A clinical comparative study on the effects of metformin and pioglitazone on clinical symptoms in cases of polycystic ovarian syndrome
Keywords:BMI, WHR, FG score
Background: The present study was aimed to evaluate the efficacy of pioglitazone and comparing the efficacy of pioglitazone with metformin in improvement of clinical characteristics of the PCOS patients.
Methods: The present study was a prospective, parallel group trial in 40 proven cases of PCOS, all the patients underwent clinical evaluations at baseline that include height, weight, BMI, waist to hip ratio (WHR) and hirsutism (FG score). There were two groups in this study group A (unmarried) and group B (married) each divided in two subgroups each having 10 patients, A1 (unmarried - metformin), A2 (unmarried - pioglitazone), B1 (married - metformin), B2 (married - pioglitazone) therapy was given for six months with regular clinical evaluation of the patients after every two months. WHR (Waist to hip ratio) was measured according to World Organization Criteria (2003), BMI was calculated by using Quetelets Index formula WHO (1995), the grade of hirsutism was detected using Ferriman-Gallwey score (1961).
Results: On comparing metformin and pioglitazone it was observed that both the drugs equally decreased the FG score; metformin significantly decreased the BMI and WHR whereas pioglitazone significantly increased the BMI and WHR.
Conclusions: Pioglitazone significantly increased the BMI and WHR, whereas it significantly decreased FG score. On comparing metformin and pioglitazone it was observed that both the drugs equally decreased the FG score, metformin significantly decreased the BMI and WHR whereas pioglitazone significantly increased the BMI and WHR.
Azziz R, Woods KS. The prevalence and features of PCOS in an unselected population. J Clin Endocrinol Metab. 2004;89:2745-9.
Hart R, Hickey M. Definitions, prevalence and symptoms of PCOS. Best Pract. Res. Clin Obstet Gynaecol. 2004;18:671-89.
Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935;29:181-91.
Revised 2003 consensus on diagnostic criteria and long term health risks related to PCOS. Fetil Steril. 2004;81:19-25.
Miller K, Nixson C Boots LR. Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertil Steril 2001;75:35-8.
Ylid BO, Yarali HI. Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:2031-6.
Escobar- Morreale HF, Luque -Ramire M, San Millan JL. The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocrinol Rev. 2005;26:251-82.
Urbenk M, Woodroffe A, Ewens K G. Candidate gene region for polycystic ovary syndrome on chromosome. J Clin Endocrinol Metab. 2005;90:6623-29.
Futterweit W. Pathophysiology of polycystic ovarian syndrome. In: Redmond GP editor. Androgenic disorders. New York: Raven Press;1995:77-166.
Kitzinger K, Willmot J. The thief of womanhood: women’s experience of polycystic ovarian syndrome. Soc Sci Med. 2002;54:349-61.
Burghen GA, Givens JR, Kitabchi AE. Correlation of hyperandrogenism with hypeinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 1980;50:113-6.
Dunaif A, Graf M, Mandeli J. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance andor hyperinsulinimia. J Clin Metab. 1987;65:499-507.
Baillargeon JP, Iuorno MJ, Nestler JE. Comparison of metformin and thiazolidinediones in the management of polycystic ovary syndrome. Curr Opin Endocrinol Diabetes. 2002;9:303-11.
Nestler JE Jakubowicz DJ, de Vargas AF, Brik C, Quintero N, Medina F. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositol glycan mediators as the signal transduction system. J Clin Endocrinol Metab. 1998;83:2001-05.
Waist circumference and waist-hip ratio report of a WHO expert consultation GENEVA, 8-11 December 2008.
Park K. Epidemiology of chronic non communicable diseases and conditions. Park’s textbook of preventive and social medicine. 20th edition. Jabalpur : M/s Banarsidas Bhanot; 2009:348.
Ferriman D, Gallwey JD. Clinical assessment of body hair in women. J Clin Endocrinol Metab 1961;21:1440-8.
Glueck CJ, Moreira A, Goldenberg N, Wang P. Pioglitazone and metformin in obese women with PCOS not optimally responsive to metformin. Hum Reprod. 2003;18(8):1618-25.
Gonzalez, Ortege , Luna S, Hernander L, Crespo G, Aguayo P. Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, resistant women with PCOS. J Clin Endocrinol Metab. 2005;90(3):1360-5.
Steiner CA, Janez A, Jensterle M, Reisinger K, Pfutzner. Impact of treatment with rosiglitazone or metformin on biomarkers for insulin resistance and metabolic syndrome in patients with PCOS. J Diabe Scinece Techno. 2007;1(2):211-5.
Cetinkalp, Svki, Karadeniz, Muammer, Erdogan. The effects of rosiglitazone, metformin and estradiol_cyproterone acetate on lean patients with PCOS. Endocrinologist. 2009;19(3):94-7.
Velazquez EM, Mendoza S, Hamer T. Metformin therapy in PCOS reduces hyperinsulinemia, insulin resistance, hyperandrogenemia and systolic blood preasure, while facilitating normal menses and pregnancy. Metbolism. 1994;43:647-54.
De Leo V, la Marca E, Morgante G, Cianci A. Effects of Metformin on gonadotropin induced ovulation in women with PCOS. Fertil Steril 1999;72:282-5.
Glueck CJ. Metformin induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with polycystic ovary syndrome. Metabolism. 1999;48:511-9.
Moghetti P, Castello R, Negri C. Metformin effects on clinical features endocrine and metabolic profiles and insulin sensitivity in PCOS: A randomized double blind placebo controlled 6 month trial, followed by open long term clinical evaluation. J Clin Endocrinol Metab. 2000;85:139-46.
Zafar S. Role of metformin in correcting hyperinsulinemia, menstrual irregularity and anovulation in PCOS. J Ayub Med. Coll Abbottabad. 2006;17(4):120-5.
Pillai A, Bang H, Green C. Metformin and glitazones: Do they really help PCOS patients ? J Fam Proct. 2007;56(6):444-53.
Gudio M, Romouldi D, Suriano R, Giuliani M, Apa R. Effect of pioglitazone treatment on the adrenal androgen response to corticotrophin in obese patients with PCOS. Hum Reprod. 2004;19(3):534-9.
Haigh. Pioglitazone treatment demonstrated improvements in insulin sensitivity. J Clin Endocrinol Metab. 2009;94:469-76.
Romualdim D, Guide M, Ciamplesi M, Gintiani M, Leoni F, Perri C. Selective effects of pioglitazone on insulin and androgen abnormalities in normal-hyper- insulinemic obese patients with PCOS. Hum Reprod. 2003;18(6):1210-8.
Nestler JE Jakubowicz DJ. Lean women with PCOS respond to insulin reduction with decrease in ovarian P450 C17 alpha activity and serum androgens. J Clin Endocrinol Metab. 1997;82:4075-9.
Magnotti M, Futterweit W. Obesity and the PCOS. Med Clin N Am. 2007;91:1151-68.
Gonzalez O, Luna S, Hernander L, Crespo G, Aguayo P. Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, resistant women with PCOS. J Clin Endocrinol Metab. 2005;90(3):1360-5.
Avandia (rosiglitazone maleate). Philadelphia, PA: Glaxo Smith Kline Pharmaceuticals; 2000.
Gambineri A Pelusi C, Vicennti V, Pasquali R. Obesity and the PCOS. Int J Obes Relat Metab Disord. 2002;883-96.
Ehrmannn DA. Effects of metformin on insulin secretion, insulin action and ovarian steroidogenesis in women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 1997;82:524-30.
Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Satttar N. Ovarian function and metabolic factors in women with oligomenorrhoea treated with metformin in a randomized double blind, placebo controlled trial. J Clin Endocrinol Metab 2002;87:569-74.
Marcondes JA, Yamashita SA, Maciel GA, Boacat EC, Halpem A. Metformin in normal weight hirsute women with PCOS with normal insulin sensitivity. Gynecol Endocrinol. 2007;23(5):273-8.
Hoeger K, Davidson K, Kochman L, Cherry T, Kopin L, Guzick DS. Impact of metformin, oral contraceptives and lifestyle modification on PCOS in obese adolescent women in two randomized placebo controlled clinical trials. J Clin Endocrinol Metab. 2008;93(11):4299-30.