White blood cells levels and PCOS: direct and indirect relationship with obesity and insulin resistance, but not with hyperandogenemia

Hormones - Tập 14 - Trang 91-100 - 2015
Olga Papalou1, Sarantis Livadas1, Athanasios Karachalios1, Nikoleta Tolia1, Panayiotis Kokkoris2, Konstantinos Tripolitakis2, Evanthia Diamanti-Kandarakis1
1Endocrine Unit, Third Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece
2Department of Endocrinology & Diabetes, 251 Hellenic Air Force & VA General Hospital, Athens, Greece

Tóm tắt

OBJECTIVE: To study white blood cells count (WBC) in women suffering from PCOS and compare these results with age and BMI-matched healthy women. The specific aim of this study was to assess the possible correlations of WBC with the major components of PCOS, obesity, insulin resistance and hyperandrogenism. DESIGN: Anthropometrical, metabolic and hormonal data were analyzed from 203 women with PCOS (NIH criteria) and 76 age-matched controls. RESULTS: In the total population studied (N=279), WBC was significantly higher (P=0.003) in the PCOS group compared with age-matched healthy women and was positively correlated with BMI (r=0.461, p<0.001), total testosterone (r= 0.210, p<0.001), insulin (r=0.271, p<.001), triglycerides (r=0.285, p<.001), HOMA score (r=0.206, p=0.001), FAI (r=0.329, p<0.001) and negatively correlated with SHBG (r=−0.300, p<.001) and HDL (r=−0.222, p<0.001). Due to the fact that WHR was only available in the group of PCOS women, the role of central adiposity is assessed only in this group. Multiple regression analysis in the PCOS group, including WHR, revealed BMI, SHBG and TGL as the main predicting factors of WBC. Multinomial logistic regression analysis was also conducted and overweight/obesity was the sole independent risk factor for elevated WBC (higher tertile) (OR:0.907 CI:0.85–0.96, p=0.002). After dividing the sample based on BMI in the lean subgroups, WBC did not differ significantly between PCOS and controls, while multiple regression analysis indicated SHBG as the main predicting factor of WBC. Finally, we picked out the group of overweight/obese (BMI ≥25 kg/m2) women with PCOS and conducted another classification based on HOMA score (HOMA-IR≤2: insulin-sensitive women, HOMA-IR>2: insulin-resistant women) in the group of overweight and obese women with PCOS separately. In overweight women with PCOS, WBC, although higher in the group of insulin-resistant, did not differ significantly between the two groups, while in the subcategory of overweight women WBC was significantly (p=0.02) higher in the group of insulin-resistant women (HOMA-IR >2). CONCLUSIONS: Chronic low-grade inflammation and increased white cell count do occur in PCOS. Obesity and insulin resistance are the two leading parameters that act accumulatively in the development of leucocytosis, whereas hyperandrogenism does not seem to affect it.

Tài liệu tham khảo

Diamanti-Kandarakis E, Kouli CR, Bergiele AT, et al, A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. 1999 J Clin Endocrinol Metab 84: 4006–4011. Azziz R, Dumesic DA, Goodarzi MO, 2011 Polycystic ovary syndrome: an ancient disorder? Fertil Steril 95: 1544–1548. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO, 2004 The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 89: 2745–2749. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ, 2010 The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 25: 544–551. Azziz R, Carmina E, Dewailly D, et al, 2006 Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 91: 4237–4245. Diamanti-Kandarakis E, Dunaif A, 2012 Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 33: 981–1030. Libby P, Theroux P, 2005 Pathophysiology of coronary artery disease. Circulation 111: 3481–3488. Libby P, 2002 Inflammation in atherosclerosis. Nature 420: 868–874. Kannel WB, Anderson K, Wilson PW, 1992 White blood cell count and cardiovascular disease. Insights from the Framingham Study. JAMA 267: 1253–1256. Tedgui A, Mallat Z, 2006 Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 86: 515–581. Jialal I, Devaraj S, 2001 Inflammation and atherosclerosis: the value of the high-sensitivity C-reactive protein assay as a risk marker. Am J Clin Pathol 116: Suppl 1: 108–115. Hulsmans M, Holvoet P, 2010 The vicious circle between oxidative stress and inflammation in atherosclerosis. J Cell Mol Med 14: 70–78. Phelan N, O’Connor A, Kyaw Tun T, et al, 2013 Leucocytosis in women with polycystic ovary syndrome (PCOS) is incompletely explained by obesity and insulin resistance. Clin Endocrinol 78: 107–113. Escobar-Morreale HF, Luque-Ramirez M, Gonzalez F, 2011 Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertil Steril 95: 1048–1058. Orio F Jr., Palomba S, Cascella T, et al, 2005 The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome J Clin Endocrinol Metab 90: 2–5. Escobar-Morreale HF, Botella-Carretero JI, Villuendas G, Sancho J, San Millán JL, 2004 Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity. J Clin Endocrinol Metab 89: 806–811. Tarkun I, Arslan BC, Canturk Z, Türemen E, Sahin T, Duman C, 2004 Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. J Clin Endocrinol Metab 89: 5592–5596. Diamanti-Kandarakis E, Paterakis T, Kandarakis HA, 2006 Indices of low-grade inflammation in polycystic ovary syndrome. Ann N Y Acad Sci 1092: 175–186. Christakou C, Economou F, Livadas S, et al, 2011 Strong and positive association of endothelin-1 with AGEs in PCOS: a causal relationship or a bystander? Hormones (Athens) 10: 292–297. Diamanti-Kandarakis E, Palioniko G, Alexandraki K, Bergiele A, Koutsouba T, Bartzis M, 2004 The prevalence of 4G5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene in polycystic ovarian syndrome and its association with plasma PAI-1 levels. Eur J Endocrinol 150: 793–798. Diamanti-Kandarakis E, Piperi C, Kalofoutis A, Creatsas G, 2005 Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome. Clin Endocrinol 62: 37–43. Diamanti-Kandarakis E, Piouka A, Livadas S, et al, 2009 Anti-mullerian hormone is associated with advanced glycosylated end products in lean women with polycystic ovary syndrome. Eur J Endocrinol 160: 847–853. Orio F, Manguso F, Di Biase S, et al, 2007 Metformin administration improves leukocyte count in women with polycystic ovary syndrome: a 6-month prospective study. Eur J Endocrinol 157: 69–73. Adams J, Franks S, Poison DW, et al, 1985 Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet 2: 1375–1379. Sathyapalan T, Atkin S, 2012 Recent advances in cardiovascular aspects of polycystic ovary syndrome. Eur J Endocrinol 166: 575–583. Duleba AJ, Dokras, 2012 Is PCOS an inflammatory process? Fertil Steril 97: 7–12. Sam S, Dunaif A, 2003 Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab 14: 365–370. Herlihy AC, Kelly RE, Hogan JL, O’Connor N, Farah N, Turner MJ, 2011 Polycystic ovary syndrome and the peripheral blood white cell count. J Obstet Gynaecol 31: 242–244. Shi Y, Han T, Cui L, et al, 2013 White blood cell differential counts in patients with polycystic ovary syndrome: a pilot study on Chinese women. Eur J Obstet Gynecol Reprod Biol 170: 162–164. Kajaia N, Binder H, Dittrich R, et al, 2007 Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome. Eur J Endocrinol 157: 499–507. Ding EL, Song Y, Manson JE, et al, 2009 Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med 361: 1152–1163. Ibanez L, Jaramillo AM, Ferrer A, de Zegher F, 2005 High neutrophil count in girls and women with hyper-insulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception. Hum Reprod 20: 2457–2462. Puder JJ, Varga S, Kraenzlin M, De Geyter C, Keller U, Müller B, 2005 Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance. J Clin Endocrinol Metab 90: 6014–6021. Alipour A, van Oostrom AJ, Izraeljan A, et al, 2008 Leukocyte activation by triglyceride-rich lipoproteins. Arterioscler Thromb Vasc Biol 28: 792–797. Wajchenberg BL, 2000 Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21: 697–738. Giallauria F, Palomba S, Maresca L, et al, 2008 Exercise training improves autonomic function and inflammatory pattern in women with polycystic ovary syndrome (PCOS). Clin Endocrinol 69: 792–798.