http://informahealthcare.com/gye ISSN: 0951-3590 (print), 1473-0766 (electronic) Gynecol Endocrinol, 2014; 30(6): 423–427 ! 2014 Informa UK Ltd. DOI: 10.3109/09513590.2014.895981

PCO

Interleukin-6 levels in relation with hormonal and metabolic profile in patients with polycystic ovary syndrome

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_ Mert Ku¨c¸u¨k1, Su¨ndu¨z O¨zlem Alt|nkaya2, Su¨meyra Nergiz2, Selda Demircan Sezer2, Hasan Yu¨ksel2, Ihsan Bag˘l|2, and 3 Gu¨lserap Y|ld|z 1

Department of Gynecology and Obstetrics, Faculty of Medicine, Mug˘la Sıtkı Koc¸man University, Mug˘la, Turkey, 2Department of Gynecology & Obstetrics, Faculty of Medicine, Adnan Menderes University, Aydın, Turkey, and 3Bursa Zu¨beyde Hanım Maternity Hospital, Bursa, Turkey Abstract

Keywords

Objective: The aim of this study was to evaluate serum concentrations of interleukin-6 (IL-6) in relation with hormonal and metabolic profile in patients with and without polycystic ovary syndrome (PCOS). Methods: A total of 40 women with PCOS and 40 age-matched controls were eligible for the study. Hirsutism scores, hormonal and metabolic profile as well as IL-6 levels were evaluated in each subject. Results: Women with PCOS exhibited higher body mass index (BMI) and serum concentrations of IL-6 levels than controls (p50.05); however, levels of IL-6 were not significantly increased when compared with BMI-matched controls (p40.05). IL-6 levels were significantly correlated positively with BMI and triglyceride levels; however, negatively correlated with high-density lipoprotein levels. Conclusion: The data of this study suggested that serum IL-6 levels were found to be higher in women with PCOS as compared to controls; however, IL-6 levels might be dependent on nutritional status but not on PCOS per se. Raised serum IL-6 levels may be related to BMI and serum lipid levels and may be a predictor for cardiometabolic risks.

Interleukin-6, inflammation, polycystic ovary syndrome

Introduction Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women, with a prevalence of 6–12% in women of reproductive age [1]. It is characterized by androgen excess, chronic oligoanovulation and polycystic ovaries (PCO) on ultrasound. Clinically, the androgen excess presents as hirsutism and acne, whereas anovulation presents as subfertility or infertility and menstrual irregularity. In addition, insulin resistance (IR), a severe physiological abnormality, caused by visceral obesity and inflammation in adipose tissue as well as adipokine secretion disturbances, is common among women with PCOS [2]. Inflammation is considered to play a key role in pathophysiologic mechanisms of atherosclerosis and cardiovascular disease [3,4]. Chronic inflammation has been reported to be a novel mechanism contributing to a greater risk for coronary heart disease in women with PCOS [5]. The chronic inflammatory milieu of PCOS patients, modulated by the high prevalence of obesity in this population, plays a central role in the development of IR and carbohydrate metabolism [6]. Furthermore, adipokine secretion disturbance is not only an exciting new link between PCOS and IR but also obesity and cardiovascular disease, hypertension as well as hyperlipidemia [7]. Since interleukin-6 (IL-6) is a regulator of C-reactive protein (CRP) and has a key role in the initiation of inflammation, it may act as a procoagulant

Address for correspondence: Mert Ku¨c¸u¨k, Department of Gynecology and Obstetrics, Faculty of Medicine, Mug˘la S|tk| Koc¸man University, Mug˘la, Turkey. E-mail: [email protected]

History Received 8 September 2013 Revised 27 January 2014 Accepted 16 February 2014 Published online 14 March 2014

and proinflammatory marker for coronary heart disease associated with atherosclerosis progression and thrombotic complications [8]. Several studies have shown higher serum IL-6 levels in women with PCOS with a positive correlation of IL-6 with obesity and IR [9–11], whereas some others [12–14] have reported contrary results. The purpose of this study was to assess serum concentrations of IL-6 in relation with nutritional status, hormonal and metabolic profile in patients with and without PCOS.

Methods The design of this study was approved by the Ethical Committee and Institutional Review Board of Adnan Menderes University, Faculty of Medicine, where the study was conducted. Written informed consents were obtained from all participants. The diagnosis of PCOS was made according to the Rotterdam criteria [15] in the presence of at least two of the following: (1) oligomenorrhea and/or anovulation, (2) biochemical and/or clinical hyperandrogenism, (3) ultrasound appearance of PCO (multiple cysts412 in number of 2–9 mm size) with the exclusion of other etiologies such as congenital adrenal hyperplasia, virilizing tumor, cushing syndrome and prolactinoma, diabetes, hypertension and other cardiovascular diseases. Over the three months preceding the study, no subject had been on hormonal contraceptives, other medications or diet, which could affect lipid and carbohydrate metabolism. No subject smoked or consumed alcohol. As controls, 40 age-matched women who had regular menses and no clinical or biochemical hyperandrogenism or PCO were eligible.

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Detailed clinical history was taken, and physical examination was performed for all participants. Body mass index (BMI) was also calculated. Subjects with BMI 525 kg/m2 were accepted normal weight, 25–25.99 kg/m2 were overweight; whereas when BMI was calculated 30 kg/m2, these participants were accepted obese. Routine laboratory investigations included fasting blood glucose, fasting insulin, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), luteinizing hormone (LH), follicle stimulating hormone, estradiol, thyroid stimulating hormone, free thyroxine levels (free T3 and free T4), dehydroepiandrosterone sulfate (DHEA-SO4) and free testosterone (fT) levels. IR was determined by the homeostasis model assessment (HOMA) index (fasting glucose (mg/dl)  fasting insulin(mU/mL)/405) [16]. All sampling procedures were performed in the early follicular phase (day 2–5 of the menstrual cycle) in the morning after an overnight fast. Serum IL-6 levels were assessed by enzyme-linked immunosorbent assay (Diasource Immunoassays S.A, Louvain-La-Neuve, Belgium). The intra- and inter-assay coefficients of variations ranged from 4.2% to 4.3% and 4.4% to 5.4%, respectively. The lower detection limit for IL-6 was 2 pg/mL. Statistical analysis was performed by Statistical Package for Social Sciences 11.5 software (SPSS Inc., Chicago, IL). Distributions of continuous and discrete variables were tested by Kolmogorov–Smirnov test. Descriptive statistics were shown as mean ± standard deviation or median (minimum to maximum) where appropriate and qualitative data were presented as percentages. Student’s t and Mann–Whitney U tests were used to determine differences between two independent groups with regard to mean and median values, respectively. Spearman’s correlation test was used to determine the correlation between continuous variables. Whether the statistically significant predictivity of PCOS on IL-6 measurements was going on or not was evaluated by Multiple Linear Regression analyses after adjustment for confounding factors (i.e. BMI, HDL and TG). Coefficient of regression (B) and 95% confidence intervals for each independent variable were also calculated. Log-transformation was applied for IL-6 measurements in regression analysis because of not normally distributed data. A p value less than 0.05 was considered as statistically significant. But, for all possible multiple comparisons, the Bonferroni correction was applied for controlling type I error.

Results A total of 40 women with PCOS and 40 controls participated in this study. Demographic, clinical, biochemical and hormonal characteristics of women with PCOS and controls regarding BMI are summarized in Table 1. BMI was significantly higher in women with PCOS compared to controls (25.69 kg/m2 versus 22.36 kg/m2, p50.001). In addition, fasting insulin, HOMA-IR, LDL, TG, fT, DHEA-SO4, LH levels were significantly higher, whereas HDL levels were lower in PCOS group compared to controls, as expected (p50.05). IL-6 levels were also found to be elevated in women with PCOS than controls (Table 1 and Figure 1); however, levels of IL-6 were not significantly increased when compared with BMI matched controls (Table 1). Among the 40 women with PCOS, 20 women were overweight/obese (13 women overweight and 7 women obese) and 20 were normal weight. In the control group, eight women were overweight. When the overweight/obese women with PCOS were compared with overweight controls, higher IL-6 levels were found in patients with PCOS; however, the difference was not significant (14 pg/mL versus 11 pg/mL, p ¼ 0.281). Similarly, when the normal weight women with PCOS were compared with normal weight controls, again higher IL-6 levels were found in the PCOS group; however, the difference was not significant (12 pg/mL

Gynecol Endocrinol, 2014; 30(6): 423–427

versus 8.5 pg/mL, p ¼ 0.088). Table 1 shows the comparable analysis between normal weight and obese/overweight PCOS and non-PCOS groups for all studied parameters. IL-6 levels were positively correlated with BMI (r ¼ 0.287, p ¼ 0.01) and TG levels (r ¼ 0.267, p ¼ 0.017), whereas it was negatively correlated with HDL levels (r ¼ 0.275, p ¼ 0.014). However, no significant correlation was found between IL-6 levels with HOMA-IR (r ¼ 0.16, p ¼ 0.156) and hyperandrogenism. Table 2 shows the correlations between IL-6 levels and metabolic, hormonal and androgen excess parameters. However, Multiple Linear Regression analyses demonstrated that the statistically significant predictivity of PCOS on IL-6 measurements was not going on after adjustment for confounding factors (i.e. BMI, HDL and TG) (B: 0.483, 95%CI: 0.001–0.967, p ¼ 0.051, Table 3).

Discussion The early presence of chronic inflammation markers in young women with PCOS may have clinical significance to estimate long-term risks for cardio metabolic disorders such as diabetes and atherosclerosis. Currently, there is still controversy on proinflammatory markers in women with PCOS and whether the early presence of chronic inflammation has clinical importance and significance. There are controversial data regarding IL-6 and other proinflammatory markers in patients with PCOS in the literature. Vgontzas et al. [9] compared IL-6 and tumor necrosis factor a (TNF-a) levels in 42 obese women with PCOS with 17 obese and 15 normal weight controls. They stated that IL-6 levels were elevated in obese women with PCOS independently of obesity and might represent a pathophysiologic link to IR. Fulghesu et al. [10] also found elevated IL-6 levels in insulin resistant women with PCOS. Their results suggested that in PCOS patients an altered immune response to inflammatory stimuli was present in IR, contributing to a low grade inflammation. In addition, Gonza´lez et al. [11] measured higher IL-6 and CRP levels in obese PCOS patients than obese controls and found IL-6 levels in correlation with truncal fat. They concluded that both PCOS and obesity contribute to an atherogenic state; but in women with PCOS, abdominal obesity and hyperandrogenism may exacerbate the risk of atherosclerosis. In contrast to the findings of the aforementioned studies, Olszanecka-Glinianowicz et al. [12] measured lower IL-6 values in 39 obese PCOS compared with 34 agematched obese controls. Furthermore, they did not observe correlations between serum IL-6 levels and any of the hormonal and metabolic profiles and BMI except for a negative linear correlation between serum IL-6 and glucose levels. They suggested that PCOS was not associated with chronic inflammation. Mo¨hlig et al. [13] investigated IL-6 and CRP levels. Their data indicated that in PCOS women IL-6 and CRP were not increased when compared with age and BMI-matched controls. They found positive correlations with IL-6 and BMI and HOMA index but not with hyperandrogenism; however, when linear regression models were calculated, HOMA lost its significant association to IL-6 after inclusion of BMI into the model. Samy et al. [14] prospectively studied CRP, IL-6 and TNF-a level in 108 women with PCOS and 75 controls, in which both groups were divided into two subgroups according to the BMI. There were no significant difference in serum inflammatory markers between PCOS and their matched controls. However, these inflammatory markers correlated with BMI and HOMA index. Two metaanalyses involving 10 studies of IL-6 revealed no significant differences between PCOS and controls [17,18]. The data of this study demonstrated that women with PCOS exhibited higher serum levels of IL-6. However, when subgroup

23.3 ± 5.4 91.1 ± 9.8 15.6 (6–95) 3.2 (1.3–24.6) 179 (146–306) 44.3 ± 12.5 112.9 ± 29.6 122.5 (70–330) 2.8 (1.2–4.2) 373.2 ± 150.4 3.2 (2.5–4.2) 1.15 ± 1.18 1.7 (0.6–3.9) 3.9 (2.3–5.5) 7 (2.1–38) 49.5 ± 21.1 15.7 ± 5.1 14 (5–638)

23.8 ± 5.6 90.3 ± 10.9 10.3 (3–39) 2.2 (0.6–11.5) 183.5 (127–247) 51.8 ± 11.9 113.5 ± 20.7 94.5 (44–163) 2.6 (1.5–4) 342.3 ± 145.2

3.2 (2.5–4.2) 1.17 ± 0.23 1.8 (0.4–3.4) 4.2 (2.7–5.5) 6.8 (2.2–19.8) 53.3 ± 28.1 15.3 ± 3.1 12 (2–87)

3.2 (2.5–4.2) 1.2 ± 0.2 1.8 (0.4–3.9) 4.2 (2.3–5.5) 7 (2.1–38) 51.4 ± 24.6 15.5 ± 4.2 14 (2–638)

23.5 ± 5.5 90.7 ± 10.3 11.0 (3–95) 2.6 (0.6–24.6) 180 (127–306) 48 ± 12.6 113.2 ± 25.2 104.5 (44–330) 2.7 (1.2–4.2) 357.8 ± 146.8 3.1 (2.4–4.1) 1.11 ± 0.13 1.8 (0.6–4.3) 4.8 (3.1–10) 4.7 (1.5–10.8) 61.1 ± 22.8 15.4 ± 4.4 8.5 (3–35)

24.9 ± 5.2 88.4 ± 4.7 8 (2.6–14) 1.7 (0.5–3) 165.5 (124–231) 55.2 ± 9.4 99.5 ± 20.5 82.5 (32–149) 1.3 (0.5–3) 259.9 ± 91.9

BMI 525 (n ¼ 32)

2.7 (2.4–3.7) 1.2 ± 0.1 1.7 (0.9–4.6) 4.3 (1.9–6.1) 5.2 (3.5–6.2) 57.1 ± 25.1 16.7 ± 3.8 11 (7–24)

29.3 ± 7.1 88.2 ± 5.8 6.7 (4.4–12.8) 1.5 (0.8–2.7) 185 (145–240) 52.0 ± 11.1 112.1 ± 26.01 99 (41–180) 1.1 (0.6–2.5) 212.5 ± 108.3

BMI 25 (n ¼ 8)

Total (n ¼ 40)

BMI  25 (n ¼ 20)

3 (2.4–4.1) 1.1 ± 0.1 1.8 (0.6–4.6) 4.7 (1.9–10) 4.8 (1.5–10.8) 60.2 ± 23 15.7 ± 4.3 9.5 (3–35)

25.8 ± 5.8 88.4 ± 4.9 7.9 (2.6–14) 1.7 (0.5–3) 168 (124–240) 54.6 ± 9.7 102 ± 21.9 85 (32–180) 1.2 (0.5–3) 250.5 ± 95.8

Total (n ¼ 40)

0.073 0.78 0.762 0.008 50.001 0.102 0.890 0.010

0.079 0.207 50.001 50.001 0.142 0.011 0.037 0.005 50.001 50.001

p*

0.475 0.265 0.679 0.014 0.001 0.286 0.926 0.088

0.473 0.468 0.080 0.096 0.132 0.256 0.020 0.110 50.001 0.031

py

0.055 0.327 0.862 0.746 0.070 0.420 0.634 0.281

0.022 0.460 0.003 0.002 0.862 0.142 0.946 0.150 50.001 0.011

pz

0.820 0.718 0.904 0.640 0.718 0.627 0.718 0.414

0.777 0.833 0.024 0.038 0.883 0.060 0.941 0.060 0.265 0.513

p{

0.209 0.483 0.703 0.134 0.396 0.674 0.440 0.209

0.051 0.924 0.434 0.539 0.325 0.408 0.148 0.454 0.359 0.216

px

BMI: body mass index, FPG: fasting plasma glucose, FI: fasting insulin, HOMA-IR: homeostasis model assessment-insulin resistence, TC: total cholesterol, HDL: high-density lipoprotein, LDL: low-density lipoprotein, TG: triglycerides, fT: free testosterone, DHEA-SO4: dehydroepiandrosterone sulfate, fT3-fT4: free thyroxine levels, TSH: thyroid-stimulating hormone, FSH: follicle stimulating hormone, LH: luteinizing hormone, E2:estradiol, PRL: prolactin and IL-6:interleukine-6. *Difference between PCOS and controls. yDifference between PCOS and controls BMI525, p value less than 0.025 was considered statistically significant with regard to Bonferroni adjustment. zDifference between PCOS and controls BMI  25, p value less than 0.025 was considered statistically significant with regard to Bonferroni adjustment. Difference between normal weight and obese/overweight subgroups in patients with PCOS, p value less than 0.025 was considered statistically significant with regard to Bonferroni adjustment. xDifference between normal weight and obese/overweight subgroups in controls, p value less than 0.025 was considered statistically significant with regard to Bonferroni adjustment. Bold values indicate statistically significant values.

Age (years) FPG (mg/dl) FI (mIU/ml) HOMA-IR TC (mg/dl) HDL (mg/dl) LDL (mg/dl) TG (mg/dl) fT (pg/ml) DHEA-SO4 (mg/dl) fT3 (pg/ml) fT4 (pg/ml) TSH (mIU/ml) FSH (mIU/ml) LH (mIU/ml) E2 (pg/ml) PRL (mIU/ml) IL-6 (pg/mL)

BMI 525 (n ¼ 20)

Controls

PCOS

Table 1. Demographic, clinical, biochemical and hormonal characteristics of women with PCOS and controls regarding BMI.

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DOI: 10.3109/09513590.2014.895981

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50

calculated, PCOS lost its significant association to IL-6 after inclusion of BMI into the model. In addition, IL-6 levels were positively correlated with BMI and TG levels, whereas it was negatively correlated with HDL levels. However, no significant correlation was found between IL-6 levels with HOMA-IR and hyperandrogenism. So the results of this study revealed that IL-6 levels might be dependent on nutritional status but not on PCOS per se. Discrepant findings among the results of the published studies may be attributed to the design and sample size and the demographic and genetic characteristics of the different populations. Prospective design of this study may provide advantages, whereas small sample size is a limitation. The particular mechanisms to clarify the associations of the underlying cardiovascular risks in women with PCOS require larger additional studies on chronic inflammation processes. In conclusion, the data of this study demonstrated that IL-6 levels might be dependent on nutritional status but not on PCOS per se. Weight loss and healthy lifestyle changes are required in these patients to achieve equivalent cardiovascular benefit to healthy women.

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IL-6 (pg/ml)

40

30

20

10

0 Controls

PCOS

Declaration of interest

Şekil 1. Distribuon of IL-6 levels in PCOS and control group

Figure 1. The horizontal lines in the middle of each box indicates the median IL-6 levels, while the top and bottom borders of the box mark the 25th and 75th percentiles, respectively. The whiskers above and below the box mark indicates the maximum and minimum IL-6 levels. Table 2. Correlations between IL-6 and metabolic and androgen excess parameters.

BMI Insulin HOMA-IR TC HDL LDL TG fT DHEA-SO4

r

p

0.287 0.151 0.160 0.086 0.275 0.072 0.267 0.199 0.084

0.010 0.182 0.156 0.450 0.014 0.524 0.017 0.077 0.461

BMI: body mass index, HOMA-IR: homeostasis model assessment-insulin resistence, TC: total cholesterole, HDL: high-density lipoprotein, LDL: low-density lipoprotein, TG: triglycerides, fT: free testosterone, DHEASO4: dehydroepiandrosterone sulphate, and r: correlation coefficient. Bold values indicate statistically significant values. Table 3. Multiple regression analysis of possible factors affecting IL-6 levels. Variables PCOS BMI HDL TG

B 0.483 0.004 0.013 0.003

95% CI 0.001 0.077 0.035 0.002

to to to to

0.967 0.070 0.009 0.007

p 0.051 0.921 0.232 0.272

PCOS: polycystic ovary syndrome, BMI: body mass index, HDL: high-density lipoprotein, TG: triglycerides, CI: confidence interval, and B: coefficient of regression.

analyses were done with regard to BMI, no significant difference was found despite higher IL-6 levels in PCOS groups. Just like Mo¨hlig et al. [13], this study indicated that in PCOS women, IL-6 levels were not increased when compared with age and BMImatched controls. When multiple linear regression models were

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article

References 1. Wojciechowski P, Lipowska A, Rys P, et al. Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis. Diabetologia 2012;55: 2636–45. 2. Farrell K, Antoni MH. Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: biobehavioral mechanisms and interventions. Fertil Steril 2010;94:1565–74. 3. Frishman WH. Biologic markers as predictors of cardiovascular disease. Am J Med 1998;104:18S–27. 4. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135–43. 5. Kelly CC, Lyall H, Petrie JR, et al. Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 2001;86:2453–5. 6. Luque-Ramı´rez M, Escobar-Morreale HF. Treatment of polycystic ovary syndrome (PCOS) with metformin ameliorates insulin resistance in parallel with the decrease of serum interleukin-6 concentrations. Horm Metab Res 2010;42:815–20. 7. Chen MP, Chung FM, Chang DM, et al. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2006;91:295–9. 8. Kaya C, Pabuc¸cu R, Koca C, et al. Relationship between interleukin6 levels and ambulatory blood pressure in women with polycystic ovary syndrome. Fertil Steril 2010;94:1437–43. 9. Vgontzas AN, Trakada G, Bixler EO, et al. Plasma interleukin 6 levels are elevated in polycystic ovary syndrome independently of obesity or sleep apnea. Metabolism 2006;55:1076–82. 10. Fulghesu AM, Sanna F, Uda S, et al. IL-6 serum levels and production is related to an altered immune response in polycystic ovary syndrome girls with insulin resistance. Mediators Inflamm 2011;2011:389317. 11. Gonza´lez F, Rote NS, Minium J, Kirwan JP. Evidence of proatherogenic inflammation in polycystic ovary syndrome. Metabolism 2009;58:954–62. 12. Olszanecka-Glinianowicz M, Banas´ M, Zahorska-Markiewicz B, et al. Is the polycystic ovary syndrome associated with chronic inflammation per se? Eur J Obstet Gynecol Reprod Biol 2007;133: 197–202. 13. Mo¨hlig M, Spranger J, Osterhoff M, et al. The polycystic ovary syndrome per se is not associated with increased chronic inflammation. Eur J Endocrinol 2004;150:525–32. 14. Samy N, Hashim M, Sayed M, Said M. Clinical significance of inflammatory markers in polycystic ovary syndrome: their relationship to insulin resistance and body mass index. Dis Markers 2009; 26:163–70.

DOI: 10.3109/09513590.2014.895981

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15. Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41–7. 16. Vonbank A, Saely CH, Rein P, Drexel H. Insulin resistance is significantly associated with the metabolic syndrome, but not with sonographically proven peripheral arterial disease. Cardiovasc Diabetol 2013;12:106.

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17. Toulis KA, Goulis DG, Mintziori G, et al. Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome. Hum Reprod Update 2011;17: 741–60. 18. Escobar-Morreale HF, Luque-Ramı´rez M, Gonza´lez F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertil Steril 2011;95: 1048–58e1–2.

Interleukin-6 levels in relation with hormonal and metabolic profile in patients with polycystic ovary syndrome.

The aim of this study was to evaluate serum concentrations of interleukin-6 (IL-6) in relation with hormonal and metabolic profile in patients with an...
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