EFFECT OF METFORMIN HYDROCHLORIDE IN CORRECTING HYPERINSULINEMIA AND HIGH LEPTIN LEVELS IN TREATMENT OF INFERTILE POLYCYSTIC PATIENTS
AbstractBackground: Research conducted over PCOS by various groups in the world indicated the effect of Metformin on PCOS. Previous studies suggest that Glucophage by reducing hyper-insulinemia is clinically useful in the treatment of polycystic ovary syndrome (PCOS). Our Objective was to observe the role of Glucophage in treating infertility of polycystic patients within three months in Group A and six months in Group B patients. Another aim was to assess the decrease in hyper-insulinemia and Leptin levels by Glucophage in our population. Methods: This study was carried out at the Department of Obstetrics and Gynaecology, Pakistan Institute of Medical Sciences, and Noor Specialised Clinic Islamabad, from Oct 2004 to Apr 2008. One hundred and seventy women in Group A and 145 in Group B fulfilling the clinical and biochemical criteria for PCOS were enrolled. Glucophage was started at an oral dose of 500 mg/day and maintained at 1500 mg for 3 months or 6 months in both Groups. Besides ultrasonography, serum FSH, LH, fasting insulin, fasting blood sugar, glucose insulin ratio, Quantitative Insulin Sensitivity Check Index (QUICKI) and leptin levels were performed. After three months in Group A and six months in Group B these criteria were again assessed. Results: After 3 and 6 months of Metformin therapy, significant reduction in biochemical parameters was observed such as fasting glucose, insulin and leptin. Data were analysed using SPSS by paired t-test and ANOVA. Conclusion: Six months treatment with Glucophage proved to be better option for infertile PCOS.Keywords: Glucophage, PCOS, Hyperinsulinemia, Leptin
Vincenzo D L, Antonio LA M, Felice P. Insulin lowering agents in the management of polycystic ovary syndrome. Hum Reprod 2003;24(5):633–67.
Myers EGR, Silva SG, Hafley G, Kunselman AR, Nestler JE, Legro RE. Estimating live birth rates after ovulation induction in polycystic ovary syndrome. Contemp clin Trials 2005;26(3):271–80.
Lanham MSM, Lebovic DI, Domino SE. Contemporary medical therapy for polycystic ovary syndrome. Intl J Gynecol Obstet 2006;95:236–41.
Cheang KI, Sharma ST, Nestler JE. Is metformin a primary ovulatory agent in patients with polycystic ovary syndrome Hum Reprod 2006;22(11):595–604.
Brezechffa PR, Jakimiuk AJ, Agarwal SK. Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1996;81:4166–9.
Morin-Papunen LC, Koivunen RM, Tomas C, Ruokonen A, Martikainen HK. Decreased serum leptin concentrations during metformin therapy in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998;83:2566–8.
Morin-Papunen LC, Vauhkonen I, Koivunen RM, Ruokonen A, Tapanainen JS. Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome. Hum Reprod 2000;15:1266–74.
Pasquali R, Gambineri A, Biscotti D, Vicennati V, Gagliardi L, Colitta D, Fiorini S, Cognigni GE, Filicori M, Morselli-Labate AM. Effect of longterm treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endcrinol Metab 2000;85:2767–74.
Koivunen RM, Morin-Papunen LC, Ruokonen A, Tapanainen JS, Martikainen HK. Ovarian steroidogenic response to human chorionic gonadotrophin in obsese women with polysystic ovary syndrome: effect of metformin. Hum Reprod 2001;16:2546–51.
Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 2005;310:1642–6.
Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994;43(5):647–54.
Velazquez E, Acosta A, Mendoza SG. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol 1997;90:392–5.
Morin-Papunen LC, Koivunen RM, Ruokonene A, Martikainen HK. Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome. Fertil Steril 1998;69:691–6.
Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998;338(26):1876–80.
Glueck CJ, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome. Metabolism 1999;48:511–19.
Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M. Zanolin E, Muggeo M. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab 2000;85:139–46.
Jakubowicz DJ, Seppala M, Jakubowicz S, Rodriguez-Armas O, Rivas-Santiago A, Koistinen H. Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome. J Clin Endocrinol Metab 2001;86:1121–26.
Eisenhardt S, Schwarzmann N, Henschel V, Germeyer A, von Wolff M, Hamann A, Strowitzki T. Early Effects of Metformin in Women with Polycystic Ovary Syndrome: A Prospective Randomized, Double- Blind, Placebo-Controlled Trial. J Clini Endocrinol Metab 2006;91(3):946–52.
Pasquali R, Gambineri A, Biscotti D, Vicennati V, Gagliardi L, Colitta D. Effect of longterm treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endcrinol Metab 2000;85:2767–74.
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 Metab 2002;87:569–74.
Bjrnotorp P. The android woman–a risky condition. J Intern Med 1996;239:105–10.
Ciaraldi TP, Morales AJ, Hickman MG. Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome subjects involves adenosine modulation of insulin sensitivity. J Clin Endocrinol Metab 1997;82:1421–25.
Morin-Papunen LC, Koivunen RM, Ruokonen A, Martikainen HK. Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome. Fertil Steril 1998;69(4):691–6