Effect of Metformin Versus Diet and Exercise on Ovulation & Menstrual Regularity in PCOS
Keywords:
Polycystic ovary syndrome , Metformin, Diet & exercise, Menstrual regularity, Ovulation.Abstract
To compare the effects of metformin with diet & exercise on ovulation & menstrual regularity in PCOS infertile women .
Study Design: Randomized clinical trial.
Place & Duration of study: Private hospital infertility clinic at Karachi from 2001-2004.
Patients & Methods: One hundred & eleven PCOS women with primary infertility were enrolled. and divided into group A & B with 57 & 54 patients
respectively. Group A received tablet metformin 500mg thrice daily along with diet & exercise advice while group B was kept on diet & exercise alone
(30-60 minutes walk daily & avoidance of oily foods, red meat & bakery products) for a period of 90 days. Menstrual regularity & plasma progesterone
level were evaluated at day-0 and day-90. Fasting serum glucose, insulin, follicle stimulating hormone, luteinizing hormone, prolactin, testosterone &
ultrasound pelvis were done at day- 0 for diagnosis of PCOS.
Results: 100 patients completed the study. 50 patients in each group.In group A, 44 (88%) patients developed regular cycles with statistically significant
increase in serum progesterone whereas in group B only 3(6%) patients developed regular cycles with non-significant increase in serum progesterone level
from day-0 to day-90. Group A showed ovulation in 82% patients in comparison to Group B where ovulation occurred in only 6% of patients.
Conclusion: Metformin produced beneficial effects in comparison to diet & exercise alone in PCOS infertile women.
References
Asuncion M, Calvo RM, San Millan JL et al. A prospective study of the prevalence of the polycystic ovary syndrome in unselected caucasian women from Spain. J Clin Endocrinol Metab 2000;85:2434-8
Knochenhauer ES, Key TJ, Kahsar-miller M et al.Prevalence of polycystic ovary syndrome in unselected black and white women of the south eastern United States. A prospective study. J Clin Endocrinol Metab 1998;83: 3078-82.
Nestler JE. Role of hyperinsulinemia in the pathgenesis of the polycystic ovarian syndrome and its clinical implications. Semin Reprod Endocrinol 1997;15:111-22
Nestler JE and Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens. J Clin Endocrinol Metab 1997;82:4075-9
Nestler JE and Jakubowicz DJ. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996;335:617-23
Lo JC, Feigenbaum SL, Yang J et al. Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome.J Clin Endocrino Metab. 2006;91:1357-63
Dunaif A. Hyperandrogenic anovulation(PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin dependent diabetes mellitus. Am J Med 1995;98:33S-9S
Ehrmann DA, Barnes RB, Rosenfield RL et al. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999;22:141-6
Solomon CG. The epidemiology of polycystic ovary syndrome: Prevalence and associated disease risks. Endocrinol Metab Clin North Am. 1999;28:247-63
Nestler JE, Powers LP, Matt DW et al. A direct effect of hyperinsulinemia on serum sex hormone binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1991; 72:83-9.
Utiger R. Insulin and the polycystic ovary syndrome. N Engl J Med 1996; 355: 657-8.
Polson DW, Franks S, Reed MJ et al. The distribution of estradiol in plasma in relation to uterine cross-sectional area in women with polycystic or multifollicular ovaries. Clin Endocrinol (Oxf) 1987;26:581-8.
Buchholz HM, Carey DGP and Norman RJ. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: Role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab 1999;84:1470-4.
Diamanti-Kandarakis E,Christakou Charikleia D, Kandaraki Eleni et al. Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome.Eur J Endocrinology 2010;162:193-212.
Palomba S, Falbo A, Zulio F et al. Evidence based and potential benefits of metformin in the polycyctic ovary syndrome: a comprehensive review. Endocrine Reviews2009;39:1-50
Tasdemir S, Ficicioglu C, Yalti S et al. The effect of metformin treatment to ovarian response in cases with PCOS.Arch Gyencol Obstet 2004; 269(2):121-4.
Diamanti-Kandarakis E and Papavasiliou A. Molecular mechanisms of Insulin resistance in polycystic ovary syndrome. Trends Molecular Med2006;12:324-32
Willis D and Franks S. Insulin action in human granulosa cells from normal & polycystic ovaries is mediated by the insulin receptor & not type-1 insulin like growth factor receptor. J Clin Endocrinol Metab 1995;80:3788-90
Jedel E, Labrie f, Oden A et al Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial.Am J Phsiol Endocrinol Metab. 2011;300:E37-E45
Jayagopal V, Kilpatrick E, Holding S. Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome. J Clin Endocrinol Metab. 2005;90(2):729-33
Yero-Hernandez A, Perez F S, Carballo G O, et al Diamel Therapy in Polycystic Ovary Syndrome reduces hyperinsulinemia, insulin resistance and hyperandrogenaemia.Int J Endocrinol.2012:2012:1155-62. doi:10.1155/2012/382719.
Fauser B C J, Tarlatzis B C, Rebar R W, et al. Consensus on women`s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS consensus Workshop Group. Fertil Steril. 2012;97(1):28-38
Polycystic ovary syndrome (PCOS). Womenshealth.gov. US Department of Health and Human services. The Federal Government source for women’s Health information. April 2007
Velazquez EM, Acosta A and Mendoza S. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol 1997; 90:392-5.
Kolodziejczyk B, Duleba AJ, Spaczynski RZ et al. Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome. Fertil Steril 2000; 73:1149-54.
Vandermolen DT, Ratts VS, Evans WS et al. 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; 75:310-15.
Acbay O and Gundogdu S. Can metformin reduce insulin resistance in polycystic ovary syndrome? Fertil Steril 1996; 65:946-49.
Ehrmann DA, Cavaghan MK, Imperial J et al. Effects of metformin on insulin secretion, insulin action and ovarian steroidogenesis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997;82:524-30.
Fleming R, Hopkinson ZE, Wallace AM et al. 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.
Jakubowicz DJ, Seppala M, Jakubowicz S et al. Insulin reduction with metformin increases luteal phase serum glycodelin and insulin like growth factor binding protein I concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome. J Clin Endocrinol Metab 2001; 86:1126-33.
Nestler JE. Insulin regulation of human ovarian androgens. Hum Reprod 1997; 12(Suppl):52-62.
Moghetti P, Castello R, Negri C et al. Metformin effects on clinical features, endocrine and metabolic profiles and insulin sensitivity in polycystic ovary syndrome: A randomized double blind, placebo controlled 6 months trial, followed by open long term clinical evaluation. J Clin Endocrinol Metab.2000;85(1):139-6
Kiddy DS, Hamilton-Fairley D, Bush A et al..Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol.1992;36:105-11.
Hutchison SK, Stepto NK, Harrison CL et al..Effects of exercise on insulin resistance and body composition in overweight and obese women with and without polycystic ovary syndrome.J Clin Endocrinol Metab.2011;96(1):E48-E56
Nestler JE, Jakubowicz DJ, Evans WS et al. Effects of metformin on spontaneous and clomiphene induced ovulation in polycystic ovary sndrome.N Engl J Med. 1998;338:1876-80
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2012 Nasim Karim, Khalid Mustafa, Talea Hoor, Riffat Farooqui
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Journal of Bahria University Medical & Dental College is an open access journal and is licensed under CC BY-NC 4.0. which permits unrestricted non commercial use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc/4.0 
