Elevation of markers of endotoxemia in women with polycystic ovary syndrome

Abstract

STUDY QUESTION Is polycystic ovary syndrome (PCOS) associated with an elevation of markers of endotoxemia? SUMMARY ANSWER In women with PCOS serum levels of lipopolysaccharides (LPS), the LPS to high-density lipoprotein (HDL) ratio and LPS-binding protein (LBP) are significantly greater than those of normal control subjects. WHAT IS KNOWN ALREADY Mononuclear cells from women with PCOS respond excessively to LPS by releasing pro-inflammatory cytokines. In rat ovarian theca-interstitial cell cultures LPS stimulates androgen production. STUDY DESIGN, SIZE, DURATION Cross-sectional study comparing markers of endotoxemia in women with PCOS (n = 62), healthy ovulatory women with polycystic ovary morphology (PCOM, n = 39) and a control group of healthy ovulatory women without PCOM [normal (NL), n = 43]. PARTICIPANTS/MATERIALS, SETTING, METHODS LPS was measured using a chromogenic assay. LBP was measured by ELISA. Total cholesterol and lipids were measured using a homogeneous enzyme colorimetric method. Androgens, gonadotrophins, prolactin, insulin, high-sensitivity C-reactive protein (hs-CRP) and sex hormone-binding globulin were determined by electrochemiluminescence assays. Glucose was measured using an enzymatic reference method with hexokinase. MAIN RESULTS AND THE ROLE OF CHANCE Women with PCOS, when compared with NL subjects, had a significantly higher mean LPS (P = 0.045), LPS/HDL ratio (P = 0.007) and LBP (P = 0.01). Women with PCOM had intermediate levels of markers of endotoxemia. Comparison among all groups revealed that markers of endotoxemia correlated positively with testosterone level, ovarian volume, number of antral follicles and hirsutism score, but negatively with the number of spontaneous menses per year. In multiple regression analysis, all measures of endotoxemia correlated independently and positively with hs-CRP and with ovarian volume. LIMITATIONS, REASONS FOR CAUTION This cross-sectional study reveals that markers of endotoxemia are associated with several clinical features observed in women with PCOS. However, responsible mechanisms and causation remain unknown. Steroid quantification was carried out by electrochemiluminescence assays and not by the current gold standard: liquid chromatography-mass spectrometry. Hence, the relationship of endotoxemia with features of PCOS and the extent to which endotoxemia contributes to reproductive and metabolic dysfunction warrants further investigation. WIDER IMPLICATIONS OF THE FINDINGS This study reveals the novel observation that markers of endotoxemia are elevated in young and otherwise healthy women with PCOS without significant metabolic dysfunction. Moreover, the association of clinical and endocrine markers of PCOS with those of endotoxemia may represent a pathophysiologic link to reproductive dysfunction as well as metabolic and long-term cardiovascular risks associated with this disorder. STUDY FUNDING/COMPETING INTEREST(S) Intramural funding from Poznan University of Medical Sciences. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A

The Release of Peripheral Immune Inflammatory Cytokines Promote an Inflammatory Cascade in PCOS Patients via Altering the Follicular Microenvironment

“…PCOS patients are more prone to intestinal flora imbalance and microbiota abnormalities caused by enteral malnutrition, which can producing metabolic endotoxin (LPS) that invades the intestinal wall and aggravates systemic inflammation (36). Therefore, we used LPS as a classic inducer to activate NF-kB pathway to simulate the similar inflammatory status of PCOS patients (19).…”

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

“…As reported, the increased circulating LPS is deemed as a risk factor for PCOS. Duleba et al demonstrated that LPS profoundly increased the expression of key genes in androgen synthesis and contributed to hyperandrogenemia ( Banaszewska et al, 2020 ). To some extent, this helps explain the reason why the administration of SGD could ameliorate the hyperandrogenism in PCOS rats by reducing the LPS level.…”

“…Thereafter, the downstream mediators [such as nuclear factor-κB (NF-κB) and phosphatidylinositol 3-kinase (PI3K)] were activated and numerous pro-inflammatory cytokines (e.g., tumor necrosis factor (TNF)-α, IL-1β and IL-18) were released consequently ( Liu et al, 2010 ). Of note, the elevated serum level of LPS had been observed in women with PCOS and the index was regarded as a risk factor of PCOS ( Banaszewska et al, 2020 ). The LPS-induced inflammatory response occurs in multiple tissues including ovarian theca.…”

A narrative review of the role of gastrointestinal dysbiosis in the pathogenesis of polycystic ovary syndrome

“…A cross-sectional study of 144 women found elevated markers of endotoxemia in women with PCOS compared with healthy ovulatory women. Women with PCOS had significantly higher mean LPS ( P =0.045), LPS to high-density lipoprotein ratio ( P =0.007), and LPS-BP ( P =0.01) [ 50 ]. All measures of endotoxemia correlated independently and positively with the inflammatory markers and ovarian volume.…”

“…All measures of endotoxemia correlated independently and positively with the inflammatory markers and ovarian volume. Taken together, the findings of these two studies suggest that women with PCOS may exhibit a pro-inflammatory state related to elevated markers of endotoxemia, including LPS and LPS-BP [ 45 , 50 ].…”