Association of Homocysteine with body mass index in women with polycystic ovary Syndrome
-
Asma Kheirollahi
,
Akram Vatannejad Vatannejad
,
Sara Bayat
,
Maryam Teimouri
,
Molood Bagherieh
,
Farzad Amiri
,
Faezeh Fattahi
,
Farah Jadidizadeh
Abstract
Objectives: Polycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder that significantly impacts women. It is closely associated with metabolic syndrome and obesity. However, the exact interplay between serum homocysteine levels and body mass index (BMI) in PCOS patients remains incompletely understood. In this study, we investigated the levels of homocysteine in normal weight and overweight/obese Iranian women with and without PCOS.
Methods: 189 women with PCOS and 86 healthy and fertile women were entered in the study. The patients and controls were divided according to BMI into two groups as follow: BMI<25 Kg/m2 and BMI≥ 25 Kg/m2. Blood Samples were collected from all participants to assess fasting blood glucose, fasting insulin, lipid profile, free testosterone and homocysteine levels.
Results: BMI, HOMA-IR, fasting insulin, TC, LDL and free testosterone levels were significantly elevated in the PCOS group when compared with controls. Homocysteine levels were increased in both overweight/obese and normal weight PCOS groups compared with controls. However, no significant association was observed between homocysteine levels in overweight/obese PCOS group vs. normal weight PCOS group.
Conclusion: The results of this study showed that homocysteine levels were notably elevated in women with PCOS, regardless of their BMI.
1. Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016;106(1):6-15. https://doi.org/10.1016/j.fertnstert.2016.05.003
2. Group REASPCW. Revised 2003 consensus on diagnostic criteria and long‐term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-7. https://doi.org/10.1093/humrep/deh098
3. Daniilidis A, Dinas K. Long term health consequences of polycystic ovarian syndrome: a review analysis. Hippokratia. 2009;13(2):90-2.
4. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013;6:1-13. https://doi.org/10.2147/CLEP.S37559
5. Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999;19(1):217-46. https://doi.org/10.1146/annurev.nutr.19.1.217
6. Gori AM, Corsi AM, Fedi S, Gazzini A, Sofi F, Bartali B, et al. A proinflammatory state is associated with hyperhomocysteinemia in the elderly. Am J Clin Nutr. 2005;82(2):335-41. https://doi.org/10.1093/ajcn/82.2.335
7. Zhang L, Jin M, Hu XS, Zhu JH. Homocysteine stimulates nuclear factor kappaB activity and interleukin-6 expression in rat vascular smooth muscle cells. Cell Biol Int. 2006;30(7):592-7. https://doi.org/10.1016/j.cellbi.2006.03.007
8. Shai I, Stampfer MJ, Ma J, Manson JE, Hankinson SE, Cannuscio C, et al. Homocysteine as a risk factor for coronary heart diseases and its association with inflammatory biomarkers, lipids and dietary factors. Atherosclerosis. 2004;177(2):375-81. https://doi.org/10.1016/j.atherosclerosis.2004.07.020
9. Bhushan R, Sinha P. Correlation of Serum Homocysteine Levels and Hyperinsulinaemia with Body Mass Index in Polycystic Ovarian Syndrome. J Hum Reprod Sci. 2022;15(1):34-41. https://doi.org/10.4103/jhrs.jhrs_147_21
10. Chang H, Xie L, Ge H, Wu Q, Wen Y, Zhang D, et al. Effects of hyperhomocysteinaemia and metabolic syndrome on reproduction in women with polycystic ovary syndrome: a secondary analysis. Reprod Biomed Online. 2019;38(6):990-8. https://doi.org/10.1016/j.rbmo.2018.12.046
11. Sreckovic B, Sreckovic VD, Soldatovic I, Colak E, Sumarac-Dumanovic M, Janeski H, et al. Homocysteine is a marker for metabolic syndrome and atherosclerosis. Diabetes Metab Syndr: Clin Res Rev. 2017;11(3):179-82. https://doi.org/10.1016/j.dsx.2016.08.026
12. Maleedhu P, M V, S SBS, Kodumuri PK, Devi DV. Status of Homocysteine in Polycystic Ovary Syndrome (PCOS). J Clin Diagn Res. 2014;8(2):31-3. https://doi.org/10.7860/JCDR/2014/7070.3999
13. Wang J, You D, Wang H, Yang Y, Zhang D, Lv J, et al. Association between homocysteine and obesity: a meta‐analysis. J Evid-Based Med. 2021;14(3):208-17. https://doi.org/10.1111/jebm.12412
14. Wang Y, Jiang Y, Wang N, Zhu M, Liu X, Wang R, et al. Central but not general obesity is positively associated with the risk of hyperhomocysteinemia in middle-aged women. Nutrients. 2019;11(7):1614. https://doi.org/10.3390/nu11071614
15. Rekha S, Patel M, Pooja G, Amita D, Pushplata S, Natu S. Correlation between elevated homocysteine levels and insulin resistance in infertile women with or without polycystic ovary syndrome in North Indian population. Int J Med Med Sci. 2013;5:116-23.
16. Fouani FZ, Fadaei R, Moradi N, Zandieh Z, Ansaripour S, Yekaninejad MS, et al. Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study. PLoS One. 2020;15(4):e0231943. https://doi.org/10.1371/journal.pone.0231943
17. Sadeghi A, Fadaei R, Moradi N, Fouani FZ, Roozbehkia M, Zandieh Z, et al. Circulating levels of C1q/TNF-alpha-related protein 6 (CTRP6) in polycystic ovary syndrome. IUBMB Life. 2020;72(7):1449-59. https://doi.org/10.1002/iub.2272
18. Vatannejad A, Salimi F, Moradi N, Fouani FZ, Zandieh Z, Ansaripour S, et al. Evaluation of angiopoietin-like protein 3 (ANGPTL3) levels in polycystic ovary syndrome. Life Sci. 2020;263:118595. https://doi.org/10.1016/j.lfs.2020.118595
19. Narani MS, Vatannejad A, Kheirollahi A, Teimouri M, Bayat S, Jadidzadeh F. Changes of biochemical parameters in normal weight and overweight/obese women with polycystic ovary Syndrome. Acta Biochim Iran. 2023;1(3):119-25. https://doi.org/10.18502/abi.v1i3.14547
20. Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Assessment of insulin sensitivity/resistance. Indian J Endocrinol Metab. 2015;19(1):160-4. https://doi.org/10.4103/2230-8210.146874
21. Wu JT. Circulating homocysteine is an inflammation marker and a risk factor of life-threatening inflammatory diseases. J Biomed Lab Sci. 2007;19(4):107-11.
22. Chen Y, Liu H, Zhang H, Liu E, Xu C-B, Su X. The sirt1/NF-kB signaling pathway is involved in regulation of endothelin type B receptors mediated by homocysteine in vascular smooth muscle cells. Biomed Pharmacother. 2016;84:1979-85. https://doi.org/10.1016/j.biopha.2016.11.011
23. Diamanti-Kandarakis E, Kandarakis H, Legro RS. The role of genes and environment in the etiology of PCOS. Endocrine. 2006;30(1):19-26. https://doi.org/10.1385/ENDO:30:1:19
24. Qi X, Zhang B, Zhao Y, Li R, Chang HM, Pang Y, et al. Hyperhomocysteinemia Promotes Insulin Resistance and Adipose Tissue Inflammation in PCOS Mice Through Modulating M2 Macrophage Polarization via Estrogen Suppression. Endocrinology. 2017;158(5):1181-93. https://doi.org/10.1210/en.2017-00039
25. Ding H, Zhang J, Zhang F, Zhang S, Chen X, Liang W, et al. Resistance to the Insulin and Elevated Level of Androgen: A Major Cause of Polycystic Ovary Syndrome. Front Endocrinol (Lausanne). 2021;12:741764. https://doi.org/10.3389/fendo.2021.741764
26. Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron‐El R. Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Hum Reprod. 2003;18(4):721-7. https://doi.org/10.1093/humrep/deg190
27. Badawy A, State O, El Gawad SSA, El Aziz OA. Plasma homocysteine and polycystic ovary syndrome: the missed link. Eur J Obstet Gynecol Reprod Biol. 2007;131(1):68-72. https://doi.org/10.1016/j.ejogrb.2006.10.015
28. Sadaria RG, Vasava SN. Association of BMI with Serum Homocysteine in Polycystic Ovarian Syndrome Women. Indian J Forensic Med Toxicol. 2021;15(2). https://doi.org/10.37506/ijfmt.v15i2.14391
29. Meyer C, McGrath BP, Teede HJ. Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease. J Clin Endocrinol Metab. 2005;90(10):5711-6. https://doi.org/10.1210/jc.2005-0011
30. Franks S. Polycystic ovary syndrome: a changing perspective. Clin Endocrinol (Oxf). 1989;31(1):87-120. https://doi.org/10.1111/j.1365-2265.1989.tb00457.x
31. Robinson S, Rodin D, Deacon A, Wheeler M, Clayton R. Which hormone tests for the diagnosis of polycystic ovary syndrome? BJOG: Int J Obstet Gynaecol. 1992;99(3):232-8. https://doi.org/10.1111/j.1471-0528.1992.tb14505.x
32. Yoshino K, Takahashi K, Eda Y, Okada S, Kitao M. Plasma androgens and sex hormone binding globulin in women with polycystic ovaries diagnosed by transvaginal ultrasound. J Reprod Med. 1993;38(11):858-62.
33. Yasmin E, Balen AH, Barth JH. The association of body mass index and biochemical hyperandrogenaemia in women with and without polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;166(2):173-7. https://doi.org/10.1016/j.ejogrb.2012.09.025
2. Group REASPCW. Revised 2003 consensus on diagnostic criteria and long‐term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-7. https://doi.org/10.1093/humrep/deh098
3. Daniilidis A, Dinas K. Long term health consequences of polycystic ovarian syndrome: a review analysis. Hippokratia. 2009;13(2):90-2.
4. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013;6:1-13. https://doi.org/10.2147/CLEP.S37559
5. Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999;19(1):217-46. https://doi.org/10.1146/annurev.nutr.19.1.217
6. Gori AM, Corsi AM, Fedi S, Gazzini A, Sofi F, Bartali B, et al. A proinflammatory state is associated with hyperhomocysteinemia in the elderly. Am J Clin Nutr. 2005;82(2):335-41. https://doi.org/10.1093/ajcn/82.2.335
7. Zhang L, Jin M, Hu XS, Zhu JH. Homocysteine stimulates nuclear factor kappaB activity and interleukin-6 expression in rat vascular smooth muscle cells. Cell Biol Int. 2006;30(7):592-7. https://doi.org/10.1016/j.cellbi.2006.03.007
8. Shai I, Stampfer MJ, Ma J, Manson JE, Hankinson SE, Cannuscio C, et al. Homocysteine as a risk factor for coronary heart diseases and its association with inflammatory biomarkers, lipids and dietary factors. Atherosclerosis. 2004;177(2):375-81. https://doi.org/10.1016/j.atherosclerosis.2004.07.020
9. Bhushan R, Sinha P. Correlation of Serum Homocysteine Levels and Hyperinsulinaemia with Body Mass Index in Polycystic Ovarian Syndrome. J Hum Reprod Sci. 2022;15(1):34-41. https://doi.org/10.4103/jhrs.jhrs_147_21
10. Chang H, Xie L, Ge H, Wu Q, Wen Y, Zhang D, et al. Effects of hyperhomocysteinaemia and metabolic syndrome on reproduction in women with polycystic ovary syndrome: a secondary analysis. Reprod Biomed Online. 2019;38(6):990-8. https://doi.org/10.1016/j.rbmo.2018.12.046
11. Sreckovic B, Sreckovic VD, Soldatovic I, Colak E, Sumarac-Dumanovic M, Janeski H, et al. Homocysteine is a marker for metabolic syndrome and atherosclerosis. Diabetes Metab Syndr: Clin Res Rev. 2017;11(3):179-82. https://doi.org/10.1016/j.dsx.2016.08.026
12. Maleedhu P, M V, S SBS, Kodumuri PK, Devi DV. Status of Homocysteine in Polycystic Ovary Syndrome (PCOS). J Clin Diagn Res. 2014;8(2):31-3. https://doi.org/10.7860/JCDR/2014/7070.3999
13. Wang J, You D, Wang H, Yang Y, Zhang D, Lv J, et al. Association between homocysteine and obesity: a meta‐analysis. J Evid-Based Med. 2021;14(3):208-17. https://doi.org/10.1111/jebm.12412
14. Wang Y, Jiang Y, Wang N, Zhu M, Liu X, Wang R, et al. Central but not general obesity is positively associated with the risk of hyperhomocysteinemia in middle-aged women. Nutrients. 2019;11(7):1614. https://doi.org/10.3390/nu11071614
15. Rekha S, Patel M, Pooja G, Amita D, Pushplata S, Natu S. Correlation between elevated homocysteine levels and insulin resistance in infertile women with or without polycystic ovary syndrome in North Indian population. Int J Med Med Sci. 2013;5:116-23.
16. Fouani FZ, Fadaei R, Moradi N, Zandieh Z, Ansaripour S, Yekaninejad MS, et al. Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study. PLoS One. 2020;15(4):e0231943. https://doi.org/10.1371/journal.pone.0231943
17. Sadeghi A, Fadaei R, Moradi N, Fouani FZ, Roozbehkia M, Zandieh Z, et al. Circulating levels of C1q/TNF-alpha-related protein 6 (CTRP6) in polycystic ovary syndrome. IUBMB Life. 2020;72(7):1449-59. https://doi.org/10.1002/iub.2272
18. Vatannejad A, Salimi F, Moradi N, Fouani FZ, Zandieh Z, Ansaripour S, et al. Evaluation of angiopoietin-like protein 3 (ANGPTL3) levels in polycystic ovary syndrome. Life Sci. 2020;263:118595. https://doi.org/10.1016/j.lfs.2020.118595
19. Narani MS, Vatannejad A, Kheirollahi A, Teimouri M, Bayat S, Jadidzadeh F. Changes of biochemical parameters in normal weight and overweight/obese women with polycystic ovary Syndrome. Acta Biochim Iran. 2023;1(3):119-25. https://doi.org/10.18502/abi.v1i3.14547
20. Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Assessment of insulin sensitivity/resistance. Indian J Endocrinol Metab. 2015;19(1):160-4. https://doi.org/10.4103/2230-8210.146874
21. Wu JT. Circulating homocysteine is an inflammation marker and a risk factor of life-threatening inflammatory diseases. J Biomed Lab Sci. 2007;19(4):107-11.
22. Chen Y, Liu H, Zhang H, Liu E, Xu C-B, Su X. The sirt1/NF-kB signaling pathway is involved in regulation of endothelin type B receptors mediated by homocysteine in vascular smooth muscle cells. Biomed Pharmacother. 2016;84:1979-85. https://doi.org/10.1016/j.biopha.2016.11.011
23. Diamanti-Kandarakis E, Kandarakis H, Legro RS. The role of genes and environment in the etiology of PCOS. Endocrine. 2006;30(1):19-26. https://doi.org/10.1385/ENDO:30:1:19
24. Qi X, Zhang B, Zhao Y, Li R, Chang HM, Pang Y, et al. Hyperhomocysteinemia Promotes Insulin Resistance and Adipose Tissue Inflammation in PCOS Mice Through Modulating M2 Macrophage Polarization via Estrogen Suppression. Endocrinology. 2017;158(5):1181-93. https://doi.org/10.1210/en.2017-00039
25. Ding H, Zhang J, Zhang F, Zhang S, Chen X, Liang W, et al. Resistance to the Insulin and Elevated Level of Androgen: A Major Cause of Polycystic Ovary Syndrome. Front Endocrinol (Lausanne). 2021;12:741764. https://doi.org/10.3389/fendo.2021.741764
26. Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron‐El R. Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Hum Reprod. 2003;18(4):721-7. https://doi.org/10.1093/humrep/deg190
27. Badawy A, State O, El Gawad SSA, El Aziz OA. Plasma homocysteine and polycystic ovary syndrome: the missed link. Eur J Obstet Gynecol Reprod Biol. 2007;131(1):68-72. https://doi.org/10.1016/j.ejogrb.2006.10.015
28. Sadaria RG, Vasava SN. Association of BMI with Serum Homocysteine in Polycystic Ovarian Syndrome Women. Indian J Forensic Med Toxicol. 2021;15(2). https://doi.org/10.37506/ijfmt.v15i2.14391
29. Meyer C, McGrath BP, Teede HJ. Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease. J Clin Endocrinol Metab. 2005;90(10):5711-6. https://doi.org/10.1210/jc.2005-0011
30. Franks S. Polycystic ovary syndrome: a changing perspective. Clin Endocrinol (Oxf). 1989;31(1):87-120. https://doi.org/10.1111/j.1365-2265.1989.tb00457.x
31. Robinson S, Rodin D, Deacon A, Wheeler M, Clayton R. Which hormone tests for the diagnosis of polycystic ovary syndrome? BJOG: Int J Obstet Gynaecol. 1992;99(3):232-8. https://doi.org/10.1111/j.1471-0528.1992.tb14505.x
32. Yoshino K, Takahashi K, Eda Y, Okada S, Kitao M. Plasma androgens and sex hormone binding globulin in women with polycystic ovaries diagnosed by transvaginal ultrasound. J Reprod Med. 1993;38(11):858-62.
33. Yasmin E, Balen AH, Barth JH. The association of body mass index and biochemical hyperandrogenaemia in women with and without polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;166(2):173-7. https://doi.org/10.1016/j.ejogrb.2012.09.025
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| Issue | Vol 3 No 1 (2025) | |
| Section | Original Articles | |
| Keywords | ||
| Polycystic ovarian syndrome Homocysteine Body mass index Obesity | ||
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How to Cite
1.
Kheirollahi A, Vatannejad AV, Bayat S, Teimouri M, Bagherieh M, Amiri F, Fattahi F, Jadidizadeh F. Association of Homocysteine with body mass index in women with polycystic ovary Syndrome. ABI. 2025;3(1):17-22.
