medigraphic.com

2022, Number 2

<< Back Next >>

Rev Cuba Endoc 2022; 33 (2)

Metformin during pregnancy in women with polycystic ovary syndrome

Monteagudo PG, Cruz HJ, Ovies CG, Gómez AM, Cabrera GM

Language: Spanish
References: 55
Page:
PDF size: 204.42 Kb.


ABSTRACT

Introduction: Insulin resistance is highly relevant in the pathogenesis of polycystic ovary syndrome, which is why it is common to use insulin sensitizers. Metformin has various therapeutic purposes and is the most recommended. During pregnancy, it plays a role in reducing the risk of miscarriage, pregnancy-induced hypertension, macrosomia, cesarean section, and neonatal hypoglycemia. With less consistent results, it also participates in reducing the risk of gestational diabetes. However, there are concerns about its long-term safety.
Objective: To update the state of the art on the use of metformin during pregnancy in women with polycystic ovary syndrome. Methods: A bibliographic review was carried out where 57 articles obtained from the Google Scholar, Medline, Pubmed, SciELO databases were consulted.
Conclusions: Treatment with metformin is easier, cheaper and less "disturbing" than insulin. Prescription and adherence are simpler, which has contributed to the fact that metformin is used in clinical practice during pregnancy with increasing frequency. The current position of the scientific community accepts metformin as a valid treatment alternative in women with polycystic ovary syndrome during pregnancy, but recommends careful observation of its long-term safety and increasing evidence.


REFERENCES

  1. Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016. DOI: https://doi.org/10.1038/nrdp.2016.571.

  2. Mohd M, Maqbool M, Dar MA, Mushtaq I. Polycystic Ovary Syndrome, a modern epidemic: An overview. JDDT. 2019 [acceso: 28/12/2021];9(3):641-4. Disponible en: http://jddtonline.info/index.php/jddt/article/view/26612.

  3. Cassar S, Misso ML, Hopkins WG, Shaw CS, Teede HJ, Stepto NK. Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies. Hum Reprod. 2016;31(11):2619-31. DOI: https://doi.org/10.1093/humrep/dew2433.

  4. Rocha AL, Oliveira FR, Azevedo RC, Silva VA, Peres TM, Candido AL, et al. Recent advances in the understanding and management of polycystic ovary syndrome. Faculty Rev. 2019;8:565. DOI: https://doi.org/10.12688/f1000research.15318.14.

  5. Barber TM, Dimitriadis GK, Andreou A, Franks S. Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance. Clin Med (Lond). 2015;15(Suppl 6):s72-6. DOI: https://doi.org/10.7861/clinmedicine.15-6-s725.

  6. Pasquali R. Contemporary approaches to the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2018;9(4):123-34. DOI: https://doi.org/10.1177/20420188187567906.

  7. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. American Association of Clinical Endocrinologists (AACE); American College of Endocrinology (ACE); Androgen Excess and PCOS Society Disease State Clinical Review (AES): guide to the best practices in the evaluation and treatment of polycystic ovary syndrome-Part 1. Endocr Pract. 2015;21(11):1291-300. DOI: https://doi.org/10.4158/EP15748.DSC7.

  8. Tay CT, Joham AE, Hiam DS, Gadalla MA, Pundir J, Thangaratinam S. Pharmacological and surgical treatment of nonreproductive outcomes in polycystic ovary syndrome: An overview of systematic reviews. Clin Endocrinol (Oxf). 2018;89(5):535-53. DOI: https://doi.org/10.1111/cen.137538.

  9. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human Reprod. 2018;33(9):1602-18. DOI: https://doi.org/10.1093/humrep/dey2569.

  10. Dumesic DA, Oberfield SE, Stener E, Marshall JC, Laven JS, Legro RS. Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome. Endocr Rev. 2015;36(5):487-525. DOI: https://doi.org/10.1210/er.2015-101810.

  11. Federação Brasileira das Associações de Ginecologia e Obstetrícia. Síndrome dos ovários policísticos. São Paulo, Série, Orientações e Recomendações. FEBRASGO. 2018 [acceso: 28/12/2021]: 103. Disponible en: https://www.passeidireto.com/arquivo/78562027/sindrom-dos-ovarios-policisticos-febrasgo11.

  12. Milewicz A, Kudla M, Spaczynski RZ, Debski R, Meczekalski B, Wielgos M, et al. The polycystic ovary syndrome: a position statement from the Polish Society of Endocrinology, the Polish Society of Gynaecologists and Obstetricians, and the Polish Society of Gynaecological Endocrinology. Endokrynol Pol. 2018;69(4):328-36. DOI: https://doi.org/10.5603/EP.2018.004612.

  13. Salzberg S, Alvariñas J, López G, Gorbán S, Linari MA, Falcón E, et al. Guías de diagnóstico y tratamiento de diabetes gestacional. ALAD. 2016. [acceso: 28/12/2021];6:155-69. Disponible en: https://www.revistaalad.com/abstract.php?id=34313.

  14. Webber J, Charlton M, Johns N. NICE guideline: Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period (NG3). Br J Diabetes Vasc Dis. 2015 [acceso: 28/12/2021];15:107-11. Disponible en: https://www.bjd-abcd.com/index.php/bjd/article/view/80/17214.

  15. American Diabetes Association. Management of Diabetes in Pregnancy. Diabetes Care 2016;39(Suppl 1):S94-8. DOI: https://doi.org/10.2337/dc16-S01515.

  16. Cruz J, Piloto M. Segundo Consenso Cubano de Diabetes y Embarazo. Rev Cubana Endocrinol. 2018 [acceso: 28/12/2021];29(1). Disponible en: http://www.revendocrinologia.sld.cu/index.php/endocrinologia/article/view/97/8616.

  17. Castro MG, Castillo V, Ochoa A, Godínez SA. La metformina y sus aplicaciones actuales en la clínica. Med Int Méx. 2014 [acceso: 28/12/2021];30:562-74. Disponible en: https://www.medigraphic.com/cgi-bin/new/resumen.cgi?IDARTICULO=5251417.

  18. Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011;50(2):81-98. DOI: https://doi.org/10.2165/11534750-000000000-0000018.

  19. Minamii T, Nogami M, Ogawa W. Mechanisms of metformin action: In and out of the gut. J Diabetes Investig. 2018;9(4):701-3. DOI: https://doi.org/10.1111/jdi.1286419.

  20. Li M, Li X, Zhang H, Lu Y. Molecular Mechanisms of Metformin for Diabetes and Cancer Treatment. Front Physiol. 2018;9:1039. DOI: https://doi.org/10.3389/fphys.2018.0103920.

  21. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108(8):1167-74. DOI: https://doi.org/10.1172/JCI1350521.

  22. Harborne L, Fleming R, Lyall H, Norman J, Sattar N. Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome. Lancet. 2003;31(9372):1894-901. DOI: https://doi.org/10.1016/S0140-6736(03)13493-922.

  23. Sam S, Ehrmann DA. Metformin therapy for the reproductive and metabolic consequences of polycystic ovary syndrome. Diabetologia. 2017;60(9):1656-61. DOI: https://doi.org/10.1007/s00125-017-4306-323.

  24. Artani M, Iftikhar MF, Khan S. Effects of Metformin on Symptoms of Polycystic Ovarian Syndrome Among Women of Reproductive Age. Cureus. 2018;10(8):e3203. DOI: https://doi.org/10.7759/cureus.320324.

  25. Glintborg D, Andersen M. Management of endocrine disease: Morbidity in polycystic ovary syndrome. Eur J Endocrinol. 2017;176(2):R53-R65. DOI: https://doi.org/10.1530/EJE-16-037325.

  26. Orio F, Muscogiuri G, Nese C, Palomba S, Savastano S, Tafuri D, et al. Obesity, type 2 diabetes mellitus and cardiovascular disease risk: an uptodate in the management of polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2016;207:214-9. DOI: https://doi.org/10.1016/j.ejogrb.2016.08.02626.

  27. Franik G, Bizon A, Wloch S, Pluta D, Blukacz L, Milnerowicz H, Madej P. The effect of abdominal obesity in patients with polycystic ovary syndrome on metabolic parameters. Eur Rev Med Pharmacol Sci. 2017 [acceso: 28/12/2021];21(21):4755-61. Disponible en: https://www.europeanreview.org/article/1371327.

  28. Lopez E; Mamani Y, Lamas GR, Herrera M, Lazo L. Metformina en el tratamiento del síndrome de ovarios poliquísticos. Un ensayo clínico aleatorizado. Rev Cient Cienc Méd. 2017 [acceso: 28/12/2021];20(2):45-52. Disponible en: http://www.scielo.org.bo/scielo.php?script=sci_arttext&pid=S1817-74332017000200008&lng=es28.

  29. Morley LC, Tang T, Yasmin E, Norman RJ, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligoamenorrhoea and subfertility. Cochrane Systematic Review. 2017. [acceso: 28/12/2021]. Disponible en: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003053.pub629.

  30. Khomami M, Boyle JA, Tay CT, Vanky E, Teede HJ, Joham AE, et al. Polycystic ovary syndrome and adverse pregnancy outcomes: Current state of knowledge, challenges and potential implications for practice. Clin Endocrinol. 2018 [acceso: 28/12/2021];88(6):761-9. Disponible en: https://onlinelibrary.wiley.com/doi/full/10.1111/cen.1357930.

  31. Palomba S, de Wilde MA, Falbo A, Koster MP, La Sala GB, Fauser BC. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015;21(5):575-92. DOI: https://doi.org/10.1093/humupd/dmv02931.

  32. Nguyen L, Chan SY, Teo AK. Metformin from mother to unborn child. Are there unwarranted effects? E Bio Medicine. 2018;35:394-404. DOI: https://doi.org/10.1016/j.ebiom.2018.08.04732.

  33. Liu W; Yang M. The pros and cons of application of metformin in the pregnant women with polycystic ovary syndrome. Chinese J Endocrinol Metabol. 2018 [acceso: 28/12/2021];34(10):809-13. Disponible en: https://pesquisa.bvsalud.org/portal/resource/pt/wpr-71000833.

  34. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP. MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358(19):2003-15. DOI: https://doi.org/10.1056/NEJMoa070719334.

  35. Vigil P, Olmedo J. Diabetes gestacional: conceptos actuales. Ginecol Obstet Mex. 2017 [acceso: 28/12/2021];85(6):380-90. Disponible en: http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0300-90412017000600380&lng=es35.

  36. Koning SH, Hoogenberg K, Lutgers HL, van den Berg PP, Wolffenbuttel BH. Gestational Diabetes Mellitus: current knowledge and unmet needs. J Diabetes. 2016;8(6):770-81. DOI: https://doi.org/10.1111/1753-0407.1242236.

  37. Balsells M, García A, Solà I, Roqué M, Gich I, Corcoy R. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ. 2015;350:h102. DOI: https://doi.org/10.1136/bmj.h10237.

  38. Cassina M, Donà M, Di Gianantonio E, Litta P, Clementi M. First-trimester exposure to metformin and risk of birth defects: a systematic review and meta-analysis. Hum Reprod Update. 2014;20(5):656-69. DOI: https://doi.org/10.1093/humupd/dmu02238.

  39. Singh N, Madhu M, Vanamail P, Malik N, Kumar S. Efficacy of metformin in improving glycaemic control & perinatal outcome in gestational diabetes mellitus: A non-randomized study. Indian J Med Res. 2017;145(5):623-8. DOI: https://doi.org/10.4103/ijmr.IJMR_1358_1539.

  40. Scherneck S, Schlinke N, Beck E, Grupe K, Weber C, Schaefer C. Pregnancy outcome after first-trimester exposure to metformin: A prospective cohort study. Reprod Toxicol. 2018;81:79-83. DOI: https://doi.org/10.1016/j.reprotox.2018.07.00440.

  41. Gui J, Liu Q, Feng L. Metformin vs. insulin in the management of gestational diabetes: a meta-analysis. PLoS One. 2013;8(5):e64585. DOI: https://doi.org/10.1371/journal.pone.006458541.

  42. Butalia S, Gutierrez L, Lodha A, Aitken E, Zakariasen A, Donovan L. Short- and long-term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta-analysis. Diabet Med. 2017;34(1):27-36. DOI: https://doi.org/10.1111/dme.1315042.

  43. Bidhendi R, Behboudi S, Amiri M, Ramezani F. Metformin therapy before conception versus throughout the pregnancy and risk of gestational diabetes mellitus in women with polycystic ovary syndrome: a systemic review, meta-analysis and meta-regression. Diabetol Metab Syndr. 2019;11:58. DOI: https://doi.org/10.1186/s13098-019-0453-743.

  44. Nawaz FH, Khalid R, Naru T, Rizvi J. Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome? J Obstet Gynaecol Res. 2008;34(5):832-7. DOI: https://doi.org/10.1111/j.1447-0756.2008.00856.x44.

  45. Shetelig T, Stridsklev S, Carlsen SM, Salvesen Ø, Vanky E. Cervical Length and Androgens in Pregnant Women With Polycystic Ovary Syndrome: Has Metformin Any Effect? J Clin Endocrinol Metab. 2016;101(6):2325-31. DOI: https://doi.org/10.1210/jc.2015-349845.

  46. Glueck CJ, Wang P, Goldenberg N, Sieve L. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod. 2002;17(11):2858-64. DOI: https://doi.org/10.1093/humrep/17.11.285846.

  47. Glueck CJ, Wang P, Kobayashi S, Phillips H, Sieve L. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril. 2002;77(3):520-5. DOI: https://doi.org/10.1016/s0015-0282(01)03202-247.

  48. Mohammed IF. Role of Metformin on Recurrent Miscarriage and Other Pregnancy Complications in Women with Polycystic Ovarian Syndrome. Iraqi J Embryo and Infertil Res. 2017 [acceso: 28/12/2021];7(Special Issue):1-6. Disponible en: https://www.researchgate.net/publication/326152850_Role_of_Metformin_on_Recurrent_Miscarriage_and_Other_Pregnancy_Complications_in_Women_with_Polycystic_Ovarian_Syndrome48.

  49. Løvvik TS, Carlsen SM, Salvesen Ø, Steffensen B, Bixo M, Gómez F, et al. Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019;7(4):256-66. DOI: https://doi.org/10.1016/S2213-8587(19)30002-649.

  50. Zeng XL, Zhang YF, Tian Q, Xue Y, An RF. Effects of metformin on pregnancy outcomes in women with polycystic ovary syndrome. A meta-analysis. Medicine (Baltimore). 2016;95(36):e4526. DOI: https://doi.org/10.1097/MD.000000000000452650.

  51. Feng L, Lin XF, Wan ZH, Hu D, Du YK. Efficacy of metformin on pregnancy complications in women with polycystic ovary syndrome: a meta-analysis. Gynecol Endocrinol. 2015;31(11):833-9. DOI: https://doi.org/10.3109/09513590.2015.104190651.

  52. Engen LG, Stridsklev S, Júlíusson PB, Salvesen Ø, Roelants M, Carlsen SM, et al. Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs. J Clin Endocrinol Metab. 2018;103(4):1612-21. DOI: https://doi.org/10.1210/jc.2017-0241952.

  53. Tarry JL, Aiken CE, Ozanne SE. Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis. PLoS Med. 2019;16(8):e1002848. DOI: https://doi.org/10.1371/journal.pmed.100284853.

  54. Tartarin P, Moison D, Guibert E, Dupont J, Habert R, Rouiller V, et al. Metformin exposure affects human and mouse fetal testicular cells. Hum Reprod. 2012;27(11):3304-14. DOI: https://doi.org/10.1093/humrep/des26454.

  55. Tartarin P, Moison D, Guibert E, Dupont J, Habert R, Rouiller V, et al. Metformin exposure affects human and mouse fetal testicular cells. Hum Reprod. 2012;27(11):3304-14. DOI: https://doi.org/10.1093/humrep/des26455.




2020     |     www.medigraphic.com