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1.
Medicine (Baltimore) ; 99(44): e22954, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126363

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS), is a common endocrine disorder in women characterized by increased androgen levels, ovulatory dysfunction, and polycystic ovaries. Western medicine is widely used for the treatment of PCOS, but patient satisfaction is low, largely due to its associated gastrointestinal symptoms of nausea and diarrhea. Guizhi Fuling Wan (GFW) is a traditional Chinese medicine used to remove blood stasis and dissipate phlegm for treating gynecological diseases that was invented by Zhang Zhongjing in the Eastern Han dynasty. In recent years, GFW has been widely used to treat patients with PCOS. This study aims to assess the efficacy and safety of GFW in the treatment of PCOS through a systematic review and meta-analysis. METHODS: All randomized controlled trials connected with GFW targeting PCOS will be searched in the following electronic bibliographic databases from their earliest recorded publications to December 2020 without any language restrictions: MEDLINE, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Chinese Biological Medicine Database, Wan-fang data, Chinese Technical Periodicals, and other databases. The primary outcomes include Sex hormone levels, ovulation rate, pregnancy rate, and total effective rate. The secondary outcomes were Total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, fasting glucose, fasting insulin, insulin sensitivity index, body mass index, hypertrichosis score, acne score, adverse reactions, etc. Two reviewers will independently conduct cations retrieval, de-duplication, filtering, quality assessment, and data analysis by Endnote X9.1 and Review Manager software (RevMan V.5.3). Meta-analysis and/or subgroup analysis will be performed on the included data. DISCUSSION: This study will investigate the application of GFW in the treatment or prevention of PCOS, and provide a high-quality synthesis to judge whether GFW is an effective and safe intervention for PCOS. PROSPERO REGISTRATION NUMBER: CRD42020192405.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Humanos , Síndrome do Ovário Policístico/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Cochrane Database Syst Rev ; 8: CD005552, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32794179

RESUMO

BACKGROUND: Metformin has been proposed as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of metformin versus OCP in the long-term treatment of women with PCOS. This is an update of a Cochrane Review comparing insulin sensitising agents with the OCP and only includes studies on metformin. OBJECTIVES: To assess the effectiveness and safety of metformin versus the OCP (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS. SEARCH METHODS: In August 2019 we searched the Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL, the trial registers, handsearched references of the identified articles, and contacted experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of the use of metformin versus the OCP (alone or in combination) for women with PCOS. DATA COLLECTION AND ANALYSIS: We used standard methods recommended by Cochrane. The primary review outcomes were the clinical parameters of hirsutism and adverse events, both severe (requiring stopping of medication), and minor. In the presence of substantial heterogeneity (I2 statistic > 50), which could be explained by pre-specified subgroup analyses on the basis of BMI, we reported the subgroups separately. MAIN RESULTS: This is a substantive update. We identified 38 additional studies. We included 44 RCTs (2253 women), which comprised 39 RCTs on adult women (2047 women) and five RCTs on adolescent women (206 women). Evidence quality ranged from very low to low. The main limitations were risk of bias, imprecision and inconsistency. Metformin versus the OCP In adult women, we are uncertain of the effect of metformin compared to the OCP on hirsutism in subgroup body mass index (BMI) < 25 kg/m2 (mean difference (MD) 0.38, 95% confidence interval (CI) -0.44 to 1.19, 3 RCTs, n = 134, I2 = 50%, very low-quality evidence) and subgroup BMI > 30 kg/m2 (MD -0.38, 95% CI -1.93 to 1.17; 2 RCTs, n = 85, I2 = 34%, low-quality evidence). Metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m2 to 30 kg/m2 (MD 1.92, 95% CI 1.21 to 2.64, 5 RCTs, n = 254, I2 = 0%, low-quality evidence). Metformin may increase severe gastro-intestinal adverse events rate compared to the OCP (Peto odds ratio (OR) 6.42, 95% CI 2.98 to 13.84, 11 RCTs, n = 602, I2 = 0%, low-quality evidence). Metformin may decrease the incidence of severe other adverse events compared to the OCP (Peto OR 0.20, 95% CI 0.09 to 0.44, 8 RCTs, n = 363, I2 = 0%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, we are uncertain whether there is a difference between Metformin and the OCP, on hirsutism and adverse events. Metformin versus metformin combined with the OCP In adult women, metformin may be less effective in improving hirsutism compared to Metformin combined with the OCP (MD 1.36, 95% CI 0.62 to 2.11, 3 RCTs, n = 135, I2= 9%, low-quality evidence). We are uncertain if there was a difference between metformin and metformin combined with the OCP for severe gastro-intestinal adverse events (OR 0.74, 95% CI 0.21 to 2.53, 3 RCTs, n = 171, I2 = 0%, low-quality evidence), or for severe other adverse events (OR 0.56, 95% CI 0.11 to 2.82, 2 RCTs, n = 109, I2 = 44%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, there were no trials for this comparison. The OCP versus metformin combined with the OCP In adult women, the OCP may be less effective in improving hirsutism compared to metformin combined with the OCP (MD 0.54, 95% CI 0.20 to 0.89, 6 RCTs, n = 389, I2= 1%, low-quality evidence). The OCP may decrease the incidence of severe gastro-intestinal adverse events compared to metformin combined with the OCP (OR 0.20, 95% CI 0.06 to 0.72, 5 RCTs, n = 228, I2 = 0%, low-quality evidence). We are uncertain if there is a difference between the OCP and metformin combined with the OCP for severe other adverse events (OR 1.61, 95% CI 0.49 to 5.37, 4 RCTs, n = 159, I2 = 12%, low-quality evidence). The OCP may decrease the incidence of minor (gastro-intestinal) adverse events compared to metformin combined with the OCP (OR 0.06, 95% CI 0.01 to 0.44, 2 RCTs, n = 98, I2 = 0%, low-quality evidence). In adolescents, we are uncertain whether there is a difference between the OCP, compared to metformin combined with the OCP, on hirsutism or adverse events. AUTHORS' CONCLUSIONS: In adult women with PCOS, metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m2 to 30 kg/m2 but we are uncertain if there was a difference between metformin and the OCP in subgroups BMI < 25 kg/m2 and BMI > 30kg/m2. Compared to the OCP, metformin may increase the incidence of severe gastro-intestinal adverse events and decrease the incidence of severe other adverse events with no trials reporting on minor adverse events. Either metformin alone or the OCP alone may be less effective in improving hirsutism compared to metformin combined with the OCP. We are uncertain whether there is a difference between the OCP alone and metformin alone compared to metformin combined with the OCP for severe or minor adverse events except for the OCP versus metformin combined with the OCP where the OCP may decrease the incidence of severe and minor gastro-intestinal adverse events. In adolescent women with PCOS, we are uncertain whether there is a difference between any of the comparisons for hirsutism and adverse events due to either no evidence or very low-quality evidence. Further large well-designed RCTs that stratify for BMI are needed to evaluate metformin versus the OCP and combinations in women with PCOS, in particular adolescent women.


Assuntos
Anticoncepcionais Orais Combinados/uso terapêutico , Hirsutismo/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Distúrbios Menstruais/tratamento farmacológico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Acne Vulgar/tratamento farmacológico , Adolescente , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Anticoncepcionais Orais Combinados/efeitos adversos , Quimioterapia Combinada , Neoplasias do Endométrio/prevenção & controle , Feminino , Humanos , Metformina/efeitos adversos , Síndrome do Ovário Policístico/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
3.
PLoS One ; 15(8): e0235404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785222

RESUMO

OBJECTIVE: To study the role of selected serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome (PCOS). METHODS: Selected serum inflammatory cytokines were analyzed in the particle cells, which were interfered by berberine, from 78 infertile women who were to be treated with In Vitro Fertilization (IVF) /Intracytoplasmic Sperm Injection-Embryo Transfer (icsi-et). Among them, 49 patients had PCOS infertility, and 29 were non-PCOS patients whose infertility resulted from fallopian tube and male factors. The elisa method was used to detect the changes in the expression levels of inflammatory factors in the cells. The correlations between the serum inflammatory cytokine expression levels and the corresponding clinical hormones were analyzed. The changes in the expression (mRNA and protein) levels of the serum inflammatory cytokines were studied by real-time quantitative PCR and protein printing. Fluorescence microscope and flow cytometry were used to detect the glucose uptake capacity of ovarian granulosa cells in PCOS patients under the action of insulin after berberine. RESULTS: In the PCOS group, IL-17a (P = 0.001), IL-1Ra (P<0.0001), and IL-6 (P = 0.035) were significantly higher than those in the non-PCOS group. In the non-PCOS group, AMH level was negatively correlated with inflammatory cytokines IL-17a (r = -0.819;P = 0.004), IL-1a (r = -0.716;P = 0.0.02), IL-1b (r = -0.678;P = 0.031), IL-2 (r = -0.765;P = 0.01), and IL-8 (r = -0.705;P = 0.023). However, in the PCOS group, AMH levels were not significantly correlated with the levels of the examined inflammatory cytokines. Berberine significantly reduced the expression level of mTOR mRNA (P = 0.001), and increased the expression level of IRS-1 mRNA (P = 0.009) in the PCOS granule cells. CONCLUSION: In this study, we find that the elevated levels of serum inflammatory factors IL-17a, IL-1Ra, and IL-6 cause women to be in a subclinical inflammatory state for a long time. Abnormal changes in inflammatory factors alter their original negative correlations with AMH levels, thereby weakening the metabolism of glycolipids, promoting insulin resistance, destroying the normal ovulation and fertilization system of women, leading to polycystic ovary syndrome characterized by menstrual thinning and abnormal ovulation. Berberine can improve the sensitivity of insulin by regulating the signal pathway of insulin receptor substrate-1 (IRS-1) and mammalian target of rapamycin (mTOR) in PCOS patients and achieve a therapeutic effect of treating PCOS.


Assuntos
Anti-Inflamatórios/uso terapêutico , Berberina/uso terapêutico , Insulina/sangue , Interleucinas/sangue , Síndrome do Ovário Policístico/metabolismo , Adulto , Anti-Inflamatórios/administração & dosagem , Hormônio Antimülleriano/metabolismo , Berberina/administração & dosagem , Células Cultivadas , Feminino , Glicolipídeos/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
4.
Medicine (Baltimore) ; 99(30): e20696, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791663

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS), an intricate and multifactorial disease, has characteristics of diverse clinical, metabolic and endocrine disorder. It represents a primary cause of infertility in reproductive women, which seriously affects the physical and mental health of patients. Several small studies have indicated that inositol and alpha lipoic acid (ALA) supplementation can ameliorate the outcomes in terms of menstrual cyclicity, ovulation and hyperinsulinemia in PCOS women. However, there is a lack of sufficient evidence to affirm this practice. Consequently, we aim to objectively review and estimate the efficacy and safety of inositol plus ALA in adult women suffering from PCOS. METHODS AND ANALYSIS: We will retrieve PubMed, EMBASE, The Web of Science, The Cochrane Library of Controlled Trials, Clinical Trials.gov, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wan-Fang database with no specific limitations on language. Simultaneously we will manually retrieve reference lists and grey literature to acquire potential eligibility. We will restrict our search to randomized controlled trials (RCTs) of inositol in combination with ALA for PCOS. Researchers will separately identify studies, extract data and evaluate the quality of studies. We will conduct risk of bias estimates, data synthesis and analysis using Review Manager 5.3 software. RESULTS AND CONCLUSION: The study will comprehensively determine the effectiveness and safety of inositol conjunct with ALA therapy for PCOS. Meanwhile we intend to disseminate the final findings in a peer-reviewed journal to help patients, clinicians and health policymakers select treatment strategy of PCOS by providing high-quality evidence.


Assuntos
Inositol/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
5.
Life Sci ; 259: 118174, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32745529

RESUMO

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in females of the reproductive age. PCOS is commonly manifested as ovulatory dysfunction, clinical and biochemical excess androgen level, and polycystic ovaries. Metabolic sequelae associated with PCOS, including insulin resistance (IR), type 2 diabetes (T2DM), obesity and increased cardiometabolic risk. The underlying pathology of PCOS is not fully understood with various genetic and environmental factors have been proposed. MicroRNAs (miRNAs), are endogenously produced, small non-coding, single-stranded RNAs that capable of regulating gene expression at the post-transcriptional level. Altered miRNAs expression has been associated with various disorders, including T2DM, IR, lipid disorder, infertility, atherosclerosis, endometriosis, and cancer. Given that PCOS also present with similar features, there is an increasing interest to investigate the role of miRNAs in the diagnosis and management of PCOS. In recent years, studies have demonstrated that miRNAs are present in various body fluids, including follicular fluid of women with PCOS. Therefore, it may act as a potential biomarker and could serve as a novel therapeutic target for the diagnosis and treatment of PCOS. This review aims to summarise the up to date research on the relation between miRNAs and PCOS and explore its potential role in the diagnosis and the management of PCOS.


Assuntos
Biomarcadores/análise , MicroRNAs/análise , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações
6.
Life Sci ; 260: 118310, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32835696

RESUMO

Polycystic ovary syndrome (PCOS) is an endocrinopathy, and it accounts for 75% of non-ovulatory infertile in women of childbearing age. It is clear that obesity, insulin resistance, dyslipidaemia coexist in PCOS. Apelin, as an endogenous ligand of the previously orphan receptor, is an adipokine that secreted by adipose tissue. Apelin and apelin receptors are expressed in many tissues and organ to regulate their physiological functions. Studies have shown that Apelin/apelin-receptor also expressed in ovary such as follicles, granulosa cells. Furthermore, Apelin/apelin-receptor play roles in vascular establishment and hormone metabolism in ovary. These indicate that the Apelin/apelin-receptor play an important role in the development of follicle. Apelin/apelin-receptor are increased in ovary of PCOS, which are associated with abnormal ovarian hormones and function. These are important causes of menstrual cycle disorders and anovulation. Moreover, apelin now appears clearly as a new player in energy metabolism. Apelin can regulate glucose and lipid metabolism but also modulate insulin secretion. And plasma apelin concentrations are elevated in obesity and type 2 diabetes patients. Interestedly, obesity and type 2 diabetes are also companied with polycystic ovary syndrome patients. We speculate apelin/apelin-receptor may play a vital role in pathogenesis of polycystic ovary syndrome, but the underlying mechanisms remain under exploration. Here, we review apelin/apelin-receptor, as a new therapeutic target, have effects on ovarian function and energy metabolism in polycystic ovary syndrome.


Assuntos
Receptores de Apelina/metabolismo , Apelina/metabolismo , Regulação da Expressão Gênica , Terapia de Alvo Molecular , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Animais , Feminino , Humanos , Síndrome do Ovário Policístico/patologia , Transdução de Sinais
7.
Rev. iberoam. fertil. reprod. hum ; 37(2): 3-11, abr.-jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-193739

RESUMO

El uso de probióticos es un área de investigación traslacional en continuo progreso debido al creciente interés de los clínicos del área de fertilidad y sus pacientes. Por lo que el objetivo principal de este trabajo es recabar y resumir la información de la literatura científica relevante sobre los probióticos y su posible papel modulador efectivo en alteraciones relacionadas con la fertilidad y reproductivas. Para ello se describen los aspectos de interés relativos a: 1. La microbiota humana y sitios naturales de colonización relacionados con la salud reproductiva: microbiota vaginal, microbiota endometrial, microbiota y embarazo. 2. A continuación, hemos resaltado las disbiosis de los sitios de colonización y las repercusiones en fertilidad del estado de salud/enfermedad y por último 3. La hipótesis sobre los tratamientos efectivos con probióticos orales vs vaginales y sus vías fisiológicas de transferencia y actuación; que lleva asociado la descripción del concepto de translocación efectiva o llegada de los probióticos alsitio natural de colonización tras su administración como suplementos. La mayoría de probióticos utilizados en disbiosis relacionadas con la fertilidad pertenecen al género Lactobacillus. Se suelen administrar principalmente por vía oral a una concentración del orden de 1x109UFC/día y una duración de4-12 semanas, siendo diferencial en función de la disbiosis a tratar


The use of probiotics is an area of translational research in continuous progress due to the growing interest of fertility clinicians and their patients. Therefore, the main objective of this work is to collect and summarise relevant information from the available scientific literature on probiotics and their effective modulating role in fertility-related and reproductive disorders. To approach this objective, we have summarised the knowledge regarding the following pertinent aspects: 1. The human microbiota: intestinal microbiota already well studied, and other natural colonization sites related to reproductive health: vaginal microbiota, endometrial microbiota, pregnancy microbiota. 2. Next, we have highlighted the dysbiosis of the colonization sites and the repercussions on the state of health / disease and finally 3. The hypothesis that exists about effective treatments with oral probiotics and their physiological transfer and performance pathways and the associated concept of translocation or arrival at the natural site of colonization. Most probiotics used in fertility-related dysbiosis be-long to the genus Lactobacillus. They are mainly administered via oral at average concentrations of 1x109CFU/day during 4-12 weeks, being differential depending on the dysbiosis to be treated


Assuntos
Humanos , Feminino , Probióticos/administração & dosagem , Disbiose/tratamento farmacológico , Microbiota/efeitos dos fármacos , Vaginose Bacteriana/tratamento farmacológico , Endometriose/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico
8.
Clin Drug Investig ; 40(8): 695-713, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32583294

RESUMO

Polycystic ovary syndrome is a complex and heterogenous disorder involving multiple organ systems and different molecular pathways. It is tightly associated with obesity and especially abdominal obesity. As body weight reduction is the main modifiable risk factor for polycystic ovary syndrome, therapeutic approaches in overweight or obese women with polycystic ovary syndrome have been developed. Liraglutide is a glucagon-like peptide-1 receptor agonist that promotes sustained weight loss, as well as abdominal fat reduction, in individuals with obesity, prediabetes, and type 2 diabetes mellitus. The majority of current clinical studies have demonstrated that liraglutide therapy achieved significant reductions in body weight, body mass index, and abdominal circumference in overweight and obese women with polycystic ovary syndrome. Liraglutide therapy promoted significant improvements in free testosterone and sex hormone-binding globulin levels in some studies. Important metabolic and hormonal improvements were also reported after the combination of liraglutide with metformin. Increased menstrual frequency, as well as potential positive effects in reproduction, were described. However, the small number of participants, short duration, and low daily liraglutide dose are some of the main limitations of these studies. Larger and longer, multi-centred, double-blind, placebo-controlled trials of liraglutide monotherapy or combination therapy, with prolonged post-interventional monitoring, are crucially anticipated. Metabolic, hormonal, and reproductive primary outcomes should be uniformly addressed, to tailor future targeted treatment approaches, according to the patient phenotype and needs. This will improve long-term therapeutic outcomes in this population.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Síndrome do Ovário Policístico/complicações , Adulto , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Metformina/administração & dosagem , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/tratamento farmacológico , Sobrepeso/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/fisiopatologia , Perda de Peso/efeitos dos fármacos
9.
Medicine (Baltimore) ; 99(25): e20590, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569186

RESUMO

BACKGROUND: This study aims to assess the efficacy and safety of clomifene citrate (CC) for the treatment of patients with polycystic ovary syndrome (PCOS). METHODS: In this study, we will comprehensively search MEDLINE, EMBASE, The Cochrane Library, Web of Science, CINAHL, ACMD, PsycINFO, and China National Knowledge Infrastructure for original articles published from their inceptions to the January 1, 2020 without language restrictions. All studies will undergo relevance and a design selecting process. Data from qualified studies will be collected by 2 independent authors. Additionally, we will conduct a risk of bias evaluation using a Cochrane risk of bias tool. We will undertake statistical analysis utilizing RevMan 5.3 software. RESULTS: This study will summarize the up-to-date evidence to investigate the efficacy and safety of CC for the treatment of patients with PCOS. CONCLUSION: The findings of this study will provide helpful evidence of CC for the treatment of patients with PCOS, as well as may help develop treatment guidelines. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020162818.


Assuntos
Clomifeno/administração & dosagem , Antagonistas de Estrogênios/administração & dosagem , Síndrome do Ovário Policístico/tratamento farmacológico , Clomifeno/efeitos adversos , Antagonistas de Estrogênios/efeitos adversos , Feminino , Humanos , Revisões Sistemáticas como Assunto
10.
Life Sci ; 256: 118003, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32589998

RESUMO

INTRODUCTION AND AIMS: Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting females. Mechanisms underlying PCOS complicated pathology remain largely unknown, making current treatment only symptomatic. Increasing reports suggest impaired PI3K/AKT/mTOR pathway and tumor necrosis factor-α (TNF-α) levels are involved in cellular proliferation and metabolism-related disorders. However, rare data explored their role in PCOS. Hence, this study investigated TNF-α and pancreatic PI3K/AKT/mTOR levels in PCOS animal model and evaluated their effects on developed pancreatic deficits. Secondly; we explored the impact of nanocurcumin as powerful anti-inflammatory supplement against these developed pancreatic pathologies. METHODS: PCOS was induced in rats using letrozole. Nanocurcumin was formulated to increase solubility and bioavailability of curcumin. Transmission electron microscopy (TEM), zeta potential and Infra-red spectroscopy (FT-IR) were used for characterization. Nanocurcumin was orally ingested for 15 days. FINDINGS: PCOS group exhibited significant disturbance in sex hormones, oxidative stress markers, and TNF-α levels as determined by immunoassay. Western blotting revealed significant reduction of PI3K/AKT/mTOR levels leading to impaired insulin sensitivity, decreased ß cells function and mass as confirmed by HOMA assessments and immunohistochemistry. Nanocurcumin significantly improved oxidative markers, glucose indices and TNF-α levels. It reinstated PI3K/AKT/mTOR levels, alleviated insulin resistance, and retained islets integrity consequently restoring normal sex hormonal levels. SIGNIFICANCE: To the best of our knowledge, the study is the first to report pancreatic role of PI3K/AKT/mTOR and TNF-α in PCOS and the first to demonstrate nanocurcumin promising potential against PCOS-related pancreatic molecular and histological pathologies that can indeed offer better control of the disease.


Assuntos
Curcumina/farmacologia , Resistência à Insulina , Nanopartículas , Pâncreas/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Animais , Curcumina/administração & dosagem , Modelos Animais de Doenças , Feminino , Pâncreas/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
Chem Biol Interact ; 324: 109093, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298659

RESUMO

Polycystic Ovary Syndrome (PCOS), as a common endocrine disorder is accompanied by hyperandrogenism, insulin resistance, ovulation problems, and infertility. Various types of off-label drugs like metformin have been used for the management of targeted problems caused by PCOS such as insulin resistance and hyperandrogenism. Nicotinamide (NAM) acts as a substrate of visfatin and Nicotinamide N-Methyltransferase (NNMT) leading to the generation of Nicotinamide Adenine Dinucleotide (NAD) and N1-Methylnicotinamide (MNAM), respectively. MNAM is known as an anti-inflammatory, anti-thrombosis, and anti-diabetic agent. In this study, the effects of NAM and MNAM on metabolic and endocrine abnormalities were evaluated in the adipose and ovarian tissues of a letrozole-induced rat model of PCOS. Our results showed that MNAM and NAM reversed abnormal estrous cycle and reduced the serum testosterone levels and CYP17A1 gene expression. Furthermore, all therapeutic factors improved HOMA-IR after treatment and NAM significantly increased the expression of GLUT4 and decreased the gene expression of visfatin. Also, MNAM diminished the gene expression of visfatin and resistin. It is noteworthy that all the therapeutic factors successfully activated the AMPK. In summary, this study is the first study reported beneficial effects of NAM and MNAM on the treatment of PCOS. Additionally, the alleviative effects of our therapeutic factors may be partially mediated by the AMPK-dependent manner due to the contribution of the AMPK in the expression of CYP17A1, visfatin, resistin, and GLUT4. Although more studies are required to unravel the exact mode of actions of MNAM and NAM in the PCOS, the findings of the current study shed light on an urgent need for discovering novel therapeutic pharmaceuticals regarding the treatment of PCOS.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hiperandrogenismo/tratamento farmacológico , Hormônio Luteinizante/metabolismo , Metformina/uso terapêutico , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Ratos Wistar , Resistina/genética , Resistina/metabolismo , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testosterona/metabolismo
13.
Nat Commun ; 11(1): 2024, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332780

RESUMO

Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.


Assuntos
Clusterina/metabolismo , Glucose/metabolismo , Resistência à Insulina , Músculo Esquelético/metabolismo , Síndrome do Ovário Policístico/metabolismo , Adulto , Animais , Linhagem Celular , Clusterina/sangue , Clusterina/genética , Modelos Animais de Doenças , Feminino , Técnica Clamp de Glucose , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Fígado/metabolismo , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Camundongos , Camundongos Knockout , Pioglitazona/farmacologia , Pioglitazona/uso terapêutico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
BMC Womens Health ; 20(1): 68, 2020 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-32248801

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting about 10% of women in reproductive age and associated with a variety of hormonal abnormalities, including hyperandrogenemia and infertility, all of which could lead to PCOS. Statins were previously introduced as a therapeutic option for reducing testosterone levels in women with PCOS, either alone or in combination. The aim of this study is to evaluate the effectiveness of different statins alone or in combination with metformin in reducing testosterone levels in women with PCOS. METHODS: Medline, Embase, and clinicaltrials.gov were searched for studies that investigated the efficacy of statins, metformin, spironolactone, or combined oral contraceptives (COCs), individually or in combination, in reducing the testosterone level in patients with PCOS. The search was limited to randomized clinical trials and conducted according to the preferred reporting items for systematic reviews and meta-analyses - extension statement for network meta-analyses (PRISMA-NMA). The quality of included studies was assessed using the Cochrane Collaboration risk of bias (RoB) assessment tool. A frequentist network meta-analysis using random-effects models was used to assess the efficacy in reducing testosterone level and were expressed as odds ratios (OR) and 95% credible interval (95%Crl). All statistical analyses were performed using netmeta Version 1.0 on R statistical package. RESULT: Nine RCTs involving 613 patients were included. Atorvastatin showed greater reduction in testosterone level compared to COC (MD -2.78, 95%CrI -3.60, -1.97), spironolactone plus metformin (MD -2.83, 95%CrI -3.80, -1.87), simvastatin (MD -2.88, 95%CrI -3.85, -1.92), spironolactone (MD -2.90, 95%CI -3.77, -2.02), simvastatin plus metformin (MD -2.93, 95%CrI -3.79, -2.06), metformin (MD -2.97, 95%CrI -3.69, -2.25), lifestyle modification (MD -3.02, 95%CrI -3.87, -2.18), and placebo (MD -3.04, 95%CrI -3.56, -2.53). CONCLUSION: Atorvastatin was found to be more effective than the other management strategies in reducing the total testosterone level for patients with PCOS. Future studies should focus on the optimal dose.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Espironolactona/uso terapêutico , Anticoncepcionais Orais Combinados/uso terapêutico , Feminino , Humanos , Metanálise em Rede , Síndrome do Ovário Policístico/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Testosterona
15.
BMC Womens Health ; 20(1): 69, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252736

RESUMO

BACKGROUND: Vitamin E, which is critically important in the whole process of reproduction, can antagonize the oxidative stress caused by the oxygen free radicals and antioxidant imbalance and regulate normal physiological function of the reproductive system. The effect of short-term supplementation of vitamin E on outcomes of infertile women with polycystic ovary syndrome (PCOS) when they underwent ovulation induction with clomiphene citrate (CC) and human menopausal gonadotropin (HMG) remains unknown. METHODS: This was a retrospective cohort clinical trial from October 2015 to April 2017. A total of 321 PCOS cases underwent ovulation induction with CC and HMG. Patients in group A (n = 110) did not receive vitamin E while patients in group B (n = 105) and group C (n = 106) received oral treatment of vitamin E at 100 mg/day during follicular phase and luteal phase, respectively. RESULTS: It was observed no significant differences of ovulation rate, clinical pregnancy rate, and ongoing pregnancy rate among the three groups. It was interesting that dosage of HMG were significant lower in group B compared with those in group A and group C (P<0.05). CONCLUSIONS: A short-term supplementation of vitamin E can improve oxidative stress, and reduce exogenous HMG dosage to lower the economic cost with a similar pregnancy rate in the ovulation induction cycle. However, the supplementation does not alter the pregnancy rate in the ovulation induction cycle. TRIAL REGISTRATION: ChiCTR-OOC-14005389, 2014.


Assuntos
Clomifeno/uso terapêutico , Suplementos Nutricionais/efeitos adversos , Fármacos para a Fertilidade Feminina/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Síndrome do Ovário Policístico/complicações , Vitamina E/uso terapêutico , Adulto , Feminino , Humanos , Indução da Ovulação , Síndrome do Ovário Policístico/tratamento farmacológico , Gravidez , Estudos Retrospectivos , Vitamina E/efeitos adversos
16.
Life Sci ; 249: 117515, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32147428

RESUMO

AIMS: This study investigated the effects of curcumin-loaded super-paramagnetic iron oxide (Fe3O4) nanoparticles (NPs) (SPIONs) on histological parameters and apoptosis-inducing factors (AIFs) in an experimental mouse model of polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A total number of 40 female prepuberal BALB/c mice were randomly divided into four groups. Group 1 was selected as control and Group 2 was considered as a vehicle taking sesame oil, in the form of a curcumin carrier. Moreover, Group 3 was administered with dehydroepiandrosterone (DHEA) at 6 mg/100 g of the body weight and Group 4 received the DHEA plus the NPs of curcumin (5.4 mg/100 g) for twenty consecutive days. Finally, histology, stereology, and apoptosis of the ovary were evaluated. KEY FINDINGS: The results revealed that the NPs of curcumin had reduced ovarian volume (p < 0.05) and a total number of primary, secondary, antral, and primordial follicles in comparison with the PCOS and vehicle groups (p < 0.05). Furthermore, curcumin treatment following administration of the DHEA resulted in a significant decrease in BAX (p < 0.001) and levels of expression of Caspase3 (CASP3) protein, increased levels of B-cell lymphoma 2 (Bcl2) expression (p < 0.05), and moderated apoptosis in granulosa cells in comparison with the ones seen in the PCOS group. SIGNIFICANCE: Ovarian injuries and DHEA-induced apoptosis were efficiently suppressed by curcumin, indicating the probable protective property of NPs of curcumin against PCOS.


Assuntos
Apoptose/efeitos dos fármacos , Curcumina/administração & dosagem , Desidroepiandrosterona/administração & dosagem , Compostos Férricos/administração & dosagem , Nanopartículas Metálicas/química , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Maturidade Sexual , Animais , Antioxidantes/administração & dosagem , Apoptose/genética , Caspase 3/metabolismo , Modelos Animais de Doenças , Feminino , Compostos Férricos/química , Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Estresse Oxidativo
17.
Medicine (Baltimore) ; 99(12): e19045, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195930

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a female endocrine disease with a high incidence. At present, drug treatment is still the main therapeutic strategy for PCOS. Traditional Chinese medicine has a long history in the treatment of menstrual disorders. Shouwu Jiangqi Decoction (SWJQD) is a traditional herbal medicine prescribed in a clinical setting as a remedy for PCOS. Acupuncture also plays an important role in regulating the menstrual cycle and treating PCOS. This study aims to examine the efficacy and safety of the combination of SWJQD and acupuncture in the treatment of PCOS. METHODS: This randomized controlled trial will be conducted with a total of 81 participants diagnosed with PCOS. The participants will be randomly divided into 3 treatment groups: group A will receive SWJQD combined with acupuncture; group B, SWJQD combined with sham acupuncture; and group C, metformin. Each treatment will last 3 months. The primary outcomes include the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index and the Oral Glucose Tolerance Test. The secondary outcome measures include sex hormone levels, body mass index, ovulation rate, clinical pregnancy rate, and complete genome sequencing data. Adverse events will be recorded during the intervention and follow-up. RESULTS: This study will investigate whether the combination of SWJQD and acupuncture can alleviate the clinical symptoms and improve insulin resistance in patients with PCOS. The results of this study are expected to provide clinical evidence for the application of the combination of SWJQD and acupuncture in patients with PCOS. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900028106, ChiMCT1900002826 (registered on December 12, 2019).


Assuntos
Terapia por Acupuntura/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome do Ovário Policístico/terapia , Terapia por Acupuntura/efeitos adversos , Adolescente , Adulto , Índice de Massa Corporal , Terapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Teste de Tolerância a Glucose , Hormônios Esteroides Gonadais/sangue , Humanos , Ovulação , Síndrome do Ovário Policístico/tratamento farmacológico , Sequenciamento Completo do Genoma , Adulto Jovem
18.
J Endocrinol ; 245(2): 281-289, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32163914

RESUMO

Polycystic ovary syndrome (PCOS) is a complex syndrome involving both endocrine and metabolic disorders. Gut microbiota and the intestinal immune factor IL-22 play an important role in the pathogenesis of PCOS. However, the therapeutic role of IL-22 in high androgen-induced PCOS mice is not clear. We aimed to determine the therapeutic effects of IL-22 on the DHEA-induced PCOS mouse model and to explore the possible mechanism of IL-22 in regulating hyperandrogenism-associated PCOS. Insulin resistance levels and ovarian functions were investigated in DHEA-induced PCOS mice with or without additional IL-22 treatment. We found that IL-22 could reverse insulin resistance, disturbed estrous cycle, abnormal ovary morphology, and decreased embryo number in DHEA mice. Mechanistically, IL-22 upregulated the browning of white adipose tissue in DHEA mice. This study demonstrated that IL-22-associated browning of white adipose tissue regulated insulin sensitivity and ovarian functions in PCOS, suggesting that IL-22 may be of value for the treatment of PCOS with a hyperandrogenism phenotype.


Assuntos
Interleucinas/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Androgênios , Animais , Modelos Animais de Doenças , Ciclo Estral/efeitos dos fármacos , Feminino , Hiperandrogenismo/induzido quimicamente , Hiperandrogenismo/complicações , Resistência à Insulina/fisiologia , Camundongos , Ovário/fisiopatologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/fisiopatologia
19.
J Ovarian Res ; 13(1): 32, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197626

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex reproduction and endocrine disorder of women in the reproductive age. Spearmint (Mentha spicata L.) has anti-androgenic activity and flaxseed (Linum usitatissimum L.) contains phytoestrogen and was reported to improve PCOS conditions. This study aimed to evaluate PCOS conditions following administration of a mixture of these two plants. METHODS: Twenty-four rats with regular cycles were randomly divided into four groups as control (C) and treatment-control (TC) received a combination of spearmint extract (SE) + flaxseed extract (FE). PCOS was induced in PCOS and treatment (T) groups by a single intramuscular injection of estradiol valerate. The treatment group received a combination of SE and FE for 30 days, 7 weeks after injection of estradiol valerate. Estrous cycles were monitored for 10 days and in the last day animals were sacrificed, ovaries were collected for the histomorphometric study and the serum levels of progesterone, testosterone, estradiol, and dehydroepiandrosterone (DHEA) were measured. RESULT: Significant rise in progesterone and a decrease in testosterone and estradiol with no significant change of DHEA in the T group, was observed in comparison with the PCOS group (P < 0.05). No significant difference noticed between T and control groups (C &CT) regarding evaluated hormones. A significant increase in primary, pre-antral and antral follicles noticed in the T group compared to the PCOS group. The number of cystic follicles decreased in the T group compared with the PCOS group. Granulosa layer thickness increased while the thickness of theca decreased significantly in the T group compared to the PCOS group (P < 0.05). No significant endocrine or histological differences noticed between C and TC groups. CONCLUSION: A combination of flaxseed and spearmint extract improved the endocrine profile and the histomorphometric features of the ovary in the T group compared to the PCOS group.


Assuntos
Sistema Endócrino/efeitos dos fármacos , Linho/química , Mentha spicata/química , Ovário/metabolismo , Ovário/patologia , Extratos Vegetais/farmacologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Animais , Biomarcadores , Biópsia , Modelos Animais de Doenças , Sinergismo Farmacológico , Ciclo Estral/efeitos dos fármacos , Feminino , Hormônios/sangue , Hormônios/metabolismo , Imuno-Histoquímica , Extratos Vegetais/química , Síndrome do Ovário Policístico/tratamento farmacológico , Ratos
20.
J Womens Health (Larchmt) ; 29(7): 937-943, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32155101

RESUMO

Contraceptives that contain estrogen and/or progestins are used by millions of women around the world to prevent pregnancy. Owing to their unique physiological mechanism of action, many of these medications can also be used to prevent cancer and treat multiple general medical conditions that are common in women. We performed a comprehensive literature search. This article will describe the specific mechanisms of action and summarize the available data documenting how hormonal contraceptives can prevent ovarian and uterine cancer and be used to treat women with a variety of gynecological and nongynecological conditions such as endometriosis, uterine fibroids, heavy menstrual bleeding, polycystic ovary syndrome, acne, and migraines. Contraceptive methods containing estrogen and progestin can be used for a wide variety of medical issues in women.


Assuntos
Anticoncepcionais Orais Hormonais/uso terapêutico , Endometriose/tratamento farmacológico , Estrogênios/uso terapêutico , Neoplasias Ovarianas/prevenção & controle , Síndrome do Ovário Policístico/tratamento farmacológico , Progestinas/uso terapêutico , Neoplasias Uterinas/prevenção & controle , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Saúde Reprodutiva
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