embase e Cochrane, foram consultados. Não houve restrição quanto ao ano de publicação e idioma. Os dados de revisão sistemática obtidos de abril de 2017 a setembro a 2017 foram analisados. A meta-análise foi conduzida pelo programa RevMan 5.3 fornecido pela Cochrane Collaboration. De um total de 570 artigos, nove foram incluídos nesta revisão. As análises foram conduzidas em mulheres com câncer de mama e pacientes controle, dos quais 10% e 90% estavam no período reprodutivo e após a menopausa, respectivamente. O nível mais baixo de melatonina foi encontrado em aproximadamente 55% dos estudos com câncer de mama na pós-menopausa. As meta-análises de estudos demonstraram os baixos níveis de melatonina em doentes com câncer da mama (n=963), em comparação com os pacientes de controle (n=1.332), sendo a diferença de médias entre os estudos da 8722;3,54 (CI 8722;6,01, 8722;1,06). Outra diferença é demonstrada nas comparações entre pacientes fumantes, sendo a diferença da média entre 1,80 [0,97-2,63]. Nossos dados sugerem que baixos níveis de melatonina podem ser um fator de risco para câncer de mama.

Secondary healing strategy for difficult wound closure in invasive vulvar cancer: a pilot case-control study

OBJECTIVES: Despite the number of surgical advances and innovations in techniques over time, radical vulvectomy frequently results in substantial loss of tissue that cannot be primarily closed without tension, the mobilization of surrounding tissues or even the rotation of myocutaneous flaps. The aim of this study was to evaluate the feasibility of leaving the surgical vulvar open wound for secondary healing in situations where primary closure of the vulvar wound is not possible. METHODS: This case-control pilot study analyzed 16 women with a diagnosis of squamous cell carcinoma of the vulva who first underwent inguinofemoral lymphadenectomy, 6-week sessions of chemotherapy and 25 daily sessions of radiotherapy. Afterward, excision of the vulvar lesion with free margins was performed between January 2011 and July 2017. Twelve patients underwent primary closure of the wound (control), and in 4 patients, the surgical wound was left open for secondary healing by means of a hydrofiber (case). The inclusion criteria were a) FIGO-2009 stage II up to IIIC; b) squamous cell carcinoma; and c) no evidence of pelvic or extrapelvic disease or pelvic nodal involvement. The exclusion criteria were extrapelvic disease or pelvic nodal involvement, another primary cancer, or a poor clinical condition. ClinicalTrials.gov: NCT02067052. RESULTS: The mean age of the patients at the time of the intervention was 62.1. The distribution of the stages was as follows: II, n=6 (37 %); IIIA, n=1 (6%), IIIB, n=1 (6%) and IIIC, n=8 (51%). The mean operative time was 45 minutes. The hospital stay duration was 2 days. Full vulvar healing occurred after an average of 30 days in the control group and after an average of 50 days in the case group. CONCLUSION: A secondary healing strategy may be an option for the treatment of vulvar cancer in situations of non-extensive surgical wounds when primary closure of the wound is not possible.

Nanotechnology for the treatment of deep endometriosis: uptake of lipid core nanoparticles by LDL receptors in endometriotic foci

OBJECTIVE: Rapidly dividing cells in multiple types of cancer and inflammatory diseases undergo high low density lipoprotein (LDL) uptake for membrane synthesis, and coupling an LDL-like nanoemulsion, containing lipid nanoparticles (LDE) to a chemotherapeutic agent efficiently targets these cells without significant systemic effects. This was a prospective exploratory study that evaluated the uptake of a radioactively labeled LDE emulsion by receptors of endometriotic foci and the capacity of the LDE for cellular internalization. METHODS: The lipid profile of each patient was determined before surgery, and labeled LDE were injected into fourteen patients with intestinal or nonintestinal endometriosis. The radioactivity of each tissue sample (intestinal endometriosis, nonintestinal endometriosis, healthy peritoneum, or topical endometrium) was measured. RESULTS: The group with intestinal endometriosis presented higher levels of plasma LDL but lower LDE uptake by foci than the nonintestinal group, suggesting less cell division and more fibrosis. The uptake of LDE was highest in the topical endometrium, followed by the healthy peritoneum, and lowest in the endometriotic lesion. Since the endometriotic foci showed significant LDE uptake, there was likely increased consumption of LDL by these cells, similar to cells in cancers and inflammatory diseases. Plasma cholesterol levels had no influence on LDE uptake, which showed that the direct delivery of the nanoemulsion to target tissues was independent of serum lipoproteins. There were no significant differences in the parameters (p>0.01) because of the small sample size, but the findings were similar to those of previous studies. CONCLUSION: Nanotechnology is a promising therapeutic option for surgery and hormonal blockage for deep endometriosis, with a lower complication rate and no systemic side effects.

Lower genital tract infections in young female juvenile idiopathic arthritis patients

Abstract Background: To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. Methods: After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. Results: The mean current age was similar in JIA patients and controls (23.3 ± 6.24 vs. 26.1 ± 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p =0.206) and biological agent use (p =0.238) were similar in both JIA groups. Conclusions: To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.

Brazilian Women's Health after 65 Years of Age / Saúde de brasileiras acima dos 65 anos de idade

Abstract Purpose The aim of this study was to evaluate the health aspects of Brazilian women older than 65 years of age. Design This was a retrospective study that included 1,001 Brazilian women cared for in the gynecological geriatric outpatient office of our institution. We report a crosssectional analysis of female adults aged over 65 years, including data on demographics, clinical symptoms such as vasomotor symptoms, associated morbidities, physical examination and sexual intercourse. We used the chi-squared test to assess the data. Results The age of the patients on their first clinic visit ranged from65 to 98 years, with a mean age of 68.56 ± 4.47 years; their mean age at the time of natural menopause was 48.76 ± 5.07 years. The most frequent clinical symptoms reported during the analyzed period were hot flashes (n = 188), followed by arthropathy, asthenia, and dry vagina. The most frequent associated morbidities after 65 years of age were systemic arterial hypertension, gastrointestinal disturbance, diabetes mellitus, and depression, among others. The assessment of the bodymass index (BMI) found decreases inBMIwith increased age. At the time of the visit, 78 patients reported sexual intercourse. The majority of women reporting sexual intercourse (89.75%, n = 70) were between 65 and 69 years of age, 8.97% (n = 7) were between 70 and 74 years of age, and only 1.28% (n = 1) of those were aged older than 75 years. Conclusions Our findings suggested that vasomotor symptoms can persist after 65 years of age. There was a significant decrease in sexual intercourse with increased age. The cardiovascular disturbances in our study are health concerns in these women.

Resumo Objetivo Avaliar os aspectos de saúde das mulheres brasileiras após os 65 anos de idade. Métodos O estudo foi retrospectivo, e incluiu 1.001mulheres brasileiras atendidas no ambulatório de ginecologia geriátrica de nossa instituição. Foi feita uma análise transversal de mulheres com idade acima de 65 anos, incluindo dados demográficos, sintomas clínicos (sintomas vasomotores), morbidades associadas, bem como alterações no exame físico e queixas em relação à atividade sexual. Utilizamos o teste qui-quadrado para avaliar os dados. Resultados A idade das pacientes na primeira visita clínica variou de 65 a 98 anos, com média etária de 68,56 ± 4,47 anos. A média etária de entrada na menopausa foi de 48,76 ± 5,07 anos. Os sintomas clínicos mais frequentes relatados durante o período analisado foram os sintomas vasomotores (n = 188), seguidos de artropatia, astenia e vagina seca. Asmorbidades associadasmais frequentes após os65anos foram hipertensão arterial sistêmica, distúrbios gastrintestinais, diabete melito e depressão, entre outras. A avaliação do índice de massa corporal (IMC) mostrou redução deste parâmetro antropométrico com o progredir da idade. No momento da visita, 78 pacientes relataram ter relações sexuais. A maioria das mulheres que relatou ter relações sexuais (89,75%, n = 70) estava entre 65 e 69 anos, 8,97% (n = 7) tinham entre 70 e 74 anos, e apenas 1,28% (n = 1) eram mais velhas do que 75 anos de idade. Conclusões Nossos achados sugerem que os sintomas vasomotores podem persistir após os 65 anos. Houve uma diminuição significativa na relação sexual com o aumento da idade. Os distúrbios cardiovasculares em nosso estudo são preocupações de saúde nestas mulheres.

The Apocrine Profile of Triple-negative Breast Carcinomas in Patients Aged 45 Years or Younger: favorable but rare features / Perfil apócrino em carcinomas mamários triplonegativos de pacientes até 45 anos: característica favorável, ainda que rara

Abstract Objective Triple-negative breast carcinomas (TNBCs) represent a heterogeneous group of neoplasias, even though they generally exhibit a clinically more aggressive phenotype, and are more prevalent in young women. To date, targeted therapies for this group of tumors have not been defined. The aim of this study was to evaluate the frequency of the apocrine subtype in TBNCs from premenopausal patients as defined by the immunohistochemical expression of the androgen receptor (AR) and its association with: histological type; tumor grade; proliferative activity; epidermal growth factor receptor (EGFR) expression; and a basal-like phenotype. Methods A total of 118 tumor samples from patients aged 45 years or younger were selected and reviewed according to histological type and grade. Ki-67 expression was also evaluated. Immunohistochemical expression of the AR, basal cytokeratin ⅚, and EGFR expression were analyzed in tissue microarrays. The apocrine subset was defined by AR-positive expression. The basal-like phenotype was characterized by cytokeratin ⅚ and/or EGFR expression. Results An apocrine profile was identified in 6/118 (5.1%) cases. This subset of cases also exhibited a lower rate of Ki-67 expression (17.5% versus 70.0%, p= 0.02), and a trend toward a lower histological grade (66.7% versus 27.9%, p= 0.06). Conclusions The apocrine subtype of TNBCs is rare among premenopausal women, and it tends to present as carcinomas of lower grade and lower proliferative activity, suggesting a less aggressive biological phenotype.

Resumo Objetivo Carcinomas mamários triplo-negativos representam um grupo heterogêneo de neoplasias, embora geralmente exibam fenótipo clinicamente mais agressivo e sejam mais prevalentes em mulheres jovens. Até o presente, terapias-alvo para esses grupos não foram definidas. O objetivo deste estudo foi avaliar a frequência do subtipo apócrino em carcinomas mamários triplo-negativos de mulheres na pré-menopausa, definido pela expressão imuno-histoquímica do receptor de androgênio, e sua associação com tipo histológico, grau histológico, atividade proliferativa, expressão do receptor do fator de crescimento epidérmico (EGFR) e o fenótipo basal-símile. Métodos Foram selecionadas 118 amostras de tecido tumoral de pacientes com até 45 anos de idade. As amostras foram revisadas quanto a tipo e grau histológicos e expressão do Ki-67. A expressão imuno-histoquímica de receptor de androgênio, citoqueratina basal ⅚, e do EGFR foram analisadas em amostras de microarranjos de tecido. O subtipo apócrino foi definido pela positividade do receptor de androgênio. O fenótipo basal-símile foi caracterizado pela expressão da citoqueratina ⅚ e/ou do EGFR. Resultados O perfil apócrino foi identificado em 6/118 (5,1%) casos. Este subgrupo apresentou menor fração de expressão do Ki-67 (17,5% versus 70,0%, p= 0,02) e uma tendência a menor grau histológico (66,7% versus 27,9%, p= 0,06). Conclusões O subtipo apócrino dos carcinomas mamários triplo-negativos é raro em mulheres na pré-menopausa, e tende a se apresentar como carcinomas de menor grau e menor atividade proliferativa, sugerindo fenótipo biológico menos agressivo.

Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome / A associação de contraceptivo hormonal oral e metformina não melhora a resistência insulínica em mulheres com síndrome dos ovários policísticos.

Summary Objective: Objective: to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS) using metformin or combined oral contraceptive (COC) after 6 months. Methods: retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16); II-metformin (850mg 12/12h, n=16); III-COC plus metformin (n=9). Body mass index (BMI), acne (% of improvement), modified Ferriman-Gallway index and menstrual cycle index (MCI), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), androstenedione (A) and homeostasis model assessment: insulin resistance (HOMA-IR) index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007). The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046). The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75), showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. Conclusion: our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone. .

Resumo Objetivo: comparar parâmetros clínicos e laboratoriais de mulheres com síndrome dos ovários policísticos (SOP) em uso de metformina ou contraceptivo hormonal oral (CHO) após 6 meses. Casuística e métodos: estudo retrospectivo com análise do prontuário de pacientes com SOP (pelos critérios da Androgen Excess and Polycystic Ovary Syndrome Society [AE-PCOS Society]), divididos em 3 grupos: (I) CHO (21 comprimidos e pausa de 7 dias; n=16), (II) metformina (850 mg a cada 12 horas; n=16) e (III) CHO associado com metformina (n=9). Foram avaliados: índice de massa corpórea (IMC), acne (% de melhora), índice de Ferriman-Gallway modificado, índice de ciclos menstruais (ICM), LH, FSH, testosterona total (TT), androstenediona (A) e resistência a insulina (HOMA-IR, do inglês homeostatic model assessment: insulin resistance). Resultados: o uso isolado de CHO comparado ao de metformina foi melhor em relação a acne, índice de Ferriman, ICM, níveis de LH, TT e A. Por outro lado, a metformina foi melhor para HOMA-IR (4,44 e 1,67; p=0,0007). O uso do CHO e metformina, em comparação com o de metformina isolada, manteve a melhora da acne, do índice de Ferriman, do ICM e dos níveis da TT. O índice de HOMA-IR manteve-se menor no grupo metformina isolada (4,19 e 1,67; p=0,046). Por sua vez, a melhora na acne, Ferriman, ICM, LH, TT e A são semelhantes nos grupos CHO associado com metformina e CHO isolado, indicando que a adição de metformina não trouxe benefícios nesses parâmetros. Ainda, o HOMA-IR foi semelhante nos dois grupos (4,19 e 4,44; p=0,75), mostrando que o uso de metformina em associação com o contraceptivo pode não melhorar a resistência insulínica como ocorre no uso isolado. Conclusão: os dados sugerem que a associação de metformina e contraceptivo não melhora a resistência insulínica como ocorre no uso da metformina isolada. .

Association of glucocorticoid receptor polymorphisms with clinical and metabolic profiles in polycystic ovary syndrome

OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1) polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment. .