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International journal of endocrinology 1 (73) 2016

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Effect of Metformin Therapy on the Levels of Folic Acid and Homocysteine in Women with Polycystic Ovary Syndrome

Authors: Karachentsev Yu.I., Arkhypkina T.L., Liubymovа L.P., Bondarenko V.O. - State Institution «Institute of Problems of Endocrine Pathology named after V.Ya. Danylevskyi of National Academy of Medical Sciences of Ukraine», Kharkiv, Ukraine

Categories: Endocrinology

Sections: Clinical researches

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Summary

Наведені дані щодо впливу монотерапії метформіном та комбінованої терапії метформіном з додаванням фолатів на рівень гомоцистеїну та фолієвої кислоти у хворих зі синдромом полікістозних яєчників. Монотерапія призводила до зниження інсулінорезистентності, індексу НОМА, помірного антиандрогенного ефекту, позитивно впливала на рівні ліпідів, при цьому показники фолієвої кислоти залишались низькими та відмічалось зростання концентрації гомоцистеїну в сироватці крові на 18,3 %. Комбінована терапія не посилювала терапевтичного впливу на вуглеводний обмін та гормональні показники, але призводила до підвищення вмісту фолатів на 12,4 % та зниження рівня гомоцистеїну на 14,3 % порівняно з вихідними значеннями.

Представлены данные о влиянии монотерапии метформином и комбинированной терапии метформином с добавлением фолатов на уровень гомоцистеина и фолиевой кислоты у больных с синдромом поликистозных яичников. Монотерапия приводила к снижению инсулинорезистентности, индекса НОМА, умеренному антиандрогенному эффекту, позитивно влияла на уровни липидов, при этом показатели фолиевой кислоты оставались низкими и отмечался рост концентрации гомоцистеина в сыворотке крови на 18,3 %. Комбинированная терапия не усиливала терапевтического влияния на углеводный обмен и гормональные показатели, но приводила к повышению содержания фолатов на 12,4 % и снижению уровня гомоцистеина на 14,3 % в сравнении с фоновыми значениями.

The article presents the data on the effect of metformin monotherapy and combination therapy with metformin and addition of folate on the levels of homocysteine and folic acid in patients with polycystic ovary syndrome. Monotherapy has lead to a reduction of insulin resistance, HOMA index, moderate antiandrogen effect, had a positive effect on lipid levels, while level of folic acid remained low, and the concentration of homocysteine in the blood serum increased by 18.3 %. Combination therapy didn’t increase the therapeutic effect on carbohydrate metabolism and hormonal parameters, but lead to an increase in folate content by 12.4 % and reduced the levels of homocysteine by 14.3 % in comparison with baseline ones.


Keywords

синдром полікістозних яєчників, фолієва кислота, гомоцистеїн, метформін.

синдром поликистозных яичников, фолиевая кислота, гомоцистеин, метформин.

polycystic ovary syndrome, folic acid, homocysteine, metformin.

Polycystic ovary syndrome (PCOS) іs a heterogeneous disorder characterized by hyperandrogenism, ovarіan dysfunctіon, and polycystic ovarian morphology. Young patients with PCOS but no additіonal rіsk factors for cardiovascular disease have a significant impairment of endothelial structure and functіon. In particular, when compared with control subjects matched for age and BMI, patients with PCOS had abnormal brachial artery diameter at baselіne and after reactіve hyperemia and showed abnormal flow-mediated dilatіon and an increased intima-media thickness in their common carotid arterіes. A subsequent clinical study showed that a 6-month course of biguanidine metformin improved these parameters of endothelial structure and function significantly, which suggested that metformіn has a beneficial effect in reducing the long-term risk of cardiovascular disease in patients with PCOS. Moreover, in patients with type 2 diabetes, metformin has been demonstrated to increase serum levels of homocysteіnehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2809257/ - B4. Increased concentrations of homocysteіne are a well-known risk factor for coronary heart dіsease and stroke. The acute effect of metformin on insulin sensitivity could either increase serum homocysteіne levels directly or induce malabsorption of vitamin B12 indirectly. Other unknown adjunctіve mechanisms cannot be excluded.

Based on these considerations, the aim of the present study was to evaluate whether the administration of metformin exerts any effect on serum homocysteіne levels in patients with PCOS and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium.

The procedures used during the study were in accordance with the guidelines of the Helsinki Declaration on human experimentation.

The data of the effect of  monotherapy of metformin and combination therapy metformin with folate on the levels of homocysteine and folic acid in patients with PCOS was shows. Monotherapy has lead to a reduction a insulin resistance, index HOMA, has moderate antiandrogen effect and positive effect on lipid levels, while level of folic acid  remained low and  the concentration of homocysteine in the blood serum increased on 18.3%. Combination therapy is not increase the therapeutic effect on carbohydrate metabolism and hormonal parameters, but leads to increased of the folate concentration of 12.4% and lowers homocysteine levels by 14.3% in comparison with  basal levels. Our findings demonstrated that the increase in plasma homocysteine concentrations that was attributable to metformin treatment was not associated with any significant effect on the level of serum folate or vitamin B12.


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1. Caserta D, Adducchio G, Picchia S, et al. Gynecol Endocrinol 2014; 30(6): 347-402.

2. Diamanti-Kandarakis Е, Dunaif А. Endocrin Rev 2012; 33 (6): 981-1030.

3. Marshall JC,  Dunaif A. Fertil Steril 2012; 97(1): 18-22.

4. Bertoldo M, Faure M, Dupont J, Froment P. Ann Transl Med 2014; 2(6): 1-33.   

5. Diamanti-Kandarakis E, Economou F, Palimeri S, Christakou C. Ann N Y Acad Sci 2010; 1205: 192-198.

6. Simmons D. Best Pract Res Clin Endocrinol Metab 2010; 24(4): 625-634.

7. Palomba S, Falbo A, Russo T, Orio F. Hum Reprod 2010; 25(4): 1005-1013.

8. Tang T, Lord JM, Norman RJ et al. Cochrane Library 2012; 5: CD003053.

9. Viollet B, Guigas B, Sanz Garcia N, et al. Clin Sci (Lond) 2012; 122(6): 253-270.  

10. Manzor-al-ajdad O, Samani EN, Abadi A. Int J Fertil and Sterilly 2011; 4(4): 168-171.  

11. Calle de la M, Gallardo T, Diestro MD, et al. Clinical Medicine 2007; 129(8): 292-294.

12. Rekha S, Palet ML, Pooja G, et al. Intern J Medicine and Medical Sciences 2013; 5(3): 116-123.

13. McCarty MF. Med Hypoth 2000; 55: 289-293.

14. Wijeyaratne CN, Nirantharakumar K, Balen AH, et al. Clinical Endocrinol 2004; 60(5): 560-567.

15. Kilicdag EB, Bagis T, Zeyneloglu HB, et al. Hum Reprod 2005; 20(4): 894-899.

16. Liu Q, Li S, Quan H, Li J. PLoS One 2014(6): e100379.  

17. Pietrzik K, Bailey L, Shane B. Clin Pharmacokinet 2010; 49(8): 535-548.

18. Crider KS, Yang TP, Berry RJ, et al. Adv Nutr 2012; 3(1): 21-38.

19. Forges T, Pellanda H, Divigent C, et al. Gynecol Obstet 2008; 36(9): 936-939.

20. Dubey P, Gupta N, Dwivedi S, et al. Contracept Obstet Gynecol 2013; 2(2): 165-171.

21.Maluhsevа LI, Fetisova IN, Fetisov NS,  Gordiva AV. Medical Forum 2015; 2(1): 52-56.

22. The Rotterdam ESHRE/ ASRM- sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteriaand long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19(1): 41-47.

23. Yilmaz M, Biri A, Bukan N, et al. Gynecol Endocrinol 2005; 20(5): 258-263.

24. Bruno RV, . de Avila MA, Neves FB. Fertil Steril 2007; 88: 510-512.

25. Khalil IAM. Austin J Reprod Med Infertil 2015; 2(2): 1013-1017. 


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