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.

Keywords: endotoxemia; lipopolysaccharide binding protein; lipopolysaccharides; polycystic ovary morphology; polycystic ovary syndrome.