scholarly journals Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Han Zhao ◽  
Chuan Xing ◽  
Jiaqi Zhang ◽  
Bing He

Abstract Background Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS. Methods We identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed. Results Twenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + d-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31–93.58]). Myo-inositol + d-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + d-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: − 0.72 [95% CI (− 1.11)–(− 0.34)] to − 0.89 [95% CI (− 1.460)–(− 0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. Conclusions Ours is the first study to report that for women with PCOS, myo-inositol combined with d-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with d-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registration PROSPERO CRD42020211524

2021 ◽  
Author(s):  
Han Zhao ◽  
Chuan Xing ◽  
Jiaqi Zhang ◽  
Bing He

Abstract BackgroundMultiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS.MethodsWe identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed.ResultsTwenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with Myo-inositol + D-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31-93.58]). Myo-inositol + D-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: -0.72 [95% CI (-1.11)- (-0.34)] to -0.89 [95% CI (-1.460)- (-0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. ConclusionsOurs is the first study to report that for women with PCOS, Myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with D-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registrationPROSPERO CRD42020211524


2021 ◽  
Vol 12 ◽  
pp. 204201882110496
Author(s):  
Gurhan Guney ◽  
Mine Islimye Taskin ◽  
Ozgur Baykan ◽  
Ertan Adali ◽  
Selin Gul Tezcan ◽  
...  

Background: Polycystic ovary syndrome is known to be the most common hormonal disorder in women of reproductive age. Current evidence shows that regulatory proteins secreted from the adipose tissue called adipokines may have a role in polycystic ovary syndrome. We planned to investigate the role of endotrophin that has never been researched in polycystic ovary syndrome before and its correlation with other metabolic parameters and adipokines such as adiponectin and ghrelin in patients with polycystic ovary syndrome. Methods: Forty-three women ( n: 43) with polycystic ovary syndrome and 43 ( n: 43) women as a control group were enrolled in this cross-sectional study. Serum levels of endotrophin, adiponectin, and ghrelin levels were measured with the enzyme-linked immunosorbent assay method. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol levels, luteinizing hormone/follicle-stimulating hormone ratio, total testosterone, and triglyceride levels were measured. Homeostasis model assessment for insulin resistance index, body mass index, Ferriman Gallwey Score, and waist-to-hip ratio were also evaluated. Results: Total testosterone, homeostasis model assessment for insulin resistance, C-reactive protein, luteinizing hormone/follicle-stimulating hormone ratio, and triglyceride levels were higher in patients with polycystic ovary syndrome ( p < 0.01). No difference was detected between the groups in terms of body mass index, Ferriman Gallwey Score, waist-to-hip ratio, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels ( p > 0.05). We did not observe any significant difference in adiponectin and ghrelin levels between the groups ( p > 0.05). Patients with polycystic ovary syndrome had significantly higher endotrophin levels ( p < 0.01). According to our regression analyses [area under the curve: 0.973 (0.935–1.000), 95% confidence interval, 95.2% sensitivity, and 100% specificity], it was shown that endotrophin greater than 92 ng/ml and homeostasis model assessment for insulin resistance greater than 2.5 might be good predictors for polycystic ovary syndrome diagnosis. Conclusion: We demonstrated that endotrophin level is higher in patients with polycystic ovary syndrome and may have predicted polycystic ovary syndrome with increased homeostasis model assessment for insulin resistance index. There was no significant difference in adiponectin and ghrelin levels in the polycystic ovary syndrome group. Endotrophin may have a role in polycystic ovary syndrome etiology rather than other adipokines.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2003
Author(s):  
Risa Araki ◽  
Akira Yada ◽  
Hirotsugu Ueda ◽  
Kenichi Tominaga ◽  
Hiroko Isoda

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): −0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: −0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.


2020 ◽  
Vol 33 (7) ◽  
pp. 933-940 ◽  
Author(s):  
Pitchaya Satitpatanapan ◽  
Somchit Jaruratanasirikul ◽  
Hutcha Sriplung

AbstractBackgroundIn 2011, we described 64 girls diagnosed with central precocious puberty (CPP) during 1995–2009. In 2019, the former CPP patients were 16–30 years of age and had been followed-up for 6–20 years after cessation of gonadotropin-releasing hormone analog (GnRHa) treatment.ObjectivesTo determine the menstrual cycle, reproductive function, and long-term sequelae of the former GnRHa-treated and untreated CPP patients.MethodsSixty-seven former CPP women diagnosed during January 1995 to December 2010 were evaluated in 2019 for current menstrual cycle and pregnancy rate and for general health status, weight, height, blood pressure, and metabolic profiles of glucose, lipids, insulin, and testosterone.ResultsIn 2019, the former CPP women averaged 20.7 ± 2.7 years of age (range: 16.5–30). Eighty-three percent had a regular menstrual cycle. Of the 14 married women, six (43%) were fertile with 1–2 children. The untreated women had a significantly higher rate of obesity (BMI >25 kg/m2) than the GnRHa-treated women (72.1% vs. 36.6%, p < 0.01). Two women (3%) had polycystic ovary syndrome (PCOS). Fasting plasma glucose, serum high-density lipoprotein cholesterol (HDL-C), and testosterone levels were normal and similar between the GnRHa-treated and untreated participants. The serum insulin, cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and homeostasis model assessment-insulin resistance (HOMA-IR) levels were higher in the untreated group than the GnRHa-treated group, but without significant differences.ConclusionsAt a 10–20-year follow-up, our former CPP patients had regular menstruation, normal reproductive function, and normal metabolic outcomes. The low prevalence of PCOS of 3% suggests that CPP is not a risk factor for PCOS, at least during early adulthood.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hong Gao ◽  
YanTao Li ◽  
WenNan Yan ◽  
Fei Gao

Purpose. Studies have found that vitamin D supplementation may improve blood lipids in patients with polycystic ovary syndrome, but the results are controversial, so this study will further analyze the effect of vitamin D supplementation on blood lipids in patients with polycystic ovary syndrome. Methods. PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched up to May 2020, to identify randomized controlled trials of the effect of vitamin D supplementation on blood lipids in patients with polycystic ovary syndrome. The Cochrane risk of bias tool was applied to assess the risk of bias, and RevMan5.3 software was used for statistical analysis. Results. Ten studies were included in this study, including 543 subjects. The results of the meta-analysis showed that, compared with placebo, vitamin D supplementation can significantly reduce total cholesterol level (WMD = –11.32, 95% CI = [–14.51, –8.41], P < 0.00001 ), low-density lipoprotein cholesterol level (WMD = –4.83, 95% CI = [–7.52, –2.14], P = 0.0004 ), and triglyceride level (WMD = –8.23, 95% CI = [–13.08, –3.38], P = 0.0009 , but the effect on high-density lipoprotein cholesterol level is not statistically significant (WMD = –0.32, 95%CI = [–1.24, 0.60], P = 0.50 ). Conclusion. Vitamin D supplementation can significantly reduce total cholesterol, low-density lipoprotein cholesterol, and triglycerides in patients with polycystic ovary syndrome. However, it has no significant effect on high-density lipoprotein cholesterol.


2020 ◽  
Vol 48 (8) ◽  
pp. 030006052093531
Author(s):  
Bihui Jin ◽  
Lingbo Qian ◽  
Xiaohua Fu ◽  
Jing Zhu ◽  
Jing Shu

Objective Observational studies have shown that circulating vitamin D (VitD) deficiency is associated with atherogenic lipid patterns among polycystic ovary syndrome (PCOS) patients. However, interventional studies have shown inconsistent results. The aim of this meta-analysis was to investigate how VitD supplementation influences lipid indices in PCOS patients. Methods The authors searched four electronic databases through August 2019 to identify randomized controlled trials (RCTs) that assessed the effect of VitD intervention on serum lipids among PCOS patients. Mean differences were generated for statistical evaluation. Results We included eight studies and performed nine comparisons across 467 participants. VitD supplementation reduced serum triglyceride levels (−11.88 mg/dL; 95% confidence interval [CI]: −17.03 to −6.73), total cholesterol (−9.09 mg/dL; 95% CI: −14.90 to −3.29), low-density lipoprotein cholesterol (−5.22 mg/dL; 95% CI: −10.32 to −0.13), and very-low-density lipoprotein cholesterol (−2.43 mg/dL; 95% CI: −3.69 to −1.17) compared with no VitD supplementation. However, high-density lipoprotein cholesterol levels showed no differences with or without VitD supplementation (−0.39 mg/dL; 95% CI: −1.39 to 0.61). Conclusions VitD supplementation improved serum lipid levels among PCOS patients, but serum high-density lipoprotein cholesterol levels were not changed. VitD intervention might benefit PCOS patients who are at high risk of an atherogenic lipid profile.


2009 ◽  
Vol 34 (6) ◽  
pp. 1032-1039 ◽  
Author(s):  
Nan F. Li ◽  
Hong M. Wang ◽  
Jin Yang ◽  
Ling Zhou ◽  
Xiao G. Yao ◽  
...  

The prevalence of hyperuricemia is low in Uygurs, who have a high prevalence of cardiovascular risk factors such as hypertension, overweight–obesity, dyslipidemia, hyperglycemia, and insulin resistance (IR). This study sought to investigate the relationships between serum uric acid (UA) and these risk factors in this population. A cross-sectional study was conducted in Uygurs (859 males, 1268 females) aged 20 to 70 years. Demographic data, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and fasting and postprandial blood were obtained, and biological measurements were determined. The mean of BMI, SBP, DBP, total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides, fasting blood glucose, fasting insulin, and homeostasis model assessment insulin resistance index (HOMA-IR), and the prevalence of hypertension, IR, hyperglycemia, overweight–obesity, hypercholesteremia, hyper-LDL-c, and hypertriglyceridemia increased with UA but the prevalence of hypo-HDL-c decreased (p < 0.05). Logistic regression analysis showed that the odds ratios for IR, overweight–obesity, hypercholesteremia, hyper-LDL-c, and hypertriglyceridemia against the lowest UA group increased but decreased for hypo-HDL-c (p < 0.05). The UA in the hypo-HDL-c group was lower than that of the controls; the prevalence of hypo-HDL-c in hyperuricemia subjects was lower than in those with normal UA (p < 0.05). But the opposite results were observed between overweight–obesity, hyperglycemia, IR, hypercholesteremia, hypertriglyceridemia, and hyper-LDL-c and correspondence controls, respectively (p < 0.05). In Uygur, elevated UA is associated with overweight–obesity, hypercholesteremia, hyper-LDL-c, hypertriglyceridemia, hyperglycemia, and IR. The HDL-c level significantly increases with UA, whereas the prevalence of hypo-HDL-c decreases. Further studies are needed to clarify why UA is positively correlated to HDL-c.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Wenjuan Shen ◽  
Bao Jin ◽  
Yaguang Han ◽  
Hongwei Wang ◽  
Huan Jiang ◽  
...  

Objective. Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. As a traditional medicine, Salvia miltiorrhiza (S. miltiorrhiza) has been widely used in the treatment of many gynecological diseases, but the efficacy of S. miltiorrhiza in women with PCOS has not been assessed. The purpose of this systematic review and meta-analysis was to evaluate the effectiveness and safety of S. miltiorrhiza in women with PCOS. Methods. We conducted searches in PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Wanfang Database, the Chinese Scientific Journal Database, and the Chinese BioMedical database from inception to December 23, 2020, to identify studies that met the inclusion criteria. The quality of the evidence was estimated using the Cochrane Reviewer Handbook 5.0.0, and the meta-analysis was performed using RevMan 5.3.5 software. Results. Six randomized controlled trials (RCTs) involving 390 patients with PCOS were included. The studies suggested that S. miltiorrhiza extract combined with letrozole (LET) was more effective in improving pregnancy rate (RR: 2.60, 95% CI: 1.06 to 6.39, P = 0.04 ) compared to LET alone. S. miltiorrhiza extract was associated with decreased fasting blood glucose (MD: –0.25, 95% CI: –0.37 to –0.13, P < 0.0001 ), fasting insulin (MD: –1.16, 95% CI: –1.74 to –0.58, P < 0.0001 ), total cholesterol (TC) (MD: –0.58, 95% CI: –0.72 to –0.43, P < 0.00001 ), and triglycerides (TG) (MD: –0.31, 95% CI: –0.35 to –0.26, P < 0.00001 ) compared with placebo, but not with improvements in body mass index or waist-to-hip ratio (MD: –1.41, 95% CI: –4.81 to 2.00, P = 0.42 ; MD: –0.02, 95% CI: –0.05 to 0.01, P = 0.16 , respectively). There was a significant difference between S. miltiorrhiza extract combined with cyproterone acetate (CPA) and CPA alone in terms of decreasing TC (MD: –0.77, 95% CI: –0.89 to –0.65, P < 0.00001 ), TG (MD: –0.43, 95% CI: –0.65 to –0.20, P < 0.0001 ), and low-density lipoprotein cholesterol (MD: –0.49, 95% CI: –0.66 to –0.33, P < 0.00001 ) and increasing high-density lipoprotein cholesterol (MD: 0.30, 95% CI: 0.20, 0.40, P < 0.00001 ). In addition, S. miltiorrhiza extract also decreased testosterone, follicle-stimulating hormone, and luteinizing hormone. The studies did not mention any adverse events with S. miltiorrhiza extract. Conclusion. The current studies indicate that S. miltiorrhiza has beneficial effects on reproduction and glucose and lipid metabolism in patients with PCOS, and it is generally safe for clinical application. However, more prospective RCTs with large samples, multiple centers, and longer intervention duration are needed in the future to obtain more reliable conclusions.


2022 ◽  
Author(s):  
Jing Xia ◽  
Yiqing Yang ◽  
Zhe Yang ◽  
Gengxiang Wu ◽  
Jing Yang

Abstract Previous studies have shown that ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) may be an inhibitor of the insulin signalling pathway, and insulin resistance (IR) is believed to be the core mechanism in the pathophysiology of polycystic ovary syndrome (PCOS). This study was aimed to investigate the expression of ENPP1 in different tissues of PCOS rats and to analyse its potential role in the pathophysiology of PCOS. Eighteen 23-day-old Sprague-Dawley rats were divided into PCOS and control groups (n= 9/group). Samples were collected after 20 days. Pathological examination and immunofluorescence were performed. Western blotting results of ENPP1 in the ovaries were analysed. Serum levels of ENPP1, hormones, fasting blood glucose (FBG), serum lipids were measured. Levels of ENPP1, testosterone (T), FBG, fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR), free fatty acids (FFAs), leptin, cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in PCOS group, while adiponectin (ADP) and high-density lipoprotein cholesterol (HDL-C) were significantly lower. Spearman’s rank correlation analysis showed that ENPP1 was correlated with T, HOMA-IR, FFAs, leptin, serum lipids and ADP. MRNA levels of ENPP1, BAX, and IRS1 were higher in the ovaries, skeletal muscle, subcutaneous fat, and visceral fat of PCOS rats, and the protein expression of ENPP1 was significantly higher in the ovaries. Our results revealed that ENPP1 is highly associated with IR and lipid metabolism-related molecules, which may have play important roles in PCOS pathophysiological changes.


2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Xiaoshuai Zhang ◽  
Yang Zheng ◽  
Yanan Guo ◽  
Zhiwen Lai

Objective. To assess the effect of a low carbohydrate diet (LCD) on women with polycystic ovary syndrome (PCOS). Methods. Data from randomized controlled trials (RCTs) were obtained to perform a meta-analysis of the effects of LCD in PCOS patients. The primary outcomes included the changes in BMI, homeostatic model assessment for insulin resistance (HOMA-IR), and blood lipids, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), follicle-stimulating hormone (FSH), luteotropic hormone (LH), total testosterone (T), and sex hormone-binding globulin (SHBG). Results. Eight RCTs involving 327 patients were included. In comparison with the control group, the LCD decreased BMI (SMD = −1.04, 95% CI (−1.38, −0.70), P<0.00001), HOMA-IR (SMD = −0.66, 95% CI (−1.01, −0.30), P<0.05), TC (SMD = −0.68, 95% CI (−1.35, −0.02), P<0.05), and LDL-C (SMD = −0.66, 95% CI (−1.30, −0.02), P<0.05). Stratified analyses indicated that LCD lasting longer than 4 weeks had a stronger effect on increasing FSH levels (MD = 0.39, 95% CI (0.08, 0.71), P<0.05), increasing SHBG levels (MD = 5.98, 95% CI (3.51, 8.46), P<0.05), and decreasing T levels (SMD = −1.79, 95% CI (−3.22, −0.36), P<0.05), and the low-fat and low-CHO LCD (fat <35% and CHO <45%) had a more significant effect on the levels of FSH (MD = 0.40, 95% CI (0.09, 0.71), P<0.05) and SHBG (MD = 6.20, 95% CI (3.68, 8.72), P<0.05) than the high-fat and low-CHO LCD (fat >35% and CHO <45%). Conclusion. Based on the current evidence, LCD, particularly long-term LCD and low-fat/low-CHO LCD, may be recommended for the reduction of BMI, treatment of PCOS with insulin resistance, prevention of high LDL-C, increasing the levels of FSH and SHBG, and decreasing the level of T level. Together, the analyzed data indicate that proper control of carbohydrate intake provides beneficial effects on some aspects of PCOS and may represent one of the important interventions improving the clinical symptoms of affected patients.


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