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Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS.

ABSTRACT: OBJECTIVE:To evaluate the efficacy of insulin sensitizers on menstrual frequency, sex hormone, and metabolic parameters in overweight women with polycystic ovary syndrome (PCOS). METHODS:We searched multiple databases from inception to September 2019 for randomized controlled trials. Network meta-analysis was conducted using multivariate random effects method. RESULTS:Fourteen trials reporting on 619 women were included. Compared with metformin, metformin?+?thiazolidinediones (TZDs) was more superior in menstrual recovery (weighted mean difference [WMD] 3.68; 95% credibility interval [CrI], 1.65 to 8.20), metformin?+? glucagon-like peptide-1 (GLP-1) receptor agonists was more effective in decreasing androstenedione (WMD -2.53; 95% CrI, -3.96 to -1.09), both metformin?+?GLP-1 receptor agonists (WMD 9.22; 95% CrI, 5.46 to 12.98) and metformin?+?TZDs (WMD 4.30; 95% CrI, 0.78 to 7.82) were more effective in increasing sex hormone-binding globulin (SHBG), while TZDs were less effective in decreasing body mass index (BMI) (WMD 1.69; 95% CrI, 0.72 to 2.66). Compared with GLP-1 receptor agonists, metformin?+?GLP-1 receptor agonists was associated with higher SHBG (WMD 7.80; 95% CrI, 4.75 to 10.85), lower free testosterone (WMD -1.77; 95% CrI, -3.25 to -0.29), lower androstenedione (WMD -2.70; 95% CrI, -3.91 to -1.50) and lower fasting blood glucose (WMD -0.41; 95% CrI, -0.73 to -0.08). CONCLUSION:For overweight women with PCOS, both metformin combined with GLP-1 receptor agonists and metformin combined with TZDs appear superior to monotherapy in improving hyperandrogenemia. Metformin combined with TZDs could be particularly effective in promoting the recovery of menstruation. Metformin combined with GLP-1 receptor agonists has the additional advantage of improving fasting glucose when compared with GLP-1 receptor agonists alone. TZDs are inferior to metformin in decreasing BMI.

SUBMITTER: Xing C

PROVIDER: S-EPMC7365687 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS.

Xing Chuan C Li Chunzhu C He Bing B

The Journal of clinical endocrinology and metabolism 20200901 9

<h4>Objective</h4>To evaluate the efficacy of insulin sensitizers on menstrual frequency, sex hormone, and metabolic parameters in overweight women with polycystic ovary syndrome (PCOS).<h4>Methods</h4>We searched multiple databases from inception to September 2019 for randomized controlled trials. Network meta-analysis was conducted using multivariate random effects method.<h4>Results</h4>Fourteen trials reporting on 619 women were included. Compared with metformin, metformin + thiazolidinedion ...[more]

PMID: 32490533

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Project description: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 registration PROSPERO CRD42020211524.

Project description:RationaleProgressive midlife weight gain is associated with multiple adverse health outcomes and may represent an early manifestation of insulin resistance in a distinct subset of women. Emerging data implicate hyperinsulinema as a proximate cause of weight gain and support strategies that attenuate insulin secretion.ObjectiveTo assess a previously reported novel hypocaloric carbohydrate modified diet alone (D), and in combination with metformin (M) and metformin plus low-dose rosiglitazone (MR), in diverse women with midlife weight gain (defined as >20lbs since the twenties), normal glucose tolerance, and hyperinsulinemia.Participants46 women, mean age 46.6±1.0, BMI 30.5±0.04 kg/m2, 54.5% white, 22.7% black, 15.9% Hispanic, at 2 university medical centers.MethodsA dietary intervention designed to reduce insulin excursions was implemented in 4 weekly nutritional group workshops prior to randomization.Main outcome measureChange in 6-month fasting insulin. Pre-specified secondary outcomes were changes in body weight, HOMA-IR, metabolic syndrome (MS) measures, leptin, and adiponectin.ResultsSix-month fasting insulin declined significantly in the M group: 12.5 to 8.0 µU/ml, p = .026. Mean 6-month weight decreased significantly and comparably in D, M, and MR groups: 4.7, 5.4, and 5.5% (p's.049, .002, and.032). HOMA-IR decreased in M and MR groups (2.5 to 1.6 and 1.9 to 1.3, p's = .054, .013). Additional improvement in MS measures included reduced waist circumference in D and MR groups and increased HDL in the D and M groups. Notably, mean fasting leptin did not decline in a subset of subjects with weight loss (26.15±2.01 ng/ml to 25.99±2.61 ng/ml, p = .907. Adiponectin increased significantly in the MR group (11.1±1.0 to 18.5±7.4, p<.001) Study medications were well tolerated.ConclusionsThese findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies.Trial registrationClinicalTrials.gov NCT00618072.

Project description:BackgroundObesity and cardiovascular diseases are increasing globally and any association between reproduction and these conditions is of concern. Unfortunately, little is known about normal levels of metabolic risk factors in women of different body mass index throughout the reproductive cycle. This study is one of the first to describe the metabolic risk profile of lactating overweight or obese women at 8-12 weeks postpartum.MethodsDuring 2007-2009, 66 overweight or obese Swedish lactating women without known diseases underwent detailed measurements of their metabolic profiles, dietary intake and general health before entering a lifestyle intervention trial. Baseline measurements took place between 8-12 wk postpartum. Almost all women were exclusively breastfeeding their term infants.ResultsThe women were regarded as healthy, as reflected in the absence of diagnosed diseases, their own perceptions and in normal hemoglobin, albumin and fasting plasma glucose values. Four women were diagnosed with metabolic syndrome. In these cases, underlying conditions included large waist circumference, low HDL cholesterol values, high triglyceride values and relatively high blood pressure. The metabolic profile differed between overweight and obese women; obese women had significantly higher levels of fasting insulin (p = 0.017), borderline higher HOMA values (p = 0.057) and significantly higher triglyceride values (p = 0.029), as well as larger waist and hip circumferences (p<0.001 and p<0.001). However, no significant differences between overweight and obese women were detected for LDL or total cholesterol levels. Overweight and obese women reported similar total energy and macronutrient intakes, but obese women tended to be less physically active (p = 0.081).ConclusionsAmong generally healthy lactating women, obesity as compared to overweight is associated with increased metabolic risk. This cut-off is thus important also in the early postpartum period, and obesity among these women should warrant proper health investigation. Macronutrient intake did not differ between the groups and, hence, cannot explain these differences.Trial registrationClinicalTrials.gov Identifier: NCT01343238.

Project description:The aim of the present study, is to investigate the influence of obesity, with and without polycystic ovarian syndrome (PCOS), on the levels of kisspeptin, vitamin D (Vit D), and vascular endothelial growth factor (VEGF) and to explore the relationship between these parameters and endocrine and metabolic variables. The study group included 126 obese Saudi females. Of these 63 were suffering from PCOS while the rest were normo-ovulatory obese women (non-PCOS obese). In the obese PCOS, VEGF was almost four times as high as in the non-PCOS obese, while kisspeptin and Vit D did not differ. A highly significant elevation was recorded in the waist/hip (WHR), cholesterol, LDL-C, fasting glucose, LH, LH/FSH ratio, estradiol (E2), and testosterone, while hip circumference, leptin, progesterone, and sex hormone binding globulin (SHBG) were lower in the obese PCOS subjects. BMI, HDL-C, ghrelin, insulin, and FSH levels did not differ significantly between the two groups. The obese PCOS had the same level of insulin resistance as the non-PCOS group, as judged by QUICK Index. Correlation studies showed a significant negative correlation between kisspeptin and glucose and LH levels, and a positive correlation with LH/FSH ratio in obese PCOS while in the non-PCOS obese, the kisspeptin correlated positively with glucose, and there was no correlation with LH or LH/FSH. VEGF negatively correlated with FSH and positively with LH/FSH ratio in the non-PCOS obese but this was lost in the obese PCOS. PCOS had no effect on the correlation between Vit D and all studied parameters. Multiple regression analysis showed triglyceride as predictor variable for kisspeptin as a dependent variable, while, leptin is a predictor variable for VEGF as a dependent variable. ROC studies showed the highest sensitivity and specificity for VEGF (AOC=1.00), followed by LH/FSH ratio (AOC=0.979). In conclusion, our study shows that PCOS results in significant elevation of VEGF in obese females, while kisspeptin and Vit D levels are not affected. It also leads to elevation in several of the lipid and hormonal abnormalities in the obese females. In addition, PCOS influences relationship between Kisspeptin and VEGF and some parameters such as glucose, LH or FSH and LH/FSH ratio in obese females, but does not affect Vit D relationship with other parameter.

Dataset Information

Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS.

Publications

Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS.

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