Human Reproduction, Vol. 17, No. 7, 1729-1737,
July 2002
© 2002 European Society of Human Reproduction and Embryology
Clinical, endocrine and metabolic effects of metformin added to ethinyl estradiol–cyproterone acetate in non-obese women with polycystic ovarian syndrome: a randomized controlled study
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Marmara University School of Medicine, Istanbul, Turkey
BACKGROUND: Oral contraceptive pills (OC) are usually the first choice of treatment for polycystic ovarian syndrome (PCOS), when fertility is not desired. However, they do not improve, or may even further induce impairment of insulin sensitivity, which is already impaired in women with PCOS. In this prospective, randomized study, we analysed the additional benefits of adding metformin to the OC treatment in non-obese women with PCOS. METHODS: After a baseline work-up including body mass index (BMI), waist:hip ratio (WHR), Ferriman–Gallwey score, ovarian volume, serum gonadotrophin, androgen and sex hormone-binding globulin (SHBG) levels, and fasting lipid, glucose and insulin levels, 40 non-obese women with PCOS were assigned either to the OC or to the OC + metformin treatment by computer-assisted randomization. At the end of the 4 month follow-up period, subjects were re-evaluated. RESULTS: The two groups were similar at baseline. After treatment, women in the OC + metformin group had significant decreases in BMI and WHR, and a significant increase in insulin sensitivity, in contrast to those in the OC group, who had insignificant changes in these parameters. Adding metformin also caused significant improvements in serum androstenedione and SHBG levels compared with the OC treatment alone. CONCLUSIONS: Adding metformin to the OC treatment may improve the insulin sensitivity, and may further suppress the hyperandrogenaemia in non-obese women with PCOS.
Key words: cyproterone acetate/insulin resistance/metformin/oral contraceptive/polycystic ovarian syndrome
1 To whom correspondence should be addressed at: Kuyubasi S. Fenik Apt., No. 20/17, 81040 Feneryolu, Istanbul, Turkey. E-mail: korayelter{at}marmara.edu.tr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Metwally, S. Amer, T.C. Li, and W.L. Ledger An RCT of metformin versus orlistat for the management of obese anovulatory women Hum. Reprod., April 1, 2009; 24(4): 966 - 975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nader and E. Diamanti-Kandarakis Polycystic ovary syndrome, oral contraceptives and metabolic issues: new perspectives and a unifying hypothesis Hum. Reprod., February 1, 2007; 22(2): 317 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pasquali and A. Gambineri Insulin-sensitizing agents in polycystic ovary syndrome. Eur. J. Endocrinol., June 1, 2006; 154(6): 763 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ibanez and F. de Zegher Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non-obese adolescents and women Hum. Reprod. Update, May 1, 2006; 12(3): 243 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lemay, S. Dodin, L. Turcot, F. Dechene, and J-C. Forest Rosiglitazone and ethinyl estradiol/cyproterone acetate as single and combined treatment of overweight women with polycystic ovary syndrome and insulin resistance Hum. Reprod., January 1, 2006; 21(1): 121 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ibanez, A. M. Jaramillo, A. Ferrer, and F. de Zegher High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception Hum. Reprod., September 1, 2005; 20(9): 2457 - 2462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Vural, E. Caliskan, E. Turkoz, T. Kilic, and A. Demirci Evaluation of metabolic syndrome frequency and premature carotid atherosclerosis in young women with polycystic ovary syndrome Hum. Reprod., September 1, 2005; 20(9): 2409 - 2413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Piltonen, L. Morin-Papunen, R. Koivunen, A. Perheentupa, A. Ruokonen, and J. S. Tapanainen Serum anti-Mullerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome Hum. Reprod., July 1, 2005; 20(7): 1820 - 1826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Vrbikova and D. Cibula Combined oral contraceptives in the treatment of polycystic ovary syndrome Hum. Reprod. Update, May 1, 2005; 11(3): 277 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Rautio, J S Tapanainen, A Ruokonen, and L C Morin-Papunen Effects of metformin and ethinyl estradiol-cyproterone acetate on lipid levels in obese and non-obese women with polycystic ovary syndrome Eur. J. Endocrinol., February 1, 2005; 152(2): 269 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cibula, M. Fanta, J. Vrbikova, S. Stanicka, K. Dvorakova, M. Hill, J. Skrha, J. Zivny, and J. Skrenkova The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients Hum. Reprod., January 1, 2005; 20(1): 180 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Brettenthaler, C. De Geyter, P. R. Huber, and U. Keller Effect of the Insulin Sensitizer Pioglitazone on Insulin Resistance, Hyperandrogenism, and Ovulatory Dysfunction in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3835 - 3840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ibanez and F. de Zegher Ethinylestradiol-Drospirenone, Flutamide-Metformin, or Both for Adolescents and Women with Hyperinsulinemic Hyperandrogenism: Opposite Effects on Adipocytokines and Body Adiposity J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1592 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Azziz, L. A. Sanchez, E. S. Knochenhauer, C. Moran, J. Lazenby, K. C. Stephens, K. Taylor, and L. R. Boots Androgen Excess in Women: Experience with Over 1000 Consecutive Patients J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 453 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.H.A. van Hooff, F.J. Voorhorst, M.B.H. Kaptein, R.A. Hirasing, C. Koppenaal, and J. Schoemaker Predictive value of menstrual cycle pattern, body mass index, hormone levels and polycystic ovaries at age 15 years for oligo-amenorrhoea at age 18 years Hum. Reprod., February 1, 2004; 19(2): 383 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. De Leo, A. la Marca, and F. Petraglia Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome Endocr. Rev., October 1, 2003; 24(5): 633 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Morin-Papunen, K. Rautio, A. Ruokonen, P. Hedberg, M. Puukka, and J. S. Tapanainen Metformin Reduces Serum C-Reactive Protein Levels in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4649 - 4654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Harborne, R. Fleming, H. Lyall, N. Sattar, and J. Norman Metformin or Antiandrogen in the Treatment of Hirsutism in Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4116 - 4123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cagnacci, A. M. Paoletti, A. Renzi, M. Orru, M. Pilloni, G. B. Melis, and A. Volpe Glucose Metabolism and Insulin Resistance in Women with Polycystic Ovary Syndrome during Therapy with Oral Contraceptives Containing Cyproterone Acetate or Desogestrel J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3621 - 3625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Diamanti-Kandarakis, J.-P. Baillargeon, M. J. Iuorno, D. J. Jakubowicz, and J. E. Nestler A Modern Medical Quandary: Polycystic Ovary Syndrome, Insulin Resistance, and Oral Contraceptive Pills J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 1927 - 1932. [Full Text] [PDF]
|
|
|
|
|
|
L. Morin-Papunen, I. Vauhkonen, R. Koivunen, A. Ruokonen, H. Martikainen, and J. S. Tapanainen Metformin Versus Ethinyl Estradiol-Cyproterone Acetate in the Treatment of Nonobese Women with Polycystic Ovary Syndrome: A Randomized Study J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 148 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ibanez and F. de Zegher Low-dose combination of flutamide, metformin and an oral contraceptive for non-obese, young women with polycystic ovary syndrome Hum. Reprod., January 1, 2003; 18(1): 57 - 60. [Abstract] [Full Text] [PDF]
|
|