Mulheres com síndrome do ovário policísticos que desenvolveram diabetes melitus 2 antes dos 35 anos: ansiedade, má qualidade do sono e não controle glicêmico / Women with polycystic ovarian syndrome who developed diabetes mellitus 2 before the age of 35: anxiety, poor sleep quality and lack of glycemic control / Mujeres con síndrome de ovario poliquístico que desarrollaron diabetes melitus 2 antes de los 35 años: ansiedad, mala calidad del sueño y sin control glucémico

Introdução: A síndrome dos ovários policísticos (SOP) consiste em uma desordem de origem endocrinológica de grande prevalência nas mulheres em idade fértil, sendo acometidas por ela aproximadamente de 6 a 16% da população feminina - em consonância com diversos critérios diagnósticos 1-4. Essa síndrome é associada ao hiperandrogenismo e à resistência insulínica (RI), com manifestações clínicas relacionadas a alterações reprodutivas 4, desenvolvimento de diabetes mellitus (DM2) e obesidade. Esta pesquisa objetiva compreender o perfil das mulheres com DM 2 antes dos 35 anos e os fatores que podem levar a esta condição. Metodologia: Este estudo se deu por meio de inquérito on-line feito a mulheres diagnosticadas com SOP, e com menos de 35 anos de idade. Foi desenvolvido de maneira virtualizada via plataforma GoogleForms® em função da pandemia do COVID-19. Tratou-se de um levantamento sobre presença de fatores de risco para DM 2, como sobrepeso e alimentação, sedentarismo e qualidade do sono; em grupos de mulheres com SOP diabéticas e não diabéticas, para efeito de comparação. Resultados e discussão: Um total de 198 mulheres responderam ao questionário, sendo divididas em Diabéticas (DM) e não diabéticas (NDM). O grupo DM foi o que mais apresentou IMC elevado (acima de 30), e o que mais se declarou seguir orientações nutricionais. Atividade física não diferenciou entre os grupos. O grupo DM foi o que declarou dormir mais tarde (pós 23:00) quando comparado com o grupo NDM. O sobrepeso indica ser um fator importante para o advento da DM 2 neste grupo, sendo as orientações nutricionais não tão efetivas, devido muito a dificuldade de aderir às orientações. O hábito de dormir tarde implica em alterações que levam a aumento da RI via estresse oxidativo, contribuindo para obesidade e DM 2. Conclusões: A obesidade é um fator decisivo para a precocidade da DM 2 em mulheres com SOP, e sua condição é multifatorial, associada a seguimento de orientações nutricionais, atividade física e qualidade do sono. O evitar da precocidade da DM 2 neste grupo passa por esta compreensão.

Introduction: Polycystic ovary syndrome (PCOS) is an endocrinological disorder with high prevalence in women of childbearing age, affected by approximately 6 to 16% of the female population - in line with several diagnostic criteria 1-4. This syndrome is associated with hyperandrogenism and insulin resistance (IR), with clinical manifestations related to reproductive changes 4, development of diabetes mellitus (DM2) and obesity. This research aims to understand the profile of women with DM 2 before the age of 35 and the factors that can lead to this condition. Methodology: This study was carried out through an online survey made to women diagnosed with PCOS, and under 35 years of age. It was developed in a virtualized way via the GoogleForms® platform due to the COVID-19 pandemic. This was a survey on the presence of risk factors for DM 2, such as overweight and diet, sedentary lifestyle and sleep quality; in groups of women with diabetic and non-diabetic PCOS for comparison purposes. Results and discussion: A total of 198 women answered the questionnaire, divided into Diabetic (DM) and non-diabetic (NDM). The DM group was the one with the highest BMI (above 30), and the one that most declared to follow nutritional guidelines. Physical activity did not differ between groups. The DM group was the one who reported sleeping later (after 11 pm) when compared to the NDM group. Overweight is an important factor for the advent of DM 2 in this group, and nutritional guidelines are not so effective, due to the difficulty in adhering to the guidelines. The habit of sleeping late implies changes that lead to increased IR via oxidative stress, contributing to obesity and DM 2. Conclusions: Obesity is a decisive factor for the precocity of DM 2 in women with PCOS, and its condition is multifactorial, associated with following nutritional guidelines, physical activity and sleep quality. Avoiding the precocity of DM 2 in this group involves this understanding.

Introducción: El síndrome de ovario poliquístico (SOP) es un trastorno de origen endocrinológico de alta prevalencia en mujeres en edad fértil, afectando aproximadamente entre el 6 y el 16% de la población femenina, de acuerdo con diversos criterios diagnósticos 1- 4 . Este síndrome se asocia con hiperandrogenismo y resistencia a la insulina (RI), con manifestaciones clínicas relacionadas con cambios reproductivos 4, desarrollo de diabetes mellitus (DM2) y obesidad. Esta investigación tiene como objetivo conocer el perfil de las mujeres con DM 2 antes de los 35 años y los factores que pueden conducir a esta condición. Metodología: Este estudio se realizó a través de una encuesta online realizada entre mujeres diagnosticadas con SOP y menores de 35 años. Fue desarrollado de manera virtualizada a través de la plataforma GoogleForms® debido a la pandemia de COVID-19. Se realizó una encuesta sobre la presencia de factores de riesgo para DM 2, como sobrepeso y alimentación, sedentarismo y calidad del sueño; en grupos de mujeres diabéticas y no diabéticas con síndrome de ovario poliquístico, con fines de comparación. Resultados y discusión: Respondieron al cuestionario un total de 198 mujeres, divididas en diabéticas (DM) y no diabéticas (NDM). El grupo DM fue el que presentó un IMC más elevado (superior a 30), y el que más declaró seguir las pautas nutricionales. La actividad física no difirió entre los grupos. El grupo DM fue el que reportó dormir más tarde (después de las 11:00 pm) en comparación con el grupo NDM. El sobrepeso indica que es un factor importante en la aparición de DM 2 en este grupo, siendo las pautas nutricionales no tan efectivas, en gran parte por la dificultad para cumplirlas. El hábito de dormir tarde implica cambios que conducen a un aumento de la RI vía estrés oxidativo, contribuyendo a la obesidad y la DM 2. Conclusiones: La obesidad es un factor decisivo en la aparición temprana de la DM 2 en mujeres con SOP, y su condición es multifactorial, asociado con el seguimiento de pautas nutricionales, actividad física y calidad del sueño. Evitar la precocidad de la DM 2 en este grupo requiere esta comprensión.

Effects of rosmarinic acid and doxorubicine on an ovarian adenocarsinoma cell line (OVCAR3) via the EGFR pathway

Purpose: We aimed to reveal the effects of rosmarinic acid (RA), which has come to the forefront with its antitumor and antioxidant properties in many studies recently in the ovarian adenocarcinoma cell line, on the epidermal growth factor receptor (EFGR) signaling pathway in the presence of doxorubicin (DOX). Methods: Ovarian adenocarcinoma cell line (OVCAR3) and human skin keratinocyte cell line human skin keratinocyte cell line (HaCaT) were used as control. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was applied to determine the effect of RA and DOX on the proliferation of OVCAR3 and HaCaT cells. Bcl2 expression and epidermal growth factor receptor (EGFR) and western blot analysis were performed to determine the expression levels of the markers. Results: It was determined that RA (IC50 = 437.6 µM) and DOX (IC50 = 0.08 µM) have the ability to inhibit the proliferation of OVCAR3 cells and induce apoptosis in a 72-hour time and dose-dependent manner. Western blot showed that the expression level of Bcl-2 and EGFR in OVCAR3 cells was down-regulated by RA and DOX. Conclusions: Apoptosis in OVCAR3 cells can potentially be induced by RA via the EGFR pathway, and RA may be a potent agent for cancer therapy.

Improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome and its mechanism / 中国药房

OBJECTIVE To study the improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome （PCOS） and its mechanism. METHODS One hundred and twenty-six female rats were randomly separated into blank group， PCOS group， poria acid low-dose group （8.33 mg/kg）， pachymic acid high-dose group （33.32 mg/kg）， ethinylestradiol cyproterone group （positive control group， 0.34 mg/kg）， recombinant rat high mobility group protein B1 protein （rHMGB1） group （8 μg/kg）， and poria acid high dose+rHMGB1 group （33.32 mg/kg poria acid+8 μg/kg rHMGB1）， with 18 rats in each group. Except for the blank group， the rats in all other groups were given Letrozole suspension intragastrically to construct the PCOS model. After successful modeling， administration was performed once a day for 4 weeks. After medication， the fasting blood glucose and fasting insulin levels， and insulin resistance index （HOMA-IR） were measured in rats； the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH） and testosterone （T） in rat serum， and the levels of interleukin-1β （IL-1β） and tumor necrosis factor- α （TNF- α） in ovarian tissue were detected； ovarian coefficients of rats were calculated； the pathological changes of ovarian tissue were observed； the expressions of HMGB1， receptor for advanced glycosylation elaine_ tanghong@sina.com end product （RAGE） and phosphorylated nuclear factor κB p65 （p-NF-κB p65） proteins were determined in ovarian tissue of rats. RESULTS Compared with the blank group， the pathological injury of ovarian tissue of rats in the PCOS group was serious， the levels of fasting blood glucose and fasting insulin， HOMA-IR and ovarian coefficient were increased， the levels of serum LH and T were increased， while the levels of FSH were decreased； the levels of IL-1β and TNF-α， the expressions of HMGB1， RAGE and p-NF-κB p65 protein in ovarian tissue were increased， with statistical significance （P＜0.05）. Compared with the PCOS group， pathological damage of ovarian tissue was reduced in poria acid low-dose and high-dose groups and ethinylestradiol cyproterone group， and fasting blood glucose， fasting insulin levels， HOMA-IR and ovarian coefficient were decreased； serum LH and T levels were decreased， while FSH levels were increased； the levels of IL-1β and TNF-α and the expressions of HMGB1， RAGE and p-NF-κB p65 protein in ovarian tissue were decreased， with statistical significance （P＜0.05）. The trend of corresponding indexes in rHMGB1 group was opposite to the above （P＜0.05）. Compared with poria acid high-dose group， the changes of the above indexes were reversed significantly in poria acid high-dose+rHMGB1 group （P＜0.05）. CONCLUSIONS Poria acid may improve insulin resistance and inhibit inflammatory reaction in PCOS rats by inhibiting HMGB1/ RAGE pathway.

Cistoadenofibroma de ovario / Ovarian cystadenofibroma

El cistoadenofibroma ovárico es un tumor benigno poco frecuente y se caracteriza por un patrón bifásico compuesto por componentes epiteliales y estromales; actualmente se desconocen los factores de riesgo asociados, aunque las mujeres obesas y las menopáusicas que consumen terapia de reemplazo hormonal tienen un mayor riesgo. Se presentó una adolescente de 17 años de edad, evaluada en consulta externa dos años antes, por un quiste de ovario izquierdo; recibió tratamiento hormonal sin resultados satisfactorios. Se le practicaron exámenes de analítica sanguínea y estudios de imagen. Con la administración de anestesia regional epidural continua se realizó anexectomía izquierda, se confirmó mediante estudio histológico, un cistoadenofibroma seroso de ovario. El objetivo del tratamiento en estas pacientes es la remoción quirúrgica completa de la lesión ante el riesgo de malignización; este tratamiento quirúrgico fue fundamental y la evolución fue favorable, tuvo un periodo de recuperación de corta duración y muy positivo.

Ovarian cystadenofibroma is a rare benign tumour characterized by a biphasic pattern made up of epithelial and stromal components; associated risk factors are currently unknown, although obese and menopausal women taking hormone replacement therapy are at increased risk. We present a 17-year-old female adolescent who was evaluated in an outpatient clinic two years earlier due to a left ovarian cyst. She received hormonal treatment without satisfactory results. She underwent blood analysis tests and imaging studies. Left adnexectomy was performed with the administration of continuous epidural regional anesthesia, and a serous ovarian cystadenofibroma was confirmed by histological study. The goal of treatment in these patients is the complete surgical removal of the lesion given the risk of malignancy; this surgical treatment was fundamental and the evolution was favourable. She had a short and very positive recovery period.

Diagnóstico y tratamiento del síndrome de ovario poliquístico

El síndrome de ovario poliquístico es un trastorno endocrino-genético-ginecológico que afecta principalmente a mujeres en edad fértil, con manifestaciones de hiperandrogenismo e infertilidad en etapas tempranas de la vida. Este trabajo tiene por objetivo describir el diagnóstico y tratamiento del síndrome de ovario poliquístico. cuya fisiopatología no ha sido del todo comprendida, de ahí que su diagnóstico continúe siendo por exclusión. Los criterios del consenso de Rotterdam han logrado mejorar la uniformidad diagnóstica; sin embargo, se hace necesario un diagnóstico individualizado, en el cual debe incluirse el estudio de la morfología de los ovarios. Aunque la literatura sugiere la asociación de esta entidad con la presencia de obesidad, resistencia a la insulina e hiperinsulinismo, no se incluyen como parte de los criterios diagnósticos actualmente. El tratamiento incluye cambios en los estilos de vida, unidos a inhibidores de la producción de andrógenos por los ovarios, inhibidores de la acción de los andrógenos y los sensibilizadores a la insulina; se establecerá según los intereses reproductivos de la paciente.

Polycystic ovary syndrome is an endocrine-genetic-gynecological disorder that mainly affects women of childbearing age, with manifestations of hyperandrogenism and infertility in early stages of life. This work aims to describe the diagnosis and treatment of polycystic ovary syndrome whose pathophysiology has not been fully understood, hence its diagnosis continues to be by exclusion. The Rotterdam consensus criteria have managed to improve diagnostic uniformity; however, an individualized diagnosis is necessary, which must include the study of the morphology of the ovaries. Although the literature suggests the association of this entity with the presence of obesity, insulin resistance and hyperinsulinism, they are not currently included as part of the diagnostic criteria. Treatment includes changes in lifestyle, together with inhibitors of androgen production by the ovaries, inhibitors of androgen action and insulin sensitizers; It will be established according to the patient´s reproductive interests.

Breast mass - An uncommon clinical manifestation of ovarian carcinoma: A case report and brief literature review

Metastasis from non-mammary malignant neoplasms to the breast is rare and represents 0.2%-1.3% of all breast malignancies. Fine needle aspiration cytology (FNAC) is the first line of investigation for any breast lump and cyto-morphological appearance of primary breast malignancies is well documented. Occasionally metastasis to the breast may be the initial presentation and can masquerade clinically as primary breast malignancy. The present case describes the clinical and cytological challenges in an unusual case of ovarian carcinoma with initial presentation as breast mass, mimicking as inflammatory carcinoma. In cytology the breast lesion was initially misdiagnosed as primary breast carcinoma and subsequently diagnosed as metastatic ovarian carcinoma based on core needle biopsy findings, aberrant immuno-profile and clinical findings; thus making the complex case worthy of discussion.

Importância do diagnóstico por imagem em pacientes com sangramento uterino anormal / Importance of diagnostic imaging in patients with abnormal uterine bleeding

O sangramento uterino anormal é diagnóstico sindrômico comum no consultório do ginecologista e pode comprometer substancialmente a qualidade de vida. O objetivo no diagnóstico de sangramento uterino anormal é distinguir pacientes com causas estruturais (anatômicas), como pólipo, adenomiose, leiomioma, malignidade e hiperplasia, de pacientes que apresentam anatomia normal, nas quais o sangramento pode ser devido a alteração dos mecanismos de coagulação, distúrbios ovulatórios, distúrbios primários do endométrio, iatrogenia, ou ter outra causa não classificada. O diagnóstico se inicia a partir de anamnese detalhada e exame físico geral e ginecológico completos, seguidos da solicitação de exames complementares (laboratoriais e de imagem), conforme indicado. O exame de imagem de primeira linha para identificação das causas estruturais inclui a ultrassonografia pélvica. Histerossonografia, histeroscopia, ressonância magnética e amostragem endometrial para exame de anatomia patológica são opções que podem ser incluídas no diagnóstico a depender da necessidade. O objetivo deste artigo é apresentar a relevância dos exames de imagem na investigação das causas de sangramento uterino anormal.

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office and may substantially affect quality of life. The aim in the diagnosis of abnormal uterine bleeding is to distinguish women with anatomic causes such as polyp, adenomyosis, leiomyoma, malignancy and hyperplasia from women with normal anatomy where the cause may be coagulopathy, ovulatory disorders, endometrial, iatrogenic and not otherwise classified. Diagnosis begins with a thorough history and physical examination followed by appropriate laboratory and imaging tests as indicated. The primary imaging test for the identification of anatomic causes include ultrasonography. Saline infusion sonohysterography, magnetic resonance, hysteroscopy, endometrial sampling are options that can be included in the diagnosis depending on the need. The aim of this article is to present the relevance of imaging exams in the investigation of the causes of abnormal uterine bleeding.

Frecuencia de la sintomatología del síndrome de ovario poliquístico y el síndrome premenstrual, relacionado con el estrés académico en estudiantes de medicina de una Universidad Privada del Perú

Introducción: El síndrome de ovario poliquístico y el síndrome premenstrual son prevalentes. Objetivo: Determinar la frecuencia de la sintomatología del síndrome de ovario poliquístico y del síndrome pre menstrual y su relación con el estrés en estudiantes de medicina. Material y métodos: Estudio analítico transversal. La población de estudio fue de 322 estudiantes de medicina del primer al sexto año, elegidas por conveniencia de una universidad privada de Trujillo. Mediante un formulario de google se aplicó el cuestionario "SPM", "el inventario SISCO del Estrés académico", y "el cuestionario sobre ovario poliquístico"; previo conocimiento informado, tuvo la aprobación del Comité de Bioética de la universidad. Resultados: El SOP presentó una probabilidad alta de 5,28%, media de 46,58% y baja de 48,13%. La frecuencia del SPM en los niveles, leve, moderado y alto fueron de 47,52%, 25,47% y 4,04% respectivamente. Los niveles de estrés fueron: leve, moderado y profundo de 4,35%, 65,22% y 30,43%, respectivamente. Se encontró asociación altamente significativa entre el estrés y SPM; estrés y SOP; p= 0,000915106 y p= 1.8589E-25 respectivamente. Conclusiones: La frecuencia de SPM, la probabilidad alta de SOP y los niveles de estrés fueron altos y existe asociación significativa entre el estrés, SPM y SOP.

Introduction: Polycystic ovarian syndrome and premenstrual syndrome are prevalent. Objective: to determine the frequency of the symptoms of polycystic ovarian syndrome and premenstrual syndrome and its relationship with stress in medical students. Methods: Cross-sectional analytical study. The study population was 322 medical students from the first to the sixth year, chosen for convenience from a private university in Trujillo. Using a google form, the "SPM" questionnaire, "the SISCO inventory of academic stress", and "the polycystic ovary questionnaire" were applied; prior informed knowledge, it had the approval of the Bioethics Committee of the university. Results: The SOP presented a high probability of 5.28%, a medium of 46.58% and a low of 48.13%.The frequency of PMS at the levels, mild, moderate and high were 47.52%, 25.47% and 4 04% respectively.The levels of stress were: mild, moderate and deep of 4.35%, 65.22% and 30.43%, respectively.A highly significant association was found between stress and SPM, stress and PCOS, p = 0.000915106 and p= 1.8589E-25 respectively. Conclusions: The frequency of PMS, the high probability of SOP and the stress levels were high and there is a significant association between stress, SPM and SOP.

Leiomioma ovárico primario

El leiomioma es un tumor mesenquimal benigno común que puede desarrollarse allí donde haya músculo liso; raro como tumor ovárico primario, su origen aún es controversial. El leiomioma ovárico primario es uno de los tumores benignos más raros del ovario, representa 0,5% a 1% de los tumores benignos y suele observase en mujeres entre 20 y 65 años. Generalmente, son asintomáticos y se les encuentra de forma incidental durante el examen pélvico o la cirugía por otra causa, pero en ocasiones puede manifestarse por dolor abdominal y masa palpable. El diagnóstico definitivo es difícil antes de la extirpación quirúrgica. Debido a que no existen síntomas patognomónicos ni tiene imágenes características, los principales diagnósticos diferenciales incluyen fibroma, tecoma, tumor estromal esclerosante y leiomiosarcoma. La tinción inmunohistoquímica es fundamental para el diagnóstico preciso y debe considerarse en el diagnóstico diferencial de los tumores ováricos de células fusiformes. Se presenta un caso de leiomioma ovárico primario.

Leiomyoma is a common benign mesenchymal tumor that can develop wherever smooth muscle is present; rare as a primary ovarian tumor, its origin is still controversial. Primary ovarian leiomyoma is one of the rarest benign ovarian tumors, accounting for 0.5% 1% of benign tumors and is usually seen in women between 20 and 65 years of age. They are usually asymptomatic and appear incidentally during a pelvic examination or surgery for another cause but can occasionally manifest by abdominal pain and palpable mass. Definitive diagnosis is difficult before surgical removal. Because there are no pathognomonic symptoms and no characteristic imaging, the main differential diagnoses include fibroma, thecoma, sclerosing stromal tumor and leiomyosarcoma. Immunohistochemical staining is essential for accurate diagnosis and should be considered in the differential diagnosis of ovarian spindle cell tumors. A case of primary ovarian leiomyoma is presented.

The effect of metabolic syndrome on controlled ovarian stimulation outcome in infertile women with polycystic ovary syndrome undergoing assisted reproductive technology cycles

ABSTRACT Objective: To evaluate the effect of metabolic syndrome (MetS) diagnosis on oocyte quality and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS) who undergoing antagonist-controlled ovarian stimulation (COS) and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Subject and methods: This prospective cohort study was conducted from November 2019 to November 2020 across two university-affiliated infertility centers in Iran. The PCOS diagnosis was defined according to the Rotterdam criteria. The patients prior to IVF/ICSI cycles were evaluated for MetS diagnosis. MetS was detected according to the National Cholesterol Education Program/Adult Treatment Panel III with the presence of at least three or more of the specific clinical criteria. The cycle outcomes were compared between MetS and non-MetS groups. Results: Overall, 68 eligible infertile PCOS patients with MetS diagnosis and 126 without MetS participated. The MetS diagnosis was associated with the increased requirement of gonadotropins and the COS duration significantly (P = 0.001). Although the total numbers of retrieved and MII oocytes, obtained and top-quality embryos as well as clinical pregnancy and live birth rates in the MetS group were lower than those of in the non-MetS group, the differences were not statistically significant (P > 0.05). In follow-up of the obstetrics complications, the rate of preeclampsia was significantly higher in patients with MetS (P = 0.02). Conclusion: MetS diagnosis in PCOS patients was associated with non-significant poor COS and pregnancy outcome. Further studies with larger sample sizes are recommended to clarify the risk of MetS in patients undergoing ART cycles.

Network pharmacology and molecular docking study of the active ingredients in Saptasaram kashayam for the treatment of Polycystic ovary syndrome-Supplemenntary data

Polycystic Ovary Syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age characterized by hyperandrogenism (HA). Current treatment options for PCOS are either with adverse effects or ineffective. Saptasaram kashayam (SK), an ayurvedic formulation is often been a safe traditional alternative medicine to improve the PCOS symptoms as well as its pathological development. However, its principle phytoconstituents or underlying mechanisms have not been investigated. In order to achieve this, the current study systematically utilized computational tools, network pharmacology approaches and molecular docking studies. All identified phytoconstituents of SK were screened by QikProp ADME prediction and 47 were selected based on oral bioavailability and drug likeliness scores. Their 3D structures were submitted to three online target fishing webservers PharmMapper, ChemMapper and Swiss Target Prediction which produced 1084 biological targets for SK comprehensively. 350 known PCOS therapeutic targets were retreived as common targets from three different interrogative disease centric bioinformatic platforms DisGeNET, OMIM and GeneCards. Intersection of 1084 biological targets of SK and 350 PCOS therapeutic targets produced, 88 potential therapeutic targets of SK against PCOS. STRING PPI and Compound-Target-Pathway networks were constructed and analysed using Cytoscape software. GO & KEGG pathway enrichment analysis was performed using DAVID database. 15 PCOS therapeutic target proteins were short listed from network analysis report- PIK3CA, PDPK1, AKT1, PIK3R1, STAT3, MAPK1, MAPK3, EGFR, AR, ESR1, ESR2, SHGB, NOS3, F2 & CREBBP. Targets that were likely to be inhibited/modulated by SK for treatment of PCOS were docked against the screened phytoconstituents and their respective standard inhibitors using GLIDE-SP of Schrodinger suite, Maestro version- 13.0. Results showed that Quercetin, Catechin, Boeravinone J, Genistein, Protocatechuic Acid, Gentisic Acid, Xanthoarnol, Luteolin, Boeravinone F, Tyrosine, Kaempferol, Dalbergioidin, etc exhibited good binding affinities when compared to standard drugs and might be responsible for synergistic/additive protective effect of SK against PCOS. Meanwhile PI3K-Akt signaling pathway, Prolactin signaling pathway, AGE-RAG diabetic complications, HIF-1 signaling pathway and Estrogen signaling pathway were found to be involving the hub genes of interest and in this way, they might be intervened during treatment of PCOS by SK. Present study succeeded in identifying the drug like principle phytoconstituents, probable PCOS therapeutic targets and the underlying molecular mechanism of SK apart from providing reliable evidence for therapeutic potential of SK against PCOS. However further validation by in vitro and in vivo investigations is necessary.

Network pharmacology and molecular docking study of the active ingredients in Saptasaram kashayam for the treatment of Polycystic ovary syndrome

Polycystic Ovary Syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age characterized by hyperandrogenism (HA). Current treatment options for PCOS are either with adverse effects or ineffective. Saptasaram kashayam (SK), an ayurvedic formulation is often been a safe traditional alternative medicine to improve the PCOS symptoms as well as its pathological development. However, its principle phytoconstituents or underlying mechanisms have not been investigated. In order to achieve this, the current study systematically utilized computational tools, network pharmacology approaches and molecular docking studies. All identified phytoconstituents of SK were screened by QikProp ADME prediction and 47 were selected based on oral bioavailability and drug likeliness scores. Their 3D structures were submitted to three online target fishing webservers PharmMapper, ChemMapper and Swiss Target Prediction which produced 1084 biological targets for SK comprehensively. 350 known PCOS therapeutic targets were retreived as common targets from three different interrogative disease centric bioinformatic platforms DisGeNET, OMIM and GeneCards. Intersection of 1084 biological targets of SK and 350 PCOS therapeutic targets produced, 88 potential therapeutic targets of SK against PCOS. STRING PPI and Compound-Target-Pathway networks were constructed and analysed using Cytoscape software. GO & KEGG pathway enrichment analysis was performed using DAVID database. 15 PCOS therapeutic target proteins were short listed from network analysis report- PIK3CA, PDPK1, AKT1, PIK3R1, STAT3, MAPK1, MAPK3, EGFR, AR, ESR1, ESR2, SHGB, NOS3, F2 & CREBBP. Targets that were likely to be inhibited/modulated by SK for treatment of PCOS were docked against the screened phytoconstituents and their respective standard inhibitors using GLIDE-SP of Schrodinger suite, Maestro version- 13.0. Results showed that Quercetin, Catechin, Boeravinone J, Genistein, Protocatechuic Acid, Gentisic Acid, Xanthoarnol, Luteolin, Boeravinone F, Tyrosine, Kaempferol, Dalbergioidin, etc exhibited good binding affinities when compared to standard drugs and might be responsible for synergistic/additive protective effect of SK against PCOS. Meanwhile PI3K-Akt signaling pathway, Prolactin signaling pathway, AGE-RAG diabetic complications, HIF-1 signaling pathway and Estrogen signaling pathway were found to be involving the hub genes of interest and in this way, they might be intervened during treatment of PCOS by SK. Present study succeeded in identifying the drug like principle phytoconstituents, probable PCOS therapeutic targets and the underlying molecular mechanism of SK apart from providing reliable evidence for therapeutic potential of SK against PCOS. However further validation by in vitro and in vivo investigations is necessary.

Ooforosalpingitis xantogranulomatosa. Comunicación de caso

La inflamación xantogranulomatosa del tracto genital femenino es infrecuente y es aún más rara en las trompas de Falopio y ovarios. Se presenta un caso de ooforosalpingitis xantogranulomatosa en una paciente femenina de 45 años quien asistió a consulta por presentar dolor en fosa iliaca izquierda acompañado de fiebre. La exploración bimanual mostró útero ligeramente aumentado de tamaño con masa anexial izquierda firme, no dolorosa, adherida al útero y con limitada movilidad. La evaluación ecográfica transvaginal determinó tumoración ovárica izquierda, heterogénea con paredes gruesas e irregulares con múltiples septos y ecos internos sin visualizar el ovario. Durante la cirugía, se encontraron adherencias densas desde la masa hacia la pared lateral pélvica, fosa ovárica y asas intestinales. El útero estaba desplazado por tumoración anexial quística izquierda, de color blanco grisáceo y paredes gruesas que drenaba líquido purulento fétido. El diagnóstico definitivo fue ooforosalpingitis xantogranulomatosa. Esta condición es un proceso inflamatorio poco frecuente que plantea dilemas diagnósticos. Sus manifestaciones clínicas y características de estudios por imágenes pueden simular una neoplasia pélvica maligna, por lo que es necesario un alto índice de sospecha para su diagnóstico, como diagnóstico diferencial en pacientes con tumoraciones ováricas quísticas complejas. El examen histopatológico es el estándar de oro para el diagnóstico.

Xanthogranulomatous inflammation of the female genital tract is infrequent and is even rarer in fallopian tubes and ovaries. We present a case of xanthogranulomatous oophorosalpingitis in a 45-year-old female patient who consulted for left iliac fossa pain accompanied by fever. Bimanual examination revealed a slightly enlarged uterus with a firm, non-painful left adnexal mass, adherent to the uterus and with limited mobility. Transvaginal ultrasound evaluation showed a heterogeneous left ovarian tumor with thick and irregular walls, multiple septa and internal echoes without visualization of the ovary. During surgery, dense adhesions were found from the mass to the pelvic lateral wall, ovarian fossa, and bowel loops. The uterus was displaced by a thick-walled, grayish-white, cystic left adnexal tumor draining foul-smelling purulent fluid. The definitive diagnosis was xanthogranulomatous oophorosalpingitis. This condition is a rare inflammatory process that poses diagnostic dilemmas. Its clinical manifestations and imaging features may mimic a malignant pelvic neoplasm, so a high index of suspicion is necessary for its diagnosis, as a differential diagnosis in patients with complex cystic ovarian tumors. Histopathological examination is the gold standard for diagnosis.

Comparative evaluation of metformin & sitaformin in classic PCOS patients undergoing intracytoplasmic sperm injection: A randomized controlled pilot study

Background & objectives: Studies have shown that insulin resistance and hyperinsulinaemia play a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, the use of insulin sensitizing drugs in the treatment of PCOS has attracted the attention of medicine and researchers. The aim of this study was to investigate the effects of sitaformin (sitagliptin/metformin) and metformin on the quality of oocyte and embryo in classic PCOS patients undergoing intracytoplasmic sperm injection (ICSI). Methods: Sixty patients of PCOS (25-35 yr) were randomly allocated into three groups (n=20, each group): a metformin-treated group (administered metformin 500 mg twice daily), a sitaformin-treated group (administered sitaformin 50/500 mg twice daily) and a placebo group. Participants in all the groups received the drug two months prior to the start of the ovulation cycle and treatment continued until the day of the oocyte aspiration. Results: Serum insulin and total testosterone levels decreaseed significantly after treatment in both the treatment groups as compared to the placebo (P<0.05). A significant decrease in the number of immature oocytes [MI + germinal vesicle (GV) stage] was observed in metformin and sitaformin groups as compared to the placebo. In addition, sitaformin group when compared to the metformin group showed a significant decrease in the number of immature oocytes (P<0.05). The number of mature and normal MII oocytes increased significantly in both the treatment groups compared to the placebo group (P<0.05). The number of mature and normal oocytes increased in sitaformin group in comparison to the metformin group, but the difference was not significant. There was a significant increase in the number of grade I embryos, fertilization and cleavage rates in the sitaformin group compared to the other groups (P<0.05). Interpretation & conclusions: This is the first study to compare the impact of sitaformin with metformin on oocyte and embryo quality in women with PCOS undergoing a gonadotropin-releasing hormone (GnRH) antagonist cycle. In conclusion, sitaformin can be more effective in decreasing immature oocytes and increasing the quality of embryos than the use of metformin.

Association of polycystic ovary syndrome with mammographic density in Turkish women: a population-based case-control study

SUMMARY OBJECTIVE: The objective of this study was to investigate the breast densities and Breast Imaging-Reporting and Data System scores of patients with polycystic ovary syndrome and normoovulatory women and to determine whether these patients constitute a high-risk population for breast cancer. METHODS: This retrospective case-control study was conducted at our institution between January 2022 and December 2022, involving patients diagnosed with polycystic ovary syndrome. Menstrual periods, hyperandrogenemic findings, and ultrasound reports of the patients were retrieved from our hospital's database. Patients who met at least two of the Rotterdam criteria were included in the polycystic ovary syndrome group. A total of 70 premenopausal patients over the age of 40 years, diagnosed with polycystic ovary syndrome, and 70 normoovulatory women, matched for age and body mass index, were included in the study. The two groups were compared regarding age at menarche, menstrual pattern, gravida, parity, levels of follicle-stimulating hormone, luteinizing hormone, and estradiol, endometrial thickness, breast density category, and Breast Imaging-Reporting and Data System classifications. RESULTS: Patients in the polycystic ovary syndrome group had a higher age at menarche (12.7 vs. 12.3, p=0.006). There was no difference between the gonadotropin levels in both groups. However, the estradiol level was higher in the polycystic ovary syndrome group (p<0.001). There was no statistically significant difference between the two groups in terms of breast density and Breast Imaging-Reporting and Data System scores (p=0.319 and p=0.650, respectively). CONCLUSION: Although we can conclude that the risk of breast malignancy is not increased in patients with polycystic ovary syndrome, the impact of the complex hormonal status of polycystic ovary syndrome on breast cancer remains unclear in the literature.

Polycystic ovary syndrome and abdominal fat: is there a relationship?

SUMMARY OBJECTIVE: The aim of this study was to compare the distribution of fat tissue in non-obese women with polycystic ovary syndrome and those without the syndrome using dual-energy radiological densitometry. METHODS: This was a case-control study in which we enrolled women aged 14-39 years with polycystic ovary syndrome according to the Rotterdam criteria with a body mass index between 18.5 and 30 kg/m2. The control group comprised women with the same profile, but without polycystic ovary syndrome. Patients were treated at the Endocrinological Gynecology Outpatient Clinic of the Department of Obstetrics and Gynecology of the Irmandade da Santa Casa de Misericórdia de São Paulo between 2019 and 2022. Anthropometric measurements were taken and the assessment of body composition was performed using dual-energy radiological densitometry. RESULTS: The sample comprised 57 women: 37 in the polycystic ovary syndrome group and 20 in the control group. The mean age of the polycystic ovary syndrome group was 24.9 years (±6.9) with a mean body mass index of 60.8 kg/m2 (±8.5), and for the control group, it was 24.2 years (±6.9) with a mean body mass index of 58 kg/m2 (±8.4). Body composition was evaluated using dual-energy radiological densitometry and showed a higher value of trunk fat in the polycystic ovary syndrome group (44.1%, ±9.0) compared to the control group (35.2%, ±11.4), which was statistically significant (p=0.002). CONCLUSION: Our study showed that non-obese polycystic ovary syndrome patients have a higher concentration of abdominal fat, which is a risk factor for increased cardiovascular risk and insulin resistance. ClinicalTrials.gov ID: NCT02467751.

Does bisphenol A (BPA) participates in the pathogenesis of Polycystic Ovary Syndrome (PCOS)?

Abstract PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erβ, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.

Dietary pattern in women with polycystic ovary syndrome with and without associated non-alcoholic fatty liver disease: A cross-sectional study

Abstract Introduction Women with Polycystic Ovary Syndrome (PCOS) have a higher prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) than the general population. PCOS and NAFLD have common metabolic risk factors, however, the role of diet in NAFLD development is still uncertain in PCOS women. Objective To evaluate and compare the dietary patterns and nutritional intake in patients with PCOS with and without NAFLD. Method Cross-sectional study that included patients with PCOS diagnosed according to Rotterdam criteria. All participants were submitted to abdominal ultrasound to investigate liver steatosis. Dietary profile was assessed by 24-hour food recall (24hR), and Food Frequency Questionnaire (FFQ). Diet quality was assessed by the Healthy Eating Index (HEI) adapted for the Brazilian population. Physical activity practice was also assessed. Results 87 participants were included (average age 35.2 ± 5.7 years), among whom, 67 (77%) had NAFLD. The group with PCOS and NAFLD presented higher body mass index (BMI) (34.9 ± 4.5 vs. 30.4 ± 4.9 kg/m2; p = 0.001), Waist Circumference (WC) (103 [97‒113] vs. 95 [87.5‒100] cm; p < 0.001) and were considered physically active less frequently than those without NAFLD (34.3% vs. 60%; p = 0.04). Food intake and dietary patterns assessed by 24hR, FFQ and HEI presented no difference between the groups. Conclusions PCOS women with coexistent NAFLD had higher BMI, WC and were less physically active than those without NAFLD. Dietary evaluation showed that PCOS women with NAFLD had no significant difference in macro and micronutrients or food group intake and diet quality in comparison to those without NAFLD.

Protective effect of nebivolol on rat ovary exposed to deltamethrin toxicity

Purpose: We aimed to investigate the antioxidant activity of nebivolol against possible damage to the ovarian tissue due to the application of deltamethrin as a toxic agent, by evaluating histopathological proliferating cell nuclear antigen (PCNA) and tumor necrosis factor-alpha (TNF-α) signal molecules immunohistochemically. Methods: The animals were divided into three groups as control, deltamethrin and deltamethrin + nebivolol groups. Vaginal smears were taken after the animals were mated and detected on the first day of pregnancy. After the sixth day, deltamethrin (0.5 mL of 30 mg/kg BW undiluted ULV), and 2 mL of sterile nebivolol solution were administered intraperitoneally every day for 6-21 periods. After routine histopathological follow-up, the ovarian tissue was stained with hematoxylin and eosin stain. Results: Control group showed normal histology of ovarium. In deltamethrin group, hyperplasic cells, degenerative follicles, pyknotic nuclei, inflammation and hemorrhagic areas were observed. Nebivolol treatment restored these pathologies. Deltamethrin treatment increased TNF-α and PCNA reaction. However, nebivolol decreased the expression. Conclusions: It was thought that deltamethrin toxicity adversely affected follicle development by inducing degeneration and apoptotic process in preantral and antra follicle cells, and nebivolol administration might reduce inflammation and slow down the apoptotic signal in the nuclear phase and regulate reorganization.

Effects of daidzein on rat ovary against ischemia-reperfusion

Purpose: Our aim was to investigate protective effects of daidzein treatment on ischemia-reperfusion (I/R) injury-induced ovarian tissue by immunohistochemical techniques. Methods: Thirty Sprague Dawley female rats were categorized into three groups as sham, I/R group, and I/R+daidzein groups. Bloods were analyzed for malondialdehyde (MDA), glutathione peroxidase (GSH), and myeloperoxidase (MPO), and ovaries were processed for histological tissue protocol. Results: Both MDA and MPO values were increased in I/R group compared to sham and I/R+daidzein groups. GSH content was increased in I/R+daidzein group compared to I/R groups. In I/R group, theca and follicular cells were degenerated with apoptosis and dilatation and congestion, edema. In I/R+daidzein group, daidzein improved pathologies. In the I/R group, Bax expression was positive with follicular cells, granulosa cells and inflammatory cells. In the I/R+daidzein group, positive Bax reaction was observed in the epithelial, antral, and inflammatory cells. In I/R group, Bcl-2 reaction was in germinative epithelial cells, cells of antral follicle. In the I/R+daidzein group, Bcl-2 expression level was reduced after daidzein treatment. Conclusions: After the I/R procedure, ovarian cells and follicles were degenerated with apoptosis and inflammation. After daidzein treatment, Bax and Bcl-2 signal were decreased. It was observed that daidzein stopped the apoptotic process.