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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.

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