Investigation of Inflammatory Markers in Patients with Polycystic Ovary Syndrome Receiving and Not Receiving Metformin Treatment
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Teede, H.J.; Tay, C.T.; Laven, J.J.; Dokras, A.; Moran, L.J.; Piltonen, T.T.; Costello, M.F.; Boivin, J.; Redman, L.M.; Boyle, J.A.; et al. Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Eur. J. Endocrinol. 2023, 189, G43–G64. [Google Scholar] [CrossRef] [PubMed]
- Barthelmess, E.K.; Naz, R.K. Polycystic ovary syndrome current status and future perspective. Front. Biosci. 2014, 6, 104–119. [Google Scholar] [CrossRef]
- Armanini, D.; Boscaro, M.; Bordin, L.; Sabbadin, C. Controversies in the Pathogenesis, Diagnosis and Treatment of PCOS: Focus on Insulin Resistance, Inflammation, and Hyperandrogenism. Int. J. Mol. Sci. 2022, 23, 4110. [Google Scholar] [CrossRef]
- Patel, S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J. Steroid Biochem. Mol. Biol. 2018, 182, 27–36. [Google Scholar] [CrossRef]
- Bjekić-Macut, J.; Vukašin, T.; Velija-Ašimi, Z.; Bureković, A.; Zdravković, M.; Andrić, Z.; Branković, M.; Crevar-Marinović, S.; Madić, T.; Stanojlović, O.; et al. Polycystic Ovary Syndrome: A Contemporary Clinical Approach. Curr. Pharm. Des. 2021, 27, 3812–3820. [Google Scholar] [CrossRef]
- Onalan, E. The relationship between monocyte to high-density lipoprotein cholesterol ratio and diabetic nephropathy. Pak. J. Med. Sci. 2019, 35, 1081–1086. [Google Scholar] [CrossRef]
- Huddleston, H.G.; Dokras, A. Diagnosis and Treatment of Polycystic Ovary Syndrome. JAMA 2022, 327, 274–275. [Google Scholar] [CrossRef]
- Sadeghi, H.M.; Adeli, I.; Calina, D.; Docea, A.O.; Mousavi, T.; Daniali, M.; Nikfar, S.; Tsatsakis, A.; Abdollahi, M. Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing. Int. J. Mol. Sci. 2022, 23, 583. [Google Scholar] [CrossRef]
- The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil. Steril. 2004, 81, 19–25. [Google Scholar] [CrossRef]
- Xu, Y.; Qiao, J. Association of Insulin Resistance and Elevated Androgen Levels with Polycystic Ovarian Syndrome (PCOS): A Review of Literature. J. Healthc. Eng. 2022, 2022, 9240569. [Google Scholar] [CrossRef]
- van der Ham, K.; Stekelenburg, K.J.; Louwers, Y.V.; van Dorp, W.; Schreurs, M.W.; van der Wal, R.; Steegers-Theunissen, R.P.; Laven, J.S. The prevalence of thyroid dysfunction and hyperprolactinemia in women with PCOS. Front. Endocrinol. 2023, 14, 1245106. [Google Scholar] [CrossRef] [PubMed]
- Meng, X.; Xu, S.; Chen, G.; Derwahl, M.; Liu, C. Metformin and thyroid disease. J. Endocrinol. 2017, 233, R43–R51. [Google Scholar] [CrossRef] [PubMed]
- Atli, H.; Onalan, E.; Yakar, B.; Duzenci, D.; Donder, E. Predictive value of inflammatory and hematological data in diabetic and non-diabetic retinopathy. Eur. Rev. Med. Pharmacol. Sci. 2022, 26, 76–83. [Google Scholar] [CrossRef]
- Qin, B.; Ma, N.; Tang, Q.; Wei, T.; Yang, M.; Fu, H.; Hu, Z.; Liang, Y.; Yang, Z.; Zhong, R. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod. Rheumatol. 2016, 26, 372–376. [Google Scholar] [CrossRef]
- Li, Q.; Chen, P.; Shi, S.; Liu, L.; Lv, J.; Zhu, L.; Zhang, H. Neutrophil-to-lymphocyte ratio as an independent inflammatory indicator of poor prognosis in IgA nephropathy. Int. Immunopharmacol. 2020, 87, 106811. [Google Scholar] [CrossRef]
- Li, L.M.; Yu, J.M.; Zhou, Z.M. Association between neutrophil-to-lymphocyte ratio and polycystic ovary syndrome: A PRISMA-compliant systematic review and meta-analysis. Medicine 2022, 101, e30579. [Google Scholar] [CrossRef]
- Taşkömür, A.T.; Erten, Ö. Relationship of inflammatory and metabolic parameters in adolescents with PCOS: BMI matched case-control study. Arq. Bras. Endocrinol. Metabol. 2022, 66, 372–381. [Google Scholar] [CrossRef]
- Çakıroğlu, Y.; Vural, F.; Vural, B. The inflammatory markers in polycystic ovary syndrome: Association with obesity and IVF outcomes. J. Endocrinol. Investig. 2016, 39, 899–907. [Google Scholar] [CrossRef]
- Abraham Gnanadass, S.; Divakar Prabhu, Y.; Valsala Gopalakrishnan, A. Association of metabolic and inflammatory markers with polycystic ovarian syndrome (PCOS): An update. Arch. Gynecol. Obstet. 2021, 303, 631–643. [Google Scholar] [CrossRef]
- Liu, W.; Li, S.; Lou, X.; Li, D.; Wang, F.; Zhang, Z. Assessment of neutrophil to lymphocyte ratio, C-reactive protein, mean platelet volume in obese, and nonobese patients with polycystic ovary syndrome. Medicine 2022, 101, e29678. [Google Scholar] [CrossRef]
- Lee, H.A.; Choi, E.J.; Park, B.; Lee, H.; Hong, Y.S.; Kim, H.S.; Shin, M.-K.; Park, H. The association between metabolic components and markers of inflammatory and endothelial dysfunction in adolescents, based on the Ewha Birth and Growth Cohort Study. PLoS ONE 2020, 15, e0233469. [Google Scholar] [CrossRef] [PubMed]
- Moin, A.S.M.; Sathyapalan, T.; Atkin, S.L.; Butler, A.E. Inflammatory Markers in Non-Obese Women with Polycystic Ovary Syndrome Are Not Elevated and Show No Correlation with Vitamin D Metabolites. Nutrients 2022, 14, 3540. [Google Scholar] [CrossRef] [PubMed]
- Onalan, E.; Bozkurt, A.; Gursu, M.F.; Yakar, B.; Donder, E. Role of Betatrophin and Inflammation Markers in Type 2 Diabetes Mellitus, Prediabetes and Metabolic Syndrome. J. Coll. Physicians Surg. Pak. 2022, 32, 303–307. [Google Scholar] [CrossRef]
Variables | Control (n = 30) | PCOS + Metformin (n = 50) | PCOS (n = 30) | p | p * |
---|---|---|---|---|---|
Age (years) | 23.50 (18.0–35.0) | 22.00 (18.0–37.0) | 22.00 (18.0–37.0) | 0.825 b | |
Height (cm) | 161.6 ± 4.2 | 163.4 ± 5.4 | 162.9 ± 5.8 | 0.327 a | |
Weight (kg) | 55.5 ± 8.9 1 | 71.5 ± 13.1 2 | 62.7 ± 10.1 3 | <0.001 a | 1–2: <0.001 1–3: 0.043 2–3: 0.003 |
BMI (kg/m2) | 21.23 (14.7–30.1) 1 | 25.45 (19.5–44.6) 2 | 22.51 (14.9–33.3) 3 | <0.001 b | 1–2: <0.001 1–3: 0.023 2–3: 0.006 |
Systolic BP (mm/Hg) | 120.0 (110.0–130.0) | 120.0 (110.0–140.0) | 120.0 (110.0–140.0) | 0.051 b | |
Diastolic BP (mm/Hg) | 80.0 (60.0–80.0) | 70.0 (60.0–90.0) | 70.0 (60.0–90.0) | 0.823 b | |
Total cholesterol (mg/dL) | 161.4 ± 22.7 | 171.8 ± 31.9 | 163.3 ± 32.9 | 0.257 a | |
LDL (mg/dL) | 89.2 ± 20.9 | 99.9 ± 27.1 | 96.2 ± 30.3 | 0.218 a | |
HDL-C (mg/dL) | 61.9 ± 16.0 | 55.5 ± 12.7 | 62.6 ± 15.3 | 0.053 a | |
Glucose (mg/dL) | 87.5 ± 6.9 | 92.1 ± 11.4 | 90.4 ± 5.8 | 0.089 a | |
Insulin (µIU/mL) | 6.56 (1.01–10.20) 1 | 12.55 (2.67–67.10) 2 | 8.40 (3.04–25.70) 3 | <0.001 b | 1–2: <0.001 1–3: 0.003 2–3: 0.121 |
HOMA-IR | 1.34 (0.45–2.29) 1 | 2.86 (0.49–16.57) 2 | 1.88 (0.68–6.54) 3 | <0.001 b | 1–2: <0.001 1–3: 0.002 2–3: 0.126 |
TSH | 1.44 (0.14–5.13) 1 | 2.24 (0.59–9.00) 2 | 1.45 (0.29–5.79) 3 | 0.037 b | 1–2: 0.016 1–3: 0.515 2–3: 0.091 |
DHEA-SO4 | 221.5 (63.3–1815.0) | 257.4 (37.4–1100.0) | 277.5 (110.0–584.0) | 0.201 b | |
FSH (IU/L) | 7.17 (2.37–16.11) | 5.65 (0.05–18.97) | 6.31 (1.76.13.79) | 0.738 b | |
LH (IU/L) | 5.35 (1.17–43.64) | 6.29 (0.01–35.09) | 7.42 (0.01–43.64) | 0.179 b | |
LH/FSH ratio | 0.93 (0.32–3.58) | 1.29 (0.01–4.53) | 1.73 (0.32–4.48) | 0.106 b | |
E2 (IU/L) | 75.0 (20.40–340.00) 1 | 46.00 (9.90–222.00) 2 | 71.00 (10.10–346.00) 3 | 0.011 b | 1–2: 0.006 1–3: 0.031 2–3: 0.603 |
Urea (mg/dL) | 22.50 (15.0–49.0) | 20.50 (13.0–35.0) | 22.50 (12.0–47.0) | 0.134 b | |
Creatinine (mg/dL) | 0.63 ± 0.07 | 0.65 ± 0.09 | 0.66 ± 0.09 | 0.261 a | |
ALT (u/L) | 12.0 (7.0–31.0) 1 | 16.0 (3.0–67.0) 2 | 14.0 (7.0–48.0) 3 | 0.001 b | 1–2: <0.001 1–3: 0.007 2–3: 0.527 |
AST (u/L) | 17.0 (11.0–25.0) | 19.0 (11.0–39.0) | 17.0 (13.0–48.0) | 0.185 b | |
HbA1c | 5.3 ± 0.4 | 5.4 ± 0.5 | 5.2 ± 0.4 | 0.087 a | |
Hemoglobin | 13.65 (12.50–15.40) | 13.70 (10.00–15.30) | 13.90 (12.10–16.20) | 0.465 b | |
WBC | 6865.0 (4250.0–8630.0) | 7260.0 (3800.0–12,200.0) | 7855.0 (1770.0–11,240.0) | 0.016 b | 1–2: 0.120 1–3: 0.004 2–3: 0.099 |
Neutrophil | 3994.3 ± 1197.4 | 4322.0 ± 1577.2 | 4666.3 ± 1557.0 | 0.217 a | |
Lymphocyte | 2004.3 ± 498.8 | 2177.6 ± 584.7 | 2256.3 ± 553.5 | 0.197 a | |
Plt (103) | 256.2 ± 57.4 1 | 287.1 ± 58.9 2 | 248.5 ± 79.8 3 | 0.021 a | 1–2: 0.042 1–3: 0.646 2–3: 0.011 |
Variables | Control (n = 30) | PCOS + Metformin (n = 50) | PCOS (n = 30) | p | p * |
---|---|---|---|---|---|
CRP | 3.10 (2.50–5.00) 1 | 4.05 (1.00–22.60) 2 | 3.20 (3.00–7.30) 3 | <0.001 b | 1–2: <0.001 1–3: 0.336 2–3: 0.006 |
NLR | 2.11 ± 0.77 | 2.07 ± 0.83 | 2.15 ± 0.84 | 0.917 a | |
PLR | 115.21 ± 41.52 1 | 138.63 ± 37.71 2 | 133.06 ± 35.37 3 | 0.031 a | 1–2: 0.009 1–3: 0.043 2–3: 0.529 |
Variables | CONTROL | PCOS + Metformin | PCOS | |||
---|---|---|---|---|---|---|
NLR | PLR | NLR | PLR | NLR | PLR | |
PLR | r: 0.658 p: <0.001 | r: 0.485 p: <0.001 | r: 0.451 p: 0.012 | |||
CRP | r: −0.187 p: 0.322 | r: −0.330 p: 0.075 | r: 0.378 p: 0.007 | r: 0.183 p: 0.203 | r: −0.063 p: 0.742 | r: −0.055 p: 0.771 |
T. cholesterol | r: −0.063 p: 0.740 | r: −0.330 p: 0.075 | r: −0.247 p: 0.083 | r: −0.076 p: 0.600 | r: −0.092 p: 0.627 | r: −0.002 p: 0.993 |
LDL(mg/dL) | r: −0.052 p: 0.786 | r: −0.041 p: 0.829 | r: −0.194 p: 0.177 | r: −0.030 p: 0.836 | r: −0.058 p: 0.762 | r: 0.094 p: 0.622 |
HDL(mg/dL) | r: −0.184 p: 0.330 | r: −0.195 p: 0.303 | r: −0.222 p: 0.121 | r: −0.084 p: 0.563 | r: −0.384 p: 0.036 | r: −0.341 p: 0.066 |
Glucose(mg/dL) | r: 0.182 p: 0.337 | r: −0.062 p: 0.747 | r: 0.071 p: 0.624 | r: 0.279 p: 0.050 | r: −0.180 p: 0.342 | r: 0.216 p: 0.251 |
ALT | r: −0.197 p: 0.296 | r: 0.118 p: 0.534 | r: 0.043 p: 0.764 | r: 0.011 p: 0.942 | r: −0.177 p: 0.351 | r: 0.017 p: 0.927 |
AST | r: −0.306 p: 0.100 | r: 0.025 p: 0.896 | r: −0.099 p: 0.493 | r: −0.177 p: 0.218 | r: −0.278 p: 0.138 | r: 0.006 p: 0.977 |
Insulin | r: 0.314 p: 0.091 | r: 0.158 p: 0.404 | r: 0.078 p: 0.588 | r: 0.067 p: 0.643 | r: 0.248 p: 0.187 | r: 0.422 p: 0.020 |
HbA1c | r: −0.021 p: 0.914 | r: −0.143 p: 0.452 | r: −0.008 p: 0.954 | r: 0.119 p: 0.410 | r: −0.210 p: 0.266 | r: −0.038 p: 0.841 |
HOMA-IR | r: 0.353 p: 0.056 | r: 0.191 p: 0.313 | r: 0.096 p: 0.508 | r: 0.107 p: 0.458 | r: 0.257 p: 0.170 | r: 0.439 p: 0.015 |
TSH | r: −0.258 p: 0.169 | r: −0.347 p: 0.060 | r: −0.244 p: 0.088 | r: −0.113 p: 0.434 | r: −0.105 p: 0.581 | r: 0.036 p: 0.850 |
DHEA-SO4 | r: 0.321 p: 0.084 | r: 0.223 p: 0.236 | r: −0.053 p: 0.716 | r: −0.022 p: 0.882 | r: 0.133 p: 0.484 | r: 0.059 p: 0.759 |
FSH | r: 0.129 p: 0.495 | r: 0.176 p: 0.352 | r: 0.121 p: 0.404 | r: 0.325 p: 0.021 | r: 0.133 p: 0.485 | r: 0.255 p: 0.174 |
LH | r: 0.229 p: 0.223 | r: 0.309 p: 0.097 | r: 0.031 p: 0.830 | r: −0.032 p: 0.827 | r: −0.061 p: 0.750 | r: −0.046 p: 0.809 |
LH/FSH ratio | r: 0.064 p: 0.736 | r: 0.150 p: 0.430 | r: −0.008 p: 0.956 | r: −0.244 p: 0.088 | r: −0.199 p: 0.291 | r: −0.199 p: 0.291 |
E2 | r: −0.181 p: 0.338 | r: 0.122 p: 0.521 | r: 0.152 p: 0.291 | r: 0.036 p: 0.805 | r: 0.018 p: 0.926 | r: −0.163 p: 0.389 |
BMI | r: −0.137 p: 0.470 | r: 0.040 p: 0.834 | r: 0.241 p: 0.092 | r: 0.070 p: 0.628 | r: 0.322 p: 0.083 | r: 0.353 p: 0.056 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bulu, A.; Onalan, E.; Yakar, B.; Bulu, G.; Onalan Yıldırım, S.; Uğur, K.; Dönder, E. Investigation of Inflammatory Markers in Patients with Polycystic Ovary Syndrome Receiving and Not Receiving Metformin Treatment. Medicina 2025, 61, 1012. https://doi.org/10.3390/medicina61061012
Bulu A, Onalan E, Yakar B, Bulu G, Onalan Yıldırım S, Uğur K, Dönder E. Investigation of Inflammatory Markers in Patients with Polycystic Ovary Syndrome Receiving and Not Receiving Metformin Treatment. Medicina. 2025; 61(6):1012. https://doi.org/10.3390/medicina61061012
Chicago/Turabian StyleBulu, Aykut, Erhan Onalan, Burkay Yakar, Gülay Bulu, Senanur Onalan Yıldırım, Kader Uğur, and Emir Dönder. 2025. "Investigation of Inflammatory Markers in Patients with Polycystic Ovary Syndrome Receiving and Not Receiving Metformin Treatment" Medicina 61, no. 6: 1012. https://doi.org/10.3390/medicina61061012
APA StyleBulu, A., Onalan, E., Yakar, B., Bulu, G., Onalan Yıldırım, S., Uğur, K., & Dönder, E. (2025). Investigation of Inflammatory Markers in Patients with Polycystic Ovary Syndrome Receiving and Not Receiving Metformin Treatment. Medicina, 61(6), 1012. https://doi.org/10.3390/medicina61061012