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

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.

Original languageEnglish
Pages (from-to)4068-4074
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number7
DOIs
Publication statusPublished - Jul 2005

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Clomiphene
Ovulation Induction
Polycystic Ovary Syndrome
Metformin
Controlled Clinical Trials
Pregnancy Rate
Ovulation
Placebos
Outcome Assessment (Health Care)
Anovulation
Induced Abortion
Birth Rate
Live Birth
Therapeutics
Italy
Progesterone
Fertility
Hemorrhage
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 7, 07.2005, p. 4068-4074.

Research output: Contribution to journalArticle

Palomba, Stefano ; Orio, Francesco ; Falbo, Angela ; Manguso, Francesco ; Russo, Tiziana ; Cascella, Teresa ; Tolino, Achille ; Carmina, Enrico ; Colao, Annamaria ; Zullo, Fulvio. / 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. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 7. pp. 4068-4074.
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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.",
author = "Stefano Palomba and Francesco Orio and Angela Falbo and Francesco Manguso and Tiziana Russo and Teresa Cascella and Achille Tolino and Enrico Carmina and Annamaria Colao and Fulvio Zullo",
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AU - Palomba, Stefano

AU - Orio, Francesco

AU - Falbo, Angela

AU - Manguso, Francesco

AU - Russo, Tiziana

AU - Cascella, Teresa

AU - Tolino, Achille

AU - Carmina, Enrico

AU - Colao, Annamaria

AU - Zullo, Fulvio

PY - 2005/7

Y1 - 2005/7

N2 - 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.

AB - 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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