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

Stefano Palomba, Francesco Orio, Angela Falbo, Francesco Manguso, Tiziana Russo, Teresa Cascella, Achille Tolino, Enrico Carmina, Annamaria Colao, Fulvio Zullo

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)4068-4074
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number7
Publication statusPublished - Jul 2005


ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this