Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin

Diamanti-Kandarakis, Evanthia; Paterakis, Thomas; Alexandraki, Krystallenia Ι.; Piperi, Christina; Aessopos, Athanasios; Katsikis, Ilias; Katsilambros, Nikolaos; Kreatsas, George; Panidis, Dimitrios

doi:10.1093/humrep/del003

Cited by 229 publications

(202 citation statements)

References 58 publications

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“…The PCOS-related low-grade chronic inflammation has been linked to IR and early development of atherosclerosis (5,16,30). As previously reported (24,28), metformin therapy is able to reduce not only endothelial dysfunction and the intima-media thickness (27), but also CRP (31) and the levels of plasma inflammatory indices (32) in PCOS women. The positive consequences on the CVR (33) and the anti-inflammatory property (34) of an insulin sensitizing drug, such as metformin, are extensively well known (33,34).…”

Section: Discussionmentioning

confidence: 64%

Metformin administration improves leukocyte count in women with polycystic ovary syndrome: a 6-month prospective study

Orio¹,

Manguso²,

Biase³

et al. 2007

European Journal of Endocrinology

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Introduction: Polycystic ovary syndrome (PCOS) is a common disorder associated with a wide range of endocrine and metabolic abnormalities. Low-grade chronic inflammation is a related complication recently observed in PCOS. Increased white blood cell (WBC) count was previously reported in PCOS women. Objective: To evaluate the effects of six months metformin administration on WBC count in PCOS women. Patients and methods: Fifty normal-weight PCOS women without additional metabolic or cardiovascular diseases were enrolled and treated with metformin (850 mg twice daily) for 6 months in a prospective baseline-controlled clinical study. At baseline and after treatment, WBC count and C-reactive protein (CRP) were evaluated in each patient. The whole hormonal profile, serum insulin and glucose levels (at fasting and during a 75 g 2-h oral glucose tolerance test), serum lipid profile were also assessed. Results: A significant difference was observed in WBC count (7050G552 vs 6080G577 cell/mm

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Section: Discussionmentioning

confidence: 64%

Metformin administration improves leukocyte count in women with polycystic ovary syndrome: a 6-month prospective study

Orio¹,

Manguso²,

Biase³

et al. 2007

European Journal of Endocrinology

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“…The most published data, but not all [20,[34][35][36], demonstrated increased levels of hsCRP in women with PCOS [10,11,[37][38][39], which are primarily dependent upon co-existent obesity [40]. Obesity, and specifically increased central adiposity, which is known to secrete many pro-inflammatory markers (IL-1, IL-6, IL-18, TNF-α), is a common PCOS feature [41].…”

Section: Discussionmentioning

confidence: 99%

The polycystic ovary syndrome (pcos) status and cardiovascular risk in young women

Ilie¹,

Pepene²,

Marian³

et al. 2010

Open Medicine

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AbstractThe study investigated the presence of early vascular damage and chronic inflammation, and their relationships with hormonal and metabolic parameters in 45 young women with PCOS in comparison with thirty-two healthy age-matched controls. Hormonal and metabolic profiles, high sensitivity C-reactive protein (hsCRP), tumoral necrosis factor-alpha (TNF-α), endothelin-1 (ET-1), brachial flow-mediated vasodilation (FMD) and carotid intima-media thickness (CIMT) were determined in both groups. Compared with the controls, women with PCOS had significantly lower FMD and respectively higher ET-1 levels (p=0.001). No differences were observed between the groups in terms of CIMT or inflammatory markers. In the PCOS group, ET-1 levels were significantly correlated with only testosterone concentrations (r = 0.31, p = 0.037), whereas the hsCRP levels were independently predicted only by body mass index (BMI). Within the total group, the PCOS status was the sole significant predictor of ET-1 levels and the only independent predictor of FMD. In conclusion, there is evidence of endothelial dysfunction associated with increased levels of androgen hormones in young women with PCOS. The combination of endothelial dysfunction and coexistent obesity promoting inflammation contributes to the progression of atherogenesis in PCOS. The PCOS status should be regarded as a predictor marker of cardiovascular risk, along with well-known cardiovascular risk factors.

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“…Lean, BMI%25; overweight, BMIO25 kg/m decreased levels of disruptors of atherosclerotic plaque may protect PCOS subjects from manifesting cardiovascular events, despite the presence of increased risk factors (20). In several studies concerning patients with PCOS, endothelial dysfunction, fibrinolytic derangements, insulin resistance, and subclinical inflammation have been detected, suggesting that these patients are at high risk of developing cardiovascular incidents (21,22). The fact that in PCOS patients overt cardiovascular incidents are not frequently encountered indicates possible protective factors in PCOS subjects that delay or inhibit atherogenic process.…”

Section: Discussionmentioning

confidence: 99%

Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: hint of a protective mechanism?

Diamanti-Kandarakis¹,

Livadas²,

Kandarakis³

et al. 2008

European Journal of Endocrinology

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Background: Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) have been considered as important mediators of vascular remodeling and plaque instability. The formation of a complex with NGAL and MMP-9 is crucial for atherotic plaque erosion and thrombus formation. In women with polycystic ovary syndrome (PCOS), the incidence of cardiovascular clinical events is not increased, despite the fact that they display a wide spectrum of risk factors. Since the instability of atherosclerotic plaque is a key factor in the clinical manifestations of cardiovascular disease, molecules challenging the plaque stability should be investigated. Aim: To determine serum levels of NGAL and MMP-9/NGAL complex in women with PCOS. Subjects and methods: PCOS subjects (40) were compared with those (40) matched for age and body mass index (BMI) controls. In each subject, fasting levels of glucose, insulin, gonadotropins, estradiol, androgens, C-reactive protein, NGAL, and MMP-9/NGAL were determined. Results: NGAL and MMP-9/NGAL complex levels were significantly lower in the PCOS group compared with controls (30.4G24.3 vs 70.7G37.9 mg/l, P!0.0001) and (31.5G26.6 vs 115.1G66.9 mg/l, P!0.0001) respectively. When patients and controls were stratified according to BMI, it was shown that NGAL and MMP-9/NGAL levels were significantly lower in lean (P!0.0002 and P!0.0001 respectively) and overweight (P!0.0004 and P!0.002 respectively) PCOS subjects compared with controls. Conclusions: These findings indicate that NGAL and MMP-9/NGAL complex, two molecules that activate atherotic plaque erosion, is in lower concentrations in PCOS subjects. The role of NGAL and MMP-9/NGAL complex needs to be further investigated, since suppression of these atheromatous molecules might have a protective role in women with PCOS.

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Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin

Abstract: These findings imply the presence of chronic inflammation in women with PCOS. Metformin decreases the levels of plasma inflammatory indices. Further investigation is required to determine whether these findings may prove to be of clinical significance for PCOS patients.

Cited by 229 publications

References 58 publications

Metformin administration improves leukocyte count in women with polycystic ovary syndrome: a 6-month prospective study

Metformin administration improves leukocyte count in women with polycystic ovary syndrome: a 6-month prospective study

The polycystic ovary syndrome (pcos) status and cardiovascular risk in young women

Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: hint of a protective mechanism?

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