Uso de metformina em mulheres obesas com Síndrome do Ovário Policístico
DOI:
https://doi.org/10.24220/2318-0897v25n2a3613Palavras-chave:
Hiperandrogenismo. Metformina. Obesidade. Síndrome do ovário policístico.Resumo
A Síndrome do Ovário Policístico caracteriza-se como uma alteração anatômica e morfológica dos ovários que acarreta hiperandrogenismo, ciclos menstruais irregulares, redução da fertilidade e múltiplos cistos ovarianos, principalmente em mulheres obesas durante a menacme. Como o aumento da resistência à insulina e a hiperinsulinemia estão frequentemente presentes, a metformina começou a ser preconizada na clínica como uma forma de tratamento da Síndrome do Ovário Policístico. Dessa forma, o presente estudo tem como objetivo realizar uma revisão de literatura sobre o uso de metformina em mulheres obesas com a síndrome citada. Para tanto, foi realizada uma pesquisa nas bases de dados PubMed/MedLine, Portal CAPES, SciELO, Cochrane e Google Acadêmico no período de fevereiro a maio de 2016. Os artigos foram identificados pelos seguintes descritores: "polycystic ovary syndrome", "metformin", "hyperandrogenism and obesity". Não houve restrição quanto à data de publicação dos artigos e idioma. Uma ampla utilização da metformina é identificável no tratamento da Síndrome do Ovário Policístico, porém ainda existe discordância sobre sua efetividade de forma isolada. Estudos utilizando monoterapia de metformina identificaram auxílio na redução de peso e melhora nas taxas de gravidez. Nos estudos utilizando terapia combinada, ocorreu melhora significativa nas taxas de ovulação e gravidez. Por fim, nos trabalhos que compararam o uso da metformina com modificação do estilo de vida, foi observado que a redução do peso teve impacto mais significativo nas taxas de ovulação e gravidez. Assim, apesar deste fármaco melhorar sintomas da síndrome do ovário policístico, o fator que mais colabora para ciclos menstruais regulares e melhoraria nas taxas de ovulação/gravidez é a redução do peso.
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Referências
Fonseca AM, Bagnoli VR, Halbe HW, Arie WMY. Síndrome dos ovários policísticos. In: Fonseca AM, Bagnoli VR, Halbe HW, Pinotti JA. Ginecologia endócrina: manual de normas. São Paulo: Roca; 2004. p.215-31.
Brasileiro Filho G. Bogliogo patologia. 8a ed. Rio de Janeiro: Guanabara Koogan; 2012.
Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double-blind placebo controlled trial. J Clin Endocrinol Metabol. 2002;87(2):569-74.
Hahn S, Quadbeck B, Elsenbruch S, Gartner R, Finke R, Mann K. Metformin, an efficacious drug in the treatment of polycystic ovary syndrome. Dtsch Med Wochenschr. 2004;129(19):1059-64.
AL-Nozha O, Habib F, Mojaddidi M, EL-Bab MF. Body weight reduction and metformin: Roles in polycystic ovary syndrome. Pathophysiology. 2013;20(2):131-7.
Glueck CJ, Awadalla SG, Phillips H, Cameron D, Wang P, Fontaine RN. Polycystyc ovary syndrome, infertility, familial thrombophilia, familial hypofibrinolysis, recurrent loss of in vitro fertilized embryos and miscarriage. Fertil Steril. 2000;74(2):394-7.
Lopes LCT. Riesgo cardiovascular en mujeres com syndrome de ovários poliquisticos. Siicsalud. 2001;4:1-6.
Sills ES, Perloe M, Palermo GD. Correction of hyperinsulinemia in oligoovulatory women with clomiphene-resistant polycystic ovary syndrome: A review of therapeutic rationale and reproductive outcomes. Eur J Obstet Gynecol Reprod Biol. 2000;91(2):135-44.
Morreale EHF, Ramírez LM, Millán SJL. The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr Rev. 2005;26(2):251-82.
Younis JS, Jadaon JE, Haddad S, Izhaki, I, Ben-Ami M. Prospective evaluation of basal stromal Doppler studies in women with good ovarian reserve and infertility undergoing in vitro fertilization-embryo transfer treatment: Patients with polycystic ovary syndrome versus ovulatory patients. Fertil Steril. 2011;95(5):1754-8.
March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544-51.
Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013;18(6):1-13.
Liu Y, Hou L, Li Y, Liu M, Xu F, Wang Y. Metformin for adolescents with polycystic ovary syndrome. J Reprod Contracept. 2015;26(2):103-11.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25
Baillargeon JP, Nestler JE. Commentary: Polycystic ovary syndrome: A syndrome of ovarian hypersensitivity to insulin? J Clin Endocrinol Metab. 2006;91(1):22-4.
Wu XK, Zhou SY, Liu JX, Pollanen P, Sallinen K, Makinen M, et al. Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome. Fertil Steril. 2003;80(4):954-65.
Arie WMY, Fonseca AM, Bagmoli VR, Fassolas G, Baracat EC. Síndrome do ovário policístico e metformina: revisão baseada em evidências. Femina. 2009;37(11):585-602.
Costello MF, Chapman M, Conway U. A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotrophin ovulation induction or IVF in women with polycystic ovary syndrome. Hum Reprod. 2006;21(6):1387-99.
Velasquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hiperinsulinemia, insulin resistance, hyperandrogenemia, and blood pressure, while facilitating normal menses and pregnancy. Metabolism.1994;43(5):647-54.
Santana LF, Ferriani RA, Sá MFS, Reis RM. Tratamento da infertilidade em mulheres com síndrome dosovários policísticos. Rev Bras Ginecol Obstet. 2008;30(4):201-9.
Dominguez LJ, Davidoff AJ, Srinivas PR, Standley PR, Walsh MF, Sowers JR. Effects of metformin on tyrosine kinase activity, glucose transport, and intracellular calcium in rat vascular smooth muscle. Endocrinology. 1996;137(1):113-21.
Santana LF, Sá MF, Ferriani RA, Moura MD, Foss MC, Reis RM. Effect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome. Gynecol Endocrinol. 2004;19(2):88-96.
Nardo LG, Rai R. Metformin therapy in the management of polycystic ovary syndrome: Endocrine, metabolic and reproductive effects. Gynecol Endocrinol. 2001;15(5):373-80.
Tso LO, Costello MF, Albuquerque LET, Andriolo RB, Marjoribanks J, Macedo CR. Metformin treatment before and during in vitro fertilization or intracytoplasmic sperm injection in women with polycystic ovary syndrome: Summary of a Cochrane review. Fertil Steril. 2015;104(3):542-4.
Kiddv DS, Hamilton-Fairley D, Bush A, Short F, Anyaoku V, Reed MJ, et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol. 1992;36(1):105-11.
Guzick DS, Wing R, Smith D, Berga SL, Winters SJ. Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women. Fertil Steril. 1994;61(4):598-604.
Lord T, Thomas R, Fox B, Acharva U, Wilkin T. The effect of metformin on fat distribution and metabolic syndrome in women with polycystic ovary syndrome: A randomized double-blind, placebo-controlled trial. BJOG. 2006;113(7):817-24.
Nieuwenhuis-Ruifrok AE, Kuchenbecker WK, Hoek A, Middleton P, Norman RJ. Insulin sensitizing drugs for weight loss in women of reproductive age who are overweight or obese: Systematic review and meta-analysis. Hum Reprod Update. 2009;15(1):57-68.
Speroff L, Fritz MA. Clinical gynecologic endocrinology and infertility. 6a ed. Baltimore: Lippincott Williams & Wilkins; 2005.
Machado RC. Avaliação do uso da metformina no resultado ovulatórios de pacientes portadoras da Síndrome de Ovários Policísticos resistentes ao uso isolado do citrato de clomifeno [tese]. Belo Horizonte: UFMG; 2008.
Balen AH. Ovulation induction in the management of anovulatory polycystic ovary syndrome. Mol Cell Endocrinol. 2013;373(1-2):77-82.
El-Khayat W, Moety GA, Mohammady MA, Hamed D. A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome. Int J Gynecol Obstetr. 2016;132(2):206-9.
Homburg R. Polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2008;22(2):261-74.
Urbanetz AA, Oliveira TCR, Gruetzmacher C, Piazza MJ, Carvalho NS. Síndrome dos ovários policísticos: aspectos atuais das abordagens terapêuticas: parte 1. Femina. 2009;37(5):255-60.
El-Biely MM, Habba M. The use of metformin to augment the induction of ovulation in obese infertile patients with polycystic ovary syndrome. MiddleEast Fertil Soc J. 2001;6(2):43-9.
Vandermolen DT, Ratts VS, Evans WS, Stovall DW, Kauma SW, Nestler JE. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil Steril. 2001;75(2):310-5.
Martins WP, Araújo CHM, Nastri CO, Reis RM, Ferriani RA, Mauad-Filho F. Síndrome dos Ovários Policísticos. Femina. 2006;34(10):659-65.
Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: Systematic review and meta-analysis. BMJ. 2003;327(7421):951-95.
Kashyap S, Wells GA, Rosenwaks Z. Insulin-sensitizing agents as primary therapy for patients with polycystic ovarian syndrome. Hum Reprod. 2004;19(11):2474-83
Kocak M, Caliskan E, Simsir C, Haberal A. Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate resistant women with polycystic ovary syndrome. Fertil Steril. 2002;77(1):101-6.
Mathur R, Alexander CJ, Yano J, Trivax B, Azziz R. Use of metformin in polycystic ovary syndrome. Am J Obstetrics Gynecol. 2008;199(6):596-609.
Seto-Young D, Paliou M, Schlosser J, Avtanski D, Park A, Patel P, et al. Direct thiazolidinedione action in the human ovary: Insulin-independent and insulin sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production. J Clin Endocrinol Metab. 2005; 90(11):6099-105.
Baillargeon JP, Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Nestler JE. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil Steril. 2004;82(4):893-902.
Sangeeta S. Metformin and pioglitazone in polycystic ovarian syndrome: A comparative study. J Obstet Gynaecol India. 2012;62(5):551-6.
Ortega-Gonzalez C, Luna S, Hernandez L, Crespo G, Aguayo P, Arteaga-Troncoso G. et al. Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90(3):1360-5.
Brunton LL. Goodman & Gilman: as bases farmacológicas da terapêutica. 12a ed. Rio de Janeiro: McGraw-Hill; 2012.
Urbanetz AA, Oliveira MTCR, Gruetzmacher C, Piazza MJ, Carvalho NS. Síndrome do ovário policístico: aspectos atuais das abordagens terapêuticas: parte 2. Femina. 2009;37(6):339-45.
Sohrabvand F, Ansari S, Bagheri M. Efficacy of combined metformin-letrozole in comparison with metformin clomiphene citrate in clomiphene-resistantin fertile women with polycystic ovarian disease. Human Reproduction. 2006;21(6):1432-5.
Bayar U, Tanriverdi HA, Barut A, Ayoglu F, Ozcan O, Kaya E. Letrozole vs. clomiphene citrate in patients with ovulatory infertility. Fertil Steril. 2006; 85(4):1045-8.
Abu Hashim H, Shokeir T, Badawy A. Letrozole versus combined metformin and clomiphene citrate for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: A randomized controlled trial. Fertil Steril. 2010;94(4):1405-9.
Tang T, Glanville J, Hayden C, White D, Barth JH, Balen AH. Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome: A randomized placebo-controlled, double-blind, multicentre study. Hum Reprod. 2006;21(1):80-9.
Qublan HS, Yannakoula EK, AL-Qudah MA, EL-Uri FI. Dietary intervention versus metformin to improve the reproductive outcome in women with polycystic ovary syndrome. A prospective comparative study. Saud Med J. 2007;28(11):1694-9.
Curi DDG. Comparação entre o tratamento com metformina e orientação dietética associada a exercícios físicos em mulheres com síndrome dos ovários policísticos [tese]. São Paulo: Universidade de São Paulo; 2007.
Hoeger KM, Kochman RNL, Wixom N, Craig K, Miller RK, Guzick DS. A randomized, 48-week, placebo controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: A pilot study. Fertility and Sterility. 2004;82(2):421-9.