Comparison of Insulin Resistance Markers in Three Groups of Iraqi Females with PCOS Taking Metformin, Spironolactone, or a Combination of Both
Keywords:
PCOS, hyperandrogenism, insulin resistance, hirsutism, metformin, spironolactoneAbstract
Background: Polycystic ovarian syndrome (PCOS) is an endocrine disrupting syndrome that affects numerous women of childbearing age. While part of the mechanism of causation in PCOS has been identified, the exact etiology and pathophysiology are not fully understood. PCOS has been related with hormonal and metabolic changes and may predispose people to a number of other conditions such as obesity, metabolic syndrome, hypertension, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).
Aim of the study: to compaire between the consequence of metformin alone versus metformin plus spironolactone combination regarding insuline resistance(insulin resistance test) in pcos Iraqi women
Patients and methods: The existing interventional prospective training included 150 patients between the ages of 18 and 40. Based on Rotterdam principles (Rotterdam, 2004), two obstetrics and gynecology specialists diagnosed those patients with polycystic ovarian syndrome (PCOS). In Iraq's Adiwaniyah Province, the Maternity and Pediatrics Teaching Hospital served as the source of the patients. The training is scheduled for September 1st, 2024, and is extended until March 1st, 2025.
Result; all three modalities of treatment, metformin, spironolactone and combination were able to reduce mean BMI, mean HOMA-IR, mean TyG, mean and TyG-BMI, mean TG/HDL significantly (p <0.001). The amount of changes in variable initiated via combination was the best.
Conclusion; The combination of spironolactone and metformin is more operative improving insulin sensitivity in women with PCOS as evident from TyG index, TyG-BMI index and HOMA-IR and (TG/HDL) index than.
References
1. 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.; et al. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. J. Clin. Endocrinol. Metab. 2023, 108, 2447–2469. [Google Scholar] [CrossRef
2. Teede, H.J.; Misso, M.L.; Costello, M.F.; Dokras, A.; Laven, J.; Moran, L.; Piltonen, T.; Norman, R.J.; on behalf of the International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil. Steril. 2018, 110, 364–379. [Google Scholar] [CrossRef]
3. Teede H, Deeks A, Moran L. Polycystic ovary syndrome: A complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 2010;8:41. doi: 10.1186/1741-7015-8-41
4. Teede HJ, Hutchison SK, Zoungas S. The management of insulin resistance in polycystic ovary syndrome. Trends Endocrinol Metab 2007;18:273–279.)
5. Amisi CA. Markers of insulin resistance in polycystic ovary syndrome women: an update. World J Diabetes. (2022) 13:129–49. doi: 10.4239/wjd.v13.i3.129
6. Pani A, Gironi I, Di Vieste G, Mion E, Bertuzzi F, Pintaudi B. From prediabetes to type 2 diabetes mellitus in women with polycystic ovary syndrome: lifestyle and pharmacological management. Int J Endocrinol. (2020) 2020:6276187. doi: 10.1155/2020/6276187
7. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. (2012) 33:981–1030. doi: 10.1210/er.2011-1034
8. Minooee, S., F.R. Tehrani, P. Mirmiran and F. Azizi, 2016. Low birth weight may increase body fat mass in adult women with polycystic ovarian syndrome. Int. J. Reprod. Biomed., 14: 335‐340.
9. Bulsara, J., P. Patel, A. Soni and S. Acharya, 2021. A review: Brief insight into polycystic ovarian syndrome. Endocr. Metab. Sci., Vol. 3. 10.1016/j.endmts.2021.100085
10. Curi, D.D.G., A.M. Fonseca, J.A.M. Marcondes, J.A.M. Almeida, V.R. Bagnoli, J.M. Soares and E.C. Baracat, 2012. Metformin versus lifestyle changes in treating women with polycystic ovary syndrome. Gynecol. Endocrinol., 28: 182‐185.
11. Demirel, F., A. Bideci, P. Cinaz, M.O. Çamurdan, G. Biberoglu, E. Yesilkaya and A. Hasanoglu, 2007. Serum leptin, oxidized low density lipoprotein and plasma asymmetric dimethylarginine and their relationship with dyslipidaemia in adolescent girls with polycystic ovary syndrome. Clin. Endocrinol., 67: 129‐134.
12. Dumesic, D.A., S.E. Oberfield, E. Stener‐Victorin, J.C. Marshall, J.S. Laven and R.S. Legro, 2015. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr. Rev., 36: 487‐525.
13. Escobar‐Morreale, H.F., 2018. Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment. Nat. Rev. Endocrinol., 14: 270‐284.
14. Azziz, R.; Carmina, E.; Chen, Z.; Dunaif, A.; Laven, J.S.; Legro, R.S.; Lizneva, D.; Natterson-Horowtiz, B.; Teede, H.J.; Yildiz, B.O. Polycystic ovary syndrome. Nat. Rev. Dis Primers 2016, 2, 16057. [Google Scholar] [CrossRef]
15. Lashan R (2010) Role of metformin in the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab 1(3):117–128
16. Mohammadi S, Kayedpoor P, Karimzadeh-Bardei (2017) The effect of Curcumin on TNF-α, IL-6 and CRP expression in a model of polycystic ovary syndrome as an infammation state. J Reprod Infertil 18(4):352–360
17. Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol (2018) 14(5):270–84. doi: 10.1038/nrendo.2018.24
18. Long, T., Zhang, Y., Zeng, C., Zheng, S., Zhou, L., & Liu, H. (2022). Effects of Low-Dose Spironolactone Combined with Metformin or Either Drug Alone on Insulin Resistance in Patients with Polycystic Ovary Syndrome: A Pilot Study. International journal of endocrinology, 2022, 9927240. https://doi.org/10.1155/2022/9927240
19. Zeng, H., Zhang, Y., Huang, S., Wu, J., Ren, W., Zhou, L., Huang, L., & Ye, Y. (2023). Metformin combined with spironolactone vs. metformin alone in polycystic ovary syndrome: a meta-analysis. Frontiers in endocrinology, 14, 1223768. https://doi.org/10.3389/fendo.2023.1223768
20. Diri, H., Karaburgu, S., Acmaz, B., Unluhizarci, K., Tanriverdi, F., Karaca, Z., & Kelestimur, F. (2016). Comparison of spironolactone and spironolactone plus metformin in the treatment of polycystic ovary syndrome. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 32(1), 42–45. https://doi.org/10.3109/09513590.2015.1080679
21. Areloegbe, S. E., Peter, M. U., Oyeleke, M. B., & Olaniyi, K. S. (2022). Low-dose spironolactone ameliorates adipose tissue inflammation and apoptosis in letrozole-induced PCOS rat model. BMC endocrine disorders, 22(1), 224. https://doi.org/10.1186/s12902-022-01143-y
22. Olaniyi, K. S., Areloegbe, S. E., Areola, E. D., Sabinari, I. W., Fafure, A. A., Agbana, R. D., Atuma, C. L., Shah, M. Z. U. H., Ajadi, I. O., & Olatunji, L. A. (2023). Low-dose spironolactone combats dyslipidemia and hepatic inflammation by modulating PCSK9 in rat model of polycystic ovarian syndrome. Toxicology and applied pharmacology, 473, 116604. https://doi.org/10.1016/j.taap.2023.116604
23. Duleba A. J. (2012). Medical management of metabolic dysfunction in PCOS. Steroids, 77(4), 306–311. https://doi.org/10.1016/j.steroids.2011.11.014
24. Shamim, H., Jean, M., Umair, M., Muddaloor, P., Farinango, M., Ansary, A., Dakka, A., Nazir, Z., White, C. T., Habbal, A. B., & Mohammed, L. (2022). Role of Metformin in the Management of Polycystic Ovarian Syndrome-Associated Acne: A Systematic Review. Cureus, 14(8), e28462. https://doi.org/10.7759/cureus.28462
25. Diamanti-Kandarakis, E., Alexandraki, K., Protogerou, A., Piperi, C., Papamichael, C., Aessopos, A., Lekakis, J., & Mavrikakis, M. (2005). Metformin administration improves endothelial function in women with polycystic ovary syndrome. European journal of endocrinology, 152(5), 749–756. https://doi.org/10.1530/eje.1.01910
26. Banaszewska, B., Pawelczyk, L., Spaczynski, R. Z., & Duleba, A. J. (2011). Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment. The Journal of clinical endocrinology and metabolism, 96(11), 3493–3501. https://doi.org/10.1210/jc.2011-0501
27. Wada, T., Kenmochi, H., Miyashita, Y., Sasaki, M., Ojima, M., Sasahara, M., Koya, D., Tsuneki, H., & Sasaoka, T. (2010). Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. Endocrinology, 151(5), 2040–2049. https://doi.org/10.1210/en.2009-0869
28. Nakhjavani M, Hamidi S, Esteghamati A, Abbasi M, Nosratian-Jahromi S, Pasalar P. Short term effects of spironolactone on blood lipid profile: a 3-month study on a cohort of young women with hirsutism. Br J Clin Pharmacol. 2009 Oct;68(4):634-7. doi: 10.1111/j.1365-2125.2009.03483.x. PMID: 19843067; PMCID: PMC2780289.
