Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone

Fertil Steril. 2001 Feb;75(2):310-5. doi: 10.1016/s0015-0282(00)01675-7.


Objective: To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Multicenter environment.

Patient(s): Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC.

Intervention(s): Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC.

Main outcome measure(s): Ovulation and pregnancy rates.

Result(s): In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant.

Conclusion(s): In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Androstenedione / blood
  • Body Mass Index
  • Clomiphene / administration & dosage
  • Clomiphene / therapeutic use*
  • Dehydroepiandrosterone Sulfate / blood
  • Double-Blind Method
  • Drug Resistance*
  • Female
  • Follicle Stimulating Hormone / blood
  • Humans
  • Infertility, Female / etiology
  • Infertility, Female / therapy*
  • Luteinizing Hormone / blood
  • Metformin / administration & dosage
  • Metformin / therapeutic use*
  • Ovulation Induction*
  • Placebos
  • Polycystic Ovary Syndrome / complications*
  • Pregnancy
  • Testosterone / blood


  • Placebos
  • Clomiphene
  • Testosterone
  • Androstenedione
  • Dehydroepiandrosterone Sulfate
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Metformin