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

J Clin Endocrinol Metab. 2005 Jul;90(7):4068-74. doi: 10.1210/jc.2005-0110. Epub 2005 Apr 19.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anovulation / drug therapy*
  • Clomiphene / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Metformin / therapeutic use*
  • Ovulation Induction*
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Prospective Studies

Substances

  • Clomiphene
  • Metformin