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Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women.

ABSTRACT: Metformin is one of the treatments used for PCOS pathology decreasing body weight, plasma androgen, FSH and glucose levels. Unfortunately, there is little known about metformin's effects on lipid metabolism, a crucial process in PCOS pathology. We have employed a lipidomic approach to explore alterations in the plasma lipid profile of patients with PCOS following metformin treatment. The aim is to offer new insights about the effect of metformin in PCOS patients. Plasma samples were obtained from 27 subjects prior to and following 12 weeks of metformin treatment. A detailed biochemical characterization and lipidomic profile was performed. Metformin reduces BMI, HOMA-IR, FSH and androstenedione and increases DHEA-S but no changes were found in glucose levels after treatment. Multivariate statistics revealed a specific lipidomic signature due to the effect of 12 weeks of metformin treatment in PCOS patients. This signature includes changes in sphingolipid metabolism suggesting a crosstalk between these lipid species and the androgenic metabolism and a decrease in oxidized lipids reinforcing that metformin treatment improves oxidative stress status. Our study confirms the specific effect of metformin in lipid metabolism on women with PCOS after 12 weeks of treatment.

SUBMITTER: Pradas I

PROVIDER: S-EPMC6831788 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women.

Pradas Irene I Rovira-Llopis Susana S Naudí Alba A Bañuls Celia C Rocha Milagros M Hernandez-Mijares Antonio A Pamplona Reinald R Victor Victor M VM Jové Mariona M

Scientific reports 20191105 1

Metformin is one of the treatments used for PCOS pathology decreasing body weight, plasma androgen, FSH and glucose levels. Unfortunately, there is little known about metformin's effects on lipid metabolism, a crucial process in PCOS pathology. We have employed a lipidomic approach to explore alterations in the plasma lipid profile of patients with PCOS following metformin treatment. The aim is to offer new insights about the effect of metformin in PCOS patients. Plasma samples were obtained fro ...[more]

PMID: 31690730

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Project description:BACKGROUND:Polycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions. OBJECTIVES:To assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS. SEARCH METHODS:We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL and AMED (date of last search March 2018). We also searched controlled trials registries, conference abstracts, relevant journals, reference lists of relevant papers and reviews, and grey literature databases, with no language restrictions applied. SELECTION CRITERIA:Randomised controlled trials (RCTs) comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS. DATA COLLECTION AND ANALYSIS:Two authors independently selected trials, assessed evidence quality and risk of bias, and extracted data. Our primary outcomes were live birth, miscarriage and pregnancy. We used inverse variance and fixed-effect models in the meta-analyses. We reported dichotomous outcomes as an odds ratio and continuous outcomes as a mean difference (MD) or standardised mean difference (SMD). MAIN RESULTS:We included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review.Lifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I2 = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I2 = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m2) (-0.34 kg/m2, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I2= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I2 = 0%, low-quality evidence). AUTHORS' CONCLUSIONS:Lifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.

Project description:Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women. It can be accompanied by many clinical manifestations that can vary between individuals. Previous studies have found that there are specific changes in the intestinal flora of PCOS patients, and interventions to modify the intestinal flora can significantly improve the symptoms of PCOS. Women with PCOS have a higher incidence of vaginitis compared to healthy women. Few studies to-date have focused on investigating vaginal flora. Here, we aimed to explore distribution changes of the vaginal microbiome in PCOS patients. We recruited 42 PCOS patients (T-PCOS) and 24 healthy controls (T-control). 16s rRNA gene sequencing was used to sequence their vaginal microbiome. Normally, Lactobacillus was dominated in vaginal. Lactobacillus-dominated-type vaginal microbiome in T-PCOS and T-control (L-PCOS and L-control) and non-Lactobacillus-dominated-type vaginal microbiome in T-PCOS and T-control (N-PCOS and N-control) were analyzed separately. A total of 655 operational taxonomic units were detected in this sequencing, including 306 unique to T-PCOS, 202 unique to T-control, and 147 common between the two groups. At the genus level, Lactobacillus accounted for more than 70% of the total microbiome. Observed species (P = 0.021), Chao1 index (P = 0.020), and ACE index (P = 0.023) decreased significantly in L-PCOS. Principal component analysis showed no statistically significant differences among the subgroups. There were significant statistical differences in principal coordinate analysis in the Jaccard distance between the T-PCOS and T-control groups and between the L-PCOS and L-control groups. Linear discriminant analysis effect size found that Enterococcus and Actinomycetes were significantly different in the T-PCOS group. Atopobium and Actinomyces were statistically significantly different in patients with L-PCOS and N-PCOS group, respectively. Environmental factor analysis found that Ezakiella was significantly negatively correlated with age, while Streptococcus was significantly negatively correlated with follicle stimulating hormone. There were statistically significant differences between PCOS patients and healthy women in the vaginal microbiome, regardless of the abundance of Lactobacillus. Alpha diversity of vaginal microbiome decreased markedly in PCOS patients when it was dominated by Lactobacillus spp. Actinomyces could be a potential biomarker to identify PCOS. Streptococcus may have an impact on the pathological changes in PCOS by affecting the female reproductive endocrine environment.

Project description:BackgroundObesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.MethodsFifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein.ResultsForty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P < 0.050). Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.ConclusionsCOM therapy was more effective than MET alone in reducing body weight, BMI, and waist circumference, and improving insulin sensitivity in overweight/obese women with PCOS, with acceptable short-term side effects.Trial registrationClinicalTrials.gov, NCT04029272. https://clinicaltrials.gov/ct2/show/NCT04029272.

Dataset Information

Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women.

Publications

Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women.

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