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PURPOSE: Metformin was the first medication targeting insulin resistance in PCOS, and it has been extensively studied as a metabolic treatment option. In recent years, inositols have emerged as potential treatment options for PCOS, but confidence in the available evidence supporting their use is limited. METHODS: We comprehensively searched PubMed, Embase, and Cochrane databases for RCTs comparing the use of combined metformin and inositol versus metformin alone in women with PCOS. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). A p-value of <0.05 was deemed as statistically significant. RESULTS: Six RCTs and 388 patients were included in the analysis, with follow-up ranging from 3 to 6 months. Combination therapy was significantly associated with improved menstrual cycle regularity (RR 1.56; 95% CI 1.01 to 2.41; p = 0.04), and lower values of modified Ferriman-Gallwey score (MD -0.97; 95% CI -1.53 to -0.40; p < 0.01) and LH/FSH ratios (MD -0.13; 95% CI -0.24 to -0.03; p = 0.01). Differences in acne (p = 0.58), body mass index (p = 0.13), fasting blood glucose (p = 0.07) and HOMA-IR (p = 0.25) were not statistically significant. CONCLUSION: In this meta-analysis of RCTs, combination therapy was associated with cycle regularization and reduction in hirsutism and LH/FSH ratio compared to metformin monotherapy. Further studies are needed to clarify the true benefits of the use of inositol in PCOS treatment.
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BACKGROUND: Some studies have reported that homocysteine, vitamin B12, and folic acid levels are associated with polycystic ovary syndrome (PCOS), whereas other studies yielded controversial results. OBJECTIVES: This study aimed to systematize the available evidence of homocysteine, vitamin B12, and folate levels in women with and without PCOS. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND METHODS: A systematic search without language restrictions was performed on PubMed, Ovid/Medline, Scopus, Embase, and Web of Science. In addition, the reference lists of the selected studies were reviewed. The Newcastle-Ottawa Scale was employed to evaluate the quality of studies. The means and standard deviations of the outcomes were pooled as standardized mean differences (SMDs) with 95% confidence intervals (CI). Furthermore, the DerSimonian and Laird method was employed for the quantitative synthesis. RESULTS: A total of 75 studies met the eligibility criteria for at least one outcome. Patients with PCOS had higher circulating homocysteine levels than those without (SMD: 0.82; 95% CI: 0.62-1.02, n = 70 studies, p < 0.001). This trend remained in the sensitivity and subgroup analyses by world regions of studies, assay methods, and insulin resistance. No significant differences were observed in circulating vitamin B12 (SMD: -0.11; 95% CI: -0.25 to 0.03; n = 17 studies, p = 0.13) and folate levels (SMD: -0.2; 95% CI: -0.68 to 0.27; n = 17 studies, p = 0.41) between patients with and without PCOS. CONCLUSIONS: (i) Patients with PCOS exhibited significantly higher homocysteine levels than those without, and (ii) no significant differences were observed in both vitamin B12 and folate levels in women with and without PCOS. REGISTRATION: PROSPERO ID (CRD42023432883).
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Ácido Fólico , Homocisteína , Síndrome del Ovario Poliquístico , Vitamina B 12 , Humanos , Síndrome del Ovario Poliquístico/sangre , Ácido Fólico/sangre , Femenino , Vitamina B 12/sangre , Homocisteína/sangreRESUMEN
Polycystic ovary syndrome (PCOS) is a prevalent gynecological-endocrinological disorder characterized by hyperandrogenism, menstrual irregularities, and metabolic disturbances. Recent research has highlighted the role of oxidative stress and chronic inflammation in exacerbating PCOS symptoms and impeding reproductive outcomes. Astaxanthin, a potent antioxidant found in marine organisms, has been suggested as a potential therapeutic intervention due to its ability to reduce oxidative stress and inflammation. This meta-analysis systematically reviews randomized controlled trials assessing the impact of astaxanthin supplementation on oxidative stress and reproductive outcomes in women with PCOS. Data from four trials were analyzed, focusing on markers of oxidative stress and reproductive health metrics. The meta-analysis utilized fixed and random-effects models to synthesize results, with heterogeneity assessed using Chi-square and I2 statistics. The findings indicate that while astaxanthin significantly improves markers of total antioxidant capacity (TAC) in follicular fluid, it does not show a consistent effect on other oxidative stress biomarkers such as malondialdehyde (MDA), catalase (CAT), or superoxide dismutase (SOD). Reproductive outcomes, including oocyte quality and the number of high-quality embryos, showed moderate improvements, although effects on fertilization rates and pregnancy outcomes were insignificant. The analysis highlights variability in study designs and dosing, suggesting a need for further research with standardized protocols and larger sample sizes. Future studies should focus on determining optimal dosing, exploring mechanistic pathways, and investigating the combined effects of astaxanthin with other interventions. Longitudinal studies are needed to assess long-term benefits and safety, and personalized approaches could enhance treatment efficacy for individuals with PCOS.
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CONTEXT: Polycystic ovary syndrome (PCOS) is often linked with obesity, and weight management can improve endocrine and cardiometabolic features. OBJECTIVE: To evaluate the effects of adding topiramate (TPM) to metformin (MTF) on weight control, hormonal and metabolic outcomes in women with PCOS. METHODS: In a randomized, double-blind, placebo-controlled trial, participants with PCOS and body mass index ≥30 kg/m² or ≥27 kg/m² associated with hypertension, type 2 diabetes, or dyslipidemia followed a 20 kcal/kg diet in addition to 850 mg of MTF or a previous MTF regimen. They were randomized to receive either TPM or placebo (P) alongside MTF. Anthropometric measurements, blood pressure, modified Ferriman-Gallwey score (mFGS), and adverse events were assessed every 4 weeks for 6 months. MAIN OUTCOME MEASURES: The primary endpoint was the percent change in body weight from baseline in both groups. Secondary endpoints included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features. RESULTS: Thirty-one participants were in the MTF+P group and 30 in the MTF+TPM group. The MTF+TPM group showed greater mean weight loss at 3 months (-3.4% vs. -1.6%, p=0.03) and 6 months (-4.5% vs. -1.4%, p=0.03). Both groups improved androgens, lipids, and psychosocial scores. Participants with ≥3% weight loss at 6 months improved mFGS (8.4 to 6.5, p=0.026). Paresthesia was more common in the MTF+TPM group (23.3% vs. 3.2%, p=0.026). CONCLUSIONS: Combining TPM with MTF and a low-calorie diet may be an effective, low-cost, easy-to-use, and safe strategy for weight management in women with PCOS, with mild adverse effects.
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BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogenous endocrine condition and combined oral contraceptives (COCs) have been demonstrated to be the first-line treatment to women who do not intend to become pregnant. The combination of COCs and PCOS may or may not amplify the risks of cardiovascular events. OBJECTIVE: To investigate whether surrogates for obesity may be influenced by the use of COCs containing different formulations in women with PCOS. METHOD: From January 2024 a literature search was conducted in Google Scholar and Pubmed databases using PCOS, COC, and obesity terms. Hand search of randomized clinical trials in the references of obtained manuscripts was also performed. After the exclusion of reviews and articles that did not fulfill eligibility criteria, compared the results obtained before and after the use of COCs in 13 randomized clinical trials (RCTs). Random-effects model was used to estimate the standardized mean differences (SMD) and standard errors (SE). Risk of bias was examined using the Rob2 tool. RESULT: Thirteen heterogeneous RCTs reported no difference in waist circumference with the use of different COC formulations (p = 0.714). On the contrary, body fat mass increased with the use of pill (p = 0.013). Waist triglyceride index and lipid accumulation product tended to be higher after the use of COCs (p = 0.073 and p = 0.064, respectively). CONCLUSION: Combined oral contraceptives with different formulations might increase fat mass accumulation in women with PCOS. Lipids may also be increased in PCOS users. Because some concerns about the quality and heterogeneity identified in various RCTs, caution should be taken before a definitive conclusion regarding the use of COCs and obesity.
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Anticonceptivos Orales Combinados , Obesidad , Síndrome del Ovario Poliquístico , Femenino , Humanos , Anticonceptivos Orales Combinados/administración & dosificación , Anticonceptivos Orales Combinados/efectos adversos , Obesidad/epidemiología , Obesidad/etiología , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Circunferencia de la Cintura/efectos de los fármacosRESUMEN
Objective: To identify the impact of redox imbalance on the clinical evolution of patients with polycystic ovary syndrome and carry out a qualitative and quantitative projection of the benefits of vitamin D supplementation. Data sources: Combinations of the keywords polycystic ovary syndrome, vitamin D, oxidative stress, reactive oxygen species, antioxidant, and free radicals were used in PubMed, Cochrane Library, LILACS, EMBASE, and Web of Science databases. The last search was conducted on August 22, 2023.Selection of studies: Based on the inclusion and exclusion criteria, studies were selected considering a low risk of bias, published in the last 5 years in English, which investigated the effects of vitamin D supplementation in women with PCOS, focusing on oxidative stress markers. Of the 136 articles retrieved, 6 intervention studies (445 women) were included. Data collection: The risk of bias in included studies was assessed using the Jadad scale, and analysis and visualization of continuous data were performed using Review Manager 5.4.1, summarized as standardized mean differences (SMD) with confidence intervals (CI) of 95%. Data synthesis: Vitamin D effectively reduced malondialdehyde (P=0.002) and total testosterone (P=0.0004) levels and increased total antioxidant capacity levels (P=0.01). Although possible improvements in the modified Ferriman-Gallwey hirsutism score, levels of sex hormone-binding globulin, and free androgen index were identified and the results were not statistically significant. Conclusion: Vitamin D is a promising alternative for the treatment of PCOS with a positive influence on the oxidative, metabolic, and endocrine disorders of this syndrome.
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Biomarcadores , Estrés Oxidativo , Síndrome del Ovario Poliquístico , Vitamina D , Femenino , Humanos , Biomarcadores/sangre , Suplementos Dietéticos , Irán , Estrés Oxidativo/efectos de los fármacos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/metabolismo , Vitamina D/sangre , Vitamina D/uso terapéutico , Vitaminas/uso terapéutico , Vitaminas/administración & dosificaciónRESUMEN
OBJECTIVE: To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and Polycystic Ovary Syndrome (PCOS) through a systematic review and meta-analysis. METHODS: The PubMed, EMBASE, Web of Science, Virtual Health Library, Scopus databases were searched using combinations of descriptors. Study quality was assessed using the Newcastle-Ottawa Scale. For data analysis, the results were grouped into PCOS group and NPCOS group (HPO axis immaturity). We performed a meta-analysis of raw data and the inverse variance method, employing the standardized mean difference, of the age at menarche and BMI of adolescents. RESULTS: Participants totaled 1,718 from nine selected studies. The meta-analysis showed that the PCOS group had a higher BMI than the NPCOS group (SMD 0.334; CI95% 0.073 - 0.595; p = .012). The degree of heterogeneity of the studies was approximately 40%. No significant difference in age at menarche (SMD - 0.027; CI95% -0.227 - 0.172; p = 0.790) and menstrual patterns was found, but amenorrhea was described only in adolescents with PCOS. CONCLUSIONS: The main characteristic in menstrual pattern that differentiated PCOS patients from girls with HPO axis immaturity was amenorrhea. Also, the BMI of PCOS patients was nearly one third higher than that of adolescents with HPO axis immaturity.
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Índice de Masa Corporal , Sistema Hipotálamo-Hipofisario , Menarquia , Síndrome del Ovario Poliquístico , Humanos , Síndrome del Ovario Poliquístico/fisiopatología , Síndrome del Ovario Poliquístico/complicaciones , Femenino , Adolescente , Menarquia/fisiología , Sistema Hipotálamo-Hipofisario/fisiopatología , Ovario/fisiopatología , Ciclo Menstrual/fisiologíaRESUMEN
Background/Purpose: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease most common in patients of childbearing age. This pathology is associated with clinical, metabolic, and reproductive complications. We evaluated the diversity of the vaginal microbiota (VM), the vaginal inflammatory reaction (VIR), the proinflammatory state, and the activation of polymorphonuclear neutrophils (PMN) with the production of neutrophil extracellular traps (NETs). Methods: Thirty-three patients who attended a consultation at the Hospital UTPL-Santa Inés, Loja, Ecuador, from May to August 2023 who were diagnosed with PCOS participated in this study. Blood samples, vaginal discharge, and a survey were obtained. Results: A high number of patients, 23/33 (69.7%), presented altered microbiota in clinical variables associated with PCOS phenotypes A and B, sexual partners (>2), and oligomenorrhoea. A significant statistical association was only observed for sexually transmitted infections at sampling (p = 0.023) and insulin (p = 0.002). All eight cases studied with VIR had PMN/NETotic activity. A high frequency of proinflammatory states was observed in all vaginal microbiota states. Conclusions: These results suggest that the PCOS could trigger a proinflammatory state in the vaginal epithelium independently of the state of the vaginal microbiota. Furthermore, the presence of NETs observed in the cases studied could decrease fertility in these PCOS patients.
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Background: Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder in women of reproductive age. Diagnosis is based on the evidence-based international guideline 2018 and the Rotterdam Consensus to classify PCOS phenotypes. This study aims to characterize the biodemographic, clinical, metabolic, and reproductive variables and their relationship with PCOS phenotypes in a population from the Ecuadorian Andes. Methodology: A cross-sectional study was conducted with a non-random consecutive sample of 92 women who attended the outpatient gynecology and endocrinology clinic at the Hospital of the Technical University of Loja (UTPL)-Santa Inés, Loja, Ecuador, between January 2022 and July 2023. Descriptive statistics, mean calculations, standard deviation, parametric and nonparametric tests, odds ratios (OR), confidence intervals (CI), and p-values were employed. Results: The average age was 22 ± 3.4 years, with a predominantly mestizo, urban, single, highly educated, and medium-high socioeconomic level population. It was identified that phenotypes A + B are at a higher risk of developing oligomenorrhea and hypertriglyceridemia compared to phenotypes C + D, with statistically significant differences (p < 0.05). Furthermore, in terms of reproductive variables, phenotypes A + B exhibit a significantly higher frequency of elevated anti-Müllerian hormone (AMH) compared to phenotypes C + D, also with statistical significance (p < 0.05). Conclusions: The classical phenotypes A and B of PCOS are the most common in Ecuadorian Andean women and carry a higher risk of insulin resistance, anovulation, metabolic disorders, and elevated triglyceride levels compared to phenotypes C and D. Ethnic diversity and sociocultural habits influence the prevalence and clinical manifestations of these phenotypes.
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OBJECTIVE: To study the combined and isolated effects of melatonin and metformin in the ovarian tissue of rats with PCOS. DESIGN: Experimental study using a rat model of PCOS induced by continuous light exposure. INTERVENTION(S): Forty adult female rats were divided into 5 groups: physiological estrus phase (Sham); permanente estrus with PCOS induced by continuous lighting exposure for 60 consecutive days (control); with PCOS treated with melatonin; with PCOS treated with metformin; with PCOS treated with melatonin + metformin. After 60 days of treatments, all rats were killed, and ovaries were collected and processed for paraffin-embedding. Formalin-fixed paraffin-embedded sections were stained with hematoxylin and eosin or subjected to immunohistochemistry for proliferation (Ki-67) and apoptosis (cleaved caspase 3) detection markers. SETTING: Federal University of São Paulo, Brazil. ANIMALS: Forty adult female Wistar rats (Rattus norvegicus albinus). MAIN OUTCOME MEASURE(S): Number of corpus luteum and ovarian cysts, number of ovarian follicles (primary and antral follicles), number of interstitial cells, percentage of ovarian follicles (primary and antral follicles), and of interstitial cells immunostained to cleaved caspase-3 and Ki-67. RESULTS: Absence of corpus luteum, a higher number of cysts, and increased nuclear volume and area of interstitial cells, along with a decrease in primary and antral follicle numbers, were noticed in the control group compared with the Sham group. Melatonin and metformin treatments attenuated these effects, although the combined treatment did not mitigate the increased number of cysts and ovaries induced by PCOS. An increase in theca interna cell apoptosis was observed in the control group, whereas melatonina and metformin treatments reduced it significantly. A higher percentage of caspase-3-immunostained granulosa cells was noted in the Sham and all treated groups compared with the control group; no aditive effects on ovarian cell apoptosis were observed in the combined treatment. The percentage of Ki-67- immunostained granulosa cells was significantly higher in the control group compared with the Sham group. However, the combined treatment, not melatonin and metformin alone, mitigated this effect. A higher percentage of Ki-67-immunostained interstitial cells was observed in all treated groups compared with the Sham and control groups, whereas no additive effects in that immunoreactivity were observed in the combined treatment. CONCLUSIONS: Melatonin and metformin may improve ovarian function in rats with PCOS. The combined melatonin and metformin treatment is more effective in attenuating excessive granulosa cell proliferation, but it is not more effective in improving ovarian function than these drugs applied alone in rats with PCOS.
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Melatonina , Metformina , Ovario , Síndrome del Ovario Poliquístico , Ratas Wistar , Animales , Femenino , Metformina/farmacología , Metformina/administración & dosificación , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/patología , Síndrome del Ovario Poliquístico/inducido químicamente , Melatonina/farmacología , Melatonina/administración & dosificación , Ovario/efectos de los fármacos , Ovario/patología , Ratas , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisisRESUMEN
Antimüllerian hormone (AMH) is a homodimeric glycoprotein secreted by granulosa cells from primary to large antral follicles, and it plays an important role in the regulation of early follicle growth. It is considered a reliable marker of ovarian reserve and a predictor of ovarian response to controlled stimulation. Polycystic ovary syndrome (PCOS) is an endocrine condition that affects women of reproductive age worldwide, and it is associated with high levels of AMH. PCOS patients may have worse maturation and fertilization rates compared to normo-ovulatory women. Some studies have demonstrated a positive correlation between AMH levels and qualitative aspects of assisted reproduction treatment; but it is not clear whether high levels of both serum and follicular fluid AMH in PCOS patients correlate with in vitro fertilization outcomes. We ran this scoping review of the literature to address this specific question. We comprehensively searched the databases PubMed and Cochrane Library until January 2023. We found that higher AMH levels are associated with higher oocyte yield, but PCOS patients tend to have fewer mature oocytes and impaired embryo quality and implantation rates. Pregnancy rates, however, are not affected by AMH levels or laboratorial outcomes. We also found that higher AMH levels are associated with worse PCOS features.
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Hormona Antimülleriana , Fertilización In Vitro , Síndrome del Ovario Poliquístico , Humanos , Síndrome del Ovario Poliquístico/sangre , Hormona Antimülleriana/sangre , Femenino , Fertilización In Vitro/métodos , Embarazo , Infertilidad Femenina/terapia , Infertilidad Femenina/sangre , Líquido Folicular/metabolismo , Índice de EmbarazoRESUMEN
Polycystic ovary syndrome (PCOS) is one of the most frequent endocrinopathology affecting women in their reproductive ages. However, PCOS is also related to metabolic abnormalities such as metabolic syndrome (MS), insulin resistance (IR), and type 2 diabetes, among others. Consequently, an inflammatory and pro-oxidative status is also present in these patients, aggravating the syndrome's symptoms. This work aims to discuss some late treatments that focus on oxidative stress (OS) as a central feature related to primary PCOS abnormalities. Therefore, this review focuses on the evidence of anti-oxidant diets, natural compounds, mineralocorticoids, and combined therapies for PCOS management. Oxidative stress (OS) is important in PCOS pathogenesis. In this regard, increased levels of oxidative oxygen species and decreased levels of anti-oxidant agents' impact PCOS's reproductive and metabolic features. In the last years, non-pharmacological therapies have been considered a first line of treatment. For these reasons, several natural compounds such as Kelult honey (KH), Foeniculum Vulgare, Calendula officinalis Linn, Eugenia caryophyllus and Myristicafragrans, vitamin C, vitamin E, selenium, zinc, beta-carotene, magnesium, curcumin, mineralocorticoids and melatonin alone or in combination are powerful anti-oxidant agents being used for PCOS management. Data presented here suggest that natural therapies are essential in managing both reproductive and metabolic features in PCOS patients. Due to the results obtained, these incipient therapies deserve further investigation.
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Polycystic ovary syndrome (PCOS) is a multifactorial disorder and obesity occurs in 38% to 88% of these women. Although hyperandrogenism may contribute to telomere lengthening, increased body mass index (BMI) is associated with telomere erosion. We sought to compare leukocyte telomere length (LTL) in PCOS women with normal, overweight, and obese BMI. We evaluated the relationship between LTL and clinical variables of PCOS and inflammatory biomarkers independent of BMI. A total of 348 women (243 PCOS and 105 non-PCOS) were evaluated for anthropometric measures, total testosterone, androstenedione, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting insulin and glycemia, lipid profile, homocysteine, C-reactive protein (CRP) and homeostatic model of insulin resistance (HOMA-IR). LTL was measured by qPCR. The PCOS group presented higher weight, waist circumference, BMI, testosterone, LH, fasting insulin, FAI, and HOMA-IR, and lower E2, SHBG, and fasting glycemia measures compared with the non-PCOS. When stratified by BMI, LTL was increased in all subgroups in PCOS compared to non-PCOS. However, in the PCOS group, LTL was lower in overweight (P = 0.0187) and obese (P = 0.0018) compared to normal-weight women. The generalized linear model showed that BMI, androstenedione, homocysteine, and CRP were associated with telomere biology. Women with PCOS had longer LTL, however, overweight or obesity progressively contributes to telomere shortening and may affect reproductive outcomes of PCOS, while androstenedione may increase LTL.
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Índice de Masa Corporal , Obesidad , Síndrome del Ovario Poliquístico , Acortamiento del Telómero , Humanos , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/metabolismo , Femenino , Obesidad/genética , Obesidad/sangre , Adulto , Adulto Joven , Resistencia a la Insulina , Telómero/metabolismo , Leucocitos/metabolismo , Biomarcadores/sangreRESUMEN
PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often linked to metabolic syndrome (MS), raising the risk of cardiovascular disease and type II diabetes. Certain indicators, such as the lipid accumulation product (LAP) and homeostatic model assessment for insulin resistance (HOMA-IR), can predict MS in PCOS patients. This study aimed to assess the predictive power of the visceral adiposity index (VAI) in comparison to LAP and HOMA-IR as predictors of MS in PCOS patients. METHODS: In this cross-sectional observational study, data from 317 diagnosed PCOS women were analyzed. VAI, LAP, and HOMA-IR were computed as indexes. Participants were categorized into two groups for index accuracy comparison: PCOS patients with and without MS. The data were assessed using a ROC curve. RESULTS: Among PCOS women with MS, 92.3% had abnormal VAI results, 94.5% had abnormal LAP results, and only 50.5% had abnormal HOMA-IR results. Conversely, the majority of PCOS women without MS had normal HOMA-IR (64.6%). When comparing these indexes using the ROC curve, VAI displayed the highest accuracy, followed by LAP and HOMA-IR. CONCLUSION: The VAI index proved to be a superior predictor of metabolic MS in PCOS women when compared to other indexes.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Síndrome Metabólico , Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/diagnóstico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/metabolismo , Adiposidad , Estudios Transversales , Índice de Masa CorporalRESUMEN
Physical activity is a first-line treatment for polycystic ovary syndrome (PCOS). Resistance or aerobic exercise improves metabolic complications, reproductive outcomes, and quality of life in PCOS. DNA methylation reprogramming during exercise may be the major modifier behind these changes. We sought to evaluate genome-wide DNA methylation changes after supervised resistance and aerobic exercise in women with PCOS. Exercises were performed in 56 women with PCOS (resistance, n = 30; aerobic, n = 26), for 16 weeks (wks), three times per week, in 50-minute to one-hour sessions. Anthropometric indices and hormonal and metabolic parameters were measured before and after training. Genome-wide leukocyte DNA methylation was analysed by Infinium Human MethylationEPIC 850K BeadChip microarrays (Illumina). Both resistance and aerobic exercise improved anthropometric indices, metabolic dysfunction, and hyperandrogenism in PCOS after the training programme, but no differences were observed between the two exercises. Resistance and aerobic exercise increased genome-wide DNA methylation, although resistance changed every category in the CpG island context (islands, shores, shelve, and open sea), whereas aerobic exercise altered CpG shores and the open sea. Using a stringent FDR (>40), 6 significantly differentially methylated regions (DMRs) were observed in the resistance exercise cohort and 14 DRMs in the aerobic cohort, all of which were hypermethylated. The increase in genome-wide DNA methylation may be related to the metabolic and hormonal changes observed in PCOS after resistance and aerobic exercise. Since the mammalian genome is hypermethylated globally to prevent genomic instability and ageing, resistance and aerobic exercise may promote health and longevity through environmentally induced epigenetic changes.
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Metilación de ADN , Síndrome del Ovario Poliquístico , Animales , Femenino , Humanos , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/terapia , Promoción de la Salud , Calidad de Vida , ADN , MamíferosRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by anovulation, hyperandrogenism, and polycystic ovarian morphology. Its etiology is uncertain and one of the hypotheses is that environmental factors, such as the bisphenol A (BPA) endocrine disruptor, may be involved. OBJECTIVE: To investigate the association between exposure to BPA and PCOS. SEARCH STRATEGY: Research was conducted focusing on studies published in English, Portuguese, and Spanish from January 2001 to March 2023 and available in Embase, Medline/PubMed, Rima, Lilacs, Scielo, Google academic, and SCI databases. SELECTION CRITERIA: Studies in humans that evaluated the association between exposure to BPA and a diagnosis of PCOS. DATA COLLECTION AND ANALYSIS: Following PRISMA guidelines, study characteristics and relevant data were extracted. MAIN RESULTS: Selection of 15 case-control and 7 cross-sectional studies with a total of 1682 PCOS patients. The studies were carried out in China, Poland, Turkey, Japan, Greece, Italy, the USA, Iran, Iraq, Egypt, India, Czechia, and Slovakia. A positive relationship between exposure to BPA and PCOS was described in19 studies (1391 [82.70%] of the PCOS patients). The fluids used in the studies were serum, urine, plasma, and follicular fluid. BPA was measured by ELISA and by chromatography (HPLC, HPLC-MS/MS, GC-MS, and GC-MS/MS). Diagnosis of PCOS used Rotterdam criteria in 15, NIH 1999 in 3, AE&PCOS Society in 2, similar to the Rotterdam criteria in 1, and criteria not informed in 1. Androgens were measured in 16 studies; in 12, hyperandrogenism was positively associated with BPA. BPA level was related to body mass index (BMI) in studies. In 15 studies independently of BMI, women with PCOS had higher BPA levels. Carbohydrate metabolism disorders were evaluated in 12 studies and in 6 a positive correlation was found with BPA levels. Lipid profile was evaluated in seven studies and in only one the correlation between lipid profile and BPA levels was present. CONCLUSIONS: Exposure to BPA is positively associated with PCOS, mainly with the hyperandrogenism.
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Compuestos de Bencidrilo , Disruptores Endocrinos , Fenoles , Síndrome del Ovario Poliquístico , Humanos , Femenino , Fenoles/efectos adversos , Fenoles/orina , Compuestos de Bencidrilo/efectos adversos , Compuestos de Bencidrilo/orina , Disruptores Endocrinos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
OBJECTIVE: To compare glycated hemoglobin (HbA1c) and the oral glucose tolerance test (OGTT) for the diagnosis of prediabetes and diabetes in young women with polycystic ovary syndrome (PCOS). PATIENTS AND DESIGN: This cross-sectional study included 154 women aged 20-40 years with a diagnosis of PCOS, who were screened for prediabetes and diabetes by the OGTT and HbA1c. Women with diabetes, hyperprolactinemia, thyroid or adrenal diseases, and anemia and users of hormonal contraception or corticosteroids were excluded. MEASUREMENTS: Clinical, biochemical and ultrasound data were collected from the electronic medical records. The women were classified as having normal glucose metabolism, prediabetes, or diabetes based on the diagnostic tests. Sensitivity and specificity were calculated and the Kappa method was used to assess agreement between the two methods. RESULTS: According to the OGTT and HbA1c values, 79.2% and 76% of the women were within the normal range, respectively, 16.8% and 19.5% had prediabetes, and 4% and 4.5% had diabetes (p > .05). The Kappa coefficient of 0.41 (95% confidence interval: 0.24-0.58) indicated medium agreement between methods. Considering the OGTT as the gold standard, the specificity of HbA1c was 89.5% and sensitivity was 85.7% in the diagnosis of prediabetes and 100% and 66.7%, respectively, in the diagnosis of diabetes. CONCLUSION: The HbA1c, when compared to the OGTT, showed high sensitivity and specificity in the diagnosis of prediabetes in young women with PCOS.
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Diabetes Mellitus , Síndrome del Ovario Poliquístico , Estado Prediabético , Femenino , Humanos , Estado Prediabético/diagnóstico , Hemoglobina Glucada , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/metabolismo , Estudios Transversales , Diabetes Mellitus/diagnóstico , GlucemiaRESUMEN
OBJECTIVE: In this narrative review, we discuss the current evidence as well as the knowledge gaps concerning assisted reproductive technology (ART) indications, protocols, and results in the presence of polycystic ovary syndrome (PCOS). METHODS: An electronic literature search was performed for English-language publications in the last decade in databases such as PubMed, Medline, the Web of Sciences, Embase, and Scopus. RESULTS: We found evidence that ovarian steroidogenesis and folliculogenesis are deeply altered by PCOS; however, the oocyte quality and pregnancy rates after ART are not affected. Patients with PCOS are more sensitive to the action of exogenous gonadotropins and more likely to develop ovarian hyperstimulation syndrome. This risk can be mitigated by the adoption of the gonadotropin-releasing hormone antagonist protocols for pituitary blockade and ovarian stimulation, along with frozen embryo transfer, without compromising the odds of achieving a live birth. Pregnancy complications, such as miscarriage, gestational diabetes, preeclampsia, and very preterm birth, are more frequent in the presence of PCOS, requiring more intense prenatal care. It remains uncertain whether weight reduction or insulin sensitizers used before ART are beneficial for the treatment outcomes. CONCLUSION: Although PCOS is not a drawback for ART treatments, the patients need special care to avoid complications. More in-depth studies are needed to uncover the mechanisms of follicular growth, gamete maturation, and endometrial differentiation during ART procedures in the presence of PCOS.
Asunto(s)
Infertilidad Femenina , Síndrome de Hiperestimulación Ovárica , Síndrome del Ovario Poliquístico , Nacimiento Prematuro , Embarazo , Femenino , Humanos , Recién Nacido , Síndrome del Ovario Poliquístico/complicaciones , Técnicas Reproductivas Asistidas/efectos adversos , Índice de Embarazo , Síndrome de Hiperestimulación Ovárica/complicaciones , Inducción de la Ovulación/efectos adversos , Inducción de la Ovulación/métodos , Infertilidad Femenina/complicaciones , Infertilidad Femenina/terapia , Fertilización In Vitro/efectos adversos , Fertilización In Vitro/métodosRESUMEN
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.
RESUMEN
Abstract Objective To identify the impact of redox imbalance on the clinical evolution of patients with polycystic ovary syndrome and carry out a qualitative and quantitative projection of the benefits of vitamin D supplementation. Data sources Combinations of the keywords polycystic ovary syndrome, vitamin D, oxidative stress, reactive oxygen species, antioxidant, and free radicals were used in PubMed, Cochrane Library, LILACS, EMBASE, and Web of Science databases. The last search was conducted on August 22, 2023.Selection of studies: Based on the inclusion and exclusion criteria, studies were selected considering a low risk of bias, published in the last 5 years in English, which investigated the effects of vitamin D supplementation in women with PCOS, focusing on oxidative stress markers. Of the 136 articles retrieved, 6 intervention studies (445 women) were included. Data collection The risk of bias in included studies was assessed using the Jadad scale, and analysis and visualization of continuous data were performed using Review Manager 5.4.1, summarized as standardized mean differences (SMD) with confidence intervals (CI) of 95%. Data synthesis Vitamin D effectively reduced malondialdehyde (P=0.002) and total testosterone (P=0.0004) levels and increased total antioxidant capacity levels (P=0.01). Although possible improvements in the modified Ferriman-Gallwey hirsutism score, levels of sex hormone-binding globulin, and free androgen index were identified and the results were not statistically significant. Conclusion Vitamin D is a promising alternative for the treatment of PCOS with a positive influence on the oxidative, metabolic, and endocrine disorders of this syndrome.