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.

Prevalence and influencing factors analysis of the polycystic ovary syndrome among female college students in Fuzhou City， Jiangxi Province / 上海预防医学

ObjectiveTo investigate the prevalence of polycystic ovary syndrome （PCOS） among female college students at a university in Fuzhou City， Jiangxi Province， and to facilitate early detection and intervention of PCOS. MethodsUsing a stratified sampling method， a total of 450 female freshmen were randomly selected for PCOS screening. A self-designed questionnaire was used for data collection， covering menstrual status， high androgen signs， lifestyle， dietary habits， and awareness of PCOS. Sample t test and χ2 test were used to compare the basic information and dietary habits between PCOS and non-PCOS cases. The correlation between various indicators and the prevalence of PCOS was analyzed by a logistic regression model. ResultsA total of 12 PCOS cases were identified， with a prevalence rate of 2.99%. PCOS cases exhibited statistically significant differences compared to non-PCOS cases in terms of waist-to-hip ratio， waist circumference， abdominal obesity， the proportion of overweight or obese individuals， and a preference for sweet food （all P<0.05）. Multivariate logistic regression analysis revealed a significant correlation between preference for sweet food and the occurrence of PCOS （OR=4.858， 95%CI=1.199‒19.675，P=0.027）， as well as a significant correlation with PCOS accompanied by abdominal obesity （OR=7.083， 95%CI=0.773‒64.937， P=0.048）. Among the female college students surveyed， 37.90% had never heard of PCOS， 51.62% were only familiar with the name of the disease， and 10.47% had attempted to search for PCOS-related information. ConclusionThe prevalence of PCOS among female college students should not be overlooked and unhealthy dietary habits may be a crucial factor contributing to the occurrence of PCOS during this period. Early screening for PCOS during puberty is crucial.

Research progress on metabolic function in patients with polycystic ovary syndrome / 公共卫生与预防医学

The incidence of infertility disorders is increasing year by year, affecting about 12-15% of women of reproductive age worldwide. Polycystic ovary syndrome (PCOS) is one of the common causes of infertility. In recent years, the incidence rate of PCOS has increased year by year, but the improvement of endocrine and metabolic dysfunction and pregnancy outcomes in patients with PCOS are not satisfactory. There is a consensus both domestically and internationally that improving metabolic function and endocrine abnormalities in PCOS patients can increase their pregnancy rate. Therefore, it is important to explore the improvement of metabolic function in patients with PCOS. This article reviews the progress of basic research on improving metabolic function in patients with PCOS.

Effect of naringenin regulating RIP1-RIP3-MLKL signaling pathway on apoptosis of ovarian granulosa cells in rats with polycystic ovary syndrome / 中国药理学通报

Aim Based on the apoptotic pathway mediated by receptor interacting protein kinase(RIP)1-RIP3-mixed spectrum kinase domain like protein(MLKL), to explore the effects of naringenin on ovarian granulosa cell apoptosis in rats with polycystic ovary syndrome(PCOS). Methods SD rats were randomly assigned into normal control group, model group, naringenin group, RIP1 inhibitor(Nec-1)group, RIP1-RIP3-MLKL necrosis signal activator(Z-VAD-fmk)group, naringenin+Z-VAD-fmk group, 15 rats per group. ELISA method was performed to measure the levels of IL-1β and TNF-α in ovarian tissue. HE method was performed to observe the shape of the ovary. Granular cells were isolated from ovarian tissue, and flow cytometry was performed to measure apoptosis rate and necrosis rate. Immunohistochemistry was performed to measure the positive expression of p-RIP1 in ovarian tissue. Western blot was employed to detect the expression of RIP1-RIP3-MLKL pathway. Results RIP1 specific inhibitor Nec-1 and naringenin could block the phosphorylation and activation of RIP1, inhibit the RIP1-RIP3-MLKL signaling pathway, reduce the inflammation level in PCOS rats, and alleviate the necrosis and apoptosis of ovarian granulosa cells(P<0.05). Z-VAD-fmk could promote the activation of RIP1-RIP3-MLKL pathway, aggravate the apoptosis of ovarian granulosa cells, and partially weaken the anti-apoptosis effect of naringenin(P<0.05). Conclusions Naringenin may inhibit the apoptosis of ovarian granulosa cells in PCOS rats by blocking the activation of the necrotic apoptotic pathway mediated by RIP1-RIP3-MLKL.

Role of Macrophage Polarization in Chronic Low-grade Inflammation of PCOS Based on Theory of Spleen Being in Charge of Defensive Function / 中国实验方剂学杂志

Polycystic ovary syndrome （PCOS） is a reproductive endocrine disorder characterized by coexisting reproductive dysfunction and glucolipid metabolic disturbance， affecting 8%-13% of women of reproductive age and 3%-11% of adolescent females. Due to the highly heterogeneous clinical features， symptom-oriented individualized strategies are commonly adopted for the treatment of PCOS. Chronic low-grade inflammation is one of the core mechanisms for the occurrence of PCOS. Macrophages， as foundational cells of innate immunity， play an indispensable role in modulating systemic inflammatory responses. The imbalance of macrophage M1/M2 polarization is involved in chronic low-grade inflammation in PCOS via pathways such as activating pro-inflammatory responses， disrupting ovarian tissue repair， stimulating excessive synthesis of androgens， and promoting the occurrence of insulin resistance. Reshaping the phenotype of macrophages might serve as a potential therapeutic strategy for PCOS. Traditional Chinese medicine （TCM） holds that spleen deficiency and phlegm dampness is a crucial pathogenesis of PCOS. The spleen， being in charge of defensive function， plays a key role in ensuring normal physiological functions such as transportation and defense against external pathogen during the occurrence and development of PCOS. The imbalance of macrophage polarization resembles the transition from spleen being in charge of defensive function to spleen losing its defensive role in TCM. Therefore， this paper， for the first time， explores the deep connection between macrophage polarization and the pathogenesis of chronic low-grade inflammation in PCOS from the TCM theory of spleen being in charge of defensive function， providing theoretical support and new research directions for the treatment and drug research of PCOS.

Effect of follicular fluid-derived exosomal mi RNAs on follicular dysplasia mediated via glycolysis of granulosa cells in patients with polycystic ovary syndrome and its mechanism / 中国生物制品学杂志

@#Objective To evaluate the effect of follicular fluid(FF)exosomal miRNAs on follicular dysplasia in patients with polycystic ovary syndrome(PCOS)mediated by glycolysis pathway of granulosa cells(GCs),and to explore the mechanism. Methods Three PCOS infertile patients and three non-PCOS infertile patients were recruited. The baseline hormone levels of the two groups were measured before ovulation induction. The bilateral FF was obtained by puncture after short-acting and long-term ovulation induction,and the exosomes were collected by ultracentrifugation and identified by transmission electron microscopy. The total exosomal RNA was extracted by Trizol method to construct the library,which was compared to the reference genome GRCh38 for statistical analysis after miRNA sequencing and quality control processing. Clustering Profiler R package was used to implement GO annotation analysis and KEGG pathway analysis of the differentially expressed genes(DEGs),and Omnipath software for miRNAs interaction analysis. A total of 16 miRNA were randomly selected and detected by qPCR to verify the accuracy of the miRNA sequencing results. Results Compared with the non-PCOS group,luteinizing hormone(LH),anti-Muerian hormone(AMH),testosterone and antral follicle counts in PCOS group increased significantly(t = 2. 479 ～ 9. 163,each P < 0. 05). The exosomes of FF in both groups showed the cup-shaped vesicles with clear edge and light staining in the center,with the diameters of 100 — 150 nm and intact structure,and the concentration was about 8 × 1010particles/mL. A total of 928 miRNAs were detected by miRNA sequencing. Compared with the non-PCOS group,59 differentially expressed miRNA(DEmiRNA)were screened out in exosomes of POCS group,of which 31 were up-regulated and 28 were down-regulated. The differential trend of gene expression detected by qPCR was highly similar to that of miRNA sequencing. In FF exosomes of PCOS patients,the glycolysis efficiency and apoptosis of GCs were significantly changed by miRNA regulating mRNA. PKM,PFKL and HK2 were the key target genes for miRNA to regulate GCs glycolysis,and SLC2A1 was the key target gene for miRNA to regulate GCs apoptosis. Conclusion The miRNAs in FF exosomes of PCOS patients can weaken the glycolysis of GCs while accelerate the apoptosis,thus reducing the production of ATP and lactic acid,resulting in follicular dysplasia.

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.

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.

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.

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.

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.

Dual-energy X-ray absorptiometry and adiposity index are sensitive methods to evaluate central fat accumulation in women with polycystic ovary syndrome and normal body mass index

ABSTRACT Objective: This study aimed to determine the differences in body fat distribution and central obesity indicators using dual-energy X-ray absorptiometry (DXA), adiposity indices, and anthropometric indices between women with and without polycystic ovary syndrome (PCOS). Materials and methods: Clinical and laboratory examination history, including transvaginal ultrasound, fasting blood samples, anthropometric measurements, and DXA scans were conducted in 179 women with PCOS (PCOS group) and 100 without PCOS (non-PCOS group). The volunteers were grouped by body mass index (BMI): normal (18-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (>30 kg/m2). The visceral adiposity index (VAI) and lipid accumulation product (LAP) were calculated, regions of interest (ROIs) were determined, and the fat mass index (FMI) was calculated using DXA. Results: VAI, LAP, ROIs, FMI, and adiposity indices by DXA were higher in women with PCOS and normal BMI. In both PCOS and non-PCOS groups, the ROIs progressively increased from normal BMI to overweight and obese, and from overweight to obese. Obese women with PCOS showed high trunk fat mass. However, obesity was not able to modify these trunk/periphery fat ratios in PCOS from overweight to higher BMI. These variables were associated with the incidence of PCOS. Conclusion: In women with PCOS and normal BMI, both DXA and the adiposity indices, VAI and LAP, are more sensitive methods to evaluate total body fat and fat accumulation in the central abdominal region. It was also observed that as BMI increased, the differences in measurements between women with and without PCOS decreased.

Association between lower urinary tract symptoms and polycystic ovary syndrome

SUMMARY OBJECTIVE: The aim of this study was to analyze the association between lower urinary tract symptoms and polycystic ovary syndrome. METHODS: A total of 180 women were enrolled in this prospective study. Demographic data, body mass index, waist circumference, modified Ferriman-Gallwey scores, biochemical parameters, ultrasonographic findings, and maximum urinary flow rate (Q max) were analyzed. In addition, the Beck Depression Inventory, Beck Anxiety Inventory, and Bristol Female Lower Urinary Tract Symptom Scored Form questionnaires were evaluated for each subject. RESULTS: The mean age of patients was calculated as 23.78±3.04 years, which was similar for both groups (p=0.340). Body mass index, waist circumference, Beck Depression Inventory, Beck Anxiety Inventory, Bristol Female Lower Urinary Tract Symptom Scored Form, and modified Ferriman-Gallwey scores were significantly higher in group 2 (p<<0.001). Hyperandrogenism, lipid profile, and glucose metabolism disorders were more frequent in group 2 (p<<0.05). Bladder capacity (Q max), bladder wall thickness, and post-void residual volume values were similar in both groups (p>>0.05). CONCLUSION: In our study, a close relationship was observed between polycystic ovary syndrome and lower urinary tract symptoms. In this context, we think that a detailed urinary system evaluation of women with polycystic ovary syndrome is extremely important.

Effect of Elevated Basal LH on IVF-ET Outcomes in Patients with Polycystic Ovary Syndrome / 中山大学学报(医学科学版)

ObjectiveTo compare the outcomes in controlled ovarian stimulation （COH） and fresh embryo transfer between women with and those without a high basal luteinizing hormone （bLH） level in polycystic ovary syndrome （PCOS）. MethodsThe clinical data of PCOS patients at the Reproductive Medicine Center of the Sixth Hospital of Sun Yat-sen University from January 2015 to December 2021 were retrospectively analyzed. They were divided into the high group （LH≥10 U/L） and normal group （LH<10 U/L） according to the bLH levels. The results of COH and pregnancy outcomes after fresh transfer were compared， including gonadotropin （Gn） initiation dose， Gn duration， total Gn dose， number of oocytes obtained， two pronuclei （2PN） rate， available embryos rate， high-quality embryos rate， blastocyst formation rate， human chorionic gonadotrophin （HCG） positive rate， clinical pregnancy rate （CPR）， spontaneous abortion rate （SAR）， ongoing pregnancy rate （OPR） and live birth rate （LBR）. The differences in hormonal trends during COH were also analyzed. ResultsThere were no statistically significant differences in age， body mass index， anti-Mullerian hormone， and type of infertility between the two groups. Compared with the normal group， the Gn initiation dose and Gn duration were not statistically significant （P>0.05）， while the total Gn dose was significantly lower （P<0.001） in the high group. The number of oocytes retrieved， 2PN rate， available embryos rate， high-quality embryos rate， and blastocyst formation rate were comparable between the two groups （all P>0.05）. After fresh embryo transfer， they had similar pregnancy outcomes in the HCG positive rate， CPR， SAR， OPR and LBR （all P > 0.05）. ConclusionsIn patients with PCOS， high bLH levels do not affect COH or pregnancy outcomes in fresh transfer cycles. Further studies are needed to determine whether LH levels need to be lowered prior to COH and whether frozen-all strategy is required in patients with elevated bLH levels.