This Article Full Text Full Text (PDF) All Versions of this Article: 90/7/4068    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Palomba, S. Articles by Zullo, F. Search for Related Content PubMed PubMed Citation Articles by Palomba, S. Articles by Zullo, F. Related Collections Female Endocrinology Pediatric Endocrinology

Prospective Parallel Randomized, Double-Blind, Double-Dummy Controlled Clinical Trial Comparing Clomiphene Citrate and Metformin as the First-Line Treatment for Ovulation Induction in Nonobese Anovulatory Women with Polycystic Ovary Syndrome

Department of Obstetrics and Gynecology (S.P., A.F., T.R., F.Z.), University "Magna Graecia" of Catanzaro, 80131 Naples, Italy; Departments of Molecular and Clinical Endocrinology and Oncology (F.O., T.C., A.C.), Internal Medicine (F.M.), and Obstetrics and Gynecology (A.T.), University "Federico II" of Naples, 80138 Naples, Italy; and Department of Endocrinology (E.C.), University of Palermo, 90128 Palermo, Italy

Address all correspondence and requests for reprints to: Stefano Palomba, M.D., Department of Gynecology and Obstetrics, University "Magna Graecia" of Catanzar, Via Nicolardi 188, 80131 Naples, Italy. E-mail: stefanopalomba{at}tin.it.

Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients.

Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS.

Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial.

Setting: The study was conducted at the University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated.

Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each.

Mean outcome measures: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates.

Results: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001).

Conclusions: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.

This article has been cited by other articles:

				S. Palomba and A. Falbo Metformin in therapy naive patients with polycystic ovary syndrome Hum. Reprod. Update, March 1, 2008; 14(2): 193 - 193. [Full Text] [PDF]

				J. E. Nestler Metformin for the Treatment of the Polycystic Ovary Syndrome N. Engl. J. Med., January 3, 2008; 358(1): 47 - 54. [Full Text] [PDF]

				S. Tan, S. Hahn, S. Benson, T. Dietz, H. Lahner, L. C Moeller, M. Schmidt, S. Elsenbruch, R. Kimmig, K. Mann, et al. Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance Eur. J. Endocrinol., November 1, 2007; 157(5): 669 - 676. [Abstract] [Full Text] [PDF]

				E. Moll, F. van der Veen, and M. van Wely The role of metformin in polycystic ovary syndrome: a systematic review Hum. Reprod. Update, November 1, 2007; 13(6): 527 - 537. [Abstract] [Full Text] [PDF]

				R. L. Barbieri Clomiphene Versus Metformin for Ovulation Induction in Polycystic Ovary Syndrome: The Winner Is .... J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3399 - 3401. [Full Text] [PDF]

				S. Palomba, F. Orio Jr., A. Falbo, T. Russo, A. Tolino, and F. Zullo Clomiphene Citrate Versus Metformin as First-Line Approach for the Treatment of Anovulation in Infertile Patients with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3498 - 3503. [Abstract] [Full Text] [PDF]

				S. Palomba, A. Falbo, T. Russo, F. Manguso, A. Tolino, F. Zullo, P. De Feo, and F. Orio Jr. Insulin Sensitivity after Metformin Suspension in Normal-Weight Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3128 - 3135. [Abstract] [Full Text] [PDF]

				D. Panidis, D. Farmakiotis, D. S.H. Bell, T. Geberhiwot, A. F. Jones, R. S. Legro, and E. R. Myers Treatment of Infertility in the Polycystic Ovary Syndrome N. Engl. J. Med., May 10, 2007; 356(19): 1999 - 2001. [Full Text] [PDF]

				R. S. Legro, H. X. Barnhart, W. D. Schlaff, B. R. Carr, M. P. Diamond, S. A. Carson, M. P. Steinkampf, C. Coutifaris, P. G. McGovern, N. A. Cataldo, et al. Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome N. Engl. J. Med., February 8, 2007; 356(6): 551 - 566. [Abstract] [Full Text] [PDF]

				D. S. Guzick Treating the Polycystic Ovary Syndrome the Old-Fashioned Way N. Engl. J. Med., February 8, 2007; 356(6): 622 - 624. [Full Text] [PDF]

				R. S. Legro A 27-Year-Old Woman With a Diagnosis of Polycystic Ovary Syndrome JAMA, February 7, 2007; 297(5): 509 - 519. [Abstract] [Full Text] [PDF]

				M. Manno, F. Tomei, and E. Marchesan Polycystic ovary-related miscarriage: should metformin be proposed to such frustrated women? Hum. Reprod., February 1, 2007; 22(2): 623 - 623. [Full Text] [PDF]

				E. Jauniaux, R. Farquharson, O. Christiansen, and N. Exalto Reply: Polycystic ovary-related miscarriage--should metformin be proposed to such frustrated women? Hum. Reprod., February 1, 2007; 22(2): 623 - 624. [Full Text] [PDF]

				S. Palomba, T. Russo, F. Orio Jr, A. Falbo, F. Manguso, A. Sammartino, A. Tolino, A. Colao, E. Carmina, and F. Zullo Uterine effects of clomiphene citrate in women with polycystic ovary syndrome: a prospective controlled study Hum. Reprod., November 1, 2006; 21(11): 2823 - 2829. [Abstract] [Full Text] [PDF]

				H. Al-Inany and N. Johnson Drugs for anovulatory infertility in polycystic ovary syndrome. BMJ, June 24, 2006; 332(7556): 1461 - 1462. [Full Text] [PDF]

				S. Palomba, T. Russo, F. Orio Jr, A. Falbo, F. Manguso, T. Cascella, A. Tolino, E. Carmina, A. Colao, and F. Zullo Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome Hum. Reprod., February 1, 2006; 21(2): 457 - 465. [Abstract] [Full Text] [PDF]