Skip to main content

Advertisement

Log in

Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome

  • News and Views
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin.

Methods

We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS—13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers.

Results

Total MPs levels were lower in treated patients (59.58 ± 28.43 MPs/µL) when compared to untreated group (97.32 ± 59.42; p = 0.033). Plasma levels of TFMPs were also significantly lower in the group of patients who used metformin (1.10 ± 0.94 MPs/µL) when compared to untreated patients (2.20 ± 1.42 MPs/µL) (p = 0.003).

Conclusions

Considering that metformin reduced the levels of total MPs and TFMPs, our results suggest that this mechanism could be involved in the antithrombotic metformin effect, corroborating with the indication of this drug in the PCOS treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Palomba S, Falbo SSA, La Sala GB (2015) Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health 7:745–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Glintborg D, Sidelmann JJ, Altinok ML, Mumma H, Andersen M (2015) Increased thrombin generation in women with polycystic ovary syndrome: a pilot study on the effect of metformin and oral contraceptives. Metabolism 64:1272–1278

    Article  CAS  PubMed  Google Scholar 

  3. Mak W, Dokras A (2009) Polycystic ovarian syndrome and the risk of cardiovascular disease and thrombosis. Semin Thromb Hemost 35:613–620

    Article  CAS  PubMed  Google Scholar 

  4. Bridges HR, Jones AJ, Pollak MN, Hirst J (2014) Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J 462(3):475–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rojas LBA, Gomes MB (2013) Metformin: an old but still the best treatment for type 2 diabetes. Diabetol Metab Syndr 5:6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Serdyńska-Szuster M, Banaszewska B, Spaczyński R, Pawelczyk L (2011) Effects of metformin therapy on markers of coagulation disorders in hyperinsulinemic women with polycystic ovary syndrome. Ginekol Pol 82:259–264

    PubMed  Google Scholar 

  7. Randriamboavonjy V, Mann WA, Elgheznawy A, Popp R, Rogowski P, Dornauf I, Dröse S, Fleming I (2015) Metformin reduces hyper-reactivity of platelets from patients with polycystic ovary syndrome by improving mitochondrial integrity. Thromb Haemost 31:569–578

    Article  Google Scholar 

  8. Gozukara IO, Pınar N, Ozcan O, Ozgur T, Dokuyucu R, Kurt RK, Kucur SK, Aksoy AN (2016) Effect of colchicine on polycystic ovary syndrome: an experimental study. Arch Gynecol Obstet 293(3):675–680

    Article  CAS  PubMed  Google Scholar 

  9. Abd Elgafor I (2013) Efficacy of combined metformin–letrozole in comparison with bilateral ovarian drilling in clomiphene-resistant infertile women with polycystic ovarian syndrome. Arch Gynecol Obstet 288(1):119–123

    Article  CAS  PubMed  Google Scholar 

  10. Gong X, Duan R, Ao JE, Ai Q, Ge P, Lin L, Zhang L (2015) Metformin suppresses intrahepatic coagulation activation in mice with lipopolysaccharide/d-galactosamine-induced fulminant hepatitis. Mol Med Rep 12:6384–6390

    Article  CAS  PubMed  Google Scholar 

  11. Krysiak R, Okopien B (2012) Haemostatic effects of metformin in simvastatin-treated volunteers with impaired fasting glucose. Basic Clin Pharmacol Toxicol 111:380–384

    Article  CAS  PubMed  Google Scholar 

  12. Grant PJ (2003) Beneficial effects of metformin on haemostasis and vascular function in man. Diabetes Metab 29:644–652

    Article  Google Scholar 

  13. Lawson C, Vicencio J, Yellon DM, Davidson SM (2016) Microvesicles and exosomes: new players in metabolic and cardiovascular disease. J Endocrinol 228:57–71

    Article  Google Scholar 

  14. Campos FMF, Franklin BS, Teixeira-Carvalho A, Filho ALS, de Paula SCO, Fontes CJ, Brito CF, Carvalho LH (2010) Augmented plasma microparticles during acute Plasmodium vivax infection. Malar J 9:327

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mooberry MJ, Bradford R, Hobl EL, Lin FC, Jilma B, Key NS (2016) Procoagulant microparticles promote coagulation in a factor XI-dependent manner in human endotoxemia. J Thromb Haemost 14:1031–1042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Koga H, Sugiyama S, Kugiyama K, Watanabe K, Fukushima H, Tanaka T, Sakamoto T, Yoshimura M, Jinnouchi H, Ogawa H (2005) Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 45:1622–1630

    Article  CAS  PubMed  Google Scholar 

  17. Carvalho LML, Ferreira CN, Sóter MO, Sales MF, Rodrigues KF, Martins SR, Candido AL, Reis FM, Silva IFO, Campos FMF, Gomes KB (2017) Microparticles: inflammatory and haemostatic biomarkers in polycystic ovary syndrome. Mol Cell Endocrinol 443:155–162

    Article  CAS  PubMed  Google Scholar 

  18. Willis GR, Connolly K, Ladell K, Davies TS, Guschina IA, Ramji D, Miners K, Prince DA, Clayton A, James PE, Rees DA (2014) Young women with polycystic ovary syndrome have raised levels of circulating annexin V-positive platelet microparticles. Hum Reprod 29:2756–2763

    Article  CAS  PubMed  Google Scholar 

  19. Koiou E, Tziomalos K, Katsiks I, Papadakis E, Kandaraki EA, Panidis D (2013) Platelet-derived microparticles in overweight/obese women with the polycystic ovary syndrome. Gynecol Endocrinol 29:250–253

    Article  CAS  PubMed  Google Scholar 

  20. Koiou E, Tziomalos K, Katsikis I, Kalaitzakis E, Kandaraki EA, Tsourdi EA, Delkos D, Papadakis E, Panidis D (2011) Circulating platelet-derived microparticles are elevated in women with polycystic ovary syndrome diagnosed with the 1990 criteria and correlate with serum testosterone levels. Eur J Endocrinol 165:63–68

    Article  CAS  PubMed  Google Scholar 

  21. Rank A, Nieuwland R, Nikolajek K, Rösner S, Wallwiener LM, Hiller E, Toth B (2012) Hormone replacement therapy leads to increased plasma levels of platelet derived microparticles in postmenopausal women. Arch Gynecol Obstet 285(4):1035–1041

    Article  CAS  PubMed  Google Scholar 

  22. Nomura S, Shimizu M (2015) Clinical significance of procoagulant microparticles. J Intensive Care 3(1):2

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mooberry MJ, Key NS (2015) Microparticle analysis in disorders of hemostasis and thrombosis. Cytometry A 89(2):111–122

    Article  PubMed  PubMed Central  Google Scholar 

  24. Van EN, Bleker S, Sturk A, Nieuwland R (2015) Clinical significance of tissue factor-exposing microparticles in arterial and venous thrombosis. Semin Thromb Hemost 41(7):718–727

    Article  Google Scholar 

  25. Świtońska M, Słomka A, Sinkiewicz W, Żekanowska E (2015) Tissue-factor-bearing microparticles (MPs-TF) in patients with acute ischaemic stroke: the influence of stroke treatment on MPs-TF generation. Eur J Neurol 22(2):395–401

    Article  PubMed  Google Scholar 

  26. Zwicker JI, Liebman HA, Neuberg D, Lacroix R, Bauer KA, Furie BC, Furie B (2009) Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 15(22):6830–6840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47

    Article  Google Scholar 

  28. WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. WHO technical report series 894, WHO, Geneva

  29. Morgante G, Cappelli V, Di Sabatino A, Massaro MG, De Leo V (2015) Polycystic ovary syndrome (PCOS) and hyperandrogenism: the role of a new natural association. Minerva Ginecol 67(5):457–463

    CAS  PubMed  Google Scholar 

  30. Misso ML, Teede HJ (2014) Metformin in women with PCOS. Endocrine 48(2):422–426

    Google Scholar 

  31. Foley JH, Conway EM (2016) Cross talk pathways between coagulation and inflammation. Circ Res 118:1392–1408

    Article  CAS  PubMed  Google Scholar 

  32. Chirinos JA, Heresi GA, Velasquez H, Jy W, Jimenez JJ, Ahn E, Horstman LL, Soriano AO, Zambrano JP, Ahn YS (2005) Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol 45:1467–1471

    Article  CAS  PubMed  Google Scholar 

  33. Del Conde I, Shrimpton CN, Thiagarajan P, López JA (2005) Tissue-factor bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106:1604–1611

    Article  PubMed  Google Scholar 

  34. De Jager J, Kooy A, Schalkwijk C, Der Kolk Van, Lehrt P, Bets D, Wulffelé MG, Donker AJ, Stehouwer CD (2014) Long-term effects of metformin on endothelial function in type 2 diabetes: a randomized controlled trial. J Intern Med 275:59–70

    Article  PubMed  Google Scholar 

  35. Kebapcilar L, Taner CE, Kebapcilar AG, Alacacioglu A, Sari I (2010) Comparison of four different treatment regimens on coagulation parameters, hormonal and metabolic changes in women with polycystic ovary syndrome. Arch Gynecol Obstet 281:35–42

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/Brazil) for financial support. FMR and KBG are grateful to CNPq Research Fellowship (PQ).

Author information

Authors and Affiliations

Authors

Contributions

LMLC: experimental design, technical analysis, data analysis, manuscript writing. CNF: technical analysis, manuscript editing. ALC: data collection. FMR: data collection, manuscript editing. MOS: data collection. MFS: data collection. IOS: data collection. FFCN: experimental design, technical analysis, data analysis, manuscript editing. KBG: experimental design, project administration, funding acquisition, supervision, data analysis, manuscript writing and review.

Corresponding author

Correspondence to Karina Braga Gomes.

Ethics declarations

Funding

FAPEMIG, CAPES, CNPq.

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This research was approved by the Ethics Committee of the university (CAAE 0379.0.203. 000-11) and all participants signed a free and informed consent form. Our decisions were taken in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carvalho, L.M.L., Ferreira, C.N., Candido, A.L. et al. Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome. Arch Gynecol Obstet 296, 617–621 (2017). https://doi.org/10.1007/s00404-017-4471-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-017-4471-0

Keywords

Navigation