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Frontiers in Nutrition 2023Polycystic ovary syndrome (PCOS) is a common endocrine disease, often accompanied by metabolic disorders. Metformin, as an insulin sensitizer, is widely used to improve...
OBJECTIVES
Polycystic ovary syndrome (PCOS) is a common endocrine disease, often accompanied by metabolic disorders. Metformin, as an insulin sensitizer, is widely used to improve the metabolic function of PCOS, but may have gastrointestinal side effects. Emerging evidence suggests that N-acetylcysteine (NAC) improves metabolic parameters in PCOS and may be a potential alternative to metformin.
METHODS
We searched four online databases, PubMed, Embase, Web of Science, and Cochrane Library, from inception to April 1, 2023. The statistic and Cochrane's Q test were employed to determine heterogeneity between studies, with an value >50% or < 0.1 considered significant. The data were expressed as standardized mean differences and corresponding 95% confidence intervals.
RESULTS
A total of 11 randomized controlled trials were included in the final analysis, including 869 women with PCOS. The results showed that NAC caused more changes in body mass index (SMD: -0.16, 95% CI: -0.40 to 0.08), body weight (SMD: -0.25, 95% CI: -0.50 to 0.00), fasting insulin (SMD: -0.24, 95% CI: -0.53 to 0.06), ratio of fasting blood glucose to fasting insulin (SMD: 0.38, 95% CI: -0.33 to 1.08), total cholesterol (SMD: -0.11, 95% CI: -0.39 to 0.17), triglycerides (SMD: -0.18, 95% CI: -0.63 to 0.28), and low-density lipoprotein (SMD: -0.09, 95% CI: -0.51 to 0.33) compared with metformin. Compared with metformin or placebo, NAC significantly reduced fasting blood-glucose levels (SMD: -0.23, 95% CI: -0.43 to -0.04; SMD: -0.54, 95% CI: -1.03 to -0.05, respectively). In addition, NAC significantly reduced total cholesterol (SMD: -0.74, 95% CI: -1.37 to -0.12), and this effect was observed when NAC was compared with placebo. However, NAC reduced HDL levels in women with PCOS compared with metformin (SMD: -0.14, 95% CI: -0.42 to 0.14).
CONCLUSION
This study suggests that NAC is effective in improving metabolic parameters in PCOS and may be a promising nutritional supplement for the treatment of PCOS.https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=415172, identifier CRD42022339171.
PubMed: 37841396
DOI: 10.3389/fnut.2023.1209614 -
Medicine Oct 2023The optimal drug for treatment with polycystic ovary syndrome (PCOS) was in debate. We did this network meta-analysis to assess the efficacy and safety of different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal drug for treatment with polycystic ovary syndrome (PCOS) was in debate. We did this network meta-analysis to assess the efficacy and safety of different drugs for reducing testosterone levels in women with PCOS.
METHODS
We searched studies from inception until January 10, 2023, through PubMed, Embase, and Cochrane Library database. All studies comparing different drugs for reducing testosterone levels in women with polycystic ovary syndrome were included in this network meta-analysis. Outcomes were total testosterone levels, free testosterone levels, and withdraw due to adverse events. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment.
RESULTS
Finally, a total of 13 studies were finally included in this network meta-analysis. In head-to-head comparison, atorvastatin (WMD -3.1, 95% CrI: -3.7 to -2.5), metformin (WMD -2.6, 95% CrI: -3.5 to -1.6), metformin + simvastatin (WMD -2.8, 95% CrI: -4.1 to -1.5), simvastatin (WMD -2.7, 95% CrI: -4.2 to -1.3), spironolactone (WMD -3.1, 95% CrI: -4.3 to -1.9), spironolactone + metformin (WMD -3.2, 95% CrI: -4.5 to -2.0) were all more effective than the placebo, and the difference was statistically significant (P < .05). The SUCRA shows that spironolactone + metformin ranked first (SUCRA, 85.0%), Atorvastatin ranked second (SUCRA, 77.7%), Spironolactone ranked third (SUCRA, 77.2%), and metformin + simvastatin ranked the fourth. The SUCRA of different drugs for free testosterone levels shows that atorvastatin ranked first (SUCRA, 75.0%), spironolactone + metformin ranked second (SUCRA, 5.3%), metformin + simvastain ranked third (SUCRA, 62.6%), and spironolactone ranked the fourth (SUCRA, 56.4%). No statistically significant differences were found between the 2 treatment groups for withdrawn due to adverse events (P > .05).
CONCLUSIONS
Considering the network meta-analysis and rankings, atorvastatin was recommended to be the optimal drug for treatment PCOS. However, the optimal dose of atorvastatin was unknown and should be verified by more randomized controlled trials.
Topics: Humans; Female; Spironolactone; Atorvastatin; Network Meta-Analysis; Polycystic Ovary Syndrome; Metformin; Simvastatin; Testosterone
PubMed: 37832133
DOI: 10.1097/MD.0000000000035152 -
Frontiers in Nutrition 2023Synbiotics, refer to a combination of probiotics and prebiotics in a form of synergism that beneficially affect the host's health by alternating the composition and/or...
BACKGROUND
Synbiotics, refer to a combination of probiotics and prebiotics in a form of synergism that beneficially affect the host's health by alternating the composition and/or function of the gut microbiota. Numerous meta-analyses of randomized clinical trials have proven that pro, pre-, and synbiotics supplementation has health outcomes in women with polycystic ovary syndrome (PCOS). However, the strength and quality of this evidence in aggregate have not yet been synthesized in great detail.
METHODS
PubMed, Scopus, Web of Sciences, and Google Scholar were searched up to March 2023. We pooled the mean difference and its 95% confidence interval (CI) by applying a random-effects model.
RESULTS
Overall, nine meta-analyses including a total of 12 trials were identified. The results of the present study indicated that probiotic supplementation significantly reduced the homeostatic model assessment for insulin resistance (HOMA-IR; WMD: -0.29, 95% CI: -0.57 to -0.02, = 0.03, = 4; moderate certainty) and fasting glucose concentration (FGC; WMD: -7.5 mg/dL, 95% CI: -13.60 to -0.51, = 0.03; = 4; low certainty). Moreover, synbiotic supplementation had beneficial effects on glycemic control, lipid profile, and hormonal parameters, but the certainty of the evidence was rated as low to very low. However, supplementation with pro-/synbiotics did not affect inflammation and oxidative stress in women with PCOS. Furthermore, waist/hip circumference, fasting glucose concentration, lipid profile, dehydroepiandrosterone sulfate, high-sensitivity C-reactive protein, and hirsutism score were significantly reduced after prebiotics supplementation with low certainty of evidence.
CONCLUSION
Although pro-, pre-, and synbiotics supplementation had beneficial effects on some PCOS-related outcomes, the certainty of the evidence was rated as low to very low. Therefore, further well-designed RCTs might help to confirm our findings in women with PCOS.
PubMed: 37829729
DOI: 10.3389/fnut.2023.1178842 -
Frontiers in Endocrinology 2023Polycystic ovary syndrome (PCOS) is a common endocrinopathy causing infertility in childbearing women. Progestin-primed ovarian stimulation (PPOS) protocol has recently... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Polycystic ovary syndrome (PCOS) is a common endocrinopathy causing infertility in childbearing women. Progestin-primed ovarian stimulation (PPOS) protocol has recently been used for infertile women. However, whether PPOS provides a significant benefit over gonadotropin-releasing hormone (GnRH) analogue protocols in PCOS is still controversial. The objective of this systematic review is to investigate the efficacy of PPOS in patients with PCOS during fertilization (IVF) or intracytoplasmic sperm injection (ICSI). We searched Medline, Embase, Google Scholar, ClinicalTrials, and Cochrane Central Register of Controlled Trials from inception to April 1, 2023. Randomized controlled trials (RCTs) and observational studies comparing the efficacy between PPOS and conventional GnRH analogue protocols in patients with PCOS in English were included. The primary outcomes included live birth rate, the incidence of moderate or severe ovarian hyperstimulation syndrome (OHSS), and the number of metaphase II oocytes. The pooled estimates were calculated using the random-effects models as odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CIs). Three RCTs and six cohort studies involving 2289 patients were included. Results from RCTs suggest that PPOS leads to no significant difference in the risk of OHSS, the number of metaphase II oocytes, or the rate of live birth when compared to GnRH analogue protocols. The pooling estimates of cohort studies showed consistent results. Additionally, in cohort studies, PPOS required a higher dose of Gn and tended to improve the implantation rate, clinical pregnancy rate, and ongoing pregnancy rate. For subgroup analyses, the higher implantation rate, clinical pregnancy rate, and ongoing pregnancy rate were found in PPOS compared to the GnRH agonist short protocol. However, the certainty of the evidence for the outcomes was generally low. Overall, There is currently no evidence to support that PPOS could reduce the risk of OHSS, increase oocyte maturation, or improve pregnancy outcomes in women with PCOS undergoing IVF/ICSI when compared to GnRH analogue protocols. Considering its efficiency and safety, this protocol could be a patient-friendly and viable alternative for PCOS patients, especially when frozen-thawed embryo transfer is planned. Future high-quality randomized trials with children's long-term safety and cost-effective analyses are still required.
SYSTEM REVIEW REGISTRATION
NPLASY (202340059). https://inplasy.com/inplasy-2023-4-0059/.
Topics: Female; Humans; Pregnancy; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Progestins; Steroids
PubMed: 37795363
DOI: 10.3389/fendo.2023.1224858 -
Communications Medicine Oct 2023Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to...
BACKGROUND
Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with responses to interventions in gestational diabetes mellitus (GDM) prevention.
METHODS
We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022.
RESULTS
From 10347 studies, 116 studies (n = 40940 women) are included. Physical activity results in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60]). Combined diet and physical activity interventions result in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78-1.61]) and in those without a history of GDM than those with unspecified GDM history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95]). Metformin interventions are more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43]), or when commenced preconception than during pregnancy (0.21 [0.11, 0.40] vs 1.15 [0.86-1.55]). Parity, history of having a large-for-gestational-age infant or family history of diabetes have no effect on intervention responses.
CONCLUSIONS
GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results disaggregated by a priori defined participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions.
PubMed: 37794119
DOI: 10.1038/s43856-023-00366-x -
Frontiers in Endocrinology 2023Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and remains widely underdiagnosed leading to significant morbidity....
INTRODUCTION
Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and remains widely underdiagnosed leading to significant morbidity. Artificial intelligence (AI) and machine learning (ML) hold promise in improving diagnostics. Thus, we performed a systematic review of literature to identify the utility of AI/ML in the diagnosis or classification of PCOS.
METHODS
We applied a search strategy using the following databases MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Web of Science, and the IEEE Xplore Digital Library using relevant keywords. Eligible studies were identified, and results were extracted for their synthesis from inception until January 1, 2022.
RESULTS
135 studies were screened and ultimately, 31 studies were included in this study. Data sources used by the AI/ML interventions included clinical data, electronic health records, and genetic and proteomic data. Ten studies (32%) employed standardized criteria (NIH, Rotterdam, or Revised International PCOS classification), while 17 (55%) used clinical information with/without imaging. The most common AI techniques employed were support vector machine (42% studies), K-nearest neighbor (26%), and regression models (23%) were the commonest AI/ML. Receiver operating curves (ROC) were employed to compare AI/ML with clinical diagnosis. Area under the ROC ranged from 73% to 100% (n=7 studies), diagnostic accuracy from 89% to 100% (n=4 studies), sensitivity from 41% to 100% (n=10 studies), specificity from 75% to 100% (n=10 studies), positive predictive value (PPV) from 68% to 95% (n=4 studies), and negative predictive value (NPV) from 94% to 99% (n=2 studies).
CONCLUSION
Artificial intelligence and machine learning provide a high diagnostic and classification performance in detecting PCOS, thereby providing an avenue for early diagnosis of this disorder. However, AI-based studies should use standardized PCOS diagnostic criteria to enhance the clinical applicability of AI/ML in PCOS and improve adherence to methodological and reporting guidelines for maximum diagnostic utility.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022295287.
Topics: Female; Humans; Artificial Intelligence; Polycystic Ovary Syndrome; Proteomics; Machine Learning; Cluster Analysis
PubMed: 37790605
DOI: 10.3389/fendo.2023.1106625 -
Endokrynologia Polska 2023There have been many studies assessing whether abnormal metabolic and hormone levels among women with polycystic ovary syndrome (PCOS) are associated with a greater risk... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
There have been many studies assessing whether abnormal metabolic and hormone levels among women with polycystic ovary syndrome (PCOS) are associated with a greater risk of non-alcoholic fatty liver disease (NAFLD). However, previous studies repported no consistent outcomes. To provide a comprehensive evaluation regarding the role of PCOS in the risk of NAFLD, we updated the published literature and conducted this systemic review and meta-analysis.
MATERIAL AND METHODS
Electronic databases (Web of Science and PubMed) were searched for literature up to October 2022. We used STATA 12.0 software to compute odds ratios (ORs) and 95% confidence intervals (CIs), to evaluate the association between PCOS and risk of NAFLD.
RESULTS
The study indicated that PCOS was significantly related to an elevated risk of NAFLD (OR = 2.93, 95% CI 2.38 to 3.62, I2 = 83.7%, p < 0.001). Meta-regression analysis showed that age and body mass index (BMI) were not responsible for heterogeneity across the studies (age: p = 0.096; BMI: p = 0.418). Sensitivity analysis indicated no alteration in the direction of effect when any study was eliminated. Begg's test, Egger's test, Begg's test, and funnel plot indicated a significant risk of publication bias (Egger's test: p = 0.028; Begg's test: p < 0.001).
CONCLUSION
This meta-analysis reported that PCOS was associated with an elevated risk of NAFLD. Early proper detection of NAFLD for PCOS women is essential. All patients with PCOS should undergo appropriate diagnostics for early detection of fatty liver and fibrosis.
Topics: Humans; Female; Polycystic Ovary Syndrome; Non-alcoholic Fatty Liver Disease; Risk Factors
PubMed: 37779372
DOI: 10.5603/ep.93291 -
Reproductive Toxicology (Elmsford, N.Y.) Oct 2023Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women, may involve both environmental and genetic factors. One potential environmental...
Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women, may involve both environmental and genetic factors. One potential environmental factor of concern is exposure to phthalates and other endocrine disrupting chemicals many of which have adverse effects on the female reproductive system. The aim of this systematic review was to evaluate possible association between prenatal phthalate exposure and PCOS. Six databases were searched for relevant human studies. Inclusion criteria were female human population diagnosed with PCOS and exposed during any lifestage to any phthalate or phthalate metabolite through oral, dermal, inhalation, or intravenous route. Search results were screened for relevance, and studies that met the inclusion criteria were evaluated for study quality using Joanna Briggs Institute (JBI) critical appraisal tools. The systematic literature search yielded seven articles, six case-control studies and one cohort study. Three studies found a significant positive association, two studies found a significant negative association, and two studies found no association between phthalate exposure and the incidence of PCOS. Even though studies found no consistent pattern on association with phthalates and PCOS, the results of analyzed studies did not exclude possible effects of phthalates on the female reproductive and metabolic system. Some of the factors in study design such as recruiting participants from IVF clinics and young age of participants may have biased the results. Further studies with more careful study design and longer follow-up time are needed to bring more reliable information about the role of phthalates in onset of PCOS.
PubMed: 37741514
DOI: 10.1016/j.reprotox.2023.108473 -
Frontiers in Endocrinology 2023Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer,... (Meta-Analysis)
Meta-Analysis
AIMS
Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer, combined with spironolactone, an antiandrogen medication, may exert complementary effects on PCOS. We therefore performed a meta-analysis of trials in which metformin combined with spironolactone was applied to treat PCOS to evaluate the efficacy and safety of the combination therapy.
METHODS
We retrieved the PubMed, Embase, Scopus, Cochrane Library, CNKI, CBM, Wangfang, and VIP databases for literatures published from their inception to December 16, 2022 on the effects of metformin combined with spironolactone in the treatment of PCOS. Inclusion criteria according to P.I.C.O.S criteria were: PCOS patients, metformin combined with spironolactone interventions, metformin alone control group, and randomized controlled trials with the following outcome data: body mass index (BMI), hirsutism score, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and side effects including nausea, vomiting, diarrhea and drug withdrawal.
RESULTS
Our results revealed that metformin combined with spironolactone significantly reduced BMI and TT, but that it exerted no significant effects on hirsutism score, or on FSH or LH concentrations. Combined treatment also resulted in a significant diminution in FBG and insulin resistance using the HOMA-IR when the interventional time was greater than 6 months. In addition, the combination did not have a higher occurrence of adverse reactions than metformin alone.
CONCLUSION
Compared with metformin alone, metformin combined with spironolactone therapy may be more effective in reducing BMI and serum androgen levels, but the combination showed no significant effect on the hirsutism score or gonadotropin hormone levels, and was not associated with an elevation in side-effects. Moreover, when the treatment course was greater than 6 months, combination therapy reduced FBG and improved insulin resistance more effectively than metformin alone. However, more research is needed to determine the most effective course of treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022355515.
Topics: Female; Humans; Hirsutism; Insulin Resistance; Polycystic Ovary Syndrome; Spironolactone; Drug-Related Side Effects and Adverse Reactions; Follicle Stimulating Hormone, Human; Luteinizing Hormone
PubMed: 37635987
DOI: 10.3389/fendo.2023.1223768 -
Genes Aug 2023Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs)...
Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs) contribute to the occurrence of metformin side effects. The aim of the present study was to identify intronic genetic variants modifying the occurrence of metformin side effects and to replicate them in individuals with T2DM and in women with PCOS. We performed Next Generation Sequencing (Illumina Next Seq) of 115 SNPs in a discovery cohort of 120 metformin users and conducted a systematic literature review. Selected SNPs were analysed in two independent cohorts of individuals with either T2DM or PCOS, using 5'-3'exonucleaseassay. A total of 14 SNPs in the organic cation transporters (OCTs) showed associations with side effects in an unadjusted binary logistic regression model, with eight SNPs remaining significantly associated after appropriate adjustment in the discovery cohort. Five SNPs were confirmed in a combined analysis of both replication cohorts but showed different association patterns in subgroup analyses. In an unweighted polygenic risk score (PRS), the risk for metformin side effects increased with the number of risk alleles. Intronic SNPs in the OCT cluster contribute to the development of metformin side effects in individuals with T2DM and in women with PCOS and are therefore of interest for personalized therapy options.
Topics: Female; Humans; Polymorphism, Single Nucleotide; Metformin; Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Introns; Membrane Transport Proteins; Polycystic Ovary Syndrome
PubMed: 37628660
DOI: 10.3390/genes14081609