Abstract
BackgroundPolycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR.MethodsA total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed.ResultsFirst, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS.ConclusionsElevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.
Highlights
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate
In the comparison of subgroups fasting plasma insulin levels and HOMA-insulin resistance (IR) were higher in the obese groups, and C-reactive protein (CRP) and alanine transaminase (ALT) levels were found to be increased in the PCOS-obese group
Associations between plasma levels of TMAO and PCOS without HA as well as biomarkers of inflammation A partial correlation was calculated to analyze whether TMAO correlated with PCOS without HA by controlling for the confounding factor body mass index (BMI), and the results showed that the plasma levels of TMAO (r = 0.423, P < 0.01), luteinizing hormone (LH) (r = 0.482, P < 0.01), luteinizing hormone/follicle-stimulating hormone (LH/follicle-stimulating hormone (FSH)) (r = 0.460, P < 0.01), and fasting blood glucose (FBG) (r = 0.408, P < 0.01) were positively correlated with the incidence of PCOS without HA
Summary
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder commonly found in women of childbearing age. Common clinical criteria include menstrual disorder, infrequent ovulation, chronic anovulation, hirsutism, hyperandrogenism (HA), insulin resistance (IR) and ovarian polycystic changes [1, 2]. PCOS is usually diagnosed according to the Rotterdam criteria, given the presence of at least two of three criteria, clinical or laboratory HA, ovulatory dysfunction or polycystic ovaries (PCO) on ultrasound [5]. Different types of PCOS have different manifestations and metabolic features, which significantly increase the risk of long-term cardiovascular disease (CVD),
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